Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanov, Sergey V., E-mail: Sergey.Ivanov@med.nyu.edu; Ivanova, Alla V.; Goparaju, Chandra M.V.

2009-05-08

Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-Cmore » demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.« less

In vivo mutagenicity of conazole fungicides correlates with tumorigenicity.

PubMed

Ross, Jeffrey A; Moore, Tanya; Leavitt, Sharon A

2009-03-01

Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity tests. We studied the in vivo mutagenicity of these three conazoles using the Big Blue mouse assay system. Groups of mice were fed either control diet or diet containing 1800 p.p.m. triadimefon, 2500 p.p.m. propiconazole or 2000 p.p.m. myclobutanil. After 4 days of feeding, mice were immediately euthanized, livers were removed, DNA isolated and lacI genes recovered into infectious bacteriophage lambda particles by in vitro packaging. Bacteriophage with mutations in the lacI gene was detected by infecting into Escherichia coli, and mutant frequencies were determined using a colorimetric plaque assay. Propiconazole induced a 1.97-fold increase in mutant frequency compared to concurrent controls (P = 0.018) and triadimefon induced a 1.94-fold increase compared to concurrent controls (P = 0.009). Myclobutanil did not induce any change in mutant frequency (P = 0.548). These results provide the first evidence that the hepatotumorigenic conazoles are capable of inducing mutations in liver in vivo while the non-tumorigen myclobutanil is not, suggesting that mutagenicity may represent a key event in conazoles tumorigenic mode of action.

A potential microRNA signature for tumorigenic conazoles in mouse liver.

PubMed

Ross, Jeffrey A; Blackman, Carl F; Thai, Sheau-Fung; Li, Zhiguang; Kohan, Michael; Jones, Carlton P; Chen, Tao

2010-04-01

Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumorigenicity, we analyzed the microRNA expression levels in control and conazole-treated mice after 90 d of administration in feed. MicroRNAs (miRNAs) are small noncoding RNAs composed of approximately 19-24 nucleotides in length, and have been shown to interact with mRNA (usually 3' UTR) to suppress its expression. MicroRNAs play a key role in diverse biological processes, including development, cell proliferation, differentiation, and apoptosis. Groups of mice were fed either control diet or diet containing 1800 ppm triadimefon, 2500 ppm propiconazole, or 2000 ppm myclobutanil. MicroRNA was isolated from livers and analyzed using Superarray whole mouse genome miRNA PCR arrays from SABioscience. Data were analyzed using the significance analysis of microarrays (SAM) procedure. We identified those miRNAs whose expression was either increased or decreased relative to untreated controls with q < or = 0.01. The tumorigenic conazoles induced many more changes in miRNA expression than the nontumorigenic conazole. A group of 19 miRNAs was identified whose expression was significantly altered in both triadimefon- and propiconazole-treated animals but not in myclobutanil-treated animals. All but one of the altered miRNAs were downregulated compared to controls. This pattern of altered miRNA expression may represent a signature for tumorigenic conazole exposure in mouse liver after 90 d of treatment.

In vivo mutagenicity of conazole fungicides correlates with tumorigenicity

EPA Science Inventory

Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity te...

Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity.

PubMed

Shoshani, Ofer; Massalha, Hassan; Shani, Nir; Kagan, Sivan; Ravid, Orly; Madar, Shalom; Trakhtenbrot, Luba; Leshkowitz, Dena; Rechavi, Gideon; Zipori, Dov

2012-12-15

Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumor-forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA.

REST Controls Self-Renewal and Tumorigenic Competence of Human Glioblastoma Cells

PubMed Central

Conti, Luciano; Crisafulli, Laura; Brilli, Elisa; Conforti, Paola; Zunino, Franco; Magrassi, Lorenzo; Schiffer, Davide; Cattaneo, Elena

2012-01-01

The Repressor Element 1 Silencing Transcription factor (REST/NRSF) is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM) specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets. PMID:22701651

Silencing of Kv4.1 potassium channels inhibits cell proliferation of tumorigenic human mammary epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, Soo Hwa; Choi, Changsun; Hong, Seong-Geun

2009-06-26

Potassium channel activity has been shown to facilitate cell proliferation in cancer cells. In the present study, the role of Kv4.1 channels in immortal and tumorigenic human mammary epithelial cells was investigated. Kv4.1 protein expression was positively correlated with tumorigenicity. Moreover, transfection with siRNAs targeting Kv4.1 mRNA suppressed proliferation of tumorigenic mammary epithelial cells. Experiments using mRNA isolated from human breast cancer tissues revealed that the level of Kv4.1 mRNA expression varied depending on the stage of the tumor. Kv4.1 protein expression increased during stages T2 and T3 compared to normal tissue. These results demonstrated that Kv4.1 plays a rolemore » in proliferation of tumorigenic human mammary epithelial cells. In addition, elevated Kv4.1 expression may be useful as a diagnostic marker for staging mammary tumors and selective blockers of Kv4.1 may serve to suppress tumor cell proliferation.« less

Altered tumor cell growth and tumorigenicity in models of microgravity

NASA Astrophysics Data System (ADS)

Yamauchi, K.; Taga, M.; Furian, L.; Odle, J.; Sundaresan, A.; Pellis, N.; Andrassy, R.; Kulkarni, A.

Spaceflight environment and microgravity (MG) causes immune dysfunction and is a major health risk to humans, especially during long-term space missions. The effects of microgravity environment on tumor growth and carcinogenesis are yet unknown. Hence, we investigated the effects of simulated MG (SMG) on tumor growth and tumorigenicity using in vivo and in vitro models. B16 melanoma cells were cultured in static flask (FL) and rotating wall vessel bioreactors (BIO) to measure growth and properties, melanin production and apoptosis. BIO cultures had 50% decreased growth (p<0.01), increased doubling time and a 150% increase in melanin production (p<0.05). Flow cytometric analysis showed increased apoptosis in BIO. When BIO cultured melanoma cells were inoculated sc in mice there was a significant increase in tumorigenicity as compared to FL cells. Thus SMG may have supported &selected highly tumorigenic cells and it is pos sible that in addition to decreased immune function MG may alter tumor cell characteristics and invasiveness. Thus it is important to study effects of microgravity environment and its stressors using experimental tumors and SMG to understand and evaluate carcinogenic responses to true microgravity. Further studies on carcinogenic events and their mechanisms will allow us develop and formulate countermeasures and protect space travelers. Additional results will be presented. (Supported by NASA NCC8-168 grant, ADK)

Molecular alterations in tumorigenic human bronchial and breast epithelial cells induced by high let radiation

NASA Astrophysics Data System (ADS)

Hei, T. K.; Zhao, Y. L.; Roy, D.; Piao, C. Q.; Calaf, G.; Hall, E. J.

Carcinogenesis is a multi-stage process with sequence of genetic events governing the phenotypic expression of a series of transformation steps leading to the development of metastatic cancer. In the present study, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells were irradiated with graded doses of either 150 keV/μm alpha particles or 1 GeV/nucleon 56Fe ions. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Cell fusion studies indicated that radiation-induced tumorigenic phenotype in BEP2D cells could be completely suppressed by fusion with non-tumorigenic BEP2D cells. The differential expressions of known genes between tumorigenic bronchial and breast cells induced by alpha particles and their respective control cultures were compared using cDNA expression array. Among the 11 genes identified to be differentially expressed in BEP2D cells, three ( DCC, DNA-PK and p21 CIPI) were shown to be consistently down-regulated by 2 to 4 fold in all the 5 tumor cell lines examined. In contrast, their expressions in the fusion cell lines were comparable to control BEP2D cells. Similarly, expression levels of a series of genes were found to be altered in a step-wise manner among tumorigenic MCF-10F cells. The results are highly suggestive that functional alterations of these genes may be causally related to the carcinogenic process.

IN VIVO MUTAGENICITY OF CONAZOLE FUNGICIDES CORRELATES WITH TUMORIGENICITY-JOURNAL

EPA Science Inventory

Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity t...

Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer

PubMed Central

Zucker, Stanley; Hymowitz, Michelle; Rollo, Ellen E.; Mann, Richard; Conner, Cathleen E.; Cao, Jian; Foda, Hussein D.; Tompkins, David C.; Toole, Bryan P.

2001-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs. PMID:11395366

A microRNA signature for tumorigenic conazoles in mouse liver.

EPA Science Inventory

Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants o...

ALG2 regulates glioblastoma cell proliferation, migration and tumorigenicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Dunke; Wang, Feng; Pang, Yi

Apoptosis-linked gene-2 (ALG-2), also known as programmed cell death 6 (PDCD6), has recently been reported to be aberrantly expressed in various tumors and required for tumor cell viability. The aim of the present study was to investigate whether ALG-2 plays a crucial role in tumor cell proliferation, migration and tumorigenicity. In this study, we examined the expression of PDCD6 in glioblastoma cell lines and found that ALG-2 was generally expressed in glioblastoma cell lines. We also performed an analysis of an online database and found that high expression of ALG-2 was associated with poor prognosis (p = 0.039). We found that over-expressionmore » of ALG2 in glioblastoma could inhibit cell proliferation and, conversely, that down-regulation of ALG2 could promote cell proliferation. Further studies showed that over-expression of ALG2 inhibited the migration of tumor cells, whereas down-regulation of ALG2 promoted tumor cell migration. Finally, in vitro and in vivo studies showed that over-expression of ALG2 inhibited the tumorigenic ability of tumor cells, while down-regulation of ALG2 promoted tumor cell tumorigenic ability. In conclusion, ALG2 has a tumor suppressive role in glioblastoma and might be a potential target for the treatment of glioblastoma. - Highlights: • Low ALG2 expression is indicative of poor prognosis in glioblastoma patients. • ALG2 is required for cell proliferation in GBM cells. • ALG2 is involved in GBM cell migration. • ALG2 is involved in GBM cell self-renewal and tumorigenesis in vitro and in vivo.« less

Tumorigenic effects of dichloroacetic acid in female F344 rats

EPA Science Inventory

Introduction: Dichloroacetic acid (DCA) is a halogenated organic acid produced during oxidant disinfection of drinking water. Prior studies indicate that DCA may increase liver tumors in mice. Here we evaluated the hepatic tumorigenicity of DCA in female rats when given alone ...

[The Fernando Henrique Cardoso (FHC) and Luiz Inácio Lula da Silva (Lula) governments and the policy for the civil servant workforce of the Brazilian government].

PubMed

Costa, Nilson do Rosario; Lamarca, Isabel

2013-06-01

This article analyzes the configuration of the active civil servant workforce of the Brazilian government during Fernando Henrique Cardoso - FHC - (1995-2002) and Luiz Inácio Lula da Silva - Lula - (2003-2010) mandates. The article associates the condition of the workforce of the Brazilian government with the changes in the government coalition. The residual participation of the Ministry of Health (MOH) in the direct provision of public services influenced the downward trend of the federal workforce.The implementation of the Unified Health System (SUS) was strongly affected by the structural adjustment of the workforce at the federal level during the decades of 1990 and 2000.

Syndecan-1 alterations during the tumorigenic progression of human colonic Caco-2 cells induced by human Ha-ras or polyoma middle T oncogenes.

PubMed Central

Levy, P.; Munier, A.; Baron-Delage, S.; Di Gioia, Y.; Gespach, C.; Capeau, J.; Cherqui, G.

1996-01-01

The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21ras and pp60c-src in human colonic Caco-2 cells is associated with specific alterations of syndecan-1, a membrane-anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated (Val 12) human Ha-ras gene or with the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. Compared with control vector-transfected Caco-2 cells, both oncogene-transfected cell lines (1) contained smaller amounts of membrane-anchored PGs; (2) exhibited decreased syndecan-1 expression at the protein but not the mRNA level; (3) synthesized 35S-labelled syndecan-1 with decreased specific activity; (4) produced a syndecan-1 ectodomain with a lower molecular mass and reduced GAG chain size and sulphation; and (5) expressed heparanase degradative activity. These results show that the dramatic activation of the tumorigenic potential induced by oncogenic p21ras or Py-MT/pp60c-src in Caco-2 cells is associated with marked alterations of syndecan-1 expression at the translational and post-translational levels. Images Figure 2 PMID:8695359

Altered microRNA expression induced by tumorigenic conazoles in mouse liver.

EPA Science Inventory

Triadimefon, propiconazole, and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants ...

Characterization of protein marker expression, tumorigenicity, and doxorubicin chemoresistance in two new canine mammary tumor cell lines.

PubMed

Hsiao, Yen-Ling; Hsieh, Tai-Zu; Liou, Chian-Jiun; Cheng, Yeong-Hsiang; Lin, Chung-Tien; Chang, Chi-Yao; Lai, Yu-Shen

2014-09-30

Canine mammary tumors (CMTs) are the most common type of cancer found in female dogs. Establishment and evaluation of tumor cell lines can facilitate investigations of the biological mechanisms of cancer. Different cell models are used to investigate genetic, epigenetic, and cellular pathways, cancer progression, and cancer therapeutics. Establishment of new cell models will greatly facilitate research in this field. In the present study, we established and characterized two new CMT cell lines derived from a single CMT. We established two cell lines from a single malignant CMT specimen: DTK-E and DTK-SME. Morphologically, the DTK-E cells were large, flat, and epithelial-like, whereas DTK-SME cells were round and epithelial-like. Doubling times were 24 h for DTK-E and 18 h for DTK-SME. On western blots, both cell lines expressed cytokeratin AE1, vimentin, cytokeratin 7 (CK7), and heat shock protein 27 (HSP27). Moreover, investigation of chemoresistance revealed that DTK-SME was more resistant to doxorubicin-induced apoptosis than DTK-E was. After xenotransplantation, both DTK-E and DTK-SME tumors appeared within 14 days, but the average size of DTK-SME tumors was greater than that of DTK-E tumors after 56 days. We established two new cell lines from a single CMT, which exhibit significant diversity in cell morphology, protein marker expression, tumorigenicity, and chemoresistance. The results of this study revealed that the DTK-SME cell line was more resistant to doxorubicin-induced apoptosis and exhibited higher tumorigenicity in vivo than the DTK-E cell line. We anticipate that the two novel CMT cell lines established in this study will be useful for investigating the tumorigenesis of mammary carcinomas and for screening anticancer drugs.

A potential microRNA signature for tumorigenic conazoles in mouse liver

EPA Science Inventory

Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. As part of a coordinated study to understand the molecular determinants of conazole tumor...

Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia–cell cycle dual reporter

PubMed Central

Le, Anne; Stine, Zachary E.; Nguyen, Christopher; Afzal, Junaid; Sun, Peng; Hamaker, Max; Siegel, Nicholas M.; Gouw, Arvin M.; Kang, Byung-hak; Yu, Shu-Han; Cochran, Rory L.; Sailor, Kurt A.; Song, Hongjun; Dang, Chi V.

2014-01-01

Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring (“non-Warburg”) cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia-inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic “non-Warburg” cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity. PMID:25114222

NFAT Signaling and the Tumorigenic Microenvironment of the Prostate

DTIC Science & Technology

2017-12-01

ABSTRACT Although the importance of microenvironment in prostate cancer is widely recognized, the molecular and cellular processes leading from genetic ...non-invasive clinical tests. Second, the illustration of the main cellular and molecular components in the tumorigenic microenvironment provides new...potential of NFATc1 as a novel biomarker for prostate cancer diagnosis/prognosis. We will take advantage of the cellular precision, genetic manipulability

Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.

PubMed

Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K

2005-07-01

Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.

Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.

PubMed

Kehrmann, Angela; Truong, Ha; Repenning, Antje; Boger, Regina; Klein-Hitpass, Ludger; Pascheberg, Ulrich; Beckmann, Alf; Opalka, Bertram; Kleine-Lowinski, Kerstin

2013-01-01

The fusion between human tumorigenic cells and normal human diploid fibroblasts results in non-tumorigenic hybrid cells, suggesting a dominant role for tumor suppressor genes in the generated hybrid cells. After long-term cultivation in vitro, tumorigenic segregants may arise. The loss of tumor suppressor genes on chromosome 11q13 has been postulated to be involved in the induction of the tumorigenic phenotype of human papillomavirus (HPV)18-positive cervical carcinoma cells and their derived tumorigenic hybrid cells after subcutaneous injection in immunocompromised mice. The aim of this study was the identification of novel cellular genes that may contribute to the suppression of the tumorigenic phenotype of non-tumorigenic hybrid cells in vivo. We used cDNA microarray technology to identify differentially expressed cellular genes in tumorigenic HPV18-positive hybrid and parental HeLa cells compared to non-tumorigenic HPV18-positive hybrid cells. We detected several as yet unknown cellular genes that play a role in cell differentiation, cell cycle progression, cell-cell communication, metastasis formation, angiogenesis, antigen presentation, and immune response. Apart from the known differentially expressed genes on 11q13 (e.g., phosphofurin acidic cluster sorting protein 1 (PACS1) and FOS ligand 1 (FOSL1 or Fra-1)), we detected novel differentially expressed cellular genes located within the tumor suppressor gene region (e.g., EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) and leucine rich repeat containing 32 (LRRC32) (also known as glycoprotein-A repetitions predominant (GARP)) that may have potential tumor suppressor functions in this model system of non-tumorigenic and tumorigenic HeLa x fibroblast hybrid cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Reduced tumorigenicity of rat glioma cells in the brain when mediated by hygromycin phosphotransferase.

PubMed

Hormigo, A; Friedlander, D R; Brittis, P A; Zagzag, D; Grumet, M

2001-04-01

A variant of C6 glioma cells, C6R-G/H cells express hygromycin phosphotransferase (HPT) and appear to have reduced tumorigenicity in the embryonic brain. The goal of this study was to investigate their reduced capacity to generate tumors in the adult rat brain. Cell lines were implanted into rat brains and tumorigenesis was evaluated. After 3 weeks, all rats with C6 cells showed signs of neurological disease, whereas rats with C6R-G/H cells did not and were either killed then or allowed to survive until later. Histological studies were performed to analyze tumor size, malignancy, angiogenesis, and cell proliferation. Cells isolated from rat brain tumors were analyzed for mutation to HPT by testing their sensitivity to hygromycin. The results indicate that HPT suppresses tumor formation. Three weeks after implantation, only 44% of animals implanted with C6R-G/H cells developed tumors, whereas all animals that received C6 glioma cells developed high-grade gliomas. The C6R-G/H cells filled a 20-fold smaller maximal cross-sectional area than the C6 cells, and exhibited less malignant characteristics, including reduced angiogenesis, mitosis, and cell proliferation. Similar results were obtained in the brain of nude rats, indicating that the immune system did not play a significant role in suppressing tumor growth. The combination of green fluorescent protein (GFP) and HPT was more effective in suppressing tumorigenesis than either plasmid by itself, indicating that the GFP may protect against inactivation of the HPT. Interestingly. hygromycin resistance was lost in tumor cells that were recovered from a group of animals in which C6R-G/H cells formed tumors, confirming the correlation of HPT with reduced tumorigenicity.

Senescence-Induced Alterations of Laminin Chain Expression Modulate Tumorigenicity of Prostate Cancer Cells1

PubMed Central

Sprenger, Cynthia C T; Drivdahl, Rolf H; Woodke, Lillie B; Eyman, Daniel; Reed, May J; Carter, William G; Plymate, Stephen R

2008-01-01

Prostate cancer is an age-associated epithelial cancer, and as such, it contributes significantly to the mortality of the elderly. Senescence is one possible mechanism by which the body defends itself against various epithelial cancers. Senescent cells alter the microenvironment, in part, through changes to the extracellular matrix. Laminins (LMs) are extracellular proteins important to both the structure and function of the microenvironment. Overexpression of the senescence-associated gene mac25 in human prostate cancer cells resulted in increased mRNA levels of the LM α4 and β2 chains compared to empty vector control cells. The purpose of this study was to examine the effects of these senescence-induced LM chains on tumorigenicity of prostate cancer cells. We created stable M12 human prostate cancer lines overexpressing either the LM α4 or β2 chain or both chains. Increased expression of either the LM α4 or β2 chain resulted in increased in vitro migration and in vivo tumorigenicity of those cells, whereas high expression of both chains led to decreased in vitro proliferation and in vivo tumorigenicity compared to M12 control cells. This study demonstrates that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer. PMID:19048114

Genomic instability and tumorigenic induction in immortalized human bronchial epithelial cells by heavy ions

NASA Astrophysics Data System (ADS)

Hei, T. K.; Piao, C. Q.; Wu, L. J.; Willey, J. C.; Hall, E. J.

1998-11-01

Carcinogenesis is postulated to be a progressive multistage process characterized by an increase in genomic instability and clonal selection with each mutational event endowing a selective growth advantage. Genomic instability as manifested by the amplification of specific gene fragments is common among tumor and transformed cells. In the present study, immortalized human bronchial (BEP2D) cells were irradiated with graded doses of either 1GeV/nucleon 56Fe ions or 150 keV/μm alpha particles. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Tumorigenic cells showed neither ras mutations nor deletion in the p16 tumor suppressor gene. In contrast, they harbored mutations in the p53 gene and over-expressed cyclin D1. Genomic instability among transformed cells at various stage of the carcinogenic process was examined based on frequencies of PALA resistance. Incidence of genomic instability was highest among established tumor cell lines relative to transformed, non-tumorigenic and control cell lines. Treatment of BEP2D cells with a 4 mM dose of the aminothiol WR-1065 significantly reduced their neoplastic transforming response to 56Fe particles. This model provides an opportunity to study the cellular and molecular mechanisms involved in malignant transformation of human epithelial cells by heavy ions.

Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

PubMed

Zheng, Y; Gao, L; Wang, D; Zang, D

2017-08-01

The aim of the study was to detect changes in the levels of ferritin heavy chain (FHC), ferritin light chain (FLC), and transferrin in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non-INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised (ALSFRS-r) scores, and disease progression rates (DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

PubMed Central

2010-01-01

Background MCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes. Results MCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation in vivo, the inhibitors of p53 (MDM2, Pirh2, and Cop1) are constantly stimulated by MCT-1 oncoprotein. Conclusions The oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development. PMID:21138557

Effects of maple (Acer) plant part extracts on proliferation, apoptosis and cell cycle arrest of human tumorigenic and non-tumorigenic colon cells.

PubMed

González-Sarrías, Antonio; Li, Liya; Seeram, Navindra P

2012-07-01

Phenolic-enriched extracts of maple sap and syrup, obtained from the sugar and red maple species (Acer saccharum Marsh, A. rubrum L., respectively), are reported to show anticancer effects. Despite traditional medicinal uses of various other parts of these plants by Native Americans, they have not been investigated for anticancer activity. Here leaves, stems/twigs, barks and sapwoods of both maple species were evaluated for antiproliferative effects against human colon tumorigenic (HCT-116, HT-29, Caco-2) and non-tumorigenic (CCD-18Co) cells. Extracts were standardized to total phenolic and ginnalin-A (isolated in our laboratory) levels. Overall, the extracts inhibited the growth of the colon cancer more than normal cells (over two-fold), their activities increased with their ginnalin-A levels, with red > sugar maple extracts. The red maple leaf extract, which contained the highest ginnalin-A content, was the most active extract (IC₅₀  = 35 and 16 µg/mL for extract and ginnalin-A, respectively). The extracts were not cytotoxic nor did they induce apoptosis of the colon cancer cells. However, cell cycle analyses revealed that the antiproliferative effects of the extracts were mediated through cell cycle arrest in the S-phase. The results from the current study suggest that these maple plant part extracts may have potential anticolon cancer effects. Copyright © 2011 John Wiley & Sons, Ltd.

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells.

PubMed

Lin, Zhiguang; Chen, Bobin; Wu, Ting; Xu, Xiaoping

2018-05-23

Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells. © 2018 S. Karger AG, Basel.

Ionizing radiation abrogates the pro-tumorigenic capacity of cancer-associated fibroblasts co-implanted in xenografts.

PubMed

Grinde, Maria Tunset; Vik, Jørg; Camilio, Ketil André; Martinez-Zubiaurre, Inigo; Hellevik, Turid

2017-04-25

Cancer-associated fibroblasts (CAFs) are abundantly present in solid tumors and affect tumorigenesis and therapeutic responses. In the context of clinical radiotherapy, the impact of irradiated CAFs to treatment outcomes is largely unexplored. Aiming at improving radiotherapy efficacy, we have here explored the effect of radiation on the inherent pro-tumorigenic capacity of CAFs in animals. Ionizing radiation was delivered to cultured CAFs as single-high or fractionated doses. Tumor development was compared in mice receiving A549 lung tumor cells admixed with irradiated or control CAFs. Biological mechanisms behind tumor growth regulation were investigated by quantitative histology and immunohistochemistry. Viability assessments confirmed that irradiated CAFs are fully functional prior to implantation. However, the enhanced tumorigenic effect observed in tumors co-implanted with control CAFs was abrogated in tumors established with irradiated CAFs. Experiments to ascertain fate of implanted fibroblasts showed that exogenously administered CAFs reside at the implantation site for few days, suggesting that tumor growth regulation from admixed CAFs take place during initial tumor formation. Our work demonstrate that irradiated CAFs lose their pro-tumorigenic potential in vivo, affecting angiogenesis and tumor engraftment. This finding propose a previously unknown advantageous effect induced by radiotherapy, adding to the direct cytotoxic effects on transformed epithelial cells.

PCDH10 is required for the tumorigenicity of glioblastoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Echizen, Kanae; Nakada, Mitsutoshi, E-mail: mnakada@med.kanazawa-u.ac.jp; Hayashi, Tomoatsu

Highlights: • PCDH10 is required for the proliferation, survival and self-renewal of glioblastoma cells. • PCDH10 is required for glioblastoma cell migration and invasion. • PCDH10 is required for the tumorigenicity of glioblastoma cells. • PCDH10 may be a promising target for the therapy of glioblastoma. - Abstract: Protocadherin10 (PCDH10)/OL-protocadherin is a cadherin-related transmembrane protein that has multiple roles in the brain, including facilitating specific cell–cell connections, cell migration and axon guidance. It has recently been reported that PCDH10 functions as a tumor suppressor and that its overexpression inhibits proliferation or invasion of multiple tumor cells. However, the function ofmore » PCDH10 in glioblastoma cells has not been elucidated. In contrast to previous reports on other tumors, we show here that suppression of the expression of PCDH10 by RNA interference (RNAi) induces the growth arrest and apoptosis of glioblastoma cells in vitro. Furthermore, we demonstrate that knockdown of PCDH10 inhibits the growth of glioblastoma cells xenografted into immunocompromised mice. These results suggest that PCDH10 is required for the proliferation and tumorigenicity of glioblastoma cells. We speculate that PCDH10 may be a promising target for the therapy of glioblastoma.« less

A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines.

PubMed

Solarte, Víctor A; Rosas, Jaiver E; Rivera, Zuly J; Arango-Rodríguez, Martha L; García, Javier E; Vernot, Jean-Paul

2015-01-01

Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20-25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells

PubMed Central

LEHMANN, CHRISTIAN; JOBS, GABRIELE; THOMAS, MARKUS; BURTSCHER, HELMUT; KUBBIES, MANFRED

2012-01-01

The tumor-initiating capacity of primary human breast cancer cells is maintained in vitro by culturing these cells as spheres/aggregates. Inoculation of small cell numbers derived from these non-adherent cultures leads to rapid xenograft tumor formation in mice. Accordingly, injection of more differentiated monolayer cells derived from spheres results in significantly decelerated tumor growth. For our study, two breast cancer cell lines were generated from primary tumors and cultured as mammospheres or as their adherent counterparts. We examined the in vivo tumorigenicity of these cells by injecting serial dilutions into immunodeficient mice. Inoculation of 106 cells per mouse led to rapid tumor formation, irrespective of cell line or culture conditions. However, after injection of only 103 cells, solely sphere cells were highly tumorigenic. In vitro, we investigated differentiation markers, established breast CSC markers and conducted mRNA profiling. Cytokeratin 5 and 18 were increased in both monolayer cell types, indicating a more differentiated phenotype. All cell lines were CD24−/CD44+ and did not express CD133, CD326 or E-cadherin. ALDH1 activity was not detectable in any cell line. A verapamil-sensitive Hoechst side population was present in sphere cells, but there was no correlation with tumorigenicity in vivo. mRNA profiling did not reveal upregulation of relevant transcription factors. In vitro cell cycle kinetics and in vivo tumor doubling times displayed no difference between sphere and monolayer cultures. Our data indicate that intrinsic genetic and functional markers investigated are not indicative of the in vivo tumori-genicity of putative breast tumor-initiating cells. PMID:23042145

Sprouty2 enhances the tumorigenic potential of glioblastoma cells.

PubMed

Park, Jong-Whi; Wollmann, Guido; Urbiola, Carles; Fogli, Barbara; Florio, Tullio; Geley, Stephan; Klimaschewski, Lars

2018-02-23

Sprouty2 (SPRY2), a feedback regulator of receptor tyrosine kinase (RTK) signaling, has been shown to be associated with drug resistance and cell proliferation in glioblastoma (GBM), but the underlying mechanisms are still poorly defined. SPRY2 expression and survival patterns of patients with gliomas were analyzed using publicly available databases. Effects of RNA interference targeting SPRY2 on cellular proliferation in established GBM or patient-derived GBM stemlike cells were examined. Loss- or gain-of-function of SPRY2 to regulate the tumorigenic capacity was assessed in both intracranial and subcutaneous xenografts. SPRY2 was found to be upregulated in GBM, which correlated with reduced survival in GBM patients. SPRY2 knockdown significantly impaired proliferation of GBM cells but not of normal astrocytes. Silencing of SPRY2 increased epidermal growth factor-induced extracellular signal-regulated kinase (ERK) and Akt activation causing premature onset of DNA replication, increased DNA damage, and impaired proliferation, suggesting that SPRY2 suppresses DNA replication stress. Abrogating SPRY2 function strongly inhibited intracranial tumor growth and led to significantly prolonged survival of U87 xenograft-bearing mice. In contrast, SPRY2 overexpression promoted tumor propagation of low-tumorigenic U251 cells. The present study highlights an antitumoral effect of SPRY2 inhibition that is based on excessive activation of ERK signaling and DNA damage response, resulting in reduced cell proliferation and increased cytotoxicity, proposing SPRY2 as a promising pharmacological target in GBM patients.

EphA2 Receptor Unliganded Dimers Suppress EphA2 Pro-tumorigenic Signaling*

PubMed Central

Singh, Deo R.; Ahmed, Fozia; King, Christopher; Gupta, Nisha; Salotto, Matt; Pasquale, Elena B.; Hristova, Kalina

2015-01-01

The EphA2 receptor tyrosine kinase promotes cell migration and cancer malignancy through a ligand- and kinase-independent distinctive mechanism that has been linked to high Ser-897 phosphorylation and low tyrosine phosphorylation. Here, we demonstrate that EphA2 forms dimers in the plasma membrane of HEK293T cells in the absence of ephrin ligand binding, suggesting that the current seeding mechanism model of EphA2 activation is incomplete. We also characterize a dimerization-deficient EphA2 mutant that shows enhanced ability to promote cell migration, concomitant with increased Ser-897 phosphorylation and decreased tyrosine phosphorylation compared with EphA2 wild type. Our data reveal a correlation between unliganded dimerization and tumorigenic signaling and suggest that EphA2 pro-tumorigenic activity is mediated by the EphA2 monomer. Thus, a therapeutic strategy that aims at the stabilization of EphA2 dimers may be beneficial for the treatment of cancers linked to EphA2 overexpression. PMID:26363067

Viral Vector-Based Innovative Approaches to Directly Abolishing Tumorigenic Pluripotent Stem Cells for Safer Regenerative Medicine.

PubMed

Mitsui, Kaoru; Ide, Kanako; Takahashi, Tomoyuki; Kosai, Ken-Ichiro

2017-06-16

Human pluripotent stem cells (hPSCs) are a promising source of regenerative material for clinical applications. However, hPSC transplant therapies pose the risk of teratoma formation and malignant transformation of undifferentiated remnants. These problems underscore the importance of developing technologies that completely prevent tumorigenesis to ensure safe clinical application. Research to date has contributed to establishing safe hPSC lines, improving the efficiency of differentiation induction, and indirectly ensuring the safety of products. Despite such efforts, guaranteeing the clinical safety of regenerative medicine products remains a key challenge. Given the intrinsic genome instability of hPSCs, selective growth advantage of cancer cells, and lessons learned through failures in previous attempts at hematopoietic stem cell gene therapy, conventional strategies are unlikely to completely overcome issues related to hPSC tumorigenesis. Researchers have recently embarked on studies aimed at locating and directly treating hPSC-derived tumorigenic cells. In particular, novel approaches to directly killing tumorigenic cells by transduction of suicide genes and oncolytic viruses are expected to improve the safety of hPSC-based therapy. This article discusses the current status and future perspectives of methods aimed at directly eradicating undifferentiated tumorigenic hPSCs, with a focus on viral vector transduction.

Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells

PubMed Central

Chao, Hsueh-Ping; Deng, Qu; Jeter, Collene; Liu, Can; Honorio, Sofia; Li, Hangwen; Davis, Tammy; Suraneni, Mahipal; Laffin, Brian; Qin, Jichao; Li, Qiuhui; Yang, Tao; Whitney, Pamela; Shen, Jianjun; Huang, Jiaoti; Tang, Dean G.

2015-01-01

Human cancers are heterogeneous containing stem-like cancer cells operationally defined as cancer stem cells (CSCs) that possess great tumor-initiating and long-term tumor-propagating properties. In this study, we systematically dissect the phenotypic, functional and tumorigenic heterogeneity in human prostate cancer (PCa) using xenograft models and >70 patient tumor samples. In the first part, we further investigate the PSA−/lo PCa cell population, which we have recently shown to harbor self-renewing long-term tumor-propagating cells and present several novel findings. We show that discordant AR and PSA expression in both untreated and castration-resistant PCa (CRPC) results in AR+PSA+, AR+PSA−, AR−PSA−, and AR−PSA+ subtypes of PCa cells that manifest differential sensitivities to therapeutics. We further demonstrate that castration leads to a great enrichment of PSA−/lo PCa cells in both xenograft tumors and CRPC samples and systemic androgen levels dynamically regulate the relative abundance of PSA+ versus PSA−/lo PCa cells that impacts the kinetics of tumor growth. We also present evidence that the PSA−/lo PCa cells possess distinct epigenetic profiles. As the PSA−/lo PCa cell population is heterogeneous, in the second part, we employ two PSA− (Du145 and PC3) and two PSA+ (LAPC9 and LAPC4) PCa models as well as patient tumor cells to further dissect the clonogenic and tumorigenic subsets. We report that different PCa models possess distinct tumorigenic subpopulations that both commonly and uniquely express important signaling pathways that could represent therapeutic targets. Our results have important implications in understanding PCa cell heterogeneity, response to clinical therapeutics, and cellular mechanisms underlying CRPC. PMID:26246472

Isolation of stem-like cells from spontaneous feline mammary carcinomas: phenotypic characterization and tumorigenic potential.

PubMed

Barbieri, Federica; Wurth, Roberto; Ratto, Alessandra; Campanella, Chiara; Vito, Guendalina; Thellung, Stefano; Daga, Antonio; Cilli, Michele; Ferrari, Angelo; Florio, Tullio

2012-04-15

Current carcinogenesis theory states that only a small subset of tumor cells, the cancer stem cells or tumor initiating cells (TICs), are responsible for tumor formation and progression. Human breast cancer-initiating cells have been identified as CD44-expressing cells, which retain tumorigenic activity and display stem cell-like properties. Spontaneous feline mammary carcinoma (FMC) is an aggressive cancer, which shows biological similarities to the human tumor counterpart. We report the isolation and phenotypic characterization of FMC-derived stem/progenitor cells, showing in vitro self-renewal, long-lasting proliferation and in vivo tumorigenicity. Twenty-one FMC samples were collected, histologically classified and characterized for the expression of Ki67, EGFR, ER-α and CD44, by immunohistochemistry. By culture in stem cell permissive conditions, we isolated, from 13 FMCs, a CD44-positive subpopulation able to survive and proliferate in vitro as mammospheres of different sizes and morphologies. When injected in NOD/SCID mice, FMC stem-like cells initiate tumors, generating cell heterogeneity and recapitulating the original histotype. In serum-containing medium, spheroid cells showed differentiation properties as shown by morphological changes, the loss of CD44 expression and tumorigenic potential. These data show that stem-defined culture of FMC enriches for TICs and validate the use of these cells as a suitable model for comparative oncology studies of mammary biology and testing therapeutic strategies aimed at eradicating TICs. Copyright © 2012 Elsevier Inc. All rights reserved.

Associations among Work and Family Health Climate, Health Behaviors, Work Schedule and Body Weight

PubMed Central

Buden, Jennifer C.; Dugan, Alicia G.; Faghri, Pouran D.; Huedo-Medina, Tania B.; Namazi, Sara; Cherniack, Martin G.

2017-01-01

Objectives Correctional employees exhibit elevated obesity rates. This study examines interrelations among health behaviors, health climate, BMI, and work schedule. Methods Using survey results from correctional supervisors (n=157), mediation and moderated-mediation analyses were performed to examine how health behaviors explain relationships between obesity, work health climate (WHC) and family health climate (FHC), and work schedule. Results Over 85% of the sample was overweight/obese (mean BMI=30.20). Higher WHC and FHC were associated with lower BMI, mediated by nutrition and physical activity. The interaction effect between health behavior and work schedule revealed a protective effect on BMI. Overtime shiftwork may share a relationship with BMI. Conclusions Findings may have implications for reexamining organizational policies on maximum weekly overtime in corrections. They provide direction for targeted obesity interventions that encourage a supportive FHC and promote healthy behaviors among supervisors working overtime. PMID:28471768

Effects of DCK knockdown on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells.

PubMed

Shang, Q-Y; Wu, C-S; Gao, H-R

2017-09-01

The present study explored the effect that deoxycytidine kinase (DCK) knockdown had on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells. Human cervical cancer HeLa cells that had received no prior treatment were selected from the HeLa group. The HeLa-negative control (NC) group consisted of cells that had undergone an empty vector treatment, and finally the HeLa-short hairpin RNA (shRNA) group included cells that were treated by means of shRNA-DCK expression. DCK expressions were evaluated by quantitative real-time polymerase chain reaction in addition to western blotting assays. Cell proliferation was estimated using the Cell Counting Kit-8 (CCK-8) assay and cell cycle progression. Cell apoptosis was determined by flow cytometry. BALB/c nude mice (n=24) were selected to establish transplanted tumor models, with gross tumor volume measured every 3 days. The results in vitro were as follows: compared with the HeLa group, the HeLa-shRNA group exhibited downregulation of DCK expression and inhibition of cell proliferation at 48, 72 and 96 h. Additionally, more cells in the HeLa-shRNA group were arrested in G0/G1 stage and less in S and G2/M stages, as well as in promotion of cell apoptosis. In vivo results are as follows: when comparing the HeLa and HeLa-NC groups, the gross tumor volume of the transplanted tumor in nude mice in the HeLa-shRNA group was found to have decreased in 13, 16, 19 and 22 days. Based on these findings, our study suggests that DCK knockdown facilitates apoptosis while inhibiting proliferation and tumorigenicity in vivo of cervical cancer HeLa cells.

A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

PubMed Central

Solarte, Víctor A.; Rosas, Jaiver E.; Rivera, Zuly J.; Arango-Rodríguez, Martha L.; García, Javier E.; Vernot, Jean-Paul

2015-01-01

Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC. PMID:26609531

EphA2 Receptor Unliganded Dimers Suppress EphA2 Pro-tumorigenic Signaling.

PubMed

Singh, Deo R; Ahmed, Fozia; King, Christopher; Gupta, Nisha; Salotto, Matt; Pasquale, Elena B; Hristova, Kalina

2015-11-06

The EphA2 receptor tyrosine kinase promotes cell migration and cancer malignancy through a ligand- and kinase-independent distinctive mechanism that has been linked to high Ser-897 phosphorylation and low tyrosine phosphorylation. Here, we demonstrate that EphA2 forms dimers in the plasma membrane of HEK293T cells in the absence of ephrin ligand binding, suggesting that the current seeding mechanism model of EphA2 activation is incomplete. We also characterize a dimerization-deficient EphA2 mutant that shows enhanced ability to promote cell migration, concomitant with increased Ser-897 phosphorylation and decreased tyrosine phosphorylation compared with EphA2 wild type. Our data reveal a correlation between unliganded dimerization and tumorigenic signaling and suggest that EphA2 pro-tumorigenic activity is mediated by the EphA2 monomer. Thus, a therapeutic strategy that aims at the stabilization of EphA2 dimers may be beneficial for the treatment of cancers linked to EphA2 overexpression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Expression of lnterleukin-8 Correlates with Angiogenesis, Tumorigenicity, and Metastasis of Human Prostate Cancer Cells Implanted Orthotopically in Nude Mice1

PubMed Central

Sun, Jin Kim; Uehara, Hisanori; Karashima, Takashi; Mccarty, Marya; Shih, Nancy; Fidler, Isaiah J

2001-01-01

Abstract We determined whether the expression of interleukin-8 (IL-8) by human prostate cancer cells correlates with induction of angiogenesis, tumorigenicity, and production of metastasis. Low and high IL-8-producing clones were isolated from the heterogeneous PC-3 human prostate cancer cell line. The secretion of IL-8 protein correlated with transcriptional activity and levels of IL-8 mRNA. All PC-3 cells expressed both IL-8 receptors, CXCR1 and CXCR2. The low and high IL-8-producing clones were injected into the prostate of nude mice. Titration studies indicated that PC-3 cells expressing high levels of IL-8 were highly tumorigenic, producing rapidly growing, highly vascularized prostate tumors with and a 100% incidence of lymph node metastasis. Low IL-8-expressing PC-3 cells were less tumorigenic, producing slower growing and less vascularized primary tumors and a significantly lower incidence of metastasis. In situ hybridization (ISH) analysis of the tumors for expression of genes that regulate angiogenesis and metastasis showed that the expression level of IL-8, matrix metalloproteinases, vascular endothelial growth factor (VEGF), and E-cadherin corresponded with microvascular density and biological behavior of the prostate cancers in nude mice. Collectively, the data show that the expression level of IL-8 in human prostate cancer cells is associated with angiogenesis, tumorigenicity, and metastasis. PMID:11326314

Tumorigenic Evaluation of Jet Fuels JP-TS and JP-7.

DTIC Science & Technology

1991-04-01

DTIC AL-TR-1991 0020 3 ELECTE0 AD-A252 012 JUN 2 6 1992• • TUMORIGENIC EVALUATION OF JET FUELS JP-TS AND JP-7 E. R. Kinkead C. L. Gaworski C. D...Evaluation of Jet Fuels JP-TS and JP-7. The research described in this report began in March 1981 and was completed in February 1991 under U.S. Air Force...of jet engines in military and commercial aircraft has led to the development of a number of petroleum distillate fuels with special properties. These

Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells

PubMed Central

Iaccino, Enrico; Scicchitano, Stefania; Lupia, Michela; Chiarella, Emanuela; Mega, Tiziana; Bernaudo, Francesca; Pelaggi, Daniela; Mesuraca, Maria; Pazzaglia, Simonetta; Semenkow, Samantha; Bar, Eli E.; Kool, Marcel; Pfister, Stefan; Bond, Heather M.; Eberhart, Charles G.; Steinkühler, Christian; Morrone, Giovanni

2013-01-01

The stem cell-associated transcription co-factor ZNF521 has been implicated in the control of hematopoietic, osteo-adipogenic and neural progenitor cells. ZNF521 is highly expressed in cerebellum and in particular in the neonatal external granule layer that contains candidate medulloblastoma cells-of-origin, and in the majority of human medulloblastomas. Here we have explored its involvement in the control of human and murine medulloblastoma cells. The effect of ZNF521 on growth and tumorigenic potential of human medulloblastoma cell lines as well as primary Ptc1−/+ mouse medulloblastoma cells was investigated in a variety of in vitro and in vivo assays, by modulating its expression using lentiviral vectors carrying the ZNF521 cDNA, or shRNAs that silence its expression. Enforced overexpression of ZNF521 in DAOY medulloblastoma cells significantly increased their proliferation, growth as spheroids and ability to generate clones in single-cell cultures and semisolid media, and enhanced their migratory ability in wound-healing assays. Importantly, ZNF521-expressing cells displayed a greatly enhanced tumorigenic potential in nude mice. All these activities required the ZNF521 N-terminal motif that recruits the nucleosome remodeling and histone deacetylase complex, which might therefore represent an appealing therapeutic target. Conversely, silencing of ZNF521 in human UW228 medulloblastoma cells that display high baseline expression decreased their proliferation, clonogenicity, sphere formation and wound-healing ability. Similarly, Zfp521 silencing in mouse Ptc1−/+ medulloblastoma cells drastically reduced their growth and tumorigenic potential. Our data strongly support the notion that ZNF521, through the recruitment of the NuRD complex, contributes to the clonogenic growth, migration and tumorigenicity of medulloblastoma cells. PMID:23907569

Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells.

PubMed

Spina, Raffaella; Filocamo, Gessica; Iaccino, Enrico; Scicchitano, Stefania; Lupia, Michela; Chiarella, Emanuela; Mega, Tiziana; Bernaudo, Francesca; Pelaggi, Daniela; Mesuraca, Maria; Pazzaglia, Simonetta; Semenkow, Samantha; Bar, Eli E; Kool, Marcel; Pfister, Stefan; Bond, Heather M; Eberhart, Charles G; Steinkühler, Christian; Morrone, Giovanni

2013-08-01

The stem cell-associated transcription co-factor ZNF521 has been implicated in the control of hematopoietic, osteo-adipogenic and neural progenitor cells. ZNF521 is highly expressed in cerebellum and in particular in the neonatal external granule layer that contains candidate medulloblastoma cells-of-origin, and in the majority of human medulloblastomas. Here we have explored its involvement in the control of human and murine medulloblastoma cells. The effect of ZNF521 on growth and tumorigenic potential of human medulloblastoma cell lines as well as primary Ptc1-/+ mouse medulloblastoma cells was investigated in a variety of in vitro and in vivo assays, by modulating its expression using lentiviral vectors carrying the ZNF521 cDNA, or shRNAs that silence its expression. Enforced overexpression of ZNF521 in DAOY medulloblastoma cells significantly increased their proliferation, growth as spheroids and ability to generate clones in single-cell cultures and semisolid media, and enhanced their migratory ability in wound-healing assays. Importantly, ZNF521-expressing cells displayed a greatly enhanced tumorigenic potential in nude mice. All these activities required the ZNF521 N-terminal motif that recruits the nucleosome remodeling and histone deacetylase complex, which might therefore represent an appealing therapeutic target. Conversely, silencing of ZNF521 in human UW228 medulloblastoma cells that display high baseline expression decreased their proliferation, clonogenicity, sphere formation and wound-healing ability. Similarly, Zfp521 silencing in mouse Ptc1-/+ medulloblastoma cells drastically reduced their growth and tumorigenic potential. Our data strongly support the notion that ZNF521, through the recruitment of the NuRD complex, contributes to the clonogenic growth, migration and tumorigenicity of medulloblastoma cells.

Quantitative changes in endogenous DNA adducts correlate with conazole in vivo mutagenicity and tumorigenicity.

PubMed

Ross, Jeffrey A; Leavitt, Sharon A; Schmid, Judith E; Nelson, Garret B

2012-09-01

The mouse liver tumorigenic conazole fungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue™ transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazole myclobutanil was not mutagenic. DNA sequencing of the mutants recovered from each treatment group as well as from animals receiving control diet revealed that propiconazole- and triadimefon-induced mutations do not represent general clonal expansion of background mutations, and support the hypothesis that they arise from the accumulation of endogenous reactive metabolic intermediates within the liver in vivo. We therefore measured the spectra of endogenous DNA adducts in the livers of mice from these studies to determine if there were quantitative or qualitative differences between mice receiving tumorigenic or nontumorigenic conazoles compared to concurrent control animals. We resolved and quantitated 16 individual adduct spots by (32)P postlabelling and thin layer chromatography using three solvent systems. Qualitatively, we observed the same DNA adducts in control mice as in mice receiving conazoles. However, the 13 adducts with the highest chromatographic mobility were, as a group, present at significantly higher amounts in the livers of mice treated with propiconazole and triadimefon than in their concurrent controls, whereas this same group of DNA adducts in the myclobutanil-treated mice was not different from controls. This same group of endogenous adducts were significantly correlated with mutant frequency across all treatment groups (P = 0.002), as were total endogenous DNA adduct levels (P = 0.005). We hypothesise that this treatment-related increase in endogenous DNA adducts, together with concomitant increases in cell proliferation previously reported to be induced by conazoles, explain the observed increased in vivo mutation frequencies previously reported to be induced by treatment with

Cell membrane-anchored MUC4 promotes tumorigenicity in epithelial carcinomas

PubMed Central

Xia, Pengpeng; Choi, Agnes Hakyung; Deng, Zengping; Yang, Yuqian; Zhao, Jing; Wang, Yiting; Hardwidge, Philip R.; Zhu, Guoqiang

2017-01-01

The cell surface membrane-bound mucin protein MUC4 promotes tumorigenicity, aggressive behavior, and poor outcomes in various types of epithelial carcinomas, including pancreatic, breast, colon, ovarian, and prostate cancer. This review summarizes the theories and findings regarding MUC4 function, and its role in epithelial carcinogenesis. Based on these insights, we developed an outline of the processes and mechanisms by which MUC4 critically supports the propagation and survival of cancer cells in various epithelial organs. MUC4 may therefore be a useful prognostic and diagnostic tool that improves our ability to eradicate various forms of cancer. PMID:27829225

Cell membrane-anchored MUC4 promotes tumorigenicity in epithelial carcinomas.

PubMed

Xia, Pengpeng; Choi, Agnes Hakyung; Deng, Zengping; Yang, Yuqian; Zhao, Jing; Wang, Yiting; Hardwidge, Philip R; Zhu, Guoqiang

2017-02-21

The cell surface membrane-bound mucin protein MUC4 promotes tumorigenicity, aggressive behavior, and poor outcomes in various types of epithelial carcinomas, including pancreatic, breast, colon, ovarian, and prostate cancer. This review summarizes the theories and findings regarding MUC4 function, and its role in epithelial carcinogenesis. Based on these insights, we developed an outline of the processes and mechanisms by which MUC4 critically supports the propagation and survival of cancer cells in various epithelial organs. MUC4 may therefore be a useful prognostic and diagnostic tool that improves our ability to eradicate various forms of cancer.

Overexpression of p42.3 promotes cell growth and tumorigenicity in hepatocellular carcinoma

PubMed Central

Sun, Wei; Dong, Wei-Wei; Mao, Lin-Lin; Li, Wen-Mei; Cui, Jian-Tao; Xing, Rui; Lu, You-Yong

2013-01-01

AIM: To investigate the association of p42.3 expression with clinicopathological characteristics and the biological function of p42.3 in human hepatocellular carcinoma (HCC). METHODS: We used reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR and western blotting to detect p42.3 mRNA and protein expression in hepatic cell lines. We examined primary HCC samples and matched adjacent normal tissue by immunohistochemistry to investigate the correlation between p42.3 expression and clinicopathological features. HepG2 cells were transfected with a pIRES2-EGFP-p42.3 expression vector to examine the function of the p42.3 gene. Transfected cells were analyzed for their viability and malignant transformation abilities by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, and tumorigenicity assay in nude mice. RESULTS: p42.3 is differentially expressed in primary HCC tumors and cell lines. Approximately 69.6% (96/138) of cells were p42.3-positive in hepatic tumor tissues, while 30.7% (35/114) were p42.3-positive in tumor-adjacent normal tissues. Clinicopathological characteristics of the HCC specimens revealed a significant correlation between p42.3 expression and tumor differentiation (P = 0.031). However, p42.3 positivity was not related to tumor tumor-node-metastasis classification, hepatitis B virus status, or hepatoma type. Regarding p42.3 overexpression in stably transfected HepG2 cells, we discovered significant enhancement of cancer cell growth and colony formation in vitro, and significantly enhanced tumorigenicity in nude mice. Western blot analysis of cell cycle proteins revealed that enhanced p42.3 levels promote upregulation of proliferating cell nuclear antigen, cyclin B1 and mitotic arrest deficient 2. CONCLUSION: p42.3 promotes tumorigenicity and tumor growth in HCC and may be a potential target for future clinical cancer therapeutics. PMID:23704824

Temozolomide-induced increase of tumorigenicity can be diminished by targeting of mitochondria in in vitro models of patient individual glioblastoma

PubMed Central

Walther, Madlin; Schneider, Björn; Linnebacher, Michael; Classen, Carl Friedrich

2018-01-01

Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro. In this study, treatment of several primary GBM cell lines with clinically relevant doses of temozolomide increased their tumorigenicity as determined by colony formation assays in soft agar. Increased tumorigenicity is a known property of CSCs. Hence, therapy options that specifically target CSCs are under investigation. CSCs appear to be particularly dependent on mitochondria biogenesis which may represent a useful target for CSC elimination. Toxicity towards mitochondria is a known side effect of several antibiotics. Thus, addition of antibiotics like doxycycline may represent a useful tool to inhibit CSCs in GBM. Here, we show that combining temozolomide treatment of primary GBM cells with doxycycline could counteract the increase of tumorigenicity induced by temozolomide treatment. PMID:29352318

Imaging in real-time with FRET the redox response of tumorigenic cells to glutathione perturbations in a microscale flow†

PubMed Central

Lin, Chunchen; Kolossov, Vladimir L.; Tsvid, Gene; Trump, Lisa; Henry, Jennifer Jo; Henderson, Jerrod L.; Rund, Laurie A.; Kenis, Paul J.A.; Schook, Lawrence B.; Gaskins, H. Rex; Timp, Gregory

2012-01-01

Despite the potential benefits of selective redox-modulating strategies for cancer therapy, an efficacious methodology for testing therapies remains elusive because of the difficulty in measuring intracellular redox potentials over time. In this report, we have incorporated a new FRET-based biosensor to follow in real time redox-sensitive processes in cells transformed to be tumorigenic and cultured in a microfluidic channel. A microfluidic network was used to control micro-scale flow near the cells and at the same time deliver drugs exogenously. Subsequently, the response of a redox homeostasis circuit was tested, namely reduced glutathione (GSH)/oxidized glutathione(GSSG), to diamide, a thiol oxidant, and two drugs used for cancer therapies: BSO (l-buthionine-[SR]-sulfoximine) and BCNU (carmustine). The main outcome from these experiments is a comparison of the temporal depletion and recovery of GSH in single living cells in real-time. These data demonstrate that mammalian cells are capable of restoring a reduced intracellular redox environment in minutes after an acute oxidative insult is removed. This recovery is significantly delayed by (i) the inhibition of GSH biosynthesis by BSO; (ii) the inactivation of glutathione reductase by BCNU; and (iii) in tumorigenic cells relative to an isogenic non-tumorigenic control cell line. PMID:21183971

Dimethyl fumarate is highly cytotoxic in KRAS mutated cancer cells but spares non-tumorigenic cells.

PubMed

Bennett Saidu, Nathaniel Edward; Bretagne, Marie; Mansuet, Audrey Lupo; Just, Pierre-Alexandre; Leroy, Karen; Cerles, Olivier; Chouzenoux, Sandrine; Nicco, Carole; Damotte, Diane; Alifano, Marco; Borghese, Bruno; Goldwasser, François; Batteux, Frédéric; Alexandre, Jérôme

2018-02-06

KRAS mutation, one of the most common molecular alterations observed in adult carcinomas, was reported to activate the anti-oxidant program driven by the transcription factor NRF2 (Nuclear factor-erythroid 2-related factor 2). We previously observed that the antitumoral effect of Dimethyl fumarate (DMF) is dependent of NRF2 pathway inhibition. We used in vitro methods to examine the effect of DMF on cell death and the activation of the NRF2/DJ-1 antioxidant pathway. We report here that DMF is preferentially cytotoxic against KRAS mutated cancer cells. This effect was observed in patient-derived cancer cell lines harbouring a G12V KRAS mutation, compared with cell lines without such a mutation. In addition, KRAS*G12V over-expression in the human Caco-2 colon cancer cell line significantly promoted DMF-induced cell death, as well as DMF-induced- reactive oxygen species (ROS) formation and -glutathione (GSH) depletion. Moreover, in contrast to malignant cells, our data confirms that the same concentration of DMF has no significant cytotoxic effects on non-tumorigenic human ARPE-19 retinal epithelial, murine 3T3 fibroblasts and primary mice bone marrow cells; but is rather associated with NRF2 activation, decreased ROS and increased GSH levels. Furthermore, DJ-1 down-regulation experiments showed that this protein does not play a protective role against NRF2 in non-tumorigenic cells, as it does in malignant ones. This, interestingly, could be at the root of the differential effect of DMF observed between malignant and non-tumorigenic cells. Our results suggest for the first time that the dependence on NRF2 observed in mutated KRAS malignant cells makes them more sensitive to the cytotoxic effect of DMF, which thus opens up new prospects for the therapeutic applications of DMF.

Soft agar-based selection of spontaneously transformed rat prostate epithelial cells with highly tumorigenic characteristics.

PubMed

Gajdošik, Martina Šrajer; Hixson, Douglas C; Brilliant, Kate E; Yang, DongQin; De Paepe, Monique E; Josić, Djuro; Mills, David R

2018-05-29

The critical molecular and cellular mechanisms involved in the development and progression of prostate cancer remain elusive. In this report, we demonstrate that normal rat prostate epithelial cells (PEC) undergo spontaneous transformation at high passage (p > 85) evidenced by the acquisition of anchorage independent growth when plated on soft agar and tumorigenicity when injected into immunodeficient mice. In addition, we also report the discovery of a minor subpopulation of spontaneously transformed PEC derived from high passage PEC with the ability to migrate through a layer of 1% agar and form expanding colonies on the underlying plastic substratum. Comparison of these soft agar invasive (SAI) cells with low (p < 35), mid (p36-84) and high passage (p > 85) PEC identified marked differences in cell morphology, proliferation and motility. The SAI subpopulation was more tumorigenic than the high passage anchorage independent cultures from which they were isolated, as manifested by a decreased latency period and an increase in the size of tumors arising in immunodeficient mice. In contrast, low and mid passage cells were unable to grow on soft agar and failed to form tumors when injected into immunodeficient mice. Screening with antibody-based signaling arrays identified several differences in the altered expression levels of signaling proteins between SAI-derived cells and low or high passage PEC, including the up-regulation of EGFR and MAPK-related signaling pathways in SAI-selected cells. In summary, these studies suggest that the SAI assay selects for a novel, highly tumorigenic subpopulation of transformed cells that may represent an early step in the progression of slow growing prostatic carcinomas into more rapidly growing and aggressive tumors. Copyright © 2017. Published by Elsevier Inc.

Diverse manifestations of tumorigenicity and immunogenicity displayed by the poorly immunogenic B16-BL6 melanoma transduced with cytokine genes.

PubMed

Arca, M J; Krauss, J C; Strome, S E; Cameron, M J; Chang, A E

1996-05-01

We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete interleukin-2 (IL-2), IL-4, interferon gamma (IFN gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFN gamma and IL-4 partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy. Neither IL-2 nor IFN gamma secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not lead to enhanced induction of immune T cells. GM-CSF secretion was found to upregulate B7-1 expression in TDLN, consistent with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T cell immune reactivity to the poorly immunogenic BL6 tumor.

Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP).

PubMed

Zscharnack, Matthias; Krause, Christoph; Aust, Gabriela; Thümmler, Christian; Peinemann, Frank; Keller, Thomas; Smink, Jeske J; Holland, Heidrun; Somerson, Jeremy S; Knauer, Jens; Schulz, Ronny M; Lehmann, Jörg

2015-05-20

The clinical development of advanced therapy medicinal products (ATMPs), a new class of drugs, requires initial safety studies that deviate from standard non-clinical safety protocols. The study provides a strategy to address the safety aspects of biodistribution and tumorigenicity of ATMPs under good laboratory practice (GLP) conditions avoiding cell product manipulation. Moreover, the strategy was applied on a human ATMP for cartilage repair. The testing strategy addresses biodistribution and tumorigenicity using a multi-step analysis without any cell manipulation to exclude changes of test item characteristics. As a safeguard measurement for meeting regulatory expectations, the project design and goals were discussed continuously with the regulatory authority using a staggered scientific advice concept. Subsequently, the strategy was applied to co.don chondrosphere® (huChon spheroid), a tissue-engineered matrix-free ATMP of human normal chondrocytes. In both the biodistribution and tumorigenicity studies, huChon spheroids were implanted subcutaneously into 40 immunodeficient mice. Biodistribution was studied 1 month after implantation. A skin disc containing the huChon spheroid, two surrounding skin rings and selected organs were analyzed by validated, gender-specific, highly-sensitive triplex qPCR and by immunohistochemistry (IHC). No human DNA was detected in distant skin rings and analyzed organs. IHC revealed no direct or indirect indications of cell migration. Tumorigenicity was assessed 6 months after huChon spheroid implantation by palpation, macroscopic inspection, histology and IHC. No mice from the huChon spheroid group developed a tumor at the implantation site. In two mice, benign tumors were detected that were negative for HLA-ABC, suggesting that they were of spontaneous murine origin. In summary, the presented strategy using a multi-step analysis was confirmed to be suitable for safety studies of ATMPs.

Role of TGF-β signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells

PubMed Central

Datta, Raktima; Halder, Sunil K.

2014-01-01

Purpose Curcumin has been shown to have potent anti-cancer activities like inhibition of cell proliferation, induction of apoptosis, and suppression of angiogenesis. Transforming growth factor-β (TGF-β) signaling plays a complex role in tumor suppression and promotion depending on the tumor type and stage. However, the effect of curcumin on TGF-β signaling in cancer cells and the role of TGF-β signaling in curcumin-induced anticancer activities have not been determined. Here, we investigate the role of curcumin on TGF-β signaling, and whether TGF-β signaling is involved in the antitumor activities of curcumin. Methods Human non-small cell lung cancer (NSCLC) cell lines, ACC-LC-176 (without TGF-β signaling), H358, and A549 (with TGF-β signaling) were treated with curcumin to determine cell growth, apoptosis, and tumorigenicity. Antitumor activities of curcumin were determined using these cell lines and an in vivo mouse model. We also tested the effect of curcumin on TGF-β/Smad signaling by western blotting and by luciferase assays. Results Curcumin inhibited cell growth and induced apoptosis of all three NSCLC cell lines in vitro and in vivo. It significantly reduced subcutaneous tumor growth by these three cell lines irrespective of TGF-β signaling status. Curcumin inhibited TGF-β-induced Smad2/3 phosphorylation and transcription in H358 and A549 cells, but not in ACC-LC-176 cells. Conclusions Curcumin reduces tumorigenicity of human lung cancer cells in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. These results suggest that TGF-β signaling is not directly involved in curcumin-mediated growth inhibition, induction of apoptosis, and inhibition of tumorigenicity. PMID:23224523

Gene expression profiling as an initial approach for mechanistic studies of toxicity and tumorigenicity of herbal plants and herbal dietary supplements.

PubMed

Guo, Lei; Mei, Nan; Xia, Qingsu; Chen, Tao; Chan, Po-Chuen; Fu, Peter P

2010-01-01

Dietary supplements are consumed by more than 300 million people worldwide, and herbal dietary supplements represent the most rapidly growing portion of this industry. Even though adverse health effects of many herbal dietary supplements have been reported, safety assurances are not being addressed adequately. Toxicological data on the identification of genotoxic and tumorigenic ingredients in many raw herbs are also lacking. Currently, more than 30 herbal dietary supplements and active ingredients have been selected by the National Toxicology Program (NTP) for toxicity and tumorigenicity studies. Due to the complexity of the chemical components present in plant extracts, there are no established methodologies for determining the mechanisms of toxicity (particularly tumorigenicity) induced by herbs, such as Gingko biloba leaf extract (GBE) and other herbal plant extracts. Consequently, the understanding of toxicity of herbal dietary supplements remains limited. We have proposed that application of DNA microarrays could be a highly practical initial approach for revealing biological pathways and networks associated with toxicity induced by herbal dietary supplements and the generation of hypotheses to address likely mechanisms. The changes in expression of subsets of genes of interest, such as the modulation of drug metabolizing genes, can be analyzed after treatment with an herbal dietary supplement. Although levels of gene expression do not represent fully the levels of protein activities, we propose that subsequent biochemical and genomic experiments based on these initial observations will enable elucidation of the mechanisms leading to toxicity, including tumorigenicity. This review summarizes the current practices of microarray analysis of gene expressions in animals treated with herbal dietary supplements and discusses perspectives for the proposed strategy.

Nitric oxide-releasing nanoparticles: synthesis, characterization, and cytotoxicity to tumorigenic cells

NASA Astrophysics Data System (ADS)

Pelegrino, Milena T.; Silva, Letícia C.; Watashi, Carolina M.; Haddad, Paula S.; Rodrigues, Tiago; Seabra, Amedea B.

2017-02-01

Nitric oxide (NO) is involved in several biological processes, including toxicity against tumor cells. The aim of this study was to synthesize, characterize, and evaluate the cytotoxicity of NO-releasing chitosan nanoparticles. A thiol-containing molecule, mercaptosuccinic acid (MSA), was encapsulated (encapsulation efficiency of 99%) in chitosan/sodium tripolyphosphate nanoparticles (CS NPs). The obtained nanoparticles showed an average hydrodynamic size of 108.40 ± 0.96 nm and polydispersity index of 0.26 ± 0.01. MSA-CS NPs were nitrosated leading to S-nitroso-MSA-CS NPs, which act as NO donor. The cytotoxicity of CS NPs, MSA-CS NPs, and S-nitroso-MSA-CS NPs were evaluated in several tumor cells, including human hepatocellular carcinoma (HepG2), mouse melanoma (B16F10), and human chronic myeloid leukemia (K562) cell lines and Lucena-1, a vincristine-resistant K562 cell line. Both CS NPs and MSA-CS NPs did not cause toxic effects in these cells, whereas S-nitroso-MSA-CS NPs caused potent cytotoxic effects in all the tested tumor cell lines. The half-maximal inhibitory concentration values of S-nitroso-MSA-CS NPs were 19.7, 10.5, 22.8, and 27.8 μg·mL-1 for HepG2, B16F10, K562, and Lucena-1 cells, respectively. In contrast, S-nitroso-MSA-CS NPs exhibited lower cytotoxic to non-tumorigenic melanocytes (Melan-A) when compared with melanoma B16F10. Therefore, the results highlight the potential use of NO-releasing CS NPs in antitumor chemotherapy.

Ferritin heavy chain is a negative regulator of ovarian cancer stem cell expansion and epithelial to mesenchymal transition

PubMed Central

Pisanu, Maria Elena; Faniello, Maria Concetta; Jakopin, Žiga; Chiarella, Emanuela; Giovannone, Emilia Dora; Mancini, Rita; Ciliberto, Gennaro

2016-01-01

Objectives Ferritin is the major intracellular iron storage protein essential for maintaining the cellular redox status. In recent years ferritin heavy chain (FHC) has been shown to be involved also in the control of cancer cell growth. Analysis of public microarray databases in ovarian cancer revealed a correlation between low FHC expression levels and shorter survival. To better understand the role of FHC in cancer, we have silenced the FHC gene in SKOV3 cells. Results FHC-KO significantly enhanced cell viability and induced a more aggressive behaviour. FHC-silenced cells showed increased ability to form 3D spheroids and enhanced expression of NANOG, OCT4, ALDH and Vimentin. These features were accompanied by augmented expression of SCD1, a major lipid metabolism enzyme. FHC apparently orchestrates part of these changes by regulating a network of miRNAs. Methods FHC-silenced and control shScr SKOV3 cells were monitored for changes in proliferation, migration, ability to propagate as 3D spheroids and for the expression of stem cell and epithelial-to-mesenchymal-transition (EMT) markers. The expression of three miRNAs relevant to spheroid formation or EMT was assessed by q-PCR. Conclusions In this paper we uncover a new function of FHC in the control of cancer stem cells. PMID:27566559

Differentiation of a Highly Tumorigenic Basal Cell Compartment in Urothelial Carcinoma

PubMed Central

He, Xiaobing; Marchionni, Luigi; Hansel, Donna E.; Yu, Wayne; Sood, Akshay; Yang, Jie; Parmigiani, Giovanni; Matsui, William; Berman, David M.

2011-01-01

Highly tumorigenic cancer cell (HTC) populations have been identified for a variety of solid tumors and assigned stem cell properties. Strategies for identifying HTCs in solid tumors have been primarily empirical rather than rational, particularly in epithelial tumors, which are responsible for 80% of cancer deaths. We report evidence for a spatially restricted bladder epithelial (urothelial) differentiation program in primary urothelial cancers (UCs) and in UC xenografts. We identified a highly tumorigenic UC cell compartment that resembles benign urothelial stem cells (basal cells), co-expresses the 67-kDa laminin receptor and the basal cell-specific cytokeratin CK17, and lacks the carcinoembryonic antigen family member CEACAM6 (CD66c). This multipotent compartment resides at the tumor-stroma interface, is easily identified on histologic sections, and possesses most, if not all, of the engraftable tumor-forming ability in the parental xenograft. We analyzed differential expression of genes and pathways in basal-like cells versus more differentiated cells. Among these, we found significant enrichment of pathways comprising “hallmarks” of cancer, and pharmacologically targetable signaling pathways, including Janus kinase-signal transducer and activator of transcription, Notch, focal adhesion, mammalian target of rapamycin, epidermal growth factor receptor (erythroblastic leukemia viral oncogene homolog [ErbB]), and wingless-type MMTV integration site family (Wnt). The basal/HTC gene expression signature was essentially invisible within the context of nontumorigenic cell gene expression and overlapped significantly with genes driving progression and death in primary human UC. The spatially restricted epithelial differentiation program described here represents a conceptual advance in understanding cellular heterogeneity of carcinomas and identifies basal-like HTCs as attractive targets for cancer therapy. PMID:19544456

Fetal head circumference, operative delivery, and fetal outcomes: a multi-ethnic population-based cohort study

PubMed Central

2013-01-01

Background Operative delivery procedures, such as primary cesarean section, vacuum-assisted, and forceps-assisted vaginal delivery increase maternal and fetal morbidity, and the cost of care. We evaluated whether large fetal head circumference (FHC) independently increases risk of such interventions, as well as fetal distress or low Apgar score, in anatomically normal infants. Methods We conducted a population-based retrospective cohort study using Washington State birth certificate data. We included singleton, term infants born to nulliparous mothers from 2003–2009. We compared mode of delivery and fetal outcomes in 10,750 large-FHC (37-41 cm) infants relative to 10,750 average-FHC (34 cm) infants, frequency matched by birth-year. Results Large-FHC infants were nearly twice as likely to be delivered by primary cesarean section as average-FHC infants (unadjusted relative risk [RR] 1.84, 95% confidence interval [CI]: 1.77, 1.92). The RR for primary cesarean section associated with large-FHC was largest for mothers aged 19 years or less (RR 2.28; 95% CI: 1.99, 2.61), and smallest for mothers aged 35 years or greater (RR 1.51; 95% CI: 1.37, 1.66) [test of homogeneity, p < 0.001]. Large-FHC infants were at increased risk of vacuum-assisted vaginal delivery (RR 1.55; 95% CI: 1.43, 1.69), and forceps-assisted vaginal delivery (RR 1.61; 95% CI: 1.32, 1.97). There was no difference in risk of fetal distress (RR 0.97; 95% CI: 0.89, 1.07) for large-FHC versus average-FHC infants. Risk estimates were unaffected by adjustment for potential confounders. Conclusions Nulliparous mothers of large-FHC infants are at increased risk of primary cesarean section, vacuum-assisted and forceps-assisted vaginal delivery relative to mothers of average-FHC infants. Maternal age modifies the association between FHC and primary cesarean section. PMID:23651454

Transfer of chromosome 3 fragments suppresses tumorigenicity of an ovarian cancer cell line monoallelic for chromosome 3p.

PubMed

Cody, N A L; Ouellet, V; Manderson, E N; Quinn, M C J; Filali-Mouhim, A; Tellis, P; Zietarska, M; Provencher, D M; Mes-Masson, A-M; Chevrette, M; Tonin, P N

2007-01-25

Multiple chromosome 3p tumor suppressor genes (TSG) have been proposed in the pathogenesis of ovarian cancer based on complex patterns of 3p loss. To attain functional evidence in support of TSGs and identify candidate regions, we applied a chromosome transfer method involving cell fusions of the tumorigenic OV90 human ovarian cancer cell line, monoallelic for 3p and an irradiated mouse cell line containing a human chromosome 3 in order to derive OV90 hybrids containing normal 3p fragments. The resulting hybrids showed complete or incomplete suppression of tumorigenicity in nude mouse xenograft assays, and varied in their ability to form colonies in soft agarose and three-dimensional spheroids in a manner consistent with alteration of their in vivo tumorigenic phenotypes. Expression microarray analysis identified a set of common differentially expressed genes, such as SPARC, DAB2 and VEGF, some of which have been shown implicated in ovarian cancer. Genotyping assays revealed that they harbored normal 3p fragments, some of which overlapped candidate TSG regions (3p25-p26, 3p24 and 3p14-pcen) identified previously in loss of heterozygosity analyses of ovarian cancers. However, only the 3p12-pcen region was acquired in common by all hybrids where expression microarray analysis identified differentially expressed genes. The correlation of 3p12-pcen transfer and tumor suppression with a concerted re-programming of the cellular transcriptome suggest that the putative TSG may have affected key underlying events in ovarian cancer.

Culture conditions tailored to the cell of origin are critical for maintaining native properties and tumorigenicity of glioma cells

PubMed Central

Ledur, Pítia F.; He, Hua; Harris, Alexandra R.; Minussi, Darlan C.; Zhou, Hai-Yan; Shaffrey, Mark E.; Asthagiri, Ashok; Lopes, Maria Beatriz S.; Schiff, David; Lu, Yi-Cheng; Mandell, James W.; Lenz, Guido; Zong, Hui

2016-01-01

Background Cell culture plays a pivotal role in cancer research. However, culture-induced changes in biological properties of tumor cells profoundly affect research reproducibility and translational potential. Establishing culture conditions tailored to the cancer cell of origin could resolve this problem. For glioma research, it has been previously shown that replacing serum with defined growth factors for neural stem cells (NSCs) greatly improved the retention of gene expression profile and tumorigenicity. However, among all molecular subtypes of glioma, our laboratory and others have previously shown that the oligodendrocyte precursor cell (OPC) rather than the NSC serves as the cell of origin for the proneural subtype, raising questions regarding the suitability of NSC-tailored media for culturing proneural glioma cells. Methods OPC-originated mouse glioma cells were cultured in conditions for normal OPCs or NSCs, respectively, for multiple passages. Gene expression profiles, morphologies, tumorigenicity, and drug responsiveness of cultured cells were examined in comparison with freshly isolated tumor cells. Results OPC media-cultured glioma cells maintained tumorigenicity, gene expression profiles, and morphologies similar to freshly isolated tumor cells. In contrast, NSC-media cultured glioma cells gradually lost their OPC features and most tumor-initiating ability and acquired heightened sensitivity to temozolomide. Conclusions To improve experimental reproducibility and translational potential of glioma research, it is important to identify the cell of origin, and subsequently apply this knowledge to establish culture conditions that allow the retention of native properties of tumor cells. PMID:27106408

The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells.

PubMed

Koyama-Nasu, R; Haruta, R; Nasu-Nishimura, Y; Taniue, K; Katou, Y; Shirahige, K; Todo, T; Ino, Y; Mukasa, A; Saito, N; Matsui, M; Takahashi, R; Hoshino-Okubo, A; Sugano, H; Manabe, E; Funato, K; Akiyama, T

2014-04-24

Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.

Tumorigenicity of acrylamide and its metabolite glycidamide in the neonatal mouse bioassay

PubMed Central

Von Tungeln, Linda S.; Doerge, Daniel R.; da Costa, Gonçalo Gamboa; Marques, M. Matilde; Witt, William M.; Koturbash, Igor; Pogribny, Igor P.; Beland, Frederick A.

2012-01-01

Acrylamide is a high-volume industrial chemical, a component of cigarette smoke, and a product formed in certain foods prepared at high temperatures. Previously, we compared the extent of DNA adduct formation and mutations in B6C3F1/Tk mice treated neonatally with acrylamide or glycidamide to obtain information concerning the mechanism of acrylamide genotoxicity. We have now examined the tumorigenicity of acrylamide and glycidamide in mice treated neonatally. Male B6C3F1 mice were injected intraperitoneally on postnatal days 1, 8, and 15 with 0.0, 0.14, or 0.70 mmol acrylamide or glycidamide per kg body weight per day and the tumorigenicity was assessed after one year. Survival in each of the groups was >87%, there were no differences in body weights among the groups, and the only treatment-related neoplasms involved the liver. The incidence of combined hepatocellular adenoma or carcinoma was 3.8% in the control group, 8.3% in the 0.14 mmol acrylamide and glycidamide per kg body weight groups, 4.2% in the 0.70 mmol acrylamide per kg body weight group, and 71.4% in the 0.70 mmol glycidamide per kg body weight group. Analysis of the hepatocellular tumors indicated that the increased incidence observed in mice administered 0.70 mmol glycidamide per kg body weight was associated with A→ G and A → T mutations at codon 61 of H-ras. These results, combined with our previous data on DNA adduct formation and mutation induction, suggest that the carcinogenicity of acrylamide is dependent upon its metabolism to glycidamide, a pathway that is deficient in neonatal mice. PMID:22336951

Pro-tumorigenic effects of transforming growth factor beta 1 in canine osteosarcoma.

PubMed

Portela, R F; Fadl-Alla, B A; Pondenis, H C; Byrum, M L; Garrett, L D; Wycislo, K L; Borst, L B; Fan, T M

2014-01-01

Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGFβ1, and active osteoblasts express cognate receptors for TGFβ1 (TGFβRI and TGFβRII). During malignant osteolysis, TGFβ1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities. Canine osteosarcoma (OS) cells will possess TGFβ1 signaling machinery. Blockade of TGFβ1 signaling will attenuate pro-tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGFβ1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGFβ1 concentrations. Thirty-three dogs with appendicular OS. Expression of TGFβ1 and its cognate receptors, as well as the biologic effects of TGFβ1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGFβRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGFβ1 concentrations were quantified and correlated with bone resorption. Canine OS cells secrete TGFβ1, express cognate receptors, and TGFβ1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGFβRI/II, and in OS-bearing dogs, circulating TGFβ1 concentrations correlate with urine N-telopeptide excretion. Canine OS cells possess TGFβ1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro-tumorigenic signaling loop. As such, TGFβ1 inhibitors might impede localized OS progression in dogs. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Increased expression of human leucocyte antigen class I free heavy chains on monocytes of patients with spondyloarthritis and cells transfected with HLA-B27.

PubMed

Ding, Jin; Feng, Yuan; Zheng, Zhao Hui; Li, Xue Yi; Wu, Zhen Biao; Zhu, Ping

2015-02-01

Human leucocyte antigen (HLA)-B27 expression is correlated with spondyloarthritis (SpA), but its role in disease pathogenesis remains unclear. The aim of the study was to determine whether HLA-B27 free heavy chain (FHC) contributes to SpA pathogenesis. Flow cytometry was used to analyse the FHC expression on CD3+ and CD14+ cells in the peripheral blood (PB) and synovial fluid (SF) from SpA patients, healthy controls, and rheumatoid arthritis (RA) patients. Human monocytic U937 cell lines stably expressing enhanced green fluorescence protein (EGFP)/HLA-B27, EGFP/HLA-A2 or EGFP alone were created to further investigate the relation between HLA-B27 and FHC expression. The relative FHC level on CD14+ PB cells was significantly higher in SpA patients than in controls, but lower than on the SF cells of SpA patients. No significant correlation was found for relative FHC expression with HLA-B27 or β2-microglobulin expression. HLA-B27-transfected U937 cells expressed higher FHC levels than either EGFP/HLA-A2- or EGFP-transfected cells. HLA class I FHC expression was significantly increased on monocytes of SpA patients and HLA-B27-transfected cells, implying that FHC, perhaps mostly derived from HLA-B27, plays an important role in SpA pathogenesis. © 2014 John Wiley & Sons Ltd.

Family Health Climate and Adolescents' Physical Activity and Healthy Eating: A Cross-Sectional Study with Mother-Father-Adolescent Triads.

PubMed

Niermann, Christina Y N; Kremers, Stef P J; Renner, Britta; Woll, Alexander

2015-01-01

The importance of the family environment for children's and adolescents' health behavior has been demonstrated, the underlying mechanisms of this influence remain unclear. Therefore, the aim of the study was to investigate the relationship between family environmental and individual determinants. It was hypothesized that the Family Health Climate (FHC) is associated with adolescents' physical activity and dietary behavior and that intrinsic motivation mediates this association. Cross-sectional data were collected from 198 families (mother, father, and child) using questionnaires. Perceptions of FHC of mothers, fathers, and their children were assessed using the FHC-scales for physical activity (FHC-PA) and nutrition (FHC-NU). The adolescents also rated their intrinsic motivation for exercise and healthy eating, their physical activity and consumption of healthful food. A structural equation model was analyzed and a bootstrapping procedure was used to test direct and indirect effects. The FHC-PA was related to the amount of weekly physical activity and the FHC-NU to the consumption of fruit, vegetables and salad. These effects were mediated by adolescents' intrinsic motivation; the indirect effects were significant for both behaviors. These results emphasize the importance of the FHC in shaping adolescents' physical activity and dietary behavior. Individual motivational factors are potential mediators of family and parental influences. Considering family-level variables and their interaction with individual factors contributes to the understanding of adolescents' health behavior.

Ineffectiveness of the presence of H-ras/p53 combination of mutations in squamous cell carcinoma cells to induce a conversion of a nontumorigenic to a tumorigenic phenotype.

PubMed

Lee, H; Li, D; Prior, T; Casto, B C; Weghorst, C M; Shuler, C F; Milo, G E

1997-10-01

Human tumor cells have properties in vitro or in surrogate hosts that are distinct from those of normal cells, such as immortality, anchorage independence, and tumor formation in nude mice. However, different cells from individual tumors may exhibit some, but not all of these features. In previous years, human tumor cell lines derived from different tumor and tissue types have been studied to determine those molecular changes that are associated with the in vitro properties listed above and with tumorigenicity in nude mice. In the present study, seven cell lines derived from human tumors were characterized for p53 and ras mutations that may occur in SCC tumor phenotypes and for tumor formation in nude mice. This investigation was designed to examine whether co-occurrence of mutated ras and p53 lead to a malignant stage in the progression process. None of the seven cell lines contained mutations in the recognized "hot spots" of the p53 tumor suppressor gene, but four had a nonsense/splice mutation in codon 126 and a mutation in codon 12 of the H-ras gene. The remaining three cell lines had p53 mutations in intron 5, in codon 193, and a missense mutation in codon 126, respectively. Four of seven cell lines were nontumorigenic; two of these cell lines contained a nonsense p53-126 mutation and mutated ras; one had a missense mutation at codon 126 but no mutated ras; the the fourth had only a p53 mutation at codon 193. Two of the nontumorigenic cell lines were converted to tumorigenicity after treatment with methyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine with no apparent additional mutations in either gene. Our analysis revealed that there was a high frequency of genetic diversity and mutations in both p53 and H-ras. There was also a lack of a causal relationship in the presence of mutations in p53 and the cells' ability to exhibit a malignant potential in nude mice.

Culture conditions tailored to the cell of origin are critical for maintaining native properties and tumorigenicity of glioma cells.

PubMed

Ledur, Pítia F; Liu, Chong; He, Hua; Harris, Alexandra R; Minussi, Darlan C; Zhou, Hai-Yan; Shaffrey, Mark E; Asthagiri, Ashok; Lopes, Maria Beatriz S; Schiff, David; Lu, Yi-Cheng; Mandell, James W; Lenz, Guido; Zong, Hui

2016-10-01

Cell culture plays a pivotal role in cancer research. However, culture-induced changes in biological properties of tumor cells profoundly affect research reproducibility and translational potential. Establishing culture conditions tailored to the cancer cell of origin could resolve this problem. For glioma research, it has been previously shown that replacing serum with defined growth factors for neural stem cells (NSCs) greatly improved the retention of gene expression profile and tumorigenicity. However, among all molecular subtypes of glioma, our laboratory and others have previously shown that the oligodendrocyte precursor cell (OPC) rather than the NSC serves as the cell of origin for the proneural subtype, raising questions regarding the suitability of NSC-tailored media for culturing proneural glioma cells. OPC-originated mouse glioma cells were cultured in conditions for normal OPCs or NSCs, respectively, for multiple passages. Gene expression profiles, morphologies, tumorigenicity, and drug responsiveness of cultured cells were examined in comparison with freshly isolated tumor cells. OPC media-cultured glioma cells maintained tumorigenicity, gene expression profiles, and morphologies similar to freshly isolated tumor cells. In contrast, NSC-media cultured glioma cells gradually lost their OPC features and most tumor-initiating ability and acquired heightened sensitivity to temozolomide. To improve experimental reproducibility and translational potential of glioma research, it is important to identify the cell of origin, and subsequently apply this knowledge to establish culture conditions that allow the retention of native properties of tumor cells. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer.

PubMed

Jackson, Amanda L; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M; Gilliam, Timothy P; Zhou, Chunxiao; Bae-Jump, Victoria L

2017-11-21

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease.

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer

PubMed Central

Jackson, Amanda L.; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M.; Gilliam, Timothy P.; Zhou, Chunxiao; Bae-Jump, Victoria L.

2017-01-01

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease. PMID:29245964

Family Health Climate and Adolescents’ Physical Activity and Healthy Eating: A Cross-Sectional Study with Mother-Father-Adolescent Triads

PubMed Central

Niermann, Christina Y. N.; Kremers, Stef P. J.; Renner, Britta; Woll, Alexander

2015-01-01

Introduction The importance of the family environment for children’s and adolescents’ health behavior has been demonstrated, the underlying mechanisms of this influence remain unclear. Therefore, the aim of the study was to investigate the relationship between family environmental and individual determinants. It was hypothesized that the Family Health Climate (FHC) is associated with adolescents’ physical activity and dietary behavior and that intrinsic motivation mediates this association. Methods Cross-sectional data were collected from 198 families (mother, father, and child) using questionnaires. Perceptions of FHC of mothers, fathers, and their children were assessed using the FHC-scales for physical activity (FHC-PA) and nutrition (FHC-NU). The adolescents also rated their intrinsic motivation for exercise and healthy eating, their physical activity and consumption of healthful food. A structural equation model was analyzed and a bootstrapping procedure was used to test direct and indirect effects. Results The FHC-PA was related to the amount of weekly physical activity and the FHC-NU to the consumption of fruit, vegetables and salad. These effects were mediated by adolescents’ intrinsic motivation; the indirect effects were significant for both behaviors. Discussion These results emphasize the importance of the FHC in shaping adolescents’ physical activity and dietary behavior. Individual motivational factors are potential mediators of family and parental influences. Considering family-level variables and their interaction with individual factors contributes to the understanding of adolescents’ health behavior. PMID:26606157

The Coordinated Actions of TIM-3 on Cancer and Myeloid Cells in the Regulation of Tumorigenicity and Clinical Prognosis in Clear Cell Renal Cell Carcinomas.

PubMed

Komohara, Yoshihiro; Morita, Tomoko; Annan, Dorcas A; Horlad, Hasita; Ohnishi, Koji; Yamada, Sohsuke; Nakayama, Toshiyuki; Kitada, Shohei; Suzu, Shinya; Kinoshita, Ichiro; Dosaka-Akita, Hirotoshi; Akashi, Koichi; Takeya, Motohiro; Jinushi, Masahisa

2015-09-01

Clear cell renal cell carcinoma (ccRCC) is one of most common cancers in urogenital organs. Although recent experimental and clinical studies have shown the immunogenic properties of ccRCC as illustrated by the clinical sensitivities to various immunotherapies, the detailed immunoregulatory machineries governing the tumorigenicity of human ccRCC remain largely obscure. In this study, we demonstrated the clinical significance and functional relevance of T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) expressed on tumor cells and myeloid cells in patients with ccRCC. TIM-3 expression was detected on cancer cells and CD204(+) tumor-associated macrophages (TAM), and higher expression level of TIM-3 was positively correlated with shorter progression-free survival (PFS) in patients with ccRCC. We found that TIM-3 expression was detected on a large number of tumors, and there was significant correlation between an increased number of TAMs and high expression level of TIM-3 in patients with ccRCC. Furthermore, TIM-3 rendered RCC cells with the ability to induce resistance to sunitinib and mTOR inhibitors, the standard regimen for patients with ccRCC, as well as stem cell activities. TIM-3 expression was induced on CD14(+) monocytes upon long-term stimulation with RCC cells, and TIM-3-expressing myeloid cells play a critical role in augmenting tumorigenic activities of TIM-3-negative RCC cells. More importantly, treatment with anti-TIM-3 mAb suppressed its tumorigenic effects in in vitro and in vivo settings. These findings indicate the coordinated action of TIM-3 in cancer cells and in myeloid cells regulates the tumorigenicity of human RCC. ©2015 American Association for Cancer Research.

Graviola: A Novel Promising Natural-Derived Drug That Inhibits Tumorigenicity and Metastasis of Pancreatic Cancer Cells In Vitro and In Vivo Through Altering Cell Metabolism

PubMed Central

Torres, María P.; Rachagani, Satyanarayana; Purohit, Vinee; Pandey, Poomy; Joshi, Suhasini; Moore, Erik D.; Johansson, Sonny L.; Singh, Pankaj K.; Ganti, Apar K.; Batra, Surinder K.

2012-01-01

Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease. PMID:22475682

Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.

PubMed

Mikheev, Andrei M; Mikheeva, Svetlana A; Severs, Liza J; Funk, Cory C; Huang, Lei; McFaline-Figueroa, José L; Schwensen, Jeanette; Trapnell, Cole; Price, Nathan D; Wong, Stephen; Rostomily, Robert C

2018-05-13

Twist1 (TW) is a bHLH transcription factor (TF) and master regulator of the epithelial to mesenchymal transition (EMT). In vitro, TW promotes mesenchymal change, invasion and self-renewal in glioblastoma (GBM) cells. However the potential therapeutic relevance of TW has not been established through loss of function studies in human GBM cell xenograft models. The effects of TW loss of function (gene editing and knock down) on inhibition of tumorigenicity of U87MG and GBM4 glioma stem cells were tested in orthotopic xenograft models and conditional knockdown in established flank xenograft tumors. RNAseq and the analysis of tumors investigated putative TW associated mechanisms. Multiple bioinformatics tools revealed significant alteration of ECM, membrane receptors, signaling transduction kinases and cytoskeleton dynamics leading to identification of PI3K/AKT signaling. We experimentally show alteration of AKT activity and periostin (POSTN) expression in vivo and/or in vitro. For the first time we show that effect of TW knockout inhibits AKT activity in U87MG cells in vivo independent of PTEN mutation. The clinical relevance of TW and candidate mechanisms was established by analysis of the TCGA and ENCODE databases. TW expression was associated with decreased patient survival and LASSO regression analysis identified POSTN as one of top targets of TW in human GBM. While we previously demonstrated the role of TW in promoting EMT and invasion of glioma cells, these studies provide direct experimental evidence supporting pro-tumorigenic role of TW independent of invasion in vivo and the therapeutic relevance of targeting TW in human GBM. Further, the role of TW driving POSTN expression and AKT signaling suggests actionable targets, which could be leveraged to mitigate the oncogenic effects of TW in GBM. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.

PubMed

Calvo, Alfonso; Xiao, Nianqing; Kang, Jason; Best, Carolyn J M; Leiva, Isabel; Emmert-Buck, Michael R; Jorcyk, Cheryl; Green, Jeffrey E

2002-09-15

To identify molecular changes that occur during prostate tumor progression, we have characterized a series of prostate cancer cell lines isolated at different stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and a lung metastasis exhibited significant differences in cell growth, tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700 features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr cells and changes in the expression levels of genes regulating cell growth, angiogenesis, and invasion. Many changes observed in transcriptional regulation in this in vitro system are similar to those reported for human prostate cancer, as well as other types of human tumors. This analysis of expression patterns has also identified novel genes that may be involved in mechanisms of prostate oncogenesis or serve as potential biomarkers or therapeutic targets for prostate cancer. Examples include the L1-cell adhesion molecule, metastasis-associated gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many genes identified in the Pr-cell line model have been shown to be altered in human prostate cancer. The comprehensive microarray data provides a rational basis for using this model system for studies where alterations of specific genes or pathways are of particular interest. Quantitative real-time reverse transcription-PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript of this gene in a subset of human prostate tumors, mouse tumors, and prostate carcinoma cell lines. This work demonstrates that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology.

Effects of Simulated Human Gastrointestinal Digestion of Two Purple-Fleshed Potato Cultivars on Anthocyanin Composition and Cytotoxicity in Colonic Cancer and Non-Tumorigenic Cells

PubMed Central

Kubow, Stan; Iskandar, Michèle M.; Melgar-Bermudez, Emiliano; Sleno, Lekha; Sabally, Kebba; Azadi, Behnam; How, Emily; Prakash, Satya; Burgos, Gabriela; zum Felde, Thomas

2017-01-01

A dynamic human gastrointestinal (GI) model was used to digest cooked tubers from purple-fleshed Amachi and Leona potato cultivars to study anthocyanin biotransformation in the stomach, small intestine and colonic vessels. Colonic Caco-2 cancer cells and non-tumorigenic colonic CCD-112CoN cells were tested for cytotoxicity and cell viability after 24 h exposure to colonic fecal water (FW) digests (0%, 10%, 25%, 75% and 100% FW in culture media). After 24 h digestion, liquid chromatography-mass spectrometry identified 36 and 15 anthocyanin species throughout the GI vessels for Amachi and Leona, respectively. The total anthocyanin concentration was over thirty-fold higher in Amachi compared to Leona digests but seven-fold higher anthocyanin concentrations were noted for Leona versus Amachi in descending colon digests. Leona FW showed greater potency to induce cytotoxicity and decrease viability of Caco-2 cells than observed with FW from Amachi. Amachi FW at 100% caused cytotoxicity in non-tumorigenic cells while FW from Leona showed no effect. The present findings indicate major variations in the pattern of anthocyanin breakdown and release during digestion of purple-fleshed cultivars. The differing microbial anthocyanin metabolite profiles in colonic vessels between cultivars could play a significant role in the impact of FW toxicity on tumor and non-tumorigenic cells. PMID:28850070

Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts.

PubMed

Tsang, Chi Man; Cheung, Yuk Chun; Lui, Vivian Wai-Yan; Yip, Yim Ling; Zhang, Guitao; Lin, Victor Weitao; Cheung, Kenneth Chat-Pan; Feng, Yibin; Tsao, Sai Wah

2013-12-31

Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC.

Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

PubMed Central

2013-01-01

Background Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. Methods In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Results Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Conclusions Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC. PMID:24380387

Drinking water disinfection byproduct iodoacetic acid induces tumorigenic transformation of NIH3T3 cells.

PubMed

Wei, Xiao; Wang, Shu; Zheng, Weiwei; Wang, Xia; Liu, Xiaolin; Jiang, Songhui; Pi, Jingbo; Zheng, Yuxin; He, Gengsheng; Qu, Weidong

2013-06-04

Iodoacetic acid (IAA) and iodoform (IF) are unregulated iodinated disinfection byproducts (DBPs) found in drinking water. Their presence in the drinking water of China has not been documented. Recently, the carcinogenic potential of IAA and IF has been a concern because of their mutagenicity in bacteria and genotoxicity in mammalian cells. Therefore, we measured their concentrations in Shanghai drinking water and assessed their cytotoxicity, genotoxicity, and ability to transform NIH3T3 cells to tumorigenic lines. The concentrations of IAA and IF in Shanghai drinking water varied between summer and winter with maximum winter levels of 2.18 μg/L IAA and 0.86 μg/L IF. IAA with a lethal concentration 50 (LC50) of 2.77 μM exhibited more potent cytotoxicity in NIH3T3 cells than IF (LC50 = 83.37 μM). IAA, but not IF, induced a concentration-dependent DNA damage measured by γ-H2AX staining and increased tail moment in single-cell gel electrophoresis. Neither IAA nor IF increased micronucleus frequency. Prolonged exposure of NIH3T3 cells to IAA increased the frequencies of transformed cells with anchorage-independent growth and agglutination with concanavalin A. IAA-transformed cells formed aggressive fibrosarcomas after inoculation into Balb/c nude mice. This study demonstrated that IAA has a biological activity that is consistent with a carcinogen and human exposure should be of concern.

Developing Toxicogenomics as a Research Tool by Applying Benchmark Dose-Response Modeling to inform Chemical Mode of Action and Tumorigenic Potency

EPA Science Inventory

ABSTRACT Results of global gene expression profiling after short-term exposures can be used to inform tumorigenic potency and chemical mode of action (MOA) and thus serve as a strategy to prioritize future or data-poor chemicals for further evaluation. This compilation of cas...

Canonical Wnt Signaling as a Specific Marker for Normal and Tumorigenic Mammary Stem Cells

DTIC Science & Technology

2012-02-01

These cells were identified by  flow   cytometry  to detect cells that were positive for CD24 and CD49f.   2. We have established that activation of Wnt...09-1-0072 TITLE: Canonical Wnt Signaling as a Specific marker for Normal and Tumorigenic Mammary Stem Cells PRINCIPAL...activation of canonical Wnt signaling may be a very specific marker for mammary stem cells and be a target for transformation that results in the

Hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity in oral squamous cell carcinoma derived cells.

PubMed

Chaudhari, Pratik Rajeev; Charles, Silvania Emlit; D'Souza, Zinia Charlotte; Vaidya, Milind Murlidhar

2017-11-15

BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells. Based on these findings, we hypothesized that linker proteins may have a role in neoplastic progression of OSCC. Downregulation of hemidesmosomal linker proteins in OSCC derived cells resulted in reduced cell migration accompanied by alterations in actin organization. Further, decreased MMP9 activity led to reduced cell invasion in linker proteins knockdown cells. Moreover, loss of these proteins resulted in reduced tumorigenic potential. SWATH analysis demonstrated upregulation of N-Myc downstream regulated gene 1 (NDRG1) in linker proteins downregulated cells as compared to vector control cells. Further, the defects in phenotype upon linker proteins ablation were rescued upon loss of NDRG1 in linker proteins knockdown background. These data together indicate that hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity possibly through NDRG1 in OSCC derived cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Soft fibrin gels promote selection and growth of tumorigenic cells

NASA Astrophysics Data System (ADS)

Liu, Jing; Tan, Youhua; Zhang, Huafeng; Zhang, Yi; Xu, Pingwei; Chen, Junwei; Poh, Yeh-Chuin; Tang, Ke; Wang, Ning; Huang, Bo

2012-08-01

The identification of stem-cell-like cancer cells through conventional methods that depend on stem cell markers is often unreliable. We developed a mechanical method for selecting tumorigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe combined immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as ten such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.

PCDH10 is required for the tumorigenicity of glioblastoma cells.

PubMed

Echizen, Kanae; Nakada, Mitsutoshi; Hayashi, Tomoatsu; Sabit, Hemragul; Furuta, Takuya; Nakai, Miyuki; Koyama-Nasu, Ryo; Nishimura, Yukiko; Taniue, Kenzui; Morishita, Yasuyuki; Hirano, Shinji; Terai, Kenta; Todo, Tomoki; Ino, Yasushi; Mukasa, Akitake; Takayanagi, Shunsaku; Ohtani, Ryohei; Saito, Nobuhito; Akiyama, Tetsu

2014-01-31

Protocadherin10 (PCDH10)/OL-protocadherin is a cadherin-related transmembrane protein that has multiple roles in the brain, including facilitating specific cell-cell connections, cell migration and axon guidance. It has recently been reported that PCDH10 functions as a tumor suppressor and that its overexpression inhibits proliferation or invasion of multiple tumor cells. However, the function of PCDH10 in glioblastoma cells has not been elucidated. In contrast to previous reports on other tumors, we show here that suppression of the expression of PCDH10 by RNA interference (RNAi) induces the growth arrest and apoptosis of glioblastoma cells in vitro. Furthermore, we demonstrate that knockdown of PCDH10 inhibits the growth of glioblastoma cells xenografted into immunocompromised mice. These results suggest that PCDH10 is required for the proliferation and tumorigenicity of glioblastoma cells. We speculate that PCDH10 may be a promising target for the therapy of glioblastoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Mammalian autophagy degrades nuclear constituents in response to tumorigenic stress.

PubMed

Dou, Zhixun; Ivanov, Andrejs; Adams, Peter D; Berger, Shelley L

2016-08-02

During autophagy, double-membrane autophagosomes are observed in the cytoplasm. Thus, extensive studies have focused on autophagic turnover of cytoplasmic material. Whether autophagy has a role in degrading nuclear constituents is poorly understood. We reveal that the autophagy protein LC3/Atg8 directly interacts with the nuclear lamina protein LMNB1 (lamin B1), and binds to LMN/lamin-associated chromatin domains (LADs). Through these interactions, autophagy specifically mediates destruction of nuclear lamina during tumorigenic stress, such as by activated oncogenes and DNA damage. This nuclear lamina degradation upon aberrant cellular stress impairs cell proliferation by inducing cellular senescence, a stable form of cell-cycle arrest and a tumor-suppressive mechanism. Our findings thus suggest that, in response to cancer-promoting stress, autophagy degrades nuclear material to drive cellular senescence, as a means to restrain tumorigenesis. Our work provokes a new direction in studying the role of autophagy in the nucleus and in tumor suppression.

MiR-16 regulates the pro-tumorigenic potential of lung fibroblasts through the inhibition of HGF production in an FGFR-1- and MEK1-dependent manner.

PubMed

Andriani, Francesca; Majorini, Maria Teresa; Mano, Miguel; Landoni, Elena; Miceli, Rosalba; Facchinetti, Federica; Mensah, Mavis; Fontanella, Enrico; Dugo, Matteo; Giacca, Mauro; Pastorino, Ugo; Sozzi, Gabriella; Delia, Domenico; Roz, Luca; Lecis, Daniele

2018-03-20

Fibroblasts are crucial mediators of tumor-stroma cross-talk through synthesis and remodeling of the extracellular matrix and production of multiple soluble factors. Nonetheless, little is still known about specific determinants of fibroblast pro-tumorigenic activity in lung cancer. Here, we aimed at understanding the role of miRNAs, which are often altered in stromal cells, in reprogramming fibroblasts towards a tumor-supporting phenotype. We employed a co-culture-based high-throughput screening to identify specific miRNAs modulating the pro-tumorigenic potential of lung fibroblasts. Multiplex assays and ELISA were instrumental to study the effect of miRNAs on the secretome of both primary and immortalized lung fibroblasts from lung cancer patients and to evaluate plasmatic levels of HGF in heavy smokers. Direct mRNA targeting by miRNAs was investigated through dual-luciferase reporter assay and western blot. Finally, the pro-tumorigenic activity of fibroblasts and their conditioned media was tested by employing in vitro migration experiments and mouse xenografts. We identified miR-16 as a master regulator of fibroblast secretome and showed that its upregulation reduces HGF secretion by fibroblasts, impairing their capacity to promote cancer cell migration. This effect is due to a pleiotropic activity of miR-16 which prevents HGF expression through direct inhibition of FGFR-1 signaling and targeting of HGF mRNA. Mechanistically, miR-16 targets FGFR-1 downstream mediator MEK1, thus reducing ERK1/2 activation. Consistently, chemical or genetic inhibition of FGFR-1 mimics miR-16 activity and prevents HGF production. Of note, we report that primary fibroblast cell lines derived from lungs of heavy smokers express reduced miR-16 levels compared to those from lungs not exposed to smoke and that HGF concentration in heavy smokers' plasma correlates with levels of tobacco exposure. Finally, in vivo experiments confirmed that restoration of miR-16 expression in fibroblasts

A physical sciences network characterization of non-tumorigenic and metastatic cells

PubMed Central

Agus, David B.; Alexander, Jenolyn F.; Arap, Wadih; Ashili, Shashanka; Aslan, Joseph E.; Austin, Robert H.; Backman, Vadim; Bethel, Kelly J.; Bonneau, Richard; Chen, Wei-Chiang; Chen-Tanyolac, Chira; Choi, Nathan C.; Curley, Steven A.; Dallas, Matthew; Damania, Dhwanil; Davies, Paul C. W.; Decuzzi, Paolo; Dickinson, Laura; Estevez-Salmeron, Luis; Estrella, Veronica; Ferrari, Mauro; Fischbach, Claudia; Foo, Jasmine; Fraley, Stephanie I.; Frantz, Christian; Fuhrmann, Alexander; Gascard, Philippe; Gatenby, Robert A.; Geng, Yue; Gerecht, Sharon; Gillies, Robert J.; Godin, Biana; Grady, William M.; Greenfield, Alex; Hemphill, Courtney; Hempstead, Barbara L.; Hielscher, Abigail; Hillis, W. Daniel; Holland, Eric C.; Ibrahim-Hashim, Arig; Jacks, Tyler; Johnson, Roger H.; Joo, Ahyoung; Katz, Jonathan E.; Kelbauskas, Laimonas; Kesselman, Carl; King, Michael R.; Konstantopoulos, Konstantinos; Kraning-Rush, Casey M.; Kuhn, Peter; Kung, Kevin; Kwee, Brian; Lakins, Johnathon N.; Lambert, Guillaume; Liao, David; Licht, Jonathan D.; Liphardt, Jan T.; Liu, Liyu; Lloyd, Mark C.; Lyubimova, Anna; Mallick, Parag; Marko, John; McCarty, Owen J. T.; Meldrum, Deirdre R.; Michor, Franziska; Mumenthaler, Shannon M.; Nandakumar, Vivek; O’Halloran, Thomas V.; Oh, Steve; Pasqualini, Renata; Paszek, Matthew J.; Philips, Kevin G.; Poultney, Christopher S.; Rana, Kuldeepsinh; Reinhart-King, Cynthia A.; Ros, Robert; Semenza, Gregg L.; Senechal, Patti; Shuler, Michael L.; Srinivasan, Srimeenakshi; Staunton, Jack R.; Stypula, Yolanda; Subramanian, Hariharan; Tlsty, Thea D.; Tormoen, Garth W.; Tseng, Yiider; van Oudenaarden, Alexander; Verbridge, Scott S.; Wan, Jenny C.; Weaver, Valerie M.; Widom, Jonathan; Will, Christine; Wirtz, Denis; Wojtkowiak, Jonathan; Wu, Pei-Hsun

2013-01-01

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis. PMID:23618955

A physical sciences network characterization of non-tumorigenic and metastatic cells.

PubMed

Agus, David B; Alexander, Jenolyn F; Arap, Wadih; Ashili, Shashanka; Aslan, Joseph E; Austin, Robert H; Backman, Vadim; Bethel, Kelly J; Bonneau, Richard; Chen, Wei-Chiang; Chen-Tanyolac, Chira; Choi, Nathan C; Curley, Steven A; Dallas, Matthew; Damania, Dhwanil; Davies, Paul C W; Decuzzi, Paolo; Dickinson, Laura; Estevez-Salmeron, Luis; Estrella, Veronica; Ferrari, Mauro; Fischbach, Claudia; Foo, Jasmine; Fraley, Stephanie I; Frantz, Christian; Fuhrmann, Alexander; Gascard, Philippe; Gatenby, Robert A; Geng, Yue; Gerecht, Sharon; Gillies, Robert J; Godin, Biana; Grady, William M; Greenfield, Alex; Hemphill, Courtney; Hempstead, Barbara L; Hielscher, Abigail; Hillis, W Daniel; Holland, Eric C; Ibrahim-Hashim, Arig; Jacks, Tyler; Johnson, Roger H; Joo, Ahyoung; Katz, Jonathan E; Kelbauskas, Laimonas; Kesselman, Carl; King, Michael R; Konstantopoulos, Konstantinos; Kraning-Rush, Casey M; Kuhn, Peter; Kung, Kevin; Kwee, Brian; Lakins, Johnathon N; Lambert, Guillaume; Liao, David; Licht, Jonathan D; Liphardt, Jan T; Liu, Liyu; Lloyd, Mark C; Lyubimova, Anna; Mallick, Parag; Marko, John; McCarty, Owen J T; Meldrum, Deirdre R; Michor, Franziska; Mumenthaler, Shannon M; Nandakumar, Vivek; O'Halloran, Thomas V; Oh, Steve; Pasqualini, Renata; Paszek, Matthew J; Philips, Kevin G; Poultney, Christopher S; Rana, Kuldeepsinh; Reinhart-King, Cynthia A; Ros, Robert; Semenza, Gregg L; Senechal, Patti; Shuler, Michael L; Srinivasan, Srimeenakshi; Staunton, Jack R; Stypula, Yolanda; Subramanian, Hariharan; Tlsty, Thea D; Tormoen, Garth W; Tseng, Yiider; van Oudenaarden, Alexander; Verbridge, Scott S; Wan, Jenny C; Weaver, Valerie M; Widom, Jonathan; Will, Christine; Wirtz, Denis; Wojtkowiak, Jonathan; Wu, Pei-Hsun

2013-01-01

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

A physical sciences network characterization of non-tumorigenic and metastatic cells

NASA Astrophysics Data System (ADS)

Physical Sciences-Oncology Centers Network; Agus, David B.; Alexander, Jenolyn F.; Arap, Wadih; Ashili, Shashanka; Aslan, Joseph E.; Austin, Robert H.; Backman, Vadim; Bethel, Kelly J.; Bonneau, Richard; Chen, Wei-Chiang; Chen-Tanyolac, Chira; Choi, Nathan C.; Curley, Steven A.; Dallas, Matthew; Damania, Dhwanil; Davies, Paul C. W.; Decuzzi, Paolo; Dickinson, Laura; Estevez-Salmeron, Luis; Estrella, Veronica; Ferrari, Mauro; Fischbach, Claudia; Foo, Jasmine; Fraley, Stephanie I.; Frantz, Christian; Fuhrmann, Alexander; Gascard, Philippe; Gatenby, Robert A.; Geng, Yue; Gerecht, Sharon; Gillies, Robert J.; Godin, Biana; Grady, William M.; Greenfield, Alex; Hemphill, Courtney; Hempstead, Barbara L.; Hielscher, Abigail; Hillis, W. Daniel; Holland, Eric C.; Ibrahim-Hashim, Arig; Jacks, Tyler; Johnson, Roger H.; Joo, Ahyoung; Katz, Jonathan E.; Kelbauskas, Laimonas; Kesselman, Carl; King, Michael R.; Konstantopoulos, Konstantinos; Kraning-Rush, Casey M.; Kuhn, Peter; Kung, Kevin; Kwee, Brian; Lakins, Johnathon N.; Lambert, Guillaume; Liao, David; Licht, Jonathan D.; Liphardt, Jan T.; Liu, Liyu; Lloyd, Mark C.; Lyubimova, Anna; Mallick, Parag; Marko, John; McCarty, Owen J. T.; Meldrum, Deirdre R.; Michor, Franziska; Mumenthaler, Shannon M.; Nandakumar, Vivek; O'Halloran, Thomas V.; Oh, Steve; Pasqualini, Renata; Paszek, Matthew J.; Philips, Kevin G.; Poultney, Christopher S.; Rana, Kuldeepsinh; Reinhart-King, Cynthia A.; Ros, Robert; Semenza, Gregg L.; Senechal, Patti; Shuler, Michael L.; Srinivasan, Srimeenakshi; Staunton, Jack R.; Stypula, Yolanda; Subramanian, Hariharan; Tlsty, Thea D.; Tormoen, Garth W.; Tseng, Yiider; van Oudenaarden, Alexander; Verbridge, Scott S.; Wan, Jenny C.; Weaver, Valerie M.; Widom, Jonathan; Will, Christine; Wirtz, Denis; Wojtkowiak, Jonathan; Wu, Pei-Hsun

2013-04-01

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

Fuchs' heterochromic cyclitis: a post-infectious manifestation of ocular toxoplasmosis?

PubMed

Jad, Akesbi; Céline, Terrada; Bahram, Bodaghi; Phuc, LeHoang; Nathalie, Cassoux

2013-04-01

The purpose of this article is to report the development of Fuchs' heterochromic cyclitis (FHC) secondary to toxoplasmosis chorioretinitis. The design is based on observational case series report. We report in this article six cases of typical FHC developing secondary to ocular toxoplasmosis. Intraocular immunoglobulin G production against Toxoplasma gondii was determined in the aqueous humor of five patients by calculation of the Goldmann-Witmer coefficient (GWC). The clinical examination revealed typical FHC with no active chorioretinal scar. We report on five women and one man (aged 33-64 years old; median 44.6 years) who developed FHC over a period of time ranging from 2-13 years. A positive GWC (>3) was found in four patients; of the two remaining patients one was negative and the other did not have anterior chamber paracentesis. Four patients were treated for an active ocular toxoplasmic lesion before the development of FHC with pyrimethamine, sulfadiazine and corticosteroids. Two patients had negative anti-toxoplasmic therapy for FHC (one with trimethoprim-sulfamethoxazole for 3 weeks and the other with pyrimethamine, sulfadiazine and corticosteroids for 8 weeks). One never had any treatment. All the patients had mild anterior chamber reaction with no synechia, diffuse and characteristic white stellate keratic precipitates and vitritis; five patients had posterior subcapsular cataract and heterochromia and three had elevated intraocular pressure. The findings help us to conclude that FHC can develop over a period of time after ocular toxoplasmosis. This could be a main association to search for when a Fuchs' uveitis is found with a chorioretinal scar. Ocular inflammation does not mean reactivation of ocular toxoplasmosis. FHC could be a secondary immune reaction with a past antigenic stimulation to a previous infection, i.e., toxoplasmosis, etc.

CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic

PubMed Central

Marshall, A D; Bailey, C G; Champ, K; Vellozzi, M; O'Young, P; Metierre, C; Feng, Y; Thoeng, A; Richards, A M; Schmitz, U; Biro, M; Jayasinghe, R; Ding, L; Anderson, L; Mardis, E R; Rasko, J E J

2017-01-01

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer. PMID:28319062

Galectin-8 induces partial epithelial–mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin–Darby canine kidney cells

PubMed Central

Oyanadel, Claudia; Holmes, Christopher; Pardo, Evelyn; Retamal, Claudio; Shaughnessy, Ronan; Smith, Patricio; Cortés, Priscilla; Bravo-Zehnder, Marcela; Metz, Claudia; Feuerhake, Teo; Romero, Diego; Roa, Juan Carlos; Montecinos, Viviana; Soza, Andrea; González, Alfonso

2018-01-01

Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial–mesenchymal-transition (EMT). The glycan-binding protein galectin-8 (Gal-8) activates selective β1-integrins involved in EMT and is overexpressed by certain carcinomas. Here we show that Gal-8 overexpression or exogenous addition promotes proliferation, migration, and invasion in nontumoral Madin–Darby canine kidney (MDCK) cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the epidermal growth factor receptor (EGFR), likely triggered by α5β1integrin binding. Under subconfluent conditions, Gal-8–overexpressing MDCK cells (MDCK-Gal-8H) display hallmarks of EMT, including decreased E-cadherin and up-regulated expression of vimentin, fibronectin, and Snail, as well as increased β-catenin activity. Changes related to migration/invasion included higher expression of α5β1 integrin, extracellular matrix-degrading MMP13 and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) protease systems. Gal-8–stimulated FAK/EGFR pathway leads to proteasome overactivity characteristic of cancer cells. Yet MDCK-Gal-8H cells still develop apical/basolateral polarity reverting EMT markers and proteasome activity under confluence. This is due to the opposite segregation of Gal-8 secretion (apical) and β1-integrins distribution (basolateral). Strikingly, MDCK-Gal-8H cells acquired tumorigenic potential, as reflected in anchorage-independent growth in soft agar and tumor generation in immunodeficient NSG mice. Therefore, Gal-8 can promote oncogenic-like transformation of epithelial cells through partial and reversible EMT, accompanied by higher proliferation, migration/invasion, and tumorigenic properties. PMID:29298841

Ultrasound assessment of fetal head circumference at the onset of labor as a predictor of operative delivery.

PubMed

Ooi, Poh Vei; Ramphul, Meenakshi; Said, Soha; Burke, Gerard; Kennelly, Mairead M; Murphy, Deirdre J

2015-01-01

This study sought to determine whether ultrasound assessment of fetal head circumference (FHC) at the onset of labor can predict the likelihood of operative delivery. We performed a prospective cohort study of 200 nulliparous women with singleton, cephalic, term pregnancies in an Irish Maternity Hospital. Transabdominal ultrasound assessment of FHC was performed when spontaneous labor was diagnosed or immediately prior to induction. Odds ratios for operative delivery (instrumental delivery or cesarean section) and maternal and neonatal morbidity were calculated using logistic regression with FHC categorized at a ≥350-mm cut-off (90th percentile). Ultrasound assessment of FHC at the onset of labor was highly correlated with post-delivery neonatal head circumference (NHC) (Pearson's correlation coefficient 0.74), suggesting that it can be measured reliably. FHC ≥350 mm was associated with more than twice the risk of any operative delivery (OR 2.5, 95% CI 1.0-6.2) and a two-fold increased risk of cesarean section for dystocia (OR 2.0, 95% CI 1.0-4.3). Differences in maternal and neonatal morbidity were not statistically significant. These preliminary data suggest that ultrasound assessment of FHC at the onset of labor may be useful in identifying women at greater risk of intrapartum intervention and warrant further research.

Validity of self-reported family history of cancer: A systematic literature review on selected cancers.

PubMed

Fiederling, Jonas; Shams, Ahmad Zia; Haug, Ulrike

2016-10-01

Evidence regarding validity of self-reported family history of cancer (FHC) has been reviewed only for breast, colorectal, prostate, ovarian, endometrial and uterine cancer. We aimed to systematically review studies assessing validity of self-reported family history for the remaining cancer sites. We searched the Medline database for relevant studies published by January 2016. We extracted information on the study design and the positive predictive value (PPV) of self-reported FHC, defined as the proportion of reported cancer diagnoses among relatives that was confirmed by a reference standard (as a measure of over-reporting). We also extracted information on sensitivity of self-reported FHC (as a measure of underreporting). Overall, 21 studies were included that provided information on the PPV of self-reported FHC for relevant cancers and four studies also provided information on sensitivity. The PPV was highest (mostly >70%) for pancreatic, lung, thyroid and urinary system cancers and for leukemia and lymphoma, while it was lowest for stomach and liver cancer. Sensitivity was highest (>70%) for pancreatic cancer, lung cancer, brain cancer, melanoma, leukemia and lymphoma. For several cancers, sample sizes were low and the number of studies limited, particularly regarding sensitivity of self-reported FHC. In conclusion, for some cancers (e.g., pancreatic cancer, lung cancer, leukemia, lymphoma) self-reported FHC can be considered sufficiently valid to be useful, for example, in preventive counseling. For several cancers, it is not sufficiently studied or the pattern is inconsistent. This needs to be taken into account when using self-reported information about FHC in clinical practice or epidemiological research. © 2016 UICC.

Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties

PubMed Central

Fessart, Delphine; Domblides, Charlotte; Avril, Tony; Eriksson, Leif A; Begueret, Hugues; Pineau, Raphael; Malrieux, Camille; Dugot-Senant, Nathalie; Lucchesi, Carlo; Chevet, Eric; Delom, Frederic

2016-01-01

The extracellular matrix (ECM) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis. Here, we show that the Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a soluble protein-disulfide isomerase involved in ER protein folding and quality control, is secreted and interacts with the ECM. Extracellular AGR2 (eAGR2) is a microenvironmental regulator of epithelial tissue architecture, which plays a role in the preneoplastic phenotype and contributes to epithelial tumorigenicity. Indeed, eAGR2, is secreted as a functionally active protein independently of its thioredoxin-like domain (CXXS) and of its ER-retention domain (KTEL), and is sufficient, by itself, to promote the acquisition of invasive and metastatic features. Therefore, we conclude that eAGR2 plays an extracellular role independent of its ER function and we elucidate this gain-of-function as a novel and unexpected critical ECM microenvironmental pro-oncogenic regulator of epithelial morphogenesis and tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.13887.001 PMID:27240165

Case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway.

PubMed

Uesugi, Noriyuki; Sugimoto, Ryo; Eizuka, Makoto; Fujita, Yasuko; Osakabe, Mitsumasa; Koeda, Keisuke; Kosaka, Takashi; Yanai, Shunichi; Ishida, Kazuyuki; Sasaki, Akira; Matsumoto, Takayuki; Sugai, Tamotsu

2017-11-16

Here, we report a case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway. A 57-year-old Japanese woman presented with epigastric tenderness, and distal gastrectomy was performed. In the surgical specimen, histologically, the tumor tissue was composed of three subtypes of tumor components showing different histological architecture and cellular atypia, diagnosed as neuroendocrine tumor (NET) G2, NET G3, and neuroendocrine carcinoma (NEC) components. Immunohistochemically, the Ki-67-positive rates of NET G2, NET G3, and NEC components were 6.5%, 99.5% and 88.1%, respectively. Although allelic imbalance (AI) on chromosomes 1p, 3p, 8q, TP53, 18q and 22q was commonly found in all components, AI of 4p was found in NET G3 and NEC components (but not in the NET G2 component). In contrast, AIs of 5q and 9p were found in only the NEC component. Thus, we showed the progression from NET G2 to NEC, via NET G3, within the same tumor.

Conformational Sampling and Binding Site Assessment of Suppression of Tumorigenicity 2 Ectodomain

PubMed Central

Yang, Chao-Yie; Delproposto, James; Chinnaswamy, Krishnapriya; Brown, William Clay; Wang, Shuying; Stuckey, Jeanne A.; Wang, Xinquan

2016-01-01

Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor (IL-1R) family, activates type 2 immune responses to pathogens and tissue damage via binding to IL-33. Dysregulated responses contribute to asthma, graft-versus-host and autoinflammatory diseases and disorders. To study ST2 structure for inhibitor development, we performed the principal component (PC) analysis on the crystal structures of IL1-1R1, IL1-1R2, ST2 and the refined ST2 ectodomain (ST2ECD) models, constructed from previously reported small-angle X-ray scattering data. The analysis facilitates mapping of the ST2ECD conformations to PC subspace for characterizing structural changes. Extensive coverage of ST2ECD conformations was then obtained using the accelerated molecular dynamics simulations started with the IL-33 bound ST2ECD structure as instructed by their projected locations on the PC subspace. Cluster analysis of all conformations further determined representative conformations of ST2ECD ensemble in solution. Alignment of the representative conformations with the ST2/IL-33 structure showed that the D3 domain of ST2ECD (containing D1-D3 domains) in most conformations exhibits no clashes with IL-33 in the crystal structure. Our experimental binding data informed that the D1-D2 domain of ST2ECD contributes predominantly to the interaction between ST2ECD and IL-33 underscoring the importance of the D1-D2 domain in binding. Computational binding site assessment revealed one third of the total detected binding sites in the representative conformations may be suitable for binding to potent small molecules. Locations of these sites include the D1-D2 domain ST2ECD and modulation sites conformed to ST2ECD conformations. Our study provides structural models and analyses of ST2ECD that could be useful for inhibitor discovery. PMID:26735493

The Tyrosine Kinase c-Met Contributes to the Pro-tumorigenic Function of the p38 Kinase in Human Bile Duct Cholangiocarcinoma Cells*

PubMed Central

Dai, Rongyang; Li, Juanjuan; Fu, Jing; Chen, Yao; Wang, Ruoyu; Zhao, Xiaofang; Luo, Tao; Zhu, Junjie; Ren, Yibin; Cao, Jie; Qian, Youwen; Li, Ning; Wang, Hongyang

2012-01-01

Pro-tumorigenic function of the p38 kinase plays a critical role in human cholangiocarcinogenesis. However, the underlying mechanism remains incompletely understood. Here, we report that c-Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), contributes to the pro-tumorigenic ability of p38 in human cholangiocarcinoma cells. Both p38 and c-Met promote the proliferation and invasion of human cholangiocarcinoma cells. Importantly, inhibition or knockdown of p38 decreased the basal activation of c-Met. Tyrosine phosphatase inhibitor studies revealed that p38 promotes the activity of c-Met, at least in part, by inhibiting dephosphorylation of the receptor. Moreover, density enhanced phosphatase-1 (DEP-1) is involved in p38-mediated inhibiting dephosphorylation of c-Met. Furthermore, p38 inhibits the degradation of c-Met. Taken together, these data provide a potential mechanism to explain how p38 promotes human cholangiocarcinoma cell proliferation and invasion. We propose that the link between p38 and c-Met is implicated in the progression of human cholangiocarcinoma. PMID:23024367

Ultra-sensitive detection of tumorigenic cellular impurities in human cell-processed therapeutic products by digital analysis of soft agar colony formation.

PubMed

Kusakawa, Shinji; Yasuda, Satoshi; Kuroda, Takuya; Kawamata, Shin; Sato, Yoji

2015-12-08

Contamination with tumorigenic cellular impurities is one of the most pressing concerns for human cell-processed therapeutic products (hCTPs). The soft agar colony formation (SACF) assay, which is a well-known in vitro assay for the detection of malignant transformed cells, is applicable for the quality assessment of hCTPs. Here we established an image-based screening system for the SACF assay using a high-content cell analyzer termed the digital SACF assay. Dual fluorescence staining of formed colonies and the dissolution of soft agar led to accurate detection of transformed cells with the imaging cytometer. Partitioning a cell sample into multiple wells of culture plates enabled digital readout of the presence of colonies and elevated the sensitivity for their detection. In practice, the digital SACF assay detected impurity levels as low as 0.00001% of the hCTPs, i.e. only one HeLa cell contained in 10,000,000 human mesenchymal stem cells, within 30 days. The digital SACF assay saves time, is more sensitive than in vivo tumorigenicity tests, and would be useful for the quality control of hCTPs in the manufacturing process.

Ultra-sensitive detection of tumorigenic cellular impurities in human cell-processed therapeutic products by digital analysis of soft agar colony formation

PubMed Central

Kusakawa, Shinji; Yasuda, Satoshi; Kuroda, Takuya; Kawamata, Shin; Sato, Yoji

2015-01-01

Contamination with tumorigenic cellular impurities is one of the most pressing concerns for human cell-processed therapeutic products (hCTPs). The soft agar colony formation (SACF) assay, which is a well-known in vitro assay for the detection of malignant transformed cells, is applicable for the quality assessment of hCTPs. Here we established an image-based screening system for the SACF assay using a high-content cell analyzer termed the digital SACF assay. Dual fluorescence staining of formed colonies and the dissolution of soft agar led to accurate detection of transformed cells with the imaging cytometer. Partitioning a cell sample into multiple wells of culture plates enabled digital readout of the presence of colonies and elevated the sensitivity for their detection. In practice, the digital SACF assay detected impurity levels as low as 0.00001% of the hCTPs, i.e. only one HeLa cell contained in 10,000,000 human mesenchymal stem cells, within 30 days. The digital SACF assay saves time, is more sensitive than in vivo tumorigenicity tests, and would be useful for the quality control of hCTPs in the manufacturing process. PMID:26644244

Downregulation of P-cadherin expression in hepatocellular carcinoma induces tumorigenicity

PubMed Central

Bauer, Richard; Valletta, Daniela; Bauer, Karin; Thasler, Wolfgang E; Hartmann, Arndt; Müller, Martina; Reichert, Torsten E; Hellerbrand, Claus

2014-01-01

P-cadherin is a major contributor to cell-cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes and in maintaining tissue integrity and homeostasis. Alterations of P-cadherin expression have been observed during the progression of several carcinomas where it appears to act as tumor suppressive or oncogenic in a context-dependent manner. Here, we found a significant downregulation of P-cadherin in hepatocellular carcinoma (HCC) cell lines and tissues compared to primary human hepatocytes and non-malignant liver tissues. Combined immunohistochemical analysis of a tissue microarray containing matched pairs of HCC tissue and corresponding non-tumorous liver tissue of 69 patients confirmed reduced P-cadherin expression in more than half of the cases. In 35 human HCC tissues, the P-cadherin immunosignal was completely lost which correlated with tumor staging and proliferation. Also in vitro, P-cadherin suppression in HCC cells via siRNA induced proliferation compared to cells transfected with control-siRNA. In summary, downregulation of P-cadherin expression appears to induce tumorigenicity in HCC. Therefore, P-cadherin expression may serve as a prognostic marker and therapeutic target of this highly aggressive tumor. PMID:25337260

Downregulation of P-cadherin expression in hepatocellular carcinoma induces tumorigenicity.

PubMed

Bauer, Richard; Valletta, Daniela; Bauer, Karin; Thasler, Wolfgang E; Hartmann, Arndt; Müller, Martina; Reichert, Torsten E; Hellerbrand, Claus

2014-01-01

P-cadherin is a major contributor to cell-cell adhesion in epithelial tissues, playing pivotal roles in important morphogenetic and differentiation processes and in maintaining tissue integrity and homeostasis. Alterations of P-cadherin expression have been observed during the progression of several carcinomas where it appears to act as tumor suppressive or oncogenic in a context-dependent manner. Here, we found a significant downregulation of P-cadherin in hepatocellular carcinoma (HCC) cell lines and tissues compared to primary human hepatocytes and non-malignant liver tissues. Combined immunohistochemical analysis of a tissue microarray containing matched pairs of HCC tissue and corresponding non-tumorous liver tissue of 69 patients confirmed reduced P-cadherin expression in more than half of the cases. In 35 human HCC tissues, the P-cadherin immunosignal was completely lost which correlated with tumor staging and proliferation. Also in vitro, P-cadherin suppression in HCC cells via siRNA induced proliferation compared to cells transfected with control-siRNA. In summary, downregulation of P-cadherin expression appears to induce tumorigenicity in HCC. Therefore, P-cadherin expression may serve as a prognostic marker and therapeutic target of this highly aggressive tumor.

Eugenia jambolana Lam. Berry Extract Inhibits Growth and Induces Apoptosis of Human Breast Cancer but not Non-Tumorigenic Breast Cells

PubMed Central

Li, Liya; Adams, Lynn S.; Chen, Shiuan; Killian, Caroline; Ahmed, Aftab; Seeram, Navindra P.

2009-01-01

The ripe purple berries of the native Indian plant, Eugenia jambolana Lam., known as Jamun, are popularly consumed and available in the United States in Florida and Hawaii. Despite the growing body of data on the chemopreventive potential of edible berry extracts, there is paucity of such data for Jamun fruit. Therefore our laboratory initiated the current study with the following objectives:1) to prepare a standardized Jamun fruit extract (JFE) for biological studies and, 2) to investigate the anti-proliferative and pro-apoptotic effects of JFE in estrogen dependent/aromatase positive (MCF-7aro), and estrogen independent (MDA-MB-231) breast cancer cells, and in a normal/non-tumorigenic (MCF-10A) breast cell line. JFE was standardized to anthocyanin content using the pH differential method, and individual anthocyanins were identified by high performance liquid chromatography with ultraviolet (HPLC-UV) and tandem mass spectrometry (LC-MS/MS) methods. JFE contained 3.5% anthocyanins (as cyanidin-3-glucoside equivalents) which occur as diglucosides of five anthocyanidins/aglycons: delphinidin, cyanidin, petunidin, peonidin and malvidin. In the proliferation assay, JFE was most effective against MCF-7aro (IC50=27 µg/mL), followed by MDA-MB-231 (IC50=40 µg/mL) breast cancer cells. Importantly, JFE exhibited only mild antiproliferative effects against the normal MCF-10A (IC50>100 µg/mL) breast cells. Similarly, JFE (at 200 µg/mL) exhibited pro-apoptotic effects against the MCF-7aro (p≤0.05) and the MDA-MB-231 (p≤0.01) breast cancer cells, but not towards the normal MCF-10A breast cells. These studies suggest that JFE may have potential beneficial effects against breast cancer. PMID:19166352

Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation

PubMed Central

Šolman, Maja; Ligabue, Alessio; Blaževitš, Olga; Jaiswal, Alok; Zhou, Yong; Liang, Hong; Lectez, Benoit; Kopra, Kari; Guzmán, Camilo; Härmä, Harri; Hancock, John F; Aittokallio, Tero; Abankwa, Daniel

2015-01-01

Hotspot mutations of Ras drive cell transformation and tumorigenesis. Less frequent mutations in Ras are poorly characterized for their oncogenic potential. Yet insight into their mechanism of action may point to novel opportunities to target Ras. Here, we show that several cancer-associated mutations in the switch III region moderately increase Ras activity in all isoforms. Mutants are biochemically inconspicuous, while their clustering into nanoscale signaling complexes on the plasma membrane, termed nanocluster, is augmented. Nanoclustering dictates downstream effector recruitment, MAPK-activity, and tumorigenic cell proliferation. Our results describe an unprecedented mechanism of signaling protein activation in cancer. DOI: http://dx.doi.org/10.7554/eLife.08905.001 PMID:26274561

AS30D Model of Hepatocellular Carcinoma: Tumorigenicity and Preliminary Characterization by Imaging, Histopathology, and Immunohistochemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Scott M.; Callstrom, Matthew R.; Knudsen, Bruce

This study was designed to determine the tumorigenicity of the AS30D HCC cell line following orthotopic injection into rat liver and preliminarily characterize the tumor model by both magnetic resonance imaging (MRI) and ultrasound (US) as well as histopathology and immunohistochemistry.MaterialsAS30D cell line in vitro proliferation was assessed by using MTT assay. Female rats (N = 5) underwent injection of the AS30D cell line into one site in the liver. Rats subsequently underwent MR imaging at days 7 and 14 to assess tumor establishment and volume. One rat underwent US of the liver at day 7. Rats were euthanized atmore » day 7 or 14 and livers were subjected to gross, histopathologic (H and E), and immunohistochemical (CD31) analysis to assess for tumor growth and neovascularization. AS30D cell line demonstrated an in vitro doubling time of 33.2 {+-} 5.3 h. MR imaging demonstrated hyperintense T2-weighted and hypointense T1-weighted lesions with tumor induction in five of five and three of three sites at days 7 and 14, respectively. The mean (SD) tumor volume was 126.1 {+-} 36.2 mm{sup 3} at day 7 (N = 5). US of the liver demonstrated a well-circumscribed, hypoechoic mass and comparison of tumor dimensions agreed well with MRI. Analysis of H and E- and CD31-stained sections demonstrated moderate-high grade epithelial tumors with minimal tumor necrosis and evidence of diffuse intratumoral and peritumoral neovascularization by day 7. AS30D HCC cell line is tumorigenic following orthotopic injection into rat liver and can be used to generate an early vascularizing, slower-growing rat HCC tumor model.« less

Tumorigenicity of MCF-7 human breast cancer cells lacking the p38α mitogen-activated protein kinase.

PubMed

Mendoza, Rhone A; Moody, Emily E; Enriquez, Marlene I; Mejia, Sylvia M; Thordarson, Gudmundur

2011-01-01

We have generated cell lines with significantly reduced expression of the p38 mitogen-activated protein kinase (p38 MAPK), Min-p38 MAPK cells, and used these cells to investigate p38 MAPK's role in tumorigenesis of breast cancer cells. MCF-7 cells were stably transfected with a plasmid producing small interfering RNA that inhibited the expression of p38 MAPK. Control cells were stably transfected with the same plasmid producing non-interfering RNA. The reduction in the p38 MAPK activity caused a significant increase in the expressions of estrogen receptor-α (ERα) and the progesterone receptor, but eliminated the expression of ERβ. Min-p38 MAPK cells showed an enhanced overall growth response to 17β-estradiol (E₂), whereas GH plus epidermal growth factor were largely ineffective growth stimulators in these cells compared to controls. Although the long-term net growth rate of the Min-p38 MAPK cells was increased in response to E₂, their proliferation rate was lower compared to controls in short-term cultures. However, the Min-p38 MAPK cells did show a significant decreased rate of apoptosis after E₂ treatment and a reduction in the basal phosphorylation of p53 tumor suppressor protein compared to controls. When the Min-p38 MAPK cells were xenografted into E₂-treated athymic nude mice, their tumorigenicity was enhanced compared to control cells. Increased tumorigenicity of Min-p38 MAPK cells was caused mainly by a decrease in the apoptosis rate indicating that the lack of the p38 MAPK caused an imbalance to increase the ERα:ERβ ratio and a reduction in the activity of the p53 tumor suppressor protein.

Antitumor effect of CXCR4 antagonist AMD3100 on the tumorigenic cell line of BHP10-3 papillary thyroid cancer cells.

PubMed

Jung, Young Ho; Lee, Doh Young; Cha, Wonjae; Kim, Bo Hae; Sung, Myung-Whun; Kim, Kwang Hyun; Ahn, Soon-Hyun

2016-10-01

A tumorigenic cell line (BHP10-3M) derived from nontumorigenic papillary thyroid carcinoma (PTC) cells (BHP10-3) having rearranged during transfection (RET)/PTC1 gene rearrangement might have a higher expression of CXCR4, either quantitatively or functionally. The authors also postulated that CXCR4-mediated invasion or tumorigenesis could be blocked by CXCR4 antagonists, including AMD3100. The expression of CXCR4 in BHP10-3 and BHP10-3M cells was assessed using immunoblot analysis, flow cytometry, and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The effect of AMD3100 on BHP10-3 and BHP10-3M cell lines was evaluated using cell proliferation assay, invasion assay, and tumor growth experiment in nude mice. Immunoblotting, flow cytometry, and quantitative RT-PCR proved that BHP10-3M cells expressed a higher level of CXCR4 than BHP10-3 cells. Although blocking CXCR4 with AMD3100 did not suppress cell proliferation in both cell lines from 1 ng/mL to 100 ng/mL concentration, AMD3100 suppressed invasion of BHP10-3M cells in vitro in a dose-dependent manner. At higher concentrations from 10(3) ng/mL to 10(5) ng/mL, the proliferation of BHP10-3M cells was inhibited more strongly by AMD3100 than that of BHP10-3 cells. Intraperitoneal injection of AMD3100 inhibited tumor formation by BHP10-3M cells in the thyroid of nude mice. A tumorigenic cell line (BHP10-3M) of PTC showed higher expression of CXCR4 quantitatively and functionally than a nontumorigenic cell line (BHP10-3). The CXCR4 antagonist (AMD3100) showed a significant antitumor effect on the tumorigenic cell line of PTC BHP10-3 cells both in vitro and in vivo. CXCR4 antagonist can be expected to have an adjuvant role in the management of PTC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1486, 2016. © 2016 Wiley Periodicals, Inc.

Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics.

PubMed

Puré, Ellen; Blomberg, Rachel

2018-05-03

Fibroblast activation protein (FAP) is a cell-surface serine protease that acts on various hormones and extracellular matrix components. FAP is highly upregulated in a wide variety of cancers, and is often used as a marker for pro-tumorigenic stroma. It has also been proposed as a molecular target of cancer therapies, and, especially in recent years, a great deal of research has gone into design and testing of diverse FAP-targeted treatments. Yet despite this growing field of research, our knowledge of FAP's basic biology and functional roles in various cancers has lagged behind its use as a tumor-stromal marker. In this review, we summarize and analyze recent advances in understanding the functions of FAP in cancer, most notably its prognostic value in various tumor types, cellular effects on various cell types, and potential as a therapeutic target. We highlight outstanding questions in the field, the answers to which could shape preclinical and clinical studies of FAP.

Abnormal cardiac response to exercise in a murine model of familial hypertrophic cardiomyopathy.

PubMed

Nguyen, Lan; Chung, Jessica; Lam, Lien; Tsoutsman, Tatiana; Semsarian, Christopher

2007-07-10

Clinical outcome in familial hypertrophic cardiomyopathy (FHC) may be influenced by modifying factors such as exercise. Transgenic mice which overexpress the human disease-causing cTnI gene mutation, Gly203Ser (designated cTnI-G203S), develop all the characteristic phenotypic features of FHC. To study the modifying effect of exercise in early disease, mice underwent swimming exercise at an early age prior to the development of the FHC phenotype. In non-transgenic and cTnI-wt mice, swimming resulted in a significant increase in left ventricular wall thickness and contractility on echocardiography, consistent with a physiological hypertrophic response to exercise. In contrast, cTnI-G203S mice showed no increase in these parameters, indicating an abnormal response to exercise. The lack of a physiological response to exercise may indicate an important novel mechanistic insight into the role of exercise in triggering adverse events in FHC.

mTORC1 Maintains the Tumorigenicity of SSEA-4+ High-Grade Osteosarcoma

PubMed Central

Zhang, Wu; Ding, Meng-Lei; Zhang, Jia-Nian; Qiu, Jian-Ru; Shen, Yu-Hui; Ding, Xiao-Yi; Deng, Lian-Fu; Zhang, Wei-Bin; Zhu, Jiang

2015-01-01

Inactivation of p53 and/or Rb pathways restrains osteoblasts from cell-cycle exit and terminal differentiation, which underpins osteosarcoma formation coupled with dedifferentiation. Recently, the level of p-S6K was shown to independently predict the prognosis for osteosarcomas, while the reason behind this is not understood. Here we show that in certain high-grade osteosarcomas, immature SSEA-4+ tumor cells represent a subset of tumor-initiating cells (TICs) whose pool size is maintained by mTORC1 activity. mTORC1 supports not only SSEA-4+ cell self-renewal through S6K but also the regeneration of SSEA-4+ TICs by SSEA-4− osteosarcoma cell dedifferentiation. Mechanistically, active mTORC1 is required to prevent a likely upregulation of the cell-cycle inhibitor p27 independently of p53 or Rb activation, which otherwise effectively drives the terminal differentiation of SSEA-4− osteosarcoma cells at the expense of dedifferentiation. Thus, mTORC1 is shown to critically regulate the retention of tumorigenicity versus differentiation in discrete differentiation phases in SSEA-4+ TICs and their progeny. PMID:25853231

KIR3DL2 binds to HLA-B27 dimers and free H chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis.

PubMed

Wong-Baeza, Isabel; Ridley, Anna; Shaw, Jackie; Hatano, Hiroko; Rysnik, Oliwia; McHugh, Kirsty; Piper, Christopher; Brackenbridge, Simon; Fernandes, Ricardo; Chan, Anthoni; Bowness, Paul; Kollnberger, Simon

2013-04-01

The human leukocyte Ag HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 can be expressed at the cell surface of APC as both classical β2-microglobulin-associated B27 and B27 free H chain forms (FHC), including disulfide-bonded H chain homodimers (termed B27(2)). B27 FHC forms, but not classical B27, bind to KIR3DL2. HLA-A3, which is not associated with spondyloarthritis (SpA), is also a ligand for KIR3DL2. In this study, we show that B27(2) and B27 FHC bind more strongly to KIR3DL2 than other HLA-class I, including HLA-A3. B27(2) tetramers bound KIR3DL2-transfected cells more strongly than HLA-A3. KIR3DL2Fc bound to HLA-B27-transfected cells more strongly than to cells transfected with other HLA-class I. KIR3DL2Fc pulled down multimeric, dimeric, and monomeric FHC from HLA-B27-expressing cell lines. Binding to B27(2) and B27 FHC stimulated greater KIR3DL2 phosphorylation than HLA-A3. B27(2) and B27 FHC stimulated KIR3DL2CD3ε-transduced T cell IL-2 production to a greater extent than control HLA-class I. KIR3DL2 binding to B27 inhibited NK IFN-γ secretion and promoted greater survival of KIR3DL2(+) CD4 T and NK cells than binding to other HLA-class I. KIR3DL2(+) T cells from B27(+) SpA patients proliferated more in response to Ag presented by syngeneic APC than the same T cell subset from healthy and disease controls. Our results suggest that expansion of KIR3DL2-expressing leukocytes observed in B27(+) SpA may be explained by the stronger interaction of KIR3DL2 with B27 FHC.

Establishment of two basal-like breast cancer cell lines with extremely low tumorigenicity from Taiwanese premenopausal women.

PubMed

Kuo, Wen-Ling; Ueng, Shir-Hwa; Wu, Chun-Hsing; Lee, Li-Yu; Lee, Yun-Shien; Yu, Ming-Chin; Chen, Shin-Cheh; Yu, Chi-Chang; Tsai, Chi-Neu

2018-04-01

The research of carcinogenetic mechanisms of breast cancer in different ethnic backgrounds is an interesting field, as clinical features of breast cancers vary among races. High premenopausal incidence is distinctive in East-Asian breast cancer. However, human cell lines derived from Asian primary breast tumor are rare. To provide alternative cell line models with a relevant genetic background, we aimed to establish breast cancer cell lines from Taiwanese patients of Han-Chinese ethnicity. Fresh tissue from mammary tumors were digested into organoids, plated and grown in basal serum-free medium of human mammary epithelial cells (HuMEC) with supplements. Cells were further enriched by positive selection with CD326 (epithelial cell adhesion molecule; EpCAM)-coated micro-magnetic beads. Two breast cancer cell lines derived from premenopausal women were successfully established by this method, and named Chang-Gung Breast Cancer 01 (CGBC 01) and 02 (CGBC 02). These two cell lines had a similar phenotype with weak expression of estrogen receptor (ER), progesterone receptor (PR), and without amplification of receptor tyrosine protein kinase erbB-2 (HER2/neu). Genome-wide Single Nucleotide Polymorphism (SNP) array showed multiple copy number alterations in both cell lines. Based on gene expression profiles, CGBC 01 and 02 were clustered into basal-like subtype with reference to the breast cancer cell line gene expression database. The tumorigenicity of both cell lines was extremely low in both anchorage-independence assay and transplantation into the mammary fat pads of nude mice. CGBC 01 and CGBC 02 are low tumorigenic breast cancer cell lines, established from Han-Chinese premenopausal breast cancer patients, which serve as in vitro models in studying the biological features of Asian breast cancer.

Tumorigenicity of MCF-7 human breast cancer cells lacking the p38α mitogen-activated protein kinase

PubMed Central

Mendoza, Rhone A; Moody, Emily E; Enriquez, Marlene I; Mejia, Sylvia M; Thordarson, Gudmundur

2011-01-01

We have generated cell lines with significantly reduced expression of the p38 mitogen-activated protein kinase (p38 MAPK), Min-p38 MAPK cells, and used these cells to investigate its role in tumorigenesis of breast cancer cells. MCF-7 cells were stably transfected with a plasmid producing small interfering RNA that inhibited the expression of p38 MAPK. Control cells were stably transfected with the same plasmid producing non-interfering RNA. The reduction in the p38 MAPK activity caused a significant increase in the expressions of the estrogen receptor-α (ERα) and the progesterone receptor, but eliminated the expression of the ERβ. Min-p38 MAPK cells showed an enhanced overall growth response to 17β-estradiol (E2), whereas growth hormone plus epidermal growth factor were largely ineffective growth stimulators in these cells compared to controls. Although the long-term net growth rate of the Min-p38 MAPK cells was increased in response to E2, their proliferation rate was not different from controls in short-term cultures. However, the Min-p38 MAPK cells did show a significant decreased rate of apoptosis after E2 treatment and a reduction in the basal phosphorylation of p53 tumor suppressor protein compared to controls. When the Min-p38 MAPK cells were xenografted into E2-treated athymic nude mice, their tumorigenicity was enhanced compared to control cells. Conclusions: increased tumorigenicity of Min-p38 MAPK cells was caused mainly by a decrease in apoptosis rate indicating that the lack of the p38 MAPK caused an imbalance to increase the ERα:ERβ ratio and a reduction in the activity of the p53 tumor suppressor protein. PMID:20974639

Transcriptional profiles in liver from rats treated with tumorigenic and non-tumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

PubMed

Hester, Susan D; Wolf, Douglas C; Nesnow, Stephen; Thai, Sheau-Fung

2006-01-01

Conazoles are a class of fungicides used as pharmaceutical and agricultural agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland, whereas, propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. These conazoles administered in the feed to male Wistar/Han rats were found to induce hepatomegaly, induce high levels of pentoxyresorufin-O-dealkylase, increase cell proliferation in the liver, increase serum cholesterol, decrease serum T3 and T4, and increase hepatic uridine diphosphoglucuronosyl transferase activity. The goal of the present study was to define pathways that explain the biologic outcomes. Male Wistar/Han rats (3 per group), were exposed to the 3 conazoles in the feed for 4, 30, or 90 days of treatment at tumorigenic and nontumorigenic doses. Hepatic gene expression was determined using high-density Affymetrix GeneChips (Rat 230_2). Differential gene expression was assessed at the probe level using Robust Multichip Average analysis. Principal component analysis by treatment and time showed within group sample similarity and that the treatment groups were distinct from each other. The number of altered genes varied by treatment, dose, and time. The greatest number of altered genes was induced by triadimefon and propiconazole after 90 days of treatment, while myclobutanil had minimal effects at that time point. Pathway level analyses revealed that after 90 days of treatment the most significant numbers of altered pathways were related to cell signaling, growth, and metabolism. Pathway level analysis for triadimefon and propiconazole resulted in 71 altered pathways common to both chemicals. These pathways controlled cholesterol metabolism, activation of nuclear receptors, and N-ras and K-ras signaling. There were 37 pathways uniquely changed by propiconazole, and triadimefon uniquely altered 34 pathways. Pathway level analysis of altered gene expression

Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

PubMed Central

Burns, Jorge S.; Kristiansen, Malthe; Kristensen, Lars P.; Larsen, Kenneth H.; Nielsen, Maria O.; Christiansen, Helle; Nehlin, Jan; Andersen, Jens S.; Kassem, Moustapha

2011-01-01

Background Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. Methodology/Principal Findings Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. Conclusions Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was

The biochemistry and immunology of non-canonical forms of HLA-B27.

PubMed

Shaw, Jacqueline; Hatano, Hiroko; Kollnberger, Simon

2014-01-01

HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 is expressed at the cell surface of antigen presenting cells (APC) both as canonical β2m-associated and non-canonical β2m-free heavy chain (FHC) forms which include B27 dimers (termed B272). B27 FHC forms arise in an endosomal compartment from recycling β2m-associated B27. Formation of cell surface FHC dimers is critically dependent on an unpaired reactive cysteine 67 in the α1 helix of the class I heavy chain. HLA-B27 also form redox-inducible β2m-associated dimers on exosomes and apoptosing cells. By contrast with cell surface expressed cysteine 67-dependent heavy chain dimers these dimers are dependent on a cytoplasmic cysteine 325 for their formation. HLA-B27 binds to immunoregulatory receptors including members of the Killer cell Immunoglobulin-like (KIR) and Leukocyte Immunoglobulin-like receptor family. B27 FHC bind to different but overlapping sets of these immunoreceptors compared to classical β2m-associated HLA-B27. B27 FHC bind more strongly to KIR3DL2 and LILRB2 immune receptor than other β2m-associated HLA-class I ligands. Genetic studies have implicated genes which control production of the important proinflammatory cytokine IL-17 in the pathogenesis of spondyloarthritis. Cell surface HLA-B27 FHC binding to these immune receptors or acting through other mechanisms could impact on the pathogenesis of spondyloarthritis by promoting immune cell production of IL-17. Here we review the literature on these non-canonical forms of HLA-B27 and the immune receptors they bind to and discuss the possible relevance of these interactions to the pathogenesis of spondyloarthropathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Substitution of Formal and Informal Home Care Service Use and Nursing Home Service Use: Health Outcomes, Decision-Making Preferences, and Implications for a Public Health Policy.

PubMed

Chen, Chia-Ching; Yamada, Tetsuji; Nakashima, Taeko; Chiu, I-Ming

2017-01-01

The purposes of this study are: (1) to empirically identify decision-making preferences of long-term health-care use, especially informal and formal home care (FHC) service use; (2) to evaluate outcomes vs. costs based on substitutability of informal and FHC service use; and (3) to investigate health outcome disparity based on substitutability. The methods of ordinary least squares, a logit model, and a bivariate probit model are used by controlling for socioeconomic, demographic, and physical/mental health factors to investigate outcomes and costs based substitutability of informal and formal health-care use. The data come from the 2013 Japanese Study of Aging and Retirement (JSTAR), which is designed by Keizai-Sangyo Kenkyu-jo, Hitotsubashi University, and the University of Tokyo. The JSTAR is a globally comparable data survey of the elderly. There exists a complement relationship between the informal home care (IHC) and community-based FHC services, and the elasticity's ranges from 0.18 to 0.22. These are reasonable results, which show that unobservable factors are positively related to IHC and community-based FHC, but negatively related to nursing home (NH) services based on our bivariate probit model. Regarding health-care outcome efficiency issue, the IHC is the best one among three types of elderly care: IHC, community-based FHC, and NH services. Health improvement/outcome of elderly with the IHC is heavier concentrated on IHC services than the elderly care services by community-based FHC and NH care services. Policy makers need to address a diversity of health outcomes and efficiency of services based on providing services to elderly through resource allocation to the different types of long-term care. A provision of partial or full compensation for elderly care at home is recommendable and a viable option to improve their quality of lives.

Overexpression of YB1 C-terminal domain inhibits proliferation, angiogenesis and tumorigenicity in a SK-BR-3 breast cancer xenograft mouse model.

PubMed

Shi, Jian-Hong; Cui, Nai-Peng; Wang, Shuo; Zhao, Ming-Zhi; Wang, Bing; Wang, Ya-Nan; Chen, Bao-Ping

2016-01-01

Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with vital roles in proliferation, differentiation and apoptosis. In this study, we have examined the role of its C-terminal domain (YB1 CTD) in proliferation, angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3 was infected with GFP-tagged YB1 CTD adenovirus expression vector. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay showed that YB1 CTD decreased SK-BR-3 cell proliferation, and down-regulated cyclin B1 and up-regulated p21 levels in SK-BR-3 cells. YB1 CTD overexpression changed the cytoskeletal organization and slightly inhibited the migration of SK-BR-3 cells. YB1 CTD also inhibited secreted VEGF expression in SK-BR-3 cells, which decreased SK-BR-3-induced EA.hy926 endothelial cell angiogenesis in vitro. YB1 CTD overexpression attenuated the ability of SK-BR-3 cells to form tumours in nude mice, and decreased in vivo VEGF levels and angiogenesis in the xenografts in SK-BR-3 tumour-bearing mice. Taken together, our findings demonstrate the vital role of YB1 CTD overexpression in inhibiting proliferation, angiogenesis and tumorigenicity of breast cancer cell line SK-BR-3.

Fail-Safe System against Potential Tumorigenicity after Transplantation of iPSC Derivatives.

PubMed

Itakura, Go; Kawabata, Soya; Ando, Miki; Nishiyama, Yuichiro; Sugai, Keiko; Ozaki, Masahiro; Iida, Tsuyoshi; Ookubo, Toshiki; Kojima, Kota; Kashiwagi, Rei; Yasutake, Kaori; Nakauchi, Hiromitsu; Miyoshi, Hiroyuki; Nagoshi, Narihito; Kohyama, Jun; Iwanami, Akio; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki

2017-03-14

Human induced pluripotent stem cells (iPSCs) are promising in regenerative medicine. However, the risks of teratoma formation and the overgrowth of the transplanted cells continue to be major hurdles that must be overcome. Here, we examined the efficacy of the inducible caspase-9 (iCaspase9) gene as a fail-safe against undesired tumorigenic transformation of iPSC-derived somatic cells. We used a lentiviral vector to transduce iCaspase9 into two iPSC lines and assessed its efficacy in vitro and in vivo. In vitro, the iCaspase9 system induced apoptosis in approximately 95% of both iPSCs and iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs). To determine in vivo function, we transplanted iPSC-NS/PCs into the injured spinal cord of NOD/SCID mice. All transplanted cells whose mass effect was hindering motor function recovery were ablated upon transduction of iCaspase9. Our results suggest that the iCaspase9 system may serve as an important countermeasure against post-transplantation adverse events in stem cell transplant therapies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors

PubMed Central

Krampitz, Geoffrey Wayne; George, Benson M.; Willingham, Stephen B.; Volkmer, Jens-Peter; Weiskopf, Kipp; Jahchan, Nadine; Newman, Aaron M.; Sahoo, Debashis; Zemek, Allison J.; Yanovsky, Rebecca L.; Nguyen, Julia K.; Schnorr, Peter J.; Mazur, Pawel K.; Sage, Julien; Longacre, Teri A.; Visser, Brendan C.; Poultsides, George A.; Norton, Jeffrey A.; Weissman, Irving L.

2016-01-01

Pancreatic neuroendocrine tumors (PanNETs) are a type of pancreatic cancer with limited therapeutic options. Consequently, most patients with advanced disease die from tumor progression. Current evidence indicates that a subset of cancer cells is responsible for tumor development, metastasis, and recurrence, and targeting these tumor-initiating cells is necessary to eradicate tumors. However, tumor-initiating cells and the biological processes that promote pathogenesis remain largely uncharacterized in PanNETs. Here we profile primary and metastatic tumors from an index patient and demonstrate that MET proto-oncogene activation is important for tumor growth in PanNET xenograft models. We identify a highly tumorigenic cell population within several independent surgically acquired PanNETs characterized by increased cell-surface protein CD90 expression and aldehyde dehydrogenase A1 (ALDHA1) activity, and provide in vitro and in vivo evidence for their stem-like properties. We performed proteomic profiling of 332 antigens in two cell lines and four primary tumors, and showed that CD47, a cell-surface protein that acts as a “don’t eat me” signal co-opted by cancers to evade innate immune surveillance, is ubiquitously expressed. Moreover, CD47 coexpresses with MET and is enriched in CD90hi cells. Furthermore, blocking CD47 signaling promotes engulfment of tumor cells by macrophages in vitro and inhibits xenograft tumor growth, prevents metastases, and prolongs survival in vivo. PMID:27035983

Final Hazard Categorization for the Remediation of Six 300-FF-2 Operable Unit Solid Waste Burial Grounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. D. Ludowise

2006-12-12

This report provides the final hazard categorization (FHC) for the remediation of six solid waste disposal sites (referred to as burial grounds) located in the 300-FF-2 Operable Unit (OU) on the Hanford Site. These six sites (618-1, 618-2, 618-3, 618-7, 618-8, and 618-13 Burial Grounds) were determined to have a total radionuclide inventory (WCH 2005a, WCH 2005d, WCH 2005e and WCH 2006b) that exceeds the DOE-STD-1027 Category 3 threshold quantity (DOE 1997) and are the subject of this analysis. This FHC document examines the hazards, identifies appropriate controls to manage the hazards, and documents the FHC and commitments for themore » 300-FF-2 Burial Grounds Remediation Project.« less

MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells*

PubMed Central

Kwon, Yoojung; Kim, Youngmi; Eom, Sangkyung; Kim, Misun; Park, Deokbum; Kim, Hyuna; Noh, Kyeonga; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

2015-01-01

Cyclooxgenase-2 (COX-2) knock-out mouse experiments showed that COX-2 was necessary for in vivo allergic inflammation, such as passive cutaneous anaphylaxis, passive systemic anaphylaxis, and triphasic cutaneous allergic reaction. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2–3′-UTR. miR-26a/-26b exerted negative effects on the features of in vitro and in vivo allergic inflammation by targeting COX-2. ChIP assays showed the binding of HDAC3 and SNAIL, but not COX-2, to the promoter sequences of miR-26a and miR-26b. Cytokine array analysis showed that the induction of chemokines, such as MIP-2, in the mouse passive systemic anaphylaxis model occurred in a COX-2-dependent manner. ChIP assays showed the binding of HDAC3 and COX-2 to the promoter sequences of MIP-2. In vitro and in vivo allergic inflammation was accompanied by the increased expression of MIP-2. miR-26a/-26b negatively regulated the expression of MIP-2. Allergic inflammation enhanced the tumorigenic and metastatic potential of cancer cells and induced positive feedback involving cancer cells and stromal cells, such as mast cells, macrophages, and endothelial cells. miR-26a mimic and miR-26b mimic negatively regulated the positive feedback between cancer cells and stromal cells and the positive feedback among stromal cells. miR-26a/-26b negatively regulated the enhanced tumorigenic potential by allergic inflammation. COX-2 was necessary for the enhanced metastatic potential of cancer cells by allergic inflammation. Taken together, our results indicate that the miR26a/-26b-COX-2-MIP-2 loop regulates allergic inflammation and the feedback relationship between allergic inflammation and the enhanced tumorigenic and metastatic potential. PMID:25907560

Effects of space flight exposure on cell growth, tumorigenicity and gene expression in cancer cells

NASA Astrophysics Data System (ADS)

Yang, Cheng; Li, Yuehui; Zhang, Zhijie; Luo, Chen; Tong, Yongqing; Zhou, Guohua; Xie, Pingli; Hu, Jinyue; Li, Guancheng

2008-12-01

It is well recognized that harsh outer space environment, consisting of microgravity and radiation, poses significant health risks for human cells. To investigate potential effects of the space environment exposure on cancer cells we examined the biological changes in Caski cells carried by the "Shen Zhou IV" spaceship. After exposure for 7 days in spaceflight, 1440 survival subclonal cell lines were established and 4 cell lines were screened. 44F10 and 17E3 were selected because of their increased cell proliferation and tumorigenesis, while 48A9 and 31F2 had slower cytological events. Experiments with cell proliferation assay, flow cytometry, soft agar assay, tumorigenesis assay and DNA microarray analysis have shown that selected cell lines presented multiple biological changes in cell morphology, cell growth, tumorigenicity and gene expression. These results suggest that space environment exposure can make significant biological impact on cancer cells and provide an entry point to find the immunological target of tumorigenesis.

Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis.

PubMed

Chen, Mei; Zhang, Yuan; Zheng, Peng-Sheng

2017-01-01

Tafazzin (TAZ) is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27), high-grade squamous intraepithelial lesions (HSIL, n = 26) and squamous cervical carcinoma (SCC, n = 41) by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.

Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis

PubMed Central

Chen, Mei; Zhang, Yuan; Zheng, Peng-Sheng

2017-01-01

Tafazzin (TAZ) is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27), high-grade squamous intraepithelial lesions (HSIL, n = 26) and squamous cervical carcinoma (SCC, n = 41) by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis. PMID:28489874

An abnormal Ca2+ response in mutant sarcomere protein–mediated familial hypertrophic cardiomyopathy

PubMed Central

Fatkin, Diane; McConnell, Bradley K.; Mudd, James O.; Semsarian, Christopher; Moskowitz, Ivan G.P.; Schoen, Frederick J.; Giewat, Michael; Seidman, Christine E.; Seidman, J.G.

2000-01-01

Dominant-negative sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), a disease characterized by left-ventricular hypertrophy, angina, and dyspnea that can result in sudden death. We report here that a murine model of FHC bearing a cardiac myosin heavy-chain gene missense mutation (αMHC403/+), when treated with calcineurin inhibitors or a K+-channel agonist, developed accentuated hypertrophy, worsened histopathology, and was at risk for early death. Despite distinct pharmacologic targets, each agent augmented diastolic Ca2+ concentrations in wild-type cardiac myocytes; αMHC403/+ myocytes failed to respond. Pretreatment with a Ca2+-channel antagonist abrogated diastolic Ca2+ changes in wild-type myocytes and prevented the exaggerated hypertrophic response of treated αMHC403/+ mice. We conclude that FHC-causing sarcomere protein gene mutations cause abnormal Ca2+ responses that initiate a hypertrophic response. These data define an important Ca2+-dependent step in the pathway by which mutant sarcomere proteins trigger myocyte growth and remodel the heart, provide definitive evidence that environment influences progression of FHC, and suggest a rational therapeutic approach to this prevalent human disease. PMID:11104788

Psychological and socio-demographic data contributing to the resilience of holocaust survivors.

PubMed

Fossion, Pierre; Leys, Christophe; Kempenaers, Chantal; Braun, Stéphanie; Verbanck, Paul; Linkowski, Paul

2014-01-01

The authors provide a within-group study of 65 Former Hidden Children (FHC; i.e., Jewish youths who spent World War II in various hideaway shelters across Nazi-occupied Europe) evaluated by the Hopkins Symptom Check List (HSCL), the Sense of Coherence Scale (SOCS), the Resilience Scale for Adults (RSA), and a socio-demographic questionnaire. The aim of the present article is to address the sensitization model of resilience (consisting in a reduction of resistance to additional stress due to previous exposure to trauma) and to identify the family, psychological, and socio-demographic characteristics that predict resilience among a group of FHC. The RSA score is negatively correlated with the number of post-war traumas and positively correlated with the SOCS score. FHC who have children present a higher RSA score than FHC who have no children. RSA global score negatively and significantly predicts HSCL score. In a global multivariate model, and in accordance with the sensitization model, the number of post-war traumas negatively predicts the RSA score. Moreover, the SOCS score and the number of children positively predict it. Therapeutic implications are discussed, limitations are considered, and further investigations are proposed.

Tumorigenic potential of pituitary tumor transforming gene (PTTG) in vivo investigated using a transgenic mouse model, and effects of cross breeding with p53 (+/-) transgenic mice.

PubMed

Fong, Miranda Y; Farghaly, Hanan; Kakar, Sham S

2012-11-20

Pituitary tumor-transforming gene (PTTG) is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis. Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals. PTTG transgenic offspring (TgPTTG) were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells. Tumorigenesis is a multi-step process, often requiring

The D0 immunoglobulin-like domain plays a central role for the stronger binding of KIR3DL2 to B27 free heavy chain dimers

PubMed Central

Hatano, Hiroko; Shaw, Jacqueline; Marquardt, Kaitlin; Zhang, Zhiyong; Gauthier, Laurent; Chanteux, Stephanie; Rossi, Benjamin; Li, Demin; Mitchell, Julie; Kollnberger, Simon

2015-01-01

We have proposed that the killer cell immunoglobulin-like receptor KIR3DL2 binding more strongly to HLA-B27 (B27) β2m-free heavy chain (FHC) dimers regulates lymphocyte function in arthritis and infection. We compared the function of B27 FHC dimers with other class I heavy chains and identified contact residues in KIR3DL2. B27 FHC dimers interacted functionally with KIR3DL2 on NK and reporter cells more strongly than other class I FHC. Mutagenesis identified key residues in the D0 and other immunoglobulin-like domains which were shared and distinct from KIR3DL1, for KIR3DL2 binding to B27 and other class I FHC. We modeled B27 dimer binding to KIR3DL2 and compared experimental mutagenesis data with computational “hot spot” predictions. Modelling predicts the stronger binding of B27 dimers to KIR3DL2 is mediated by non-symmetrical complementary contacts of the D0 and D1 domains with the α1, α2 and α3 domains of both B27 heavy chains. By contrast, the D2 domain primarily contacts residues in the α2 domain of one B27 heavy chain. These findings both provide novel insights about the molecular basis of KIR3DL2 binding to HLA-B27 and other ligands and suggest an important role for KIR3DL2 HLA-B27 interactions in controlling the function of NK cells in HLA-B27+ individuals. PMID:25582852

KIR3DL2 binds to HLA-B27 dimers and free heavy chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis

PubMed Central

Wong-Baeza, Isabel; Ridley, Anna; Shaw, Jackie; Hatano, Hiroko; Rysnik, Oliwia; McHugh, Kirsty; Piper, Christopher; Brackenbridge, Simon; Fernandes, Ricardo; Chan, Anthoni; Bowness, Paul; Kollnberger, Simon

2013-01-01

1Abstract The Human Leukocyte Antigen HLA-B27(B27) is strongly associated with the spondyloarthritides. B27 can be expressed at the cell surface of antigen presenting cells (APC) as both classical β2m-associated B27 and as B27 free heavy chain forms (FHC) including disulphide-bonded heavy chain homodimers (termed B272). B27 FHC forms but not classical B27 bind to KIR3DL2. HLA-A3 which is not associated with spondyloarthritis (SpA) is also a ligand for KIR3DL2. Here we show that B272 and B27 FHC bind more strongly to KIR3DL2 than other HLA-class I, including HLA-A3. B272 tetramers bound KIR3DL2 transfected cells more strongly than HLA-A3. KIR3DL2Fc bound to HLA-B27-transfected cells more strongly than to cells transfected with other HLA-class I. KIR3DL2Fc pulled down multimeric, dimeric and monomeric free heavy chains from HLA-B27 expressing cell lines. Binding to B272 and B27 FHC stimulated greater KIR3DL2 phosphorylation than HLA-A3. B272 and B27 FHC stimulated KIR3DL2CD3ε–transduced T cell IL-2 production to a greater extent than control HLA-class I. KIR3DL2 binding to B27 inhibited NK IFNγ secretion and promoted greater survival of KIR3DL2+CD4 T and NK cells than binding to other HLA-class I. KIR3DL2+ T cells from B27+SpA patients proliferated more in response to antigen presented by syngeneic APC than the same T cell subset from healthy and disease controls. Our results suggest that expansion of KIR3DL2-expressing leukocytes observed in B27+ SpA may be explained by the stronger interaction of KIR3DL2 with B27 FHC. PMID:23440420

Lead discovery and in silico 3D structure modeling of tumorigenic FAM72A (p17).

PubMed

Pramanik, Subrata; Kutzner, Arne; Heese, Klaus

2015-01-01

FAM72A (p17) is a novel neuronal protein that has been linked to tumorigenic effects in non-neuronal tissue. Using state of the art in silico physicochemical analyses (e.g., I-TASSER, RaptorX, and Modeller), we determined the three-dimensional (3D) protein structure of FAM72A and further identified potential ligand-protein interactions. Our data indicate a Zn(2+)/Fe(3+)-containing 3D protein structure, based on a 3GA3_A model template, which potentially interacts with the organic molecule RSM ((2s)-2-(acetylamino)-N-methyl-4-[(R)-methylsulfinyl] butanamide). The discovery of RSM may serve as potential lead for further anti-FAM72A drug screening tests in the pharmaceutical industry because interference with FAM72A's activities via RSM-related molecules might be a novel option to influence the tumor suppressor protein p53 signaling pathways for the treatment of various types of cancers.

Comparative architecture of silks, fibrous proteins and their encoding genes in insects and spiders.

PubMed

Craig, Catherine L; Riekel, Christian

2002-12-01

The known silk fibroins and fibrous glues are thought to be encoded by members of the same gene family. All silk fibroins sequenced to date contain regions of long-range order (crystalline regions) and/or short-range order (non-crystalline regions). All of the sequenced fibroin silks (Flag or silk from flagelliform gland in spiders; Fhc or heavy chain fibroin silks produced by Lepidoptera larvae) are made up of hierarchically organized, repetitive arrays of amino acids. Fhc fibroin genes are characterized by a similar molecular genetic architecture of two exons and one intron, but the organization and size of these units differs. The Flag, Ser (sericin gene) and BR (Balbiani ring genes; both fibrous proteins) genes are made up of multiple exons and introns. Sequences coding for crystalline and non-crystalline protein domains are integrated in the repetitive regions of Fhc and MA exons, but not in the protein glues Ser1 and BR-1. Genetic 'hot-spots' promote recombination errors in Fhc, MA, and Flag. Codon bias, structural constraint, point mutations, and shortened coding arrays may be alternative means of stabilizing precursor mRNA transcripts. Differential regulation of gene expression and selective splicing of the mRNA transcript may allow rapid adaptation of silk functional properties to different physical environments.

Traveling Exhibitions: translating current science into effective science exhibitions

NASA Astrophysics Data System (ADS)

Dusenbery, P.; Morrow, C.; Harold, J.

The Space Science Institute (SSI) of Boulder, Colorado has recently developed two museum exhibits called the Space Weather Center and MarsQuest. It is currently planning to develop two other exhibitions called Cosmic Origins and InterActive Earth. Museum exhibitions provide research scientists the opportunity to engage in a number of activities that are vital to the success of earth and space outreach programs. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. The focus of the presentation will be on the Institute's MarsQuest exhibition. This project is a 5000 square-foot, 2.5M, traveling exhibition that is now touring the country. The exhibit's 3-year tour is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. The associated planetarium show and education program will also be described, with particular emphasis on workshops to orient host museum staff (e.g. museum educators and docents). The workshops make innovative connections between the exhibitions interactive experiences and lesson plans aligned with the National Science Education Standards. SSI is also developing an interactive web site called MarsQuest On-line. The linkage between the web site, education program and exhibit will be discussed. MarsQuest and SSI's other exhibitions are good models for actively involving scientists and their discoveries to help improve informal science education in the museum community and for forging a stronger connection between formal and informal education.

Membrane-type matrix metalloproteinases mediate curcumin-induced cell migration in non-tumorigenic colon epithelial cells differing in Apc genotype.

PubMed

Fenton, Jenifer I; Wolff, Margaret S; Orth, Michael W; Hord, Norman G

2002-06-01

Colonic epithelial cell migration is required for normal differentiated cell function. This migratory phenotype is dependent upon wild-type adenomatous polyposis coli (Apc) expression. Non-tumorigenic murine colon epithelial cell lines with distinct Apc genotypes, i.e. young adult mouse colon (YAMC; Apc(+/+)) and immortomouse/Min colon epithelial (IMCE; Apc(Min/+) cells) were used to assess the association between the Apc genotype, cell motility and matrix metalloproteinase (MMP) activity. Cells were treated with epidermal growth factor (EGF; 1, 10 and 25 ng/ml), hepatocyte growth factor (HGF; 1, 10 and 25 ng/ml) and/or curcumin (0.1-100 microM). EGF (25 ng/ml) and HGF (25 ng/ml) induced a greater migratory response in YAMC compared with IMCE cells after 24 h (P < 0.05). Treatment with curcumin induced a greater or equivalent migratory response in IMCE than YAMC cells. When migrating cells were treated with Ilomastat (MMP inhibitor), migration was inhibited in both cell types. High concentrations of Ilomastat (25 and 50 microM) inhibited migration in both cell types, while low concentrations (10 microM) inhibited HGF-induced IMCE migration. Curcumin-induced migration was inhibited in both cell types at the highest concentration of Ilomastat (50 microM). Immuno-localization analysis of membrane type-1 (MT1)-MMP indicated that migration is associated with the redistribution of this protein from the endoplasmic reticulum to the plasma membrane. Addition of neutralizing polyclonal antibodies against MT1-MMP or a mixture of MT1, 2- and 3-MMPs demonstrated partial or complete inhibition of cell migration in both cell types, respectively. The data provide the first evidence that migration in non-tumorigenic murine colon epithelial cells is: (i) inducible by EGF and HGF in an Apc genotype-dependent manner, (ii) dependent on MT-MMP activity and (iii) inducible by curcumin in an Apc genotype-independent manner. The data suggest a potential mechanism by which curcumin may

Familial history of cancer and leukemia in children younger than 2 years of age in Brazil.

PubMed

Couto, Arnaldo C; Ferreira, Jeniffer D; Koifman, Sérgio; Pombo-de-Oliveira, Maria S

2013-03-01

The objective of this study was to determine the contribution of a familial history of cancer (FHC) to the development of leukemia in children below 2 years of age. This is a national hospital-based case-control study of children 0-24 months of age recruited from 15 Brazilian hospitals from several regions providing oncological care and local general hospitals. Participants' FHC antecedents were obtained through face-to-face interviews with the mothers of cases and controls using a standardized questionnaire. Unconditional logistic regression was used to determine crude and adjusted (adj.) odds ratios (OR), and the respective 95% confidence intervals (CI), of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) after adjustment for selected variables. FHC antecedents were obtained from 178 ALL, 51 AML, and 428 controls. FHC in second-degree relatives (grandparents, uncles, cousins) showed an adj. OR=1.66 (95% CI 1.12-2.45) for ALL. Antecedents of two or more relatives with cancer showed a statistically significant two-fold higher risk of either ALL or AML. Paternal, and joint paternal and maternal antecedents of cancer also showed statistically significant higher adj. OR, respectively: 1.80 and 1.89 for ALL, and 2.34 and 3.23 for AML. Hematological malignancies among second-degree relatives showed an adj. OR=3.48 (95% CI 1.72-7.09) for ALL. According to the anatomic site, antecedents of leukemia/lymphoma among case relatives, compared with the control ones, showed an OR=2.98 (95% CI 1.52-5.82) for ALL, whereas stomach cancer antecedents showed an OR=3.55 (95% CI 1.02-12.39) for AML. The observed results support the hypothesis that FHC antecedents are associated with leukemogenesis in children below 2 years of age.

Transgenic mouse α- and β-cardiac myosins containing the R403Q mutation show isoform-dependent transient kinetic differences.

PubMed

Lowey, Susan; Bretton, Vera; Gulick, James; Robbins, Jeffrey; Trybus, Kathleen M

2013-05-24

Familial hypertrophic cardiomyopathy (FHC) is a major cause of sudden cardiac death in young athletes. The discovery in 1990 that a point mutation at residue 403 (R403Q) in the β-myosin heavy chain (MHC) caused a severe form of FHC was the first of many demonstrations linking FHC to mutations in muscle proteins. A mouse model for FHC has been widely used to study the mechanochemical properties of mutated cardiac myosin, but mouse hearts express α-MHC, whereas the ventricles of larger mammals express predominantly β-MHC. To address the role of the isoform backbone on function, we generated a transgenic mouse in which the endogenous α-MHC was partially replaced with transgenically encoded β-MHC or α-MHC. A His6 tag was cloned at the N terminus, along with R403Q, to facilitate isolation of myosin subfragment 1 (S1). Stopped flow kinetics were used to measure the equilibrium constants and rates of nucleotide binding and release for the mouse S1 isoforms bound to actin. For the wild-type isoforms, we found that the affinity of MgADP for α-S1 (100 μM) is ~ 4-fold weaker than for β-S1 (25 μM). Correspondingly, the MgADP release rate for α-S1 (350 s(-1)) is ~3-fold greater than for β-S1 (120 s(-1)). Introducing the R403Q mutation caused only a minor reduction in kinetics for β-S1, but R403Q in α-S1 caused the ADP release rate to increase by 20% (430 s(-1)). These transient kinetic studies on mouse cardiac myosins provide strong evidence that the functional impact of an FHC mutation on myosin depends on the isoform backbone.

Reduced 4-Aminobiphenyl-Induced Liver Tumorigenicity but not DNA Damage in Arylamine N-Acetyltransferase Null Mice

PubMed Central

Sugamori, Kim S.; Brenneman, Debbie; Sanchez, Otto; Doll, Mark A.; Hein, David W.; Pierce, William M.; Grant, Denis M.

2012-01-01

The aromatic amine 4-aminobiphenyl (ABP) is a liver procarcinogen in mice, requiring enzymatic bioactivation to exert its tumorigenic effect. To assess the role of arylamine N-acetyltransferase (NAT)-dependent acetylation capacity in the risk for ABP-induced liver tumors, we compared 1-year liver tumor incidence following the postnatal exposure of wild-type and NAT-deficient Nat1/2(−/−) mice to ABP. At an ABP exposure of 1200 nmoles, male Nat1/2(−/−) mice had a liver tumor incidence of 36% compared to 69% in wild-type males, and at 600 nmoles there was a complete absence of tumors compared to 60% in wild-type mice. Only one female wild-type mouse had a tumor using this exposure protocol. However, levels of N-deoxyguanosin-8-yl-ABP-DNA adducts did not correlate with either the strain or sex differences in tumor incidence. These results suggest that female sex and NAT deficiency reduce risk for ABP-induced liver tumors, but by mechanisms unrelated to differences in DNA-damaging events. PMID:22193722

microRNA-625 inhibits tumorigenicity by suppressing proliferation, migration and invasion in malignant melanoma.

PubMed

Fang, Wei; Fan, Yibin; Fa, Zhenzong; Xu, Jinhua; Yu, Hongyu; Li, Pu; Gu, Julin

2017-02-21

Dysregulated microRNA (miR)-625 expression has been observed in several kinds of cancer. MicroRNAs are important factors in the development and progression of malignant melanoma, though the clinical significance and function of miR-625 in human malignant melanoma remain unclear. Levels of miR-625 expression were therefore determined in 36 pairs of malignant melanoma and adjacent non-tumor tissue using qPCR. The effects of miR-625 dysregulation on malignant melanoma cell proliferation, wound healing, migration and invasion in vitro and tumorigenicity in vivo were investigated using CCK-8, transwell assays, and a nude mouse subcutaneous tumor model. Bioinformatics analysis and luciferase reporter system were used to predict and confirm the target gene of miR-625. miR-625 levels were frequently decreased in malignant melanoma. Ectopic expression of miR-625 suppressed proliferation, wound healing, migration, and tumorgenicity in malignant melanoma. Moreover, miR-625 acted, at least in part, by suppressing potential target SOX2. These results show that miR-625 is a tumor suppressor that inhibits the development and progression of malignant melanoma, which suggests miR-625 is potentially a new diagnostic marker and therapeutic target of malignant melanoma.

Multistep carcinogenesis of normal human fibroblasts. Human fibroblasts immortalized by repeated treatment with Co-60 gamma rays were transformed into tumorigenic cells with Ha-ras oncogenes.

PubMed

Namba, M; Nishitani, K; Fukushima, F; Kimoto, T

1988-01-01

Two normal mortal human fibroblast cell strains were transformed into immortal cell lines, SUSM-1 and KMST-6, by treatment with 4-nitroquinoline 1-oxide (4NQO) and Co-60 gamma rays, respectively. These immortalized cell lines showed morphological changes of cells and remarkable chromosome aberrations, but neither of them grew in soft agar or formed tumors in nude mice. The immortal cell line, KMST-6, was then converted into neoplastic cells by treatment with Harvey murine sarcoma virus (Ha-MSV) or the c-Ha-ras oncogene derived from a human lung carcinoma. These neoplastically transformed cells acquired anchorage-independent growth potential and developed tumors when transplanted into nude mice. All the tumors grew progressively without regression until the animals died of tumors. In addition, the tumors were transplantable into other nude mice. Normal human fibroblasts, on the other hand, were not transformed into either immortal or tumorigenic cells by treatment with Ha-MSV or c-Ha-ras alone. Our present data indicate that (1) the chemical carcinogen, 4NQO, or gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to immortality, and (2) the ras gene played a role in the progression of the immortally transformed cells to more malignant cells showing anchorage-independent growth and tumorigenicity. In other words, the immortalization process of human cells seems to be a pivotal or rate-limiting step in the carcinogenesis of human cells.

Anatomy and histology of the Fibrocartilago humerocapsularis in some species of European wild birds.

PubMed

Canova, Marco; Bombardi, Cristiano; De Sordi, Nadia; Clavenzani, Paolo; Grandis, Annamaria

2014-07-01

The occurrence and structure of the fibrocartilago humerocapsularis (FHC) in the shoulders of 72 subjects of various species of wild birds were evaluated by gross dissection and histological examination with the purpose of increasing the body of knowledge regarding this structure and verifying the functional hypotheses submitted in the past in other species. The results showed that the FHC has a conical shape with a narrow cavity on the inside. The structure is heterogeneous in the various species and consists of different tissues, such as hyaline cartilage, fibrous cartilage, and bone. From the data obtained in this study, there does not appear to be any correlation between ossification and the weight of the prey lifted, wing shape, and aging. This study also provided interesting preliminary data regarding the ossification of the FHC. In fact, in the Hooded Crow (Corvus cornix), the ossification seemed to be correlated with the mechanical stimulation of flying. Additional studies are necessary to confirm this hypothesis. © 2014 Wiley Periodicals, Inc.

α-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy

PubMed Central

Mogensen, Jens; Klausen, Ib C.; Pedersen, Anders K.; Egeblad, Henrik; Bross, Peter; Kruse, Torben A.; Gregersen, Niels; Hansen, Peter S.; Baandrup, Ulrik; Børglum, Anders D.

1999-01-01

We identified the α-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between –2.5 and –6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC. PMID:10330430

Imide modified epoxy matrix resins

NASA Technical Reports Server (NTRS)

Scola, D. A.

1984-01-01

The results of a program designed to develop tough imide modified epoxy resins cured by bisimide amine (BIA) hardeners are described. State-of-the-art epoxides MY720 and DER383 were used, and four bismide amines were evaluated. These were the BIA's derived from the 6F anhydride (4,4'-(hexafluoroisopropylidene) bis(phthalic anhydride) and the diamines 3,3'-diaminodiphynyl sulfone, 4,4'-oxygianiline, 4,4'-methylene dianiline, and 1,12-dodecane diamine. A key intermediate, designated 6F anhydride, is required for the synthesis of the bisimide amines. Reaction parameters to synthesize a precursor to the 6F anhydride (6FHC) in high yields were investigated. The catalyst trifluoromethane sulfonic acid was studied. Although small scale runs yielded the 6FHC in 50 percent yield, efforts to ranslate these results to a larger scale synthesis gave the 6FHC in only 9 percent yield. Results show that the concept of using bisimide amine as curing agents to improve the toughness properties of epoxies is valid.

Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines

PubMed Central

Dithmer, Michaela; Kirsch, Anna-Maria; Richert, Elisabeth; Fuchs, Sabine; Wang, Fanlu; Schmidt, Harald; Coupland, Sarah E.; Roider, Johann; Klettner, Alexa

2017-01-01

Background. The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. Methods. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL–1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot. Results. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Conclusion. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma. PMID:28640204

Comparative Studies in the Fluorescence and Excitation Spectra of 3-Hydroxyflavone and 2(2 '-Heteroaryl)-3-Hydroxy-4H-Chromen-4-Ones

NASA Astrophysics Data System (ADS)

Kaur, R.; Kaur, K.; Bansal, M.

2017-05-01

The absorption, fluorescence, and excitation spectra of FHC and THC have been studied and compared with 3HF in cyclohexane, acetonitrile, and methanol. Anion formation in acetonitrile and methanol has been observed in all three flavonols in the order THC-FHC-3HF in their ground states. As excitation and absorption spectra are similar in all the cases (including the anion one), it is possible to observe the absorption spectra of the pure anion of the flavonols in neutral solvents, which is difficult to measure directly.

Phosphatidylcholine-specific phospholipase C inhibition reduces HER2-overexpression, cell proliferation and in vivo tumor growth in a highly tumorigenic ovarian cancer model

PubMed Central

Spadaro, Francesca; Abalsamo, Laura; Pisanu, Maria Elena; Ricci, Alessandro; Cecchetti, Serena; Altabella, Luisa; Buoncervello, Maria; Lozneanu, Ludmila; Bagnoli, Marina; Ramoni, Carlo; Canevari, Silvana; Mezzanzanica, Delia

2017-01-01

Antagonizing the oncogenic effects of human epidermal growth factor receptor 2 (HER2) with current anti-HER2 agents has not yet yielded major progress in the treatment of advanced HER2-positive epithelial ovarian cancer (EOC). Using preclinical models to explore alternative molecular mechanisms affecting HER2 overexpression and oncogenicity may lead to new strategies for EOC patient treatment. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) exerts a pivotal role in regulating HER2 overexpression in breast cancer cells. The present study, conducted on two human HER2-overexpressing EOC cell lines - SKOV3 and its in vivo-passaged SKOV3.ip cell variant characterized by enhanced in vivo tumorigenicity - and on SKOV3.ip xenografts implanted in SCID mice, showed: a) about 2-fold higher PC-PLC and HER2 protein expression levels in SKOV3.ip compared to SKOV3 cells; b) physical association of PC-PLC with HER2 in non-raft domains; c) HER2 internalization and ca. 50% reduction of HER2 mRNA and protein expression levels in SKOV3.ip cells exposed to the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609); d) differential effects of D609 and trastuzumab on HER2 protein expression and cell proliferation; e) decreased in vivo tumor growth in SKOV3.ip xenografts during in vivo treatment with D609; f) potential use of in vivo magnetic resonance spectroscopy (MRS) and imaging (MRI) parameters as biomarkers of EOC response to PC-PLC inhibition. Overall, these findings support the view that PC-PLC inhibition may represent an effective means to target the tumorigenic effects of HER2 overexpression in EOC and that in vivo MR approaches can efficiently monitor its effects. PMID:28903399

Role of mitogen activated protein kinases in skin tumorigenicity of Patulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saxena, Neha; Ansari, Kausar M.; Kumar, Rahul

2011-12-15

WHO has highlighted the need to evaluate dermal toxicity of mycotoxins including Patulin (PAT), detected in several fruits. In this study the skin carcinogenic potential of topically applied PAT was investigated. Single topical application of PAT (400 nmol) showed enhanced cell proliferation ({approx} 2 fold), along with increased generation of ROS and activation of ERK, p38 and JNK MAPKs, in mouse skin. PAT exposure also showed activation of downstream target proteins, c-fos, c-Jun and NF-{kappa}B transcription factors. Further, single topical application of PAT (400 nmol) followed by twice weekly application of TPA resulted in tumor formation after 14 weeks, indicatingmore » the tumor initiating activity of PAT. However no tumors were observed when PAT was used either as a complete carcinogen (80 nmol) or as a tumor promoter (20 nmol and 40 nmol) for 25 weeks. Histopathological findings of tumors found in PAT/TPA treated mice showed that these tumors were of squamous cell carcinoma type and similar to those found in the positive control group (DMBA/TPA) along with significant increase of lipid peroxidation and decrease in free sulfydryls, catalase, superoxide dismutase and glutathione reductase activities. The results suggest the possible role of free radicals in PAT mediated dermal tumorigenicity involving MAPKs. -- Highlights: Black-Right-Pointing-Pointer Single topical application of Patulin showed enhanced cell proliferation. Black-Right-Pointing-Pointer Patulin activate MAPKs, c-fos, c-Jun and NF-{kappa}B transcription factors. Black-Right-Pointing-Pointer Patulin showed skin tumor initiating potential. Black-Right-Pointing-Pointer We could not detect skin tumor promoting potential of Patulin at the tested dose. Black-Right-Pointing-Pointer However prolonged exposure of Patulin at a higher dose may promote tumor.« less

Knockdown of Pentraxin 3 suppresses tumorigenicity and metastasis of human cervical cancer cells.

PubMed

Ying, Tsung-Ho; Lee, Chien-Hsing; Chiou, Hui-Ling; Yang, Shun-Fa; Lin, Chu-Liang; Hung, Chia-Hung; Tsai, Jen-Pi; Hsieh, Yi-Hsien

2016-07-05

Pentraxin 3 (PTX3) as an inflammatory molecule has been shown to be involved in immune response, inflammation, and cancer. However, the effects of PTX3 on the biological features of cervical cancer cells in vitro and in vivo have not been delineated. Immunohistochemical staining showed that increased PTX3 expression was significantly associated with tumor grade (P < 0.011) and differentiation (P < 0.019). Knocking down PTX3 with lentivirus-mediated small hairpin RNA (shRNA) in cervical cancer cell lines resulted in inhibited cell viability, diminished colony-forming ability, and induced cell cycle arrest at the G2/M phase of the cell cycle, along with downregulated expression of cyclin B1, cdc2, and cdc25c, and upregulated expression of p-cdc2, p-cdc25c, p21, and p27. Furthermore, knockdown of PTX3 significantly decreased the potential of migration and invasion of cervical cancer cells by inhibiting matrix metalloproteidase-2 (MMP-2), MMP-9, and urokinase plasminogen activator (uPA). Moreover, in vivo functional studies showed PTX3-knockdown in mice suppressed tumorigenicity and lung metastatic potential. Conversely, overexpression of PTX3 enhanced proliferation and invasion both in vitro and in vivo. Our results demonstrated that PTX3 contributes to tumorigenesis and metastasis of human cervical cancer cells. Further studies are warranted to demonstrate PTX3 as a novel therapeutic biomarker for human cervical cancer.

PD-L1 Promotes Self-Renewal and Tumorigenicity of Malignant Melanoma Initiating Cells

PubMed Central

Dang, Jianzhong; Zha, Hui; Zhang, Bingyu; Lin, Ming

2017-01-01

Recent studies have indicated that therapeutic antibodies targeting PD-L1 show remarkable efficacy in clinical trials in multiple tumors and that a melanoma cell-intrinsic PD-1: PD-L1 axis promotes tumor growth. However, few studies have shown tumor-intrinsic PD-L1 effects in malignant melanoma initiating cells (MMICs). Here, we aim to determine the possible regulatory effects of PD-L1 on MMICs. The ALDEFLUOR kit was used to identify ALDH+ MMICs. Flow cytometry was used to examine the expression of PD-L1 on ALDH+ MMICs. To determine the role of PD-L1 in MMICs self-renewal, we cultured melanoma cells with anti-PD-L1 and measured tumorsphere formation and apoptosis. In addition, the effects of anti-PD-L1 on tumorigenicity and residual ALDH+ MMICs in tumors were evaluated in vivo. We demonstrated that melanoma cell-intrinsic PD-L1 was expressed in ALDH+ MMICs. Blocking PD-L1 in melanoma cell lines impaired tumorsphere formation and induced the apoptosis of sphere cells. In addition, blocking PD-L1 inhibited tumor growth in vivo. We observed residual ALDH+ MMICs within the tumor. The results showed that blocking PD-L1 also significantly decreased the residual ALDH+ MMICs in the tumors. In conclusion, these results suggest a new mechanism underlying melanoma progression and PD-L1-targeted therapy, which is distinct from the immunomodulatory actions of PD-L1. PMID:29250533

Alterations of p53 in tumorigenic human bronchial epithelial cells correlate with metastatic potential

NASA Technical Reports Server (NTRS)

Piao, C. Q.; Willey, J. C.; Hei, T. K.; Hall, E. J. (Principal Investigator)

1999-01-01

The cellular and molecular mechanisms of radiation-induced lung cancer are not known. In the present study, alterations of p53 in tumorigenic human papillomavirus-immortalized human bronchial epithelial (BEP2D) cells induced by a single low dose of either alpha-particles or 1 GeV/nucleon (56)Fe were analyzed by PCR-single-stranded conformation polymorphism (SSCP) coupled with sequencing analysis and immunoprecipitation assay. A total of nine primary and four secondary tumor cell lines, three of which were metastatic, together with the parental BEP2D and primary human bronchial epithelial (NHBE) cells were studied. The immunoprecipitation assay showed overexpression of mutant p53 proteins in all the tumor lines but not in NHBE and BEP2D cells. PCR-SSCP and sequencing analysis found band shifts and gene mutations in all four of the secondary tumors. A G-->T transversion in codon 139 in exon 5 that replaced Lys with Asn was detected in two tumor lines. One mutation each, involving a G-->T transversion in codon 215 in exon 6 (Ser-->lle) and a G-->A transition in codon 373 in exon 8 (Arg-->His), was identified in the remaining two secondary tumors. These results suggest that p53 alterations correlate with tumorigenesis in the BEP2D cell model and that mutations in the p53 gene may be indicative of metastatic potential.

A comparison of continuous- and discrete- time three-state models for rodent tumorigenicity experiments.

PubMed Central

Lindsey, J C; Ryan, L M

1994-01-01

The three-state illness-death model provides a useful way to characterize data from a rodent tumorigenicity experiment. Most parametrizations proposed recently in the literature assume discrete time for the death process and either discrete or continuous time for the tumor onset process. We compare these approaches with a third alternative that uses a piecewise continuous model on the hazards for tumor onset and death. All three models assume proportional hazards to characterize tumor lethality and the effect of dose on tumor onset and death rate. All of the models can easily be fitted using an Expectation Maximization (EM) algorithm. The piecewise continuous model is particularly appealing in this context because the complete data likelihood corresponds to a standard piecewise exponential model with tumor presence as a time-varying covariate. It can be shown analytically that differences between the parameter estimates given by each model are explained by varying assumptions about when tumor onsets, deaths, and sacrifices occur within intervals. The mixed-time model is seen to be an extension of the grouped data proportional hazards model [Mutat. Res. 24:267-278 (1981)]. We argue that the continuous-time model is preferable to the discrete- and mixed-time models because it gives reasonable estimates with relatively few intervals while still making full use of the available information. Data from the ED01 experiment illustrate the results. PMID:8187731

Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor.

PubMed Central

Cheng, S Y; Huang, H J; Nagane, M; Ji, X D; Wang, D; Shih, C C; Arap, W; Huang, C M; Cavenee, W K

1996-01-01

The development of new capillary networks from the normal microvasculature of the host appears to be required for growth of solid tumors. Tumor cells influence this process by producing both inhibitors and positive effectors of angiogenesis. Among the latter, the vascular endothelial growth factor (VEGF) has assumed prime candidacy as a major positive physiological effector. Here, we have directly tested this hypothesis in the brain tumor, glioblastoma multiforme, one of the most highly vascularized human cancers. We introduced an antisense VEGF expression construct into glioblastoma cells and found that (i) VEGF mRNA and protein levels were markedly reduced, (ii) the modified cells did not secrete sufficient factors so as to be chemoattractive for primary human microvascular endothelial cells, (iii) the modified cells were not able to sustain tumor growth in immunodeficient animals, and (iv) the density of in vivo blood vessel formation was reduced in direct relation to the reduction of VEGF secretion and tumor formation. Moreover, revertant cells that recovered the ability to secrete VEGF regained each of these tumorigenic properties. These results suggest that VEGF plays a major angiogenic role in glioblastoma. Images Fig. 1 Fig. 4 PMID:8710899

Silencing or inhibition of endoplasmic reticulum aminopeptidase 1 (ERAP1) suppresses free heavy chain expression and Th17 responses in ankylosing spondylitis

PubMed Central

Chen, Liye; Ridley, Anna; Hammitzsch, Ariane; Al-Mossawi, Mohammad Hussein; Bunting, Helen; Georgiadis, Dimitris; Chan, Antoni; Kollnberger, Simon; Bowness, Paul

2016-01-01

Objective Human leucocyte antigen (HLA)-B27 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly associated with ankylosing spondylitis (AS). ERAP1 is a key aminopeptidase in HLA class I presentation and can potentially alter surface expression of HLA-B27 free heavy chains (FHCs). We studied the effects of ERAP1 silencing/inhibition/variations on HLA-B27 FHC expression and Th17 responses in AS. Methods Flow cytometry was used to measure surface expression of HLA class I in peripheral blood mononuclear cells (PBMCs) from patients with AS carrying different ERAP1 genotypes (rs2287987, rs30187 and rs27044) and in ERAP1-silenced/inhibited/mutated HLA-B27-expressing antigen presenting cells (APCs). ERAP1-silenced/inhibited APCs were cocultured with KIR3DL2CD3ε-reporter cells or AS CD4+ T cells. Th17 responses of AS CD4+ T cells were measured by interleukin (IL)-17A ELISA and Th17 intracellular cytokine staining. FHC cell surface expression and Th17 responses were also measured in AS PBMCs following ERAP1 inhibition. Results The AS-protective ERAP1 variants, K528R and Q730E, were associated with reduced surface FHC expression by monocytes from patients with AS and HLA-B27-expressing APCs. ERAP1 silencing or inhibition in APCs downregulated HLA-B27 FHC surface expression, reduced IL-2 production by KIR3DL2CD3ε-reporter cells and suppressed the Th17 expansion and IL-17A secretion by AS CD4+ T cells. ERAP1 inhibition of AS PBMCs reduced HLA class I FHC surface expression by monocytes and B cells, and suppressed Th17 expansion. Conclusions ERAP1 activity determines surface expression of HLA-B27 FHCs and potentially promotes Th17 responses in AS through binding of HLA-B27 FHCs to KIR3DL2. Our data suggest that ERAP1 inhibition has potential for AS treatment. PMID:26130142

Communicating Science through Exhibitions

NASA Astrophysics Data System (ADS)

Dusenbery, P.; Harold, J.; Morrow, C.

It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. There are many ways for scientists to help develop science exhibitions. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). Two of its exhibitions, Space Weather Center and MarsQuest, are currently on tour. Another exhibition, Alien Earths, is in development. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. MarsQuest is a 5000 square-foot traveling exhibition. The exhibit's second 3-year tour began this January at the Detroit Science Center. It is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. The 3,000 square-foot traveling exhibition, called Alien Earths, will bring origins-related research and discoveries to students and the American public. Alien Earths has four interrelated exhibit areas: Our Place in Space, Star Birth, PlanetQuest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in ``habitable zones'' around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. Besides the exhibits, SSI is also developing interactive web sites based on exhibit themes. New technologies are transforming the Web from a static medium to an interactive environment with tremendous

New Hurricane Exhibit

NASA Image and Video Library

2007-08-29

A new exhibit in StenniSphere depicting NASA's role in hurricane prediction and research and SSC's role in helping the region recover from Hurricane Katrina. The cyclone-shaped exhibit focuses on the effects of the Aug. 29, 2005 storm and outlines how NASA is working to improve weather forecasting. Through photos, 3-D models and digital animations, the exhibit tells the story of what happened inside the storm and how NASA's scientific research can increase the accuracy of hurricane tracking and modeling.

New Hurricane Exhibit

NASA Technical Reports Server (NTRS)

2007-01-01

A new exhibit in StenniSphere depicting NASA's role in hurricane prediction and research and SSC's role in helping the region recover from Hurricane Katrina. The cyclone-shaped exhibit focuses on the effects of the Aug. 29, 2005 storm and outlines how NASA is working to improve weather forecasting. Through photos, 3-D models and digital animations, the exhibit tells the story of what happened inside the storm and how NASA's scientific research can increase the accuracy of hurricane tracking and modeling.

IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.

PubMed

Benevides, Luciana; da Fonseca, Denise Morais; Donate, Paula Barbim; Tiezzi, Daniel Guimarães; De Carvalho, Daniel D; de Andrade, Jurandyr M; Martins, Gislaine A; Silva, João S

2015-09-15

The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors. ©2015 American Association for Cancer Research.

miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway

PubMed Central

Isobe, Taichi; Hisamori, Shigeo; Hogan, Daniel J; Zabala, Maider; Hendrickson, David G; Dalerba, Piero; Cai, Shang; Scheeren, Ferenc; Kuo, Angera H; Sikandar, Shaheen S; Lam, Jessica S; Qian, Dalong; Dirbas, Frederick M; Somlo, George; Lao, Kaiqin; Brown, Patrick O; Clarke, Michael F; Shimono, Yohei

2014-01-01

MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. We previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. In this study, we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing complex, activates the canonical WNT signaling pathway in an APC-suppression dependent manner, and activates the expression of miR-150. Enforced expression of miR-142 or miR-150 in normal mouse mammary stem cells resulted in the regeneration of hyperproliferative mammary glands in vivo. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. These results suggest that in some tumors, miR-142 regulates the properties of BCSCs at least in part by activating the WNT signaling pathway and miR-150 expression. DOI: http://dx.doi.org/10.7554/eLife.01977.001 PMID:25406066

Acyl-CoA Synthetase VL3 Knockdown Inhibits Human Glioma Cell Proliferation and Tumorigenicity

PubMed Central

Pei, Zhengtong; Sun, Peng; Huang, Ping; Lal, Bachchu; Laterra, John; Watkins, Paul A.

2009-01-01

The contribution of lipid metabolic pathways to malignancy is poorly understood. Expression of the fatty acyl-CoA synthetase, ACSVL3, was found to be markedly elevated in clinical malignant glioma specimens but nearly undetectable in normal glia. ACSVL3 levels correlated with the malignant behavior of human glioma cell lines and glioma cells propagated as xenografts. ACSVL3 expression was induced by the activation of oncogenic receptor tyrosine kinases (RTK) c-Met and EGFR. Inhibiting c-Met activation with neutralizing anti-HGF monoclonal antibodies reduced ACSVL3 expression concurrent with tumor growth inhibition in vivo. ACSVL3 expression knockdown using RNA interference, which decreased long-chain fatty acid activation, inhibited anchorage-dependent and anchorage-independent glioma cell growth by ~70% and ~ 90%, respectively. ACSVL3-depleted cells were less tumorigenic than control cells and subcutaneous xenografts grew ~60% slower than control tumors. Orthotopic xenografts produced by ACSVL3-depleted cells were 82–86 % smaller than control xenografts. ACSVL3 knockdown disrupted Akt function as evidenced by RTK-induced transient decreases in total and phosphorylated Akt, as well as GSK3β, via a caspase-dependent mechanism. Expressing constitutively active myr-Akt rescued cells from the anchorage-dependent and anchorage-independent growth inhibitory effects of ACSVL3 depletion. These studies show that ACSVL3 maintains oncogenic properties of malignant glioma cells via a mechanism that involves, in part, the regulation of Akt function. PMID:19920185

Reduction of the tumorigenic potential of human retinoblastoma cell lines by TFF1 overexpression involves p53/caspase signaling and miR-18a regulation.

PubMed

Busch, Maike; Große-Kreul, Jan; Wirtz, Janina Jasmin; Beier, Manfred; Stephan, Harald; Royer-Pokora, Brigitte; Metz, Klaus; Dünker, Nicole

2017-08-01

Trefoil factor family (TFF) peptides have been shown to play a pivotal role in oncogenic transformation, tumorigenesis and metastasis by changing cell proliferation, apoptosis, migration and invasion behavior of various cancer cell lines. In the study presented, we investigated the effect of TFF1 overexpression on cell growth, viability, migration and tumorigenicity of different retinoblastoma (RB) cell lines. Transient TFF1 overexpression significantly increases RB cell apoptosis levels. Stable, lentiviral TFF1 overexpression likewise decreases RB cell viability, proliferation and growth and significantly increases apoptosis as revealed by WST-1 assays, BrdU and DAPI cell counts. TFF1-induced apoptosis is executed via cleaved caspase-3 activation as revealed by caspase blockage experiments and caspase-3 immunocytochemistry. Results from pG13-luciferase reporter assays and Western blot analyses indicate that TFF1-induced apoptosis is mediated through transcriptional activity of p53 with concurrently downregulated miR-18a expression. In ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF1 overexpression significantly decreases the size of tumors forming from Y79 and RB355 cells and reduces the migration potential of RB355 cells. Differentially expressed genes and pathways involved in cancer progression were identified after TFF1 overexpression in Y79 cells by gene expression array analysis, underlining the effects on reduced tumorigenicity. TFF1 knockdown in RBL30 cells revealed caspase-3/7-independent apoptosis induction, but no changes on cell proliferation level. In summary, the in vitro and in vivo data demonstrate for the first time a tumor suppressor function of TFF1 in RB cells which is at least partly mediated by p53 activation and miR-18a downregulation. © 2017 UICC.

The pVHL172 isoform is not a tumor suppressor and up-regulates a subset of pro-tumorigenic genes including TGFB1 and MMP13

PubMed Central

Hascoet, Pauline; Chesnel, Franck; Jouan, Florence; Goff, Cathy Le; Couturier, Anne; Darrigrand, Eric; Mahe, Fabrice; Rioux-Leclercq, Nathalie; Goff, Xavier Le; Arlot-Bonnemains, Yannick

2017-01-01

The von Hippel-Lindau (VHL) tumor suppressor gene is often deleted or mutated in ccRCC (clear cell renal cell carcinoma) producing a non-functional protein. The gene encodes two mRNA, and three protein isoforms (pVHL213, pVHL160 and pVHL172). The pVHL protein is part of an E3 ligase complex involved in the ubiquitination and proteasomal degradation of different proteins, particularly hypoxia inducible factors (HIF) that drive the transcription of genes involved in the regulation of cell proliferation, angiogenesis or extracellular matrix remodelling. Other non-canonical (HIF-independent) pVHL functions have been described. A recent work reported the expression of the uncharacterized protein isoform pVHL172 which is translated from the variant 2 by alternative splicing of the exon 2. This splice variant is sometimes enriched in the ccRCCs and the protein has been identified in the respective samples of ccRCCs and different renal cell lines. Functional studies on pVHL have only concerned the pVHL213 and pVHL160 isoforms, but no function was assigned to pVHL172. Here we show that pVHL172 stable expression in renal cancer cells does not regulate the level of HIF, exacerbates tumorigenicity when 786-O-pVHL172 cells were xenografted in mice. The pVHL172-induced tumors developed a sarcomatoid phenotype. Moreover, pVHL172 expression was shown to up regulate a subset of pro-tumorigenic genes including TGFB1, MMP1 and MMP13. In summary we identified that pVHL172 is not a tumor suppressor. Furthermore our findings suggest an antagonistic function of this pVHL isoform in the HIF-independent aggressiveness of renal tumors compared to pVHL213. PMID:29100286

Wip1 is associated with tumorigenity and metastasis through MMP-2 in human intrahepatic cholangiocarcinoma

PubMed Central

Liu, Sulai; Jiang, Bo; Li, Hao; He, Zili; Lv, Pin; Peng, Chuang; Wang, Yonggang; Cheng, Wei; Xu, Zhengquan; Chen, Wei; Liu, Zhengkai; Zhang, Bao; Shen, Shengqian; Xiang, Shuanglin

2017-01-01

Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78.3%). High levels of Wip1 in human ICC correlated with metastasis to the lymph metastasis (P=0.022). Genetic depletion of Wip1 in ICC cells resulted in significantly inhibited proliferation and invasion compared with controls. Most importantly, Wip1 down-regulation impaired tumor migration capacity of ICC cells in vivo. Subsequent investigations revealed that matrix metalloproteinase-2 (MMP-2) is an important target of Wip1. Consistently, in human ICC tissues, Wip1 level was positively correlated with MMP-2 expression. Taken together, our founding indicates that Wip1 may be a crucial regulator in the tumorigenicity and invasion of human ICC, Wip1 exerts its pro-invasion function at least in part through the MMP-2 signaling pathway, suggesting Wip1 as a potential therapeutic target for ICC. PMID:28915621

Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines.

PubMed

Sass, Stephanie N; Ramsey, Kimberley D; Egan, Shawn M; Wang, Jianmin; Cortes Gomez, Eduardo; Gollnick, Sandra O

2018-06-01

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined. Prostate inflammation and carcinoma are associated with high levels of myeloid cell infiltration; these cells are linked to disease progression in other cancers, but their role in prostate cancer is unclear. To determine whether myeloid cells contribute to prostate cancer progression, the ability of prostate tumor-associated CD11b + cells (TAMC) to drive prostate epithelial cell tumorigenesis was tested. Co-culture of CD11b + TAMC with non-tumorigenic genetically primed prostate epithelial cells resulted in stable transformation and induction of tumorigenesis. RNA sequencing identified the IL-1α pathway as a potential molecular mechanism responsible for tumor promotion by TAMC. Inhibition of IL-1α delayed growth of TAMC-induced tumors. Further analysis showed that IL-1α inhibition led to decreased angiogenesis within tumors, suggesting that IL-1α promotes prostate tumor progression, potentially through augmentation of angiogenesis.

The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma.

PubMed

Parker, Brittany C; Annala, Matti J; Cogdell, David E; Granberg, Kirsi J; Sun, Yan; Ji, Ping; Li, Xia; Gumin, Joy; Zheng, Hong; Hu, Limei; Yli-Harja, Olli; Haapasalo, Hannu; Visakorpi, Tapio; Liu, Xiuping; Liu, Chang-Gong; Sawaya, Raymond; Fuller, Gregory N; Chen, Kexin; Lang, Frederick F; Nykter, Matti; Zhang, Wei

2013-02-01

Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3'-untranslated region (3'-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3'-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma.

Transcriptional Profiling Reveals a Common Metabolic Program for Tumorigenicity in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells

PubMed Central

Liu, Mengling; Xia, Yingfeng; Ding, Jane; Ye, Bingwei; Zhao, Erhu; Choi, Jeong-Hyeon; Alptekin, Ahmet; Yan, Chunhong; Dong, Zheng; Huang, Shuang; Yang, Liqun; Cui, Hongjuan; Zha, Yunhong; Ding, Han-Fei

2017-01-01

Summary High-risk neuroblastoma remains one of the deadliest childhood cancers. Identification of metabolic pathways that drive or maintain high-risk neuroblastoma may open new avenues of therapeutic interventions. Here we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of TH-MYCN mice, an animal model of high-risk neuroblastoma with MYCN amplification. Transcriptional profiling reveals that mouse neuroblastoma sphere-forming cells acquire a metabolic program characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways, primarily as a result of increased expression of sterol regulatory element-binding factors and Atf4, respectively. This metabolic reprogramming is recapitulated in high-risk human neuroblastomas and is prognostic for poor clinical outcome. Genetic and pharmacological inhibition of the metabolic program markedly decreases the growth and tumorigenicity of both mouse neuroblastoma sphere-forming cells and human neuroblastoma cell lines. These findings suggest a therapeutic strategy for targeting the metabolic program of high-risk neuroblastoma. PMID:27705805

Visitors Center Exhibits

NASA Technical Reports Server (NTRS)

1997-01-01

A child enjoys building his own LEGO model at a play table which was included in the exhibit 'Travel in Space' World Show. The exhibit consisted of 21 displays designed to teach children about flight and space travel from the Wright brothers to future generations of space vehicles.

A novel missense mutation, Leu390Val, in the cardiac beta-myosin heavy chain associated with pronounced septal hypertrophy in two families with hypertrophic cardiomyopathy.

PubMed

Havndrup, O; Bundgaard, H; Andersen, P S; Larsen, L A; Vuust, J; Kjeldsen, K; Christiansen, M

2000-12-01

An examination of the genetic background and phenotypic presentation of familial hypertrophic cardiomyopathy (FHC) with respect to specific mutations in the MYH7-gene encoding the cardiac beta-myosin heavy chain. Two families (n = 22) from a cohort of 67 families with FHC were studied at the National University Hospital, Rigshospitalet, Copenhagen. Clinical, non-invasive examinations of all included family members followed by molecular genetic analysis including PCR-single strand conformation polymorphism/heteroduplex (SSCP/HD) analysis and sequencing of exon 3-23 of the MYH7-gene. We found FHC associated with a missense mutation in two families, i.e. a C > G transversion at position g10124 and a G > T transversion at position g10126 causing the change of a leucine residue at codon 390 to a valine residue. The mutation is located in the actin-binding region of the beta-myosin heavy chain. The leucine residue is evolutionarily conserved in vertebrate myosins. In the two families, the phenotypic presentations in the clinically affected were characterized by asymmetric septal hypertrophy (septum diameter 18.8 (5.0) mm (mean (SD)) with only minor involvement of the left ventricular free wall (posterior wall diameter 11.0 (2.2) mm). Furthermore, the left ventricular systolic and diastolic functions were well preserved, even at a high age. The symptomatic status of the clinically affected patients depended on the presence or absence of a concomitant left ventricular outflow tract gradient. We report a novel missense mutation associated with FHC caused by a double nucleotide transversion. The penetrance of the mutation was not complete, but in clinically affected patients the mutation gives rise to an echocardiographic phenotype, predominantly characterized by pronounced septal hypertrophy.

Application of an imaging system to a museum exhibition for developing interactive exhibitions

NASA Astrophysics Data System (ADS)

Miyata, Kimiyoshi; Inoue, Yuka; Takiguchi, Takahiro; Tsumura, Norimichi; Nakaguchi, Toshiya; Miyake, Yoichi

2009-10-01

In the National Museum of Japanese History, 215,759 artifacts are stored and used for research and exhibitions. In museums, due to the limitation of space in the galleries, a guidance system is required to satisfy visitors' needs and to enhance their understanding of the artifacts. We introduce one exhibition using imaging technology to improve visitors' understanding of a kimono (traditional Japanese clothing) exhibition. In the imaging technology introduced, one data projector, one display with touch panel interface, and magnifiers were used as exhibition tools together with a real kimono. The validity of this exhibition method was confirmed by results from a visitors' interview survey. Second, to further develop the interactive guidance system, an augmented reality system that consisted of cooperation between the projector and a digital video camera was also examined. A white paper board in the observer's hand was used as a projection screen and also as an interface to control the images projected on the board. The basic performance of the proposed system was confirmed; however continuous development was necessary for applying the system to actual exhibitions.

Female condom importance acknowledged in HIV prevention.

PubMed

1996-12-09

The Female Health Co. (FHC), London, United Kingdom, has signed a three-year agreement with the Joint United Nations Program on HIV/AIDS (UNAIDS) to provide a global public sector price for the female condom to 193 affiliated countries. An adjunct education and social marketing program, supported by UNAIDS, will be launched. High rates of acceptance have been shown previously when the female condom has been introduced with an effective educational approach. Negotiations between FHC and UNAIDS began in September 1996; 80 of 193 countries, upon inquiry, have already identified a requirement for over 7 million female condoms in 1997. UNAIDS estimates that nearly 50% of new human immunodeficiency virus (HIV) infections are in women; the female condom is the only woman-controlled product providing protection against sexually transmitted diseases (STDs), including HIV and acquired immunodeficiency syndrome (AIDS). Studies have indicated that the number of unprotected sex acts decreases when the female condom is available. Dr. Peter Piot (UNAIDS) states that the female condom is important in those cultures and situations where women have limited control over sexual decisions. Dr. Mary Ann Leeper (FHC) states that the company is committed to making the female condom available in developing countries.

Comparable ultrasound measurements of ten anatomical specimens of infant hip joints by the methods of Graf and Terjesen.

PubMed

Falliner, A; Hahne, H J; Hedderich, J; Brossmann, J; Hassenpflug, J

2004-04-01

To define which sonographic section planes relative to the acetabular inlet plane will produce analyzable images with the methods of Graf and Terjesen. Anatomical specimens of infant hip joints were investigated in a water bath using the methods of Graf and Terjesen. Acetabular position was varied in defined increments with respect to the ultrasound beam. The alpha angles and the femoral head coverage (FHC) were measured. To obtain images analyzable by the two methods, the ultrasound beam had to intersect with the acetabular inlet plane at defined angles. The acetabular notch had to be anteriorly rotated from the ultrasound beam plane by at least 20 degrees. Beam entry within a 50 degrees sector posterior to the perpendicular on the inlet plane resulted in analyzable images. The stepwise multiple linear regression analysis showed that alpha angles and FHC were much affected by the coronal-plane transducer tilt. The fact that caudal tilts of the transducer are associated with reduced alpha angles and FHC values should be kept in mind in clinical ultrasound investigations. It is recommended that the transducer should be put on the greater trochanter perpendicular to the transverse axis of the body.

A study exploring knowledge, attitudes and behaviours towards autism among adults applying to a Family Health Center in Istanbul

PubMed Central

Surmen, Aysen; Hidiroglu, Seyhan; Usta, Hamide Hande; Awiwi, Muhammed; Oguz, Ahmet Saki; Karavus, Melda; Karavus, Ahmet

2015-01-01

OBJECTIVE: The aim of this study was to assess knowledge, awareness, behavior and attitudes towards autism among applicants to a Family Health Center (FHC). METHODS: This descriptive study was performed at a Family Health Center (FHC) in Istanbul in August 2013. Data was obtained via face-to-face interviews with participants older than 18 years who were admitted to the FHC. The questionnaire consisted of questions on sociodemographic characteristics, applicants’ knowledge of autism and their approach to autism. RESULTS: 160 applicants participated in our survey of which 38.8% had heard the word ‘autism’. Knowledge and awareness of autism, and attitudes and behaviours towards this disorder differed significantly with the educational level of the study participants (p<0.05) However, these parameters did not change with gender and income level of the participants (p>0.05). CONCLUSION: The most important outcome of our study is that awareness, or even having knowledge of the word autism is significant in breaking down stereotypes. Despite the low level of awareness of the disease, the majority of the participitants had a positive attitude towards autism. PMID:28058334

Loss of HSulf-1 expression enhances tumorigenicity by inhibiting Bim expression in ovarian cancer.

PubMed

He, Xiaoping; Khurana, Ashwani; Roy, Debarshi; Kaufmann, Scott; Shridhar, Viji

2014-10-15

The expression of human Sulfatase1 (HSulf-1) is downregulated in the majority of primary ovarian cancer tumors, but the functional consequence of this downregulation remains unclear. Using two different shRNAs (Sh1 and Sh2), HSulf-1 expression was stably downregulated in ovarian cancer OV202 cells. We found that HSulf-1-deficient OV202 Sh1 and Sh2 cells formed colonies in soft agar. In contrast, nontargeting control (NTC) shRNA-transduced OV202 cells did not form any colonies. Moreover, subcutaneous injection of OV202 HSulf-1-deficient cells resulted in tumor formation in nude mice, whereas OV202 NTC cells did not. Also, ectopic expression of HSulf-1 in ovarian cancer SKOV3 cells significantly suppressed tumor growth in nude mice. Here, we show that HSulf-1-deficient OV202 cells have markedly decreased expression of proapoptotic Bim protein, which can be rescued by restoring HSulf-1 expression in OV202 Sh1 cells. Enhanced expression of HSulf-1 in HSulf-1-deficient SKOV3 cells resulted in increased Bim expression. Decreased Bim levels after loss of HSulf-1 were due to increased p-ERK, because inhibition of ERK activity with PD98059 resulted in increased Bim expression. However, treatment with a PI3 kinase/AKT inhibitor, LY294002, failed to show any change in Bim protein level. Importantly, rescuing Bim expression in HSulf-1 knockdown cells significantly retarded tumor growth in nude mice. Collectively, these results suggest that loss of HSulf-1 expression promotes tumorigenicity in ovarian cancer through regulating Bim expression. © 2014 UICC.

Novel HER3/MUC4 oncogenic signaling aggravates the tumorigenic phenotypes of pancreatic cancer cells.

PubMed

Lakshmanan, Imayavaramban; Seshacharyulu, Parthasarathy; Haridas, Dhanya; Rachagani, Satyanarayana; Gupta, Suprit; Joshi, Suhasini; Guda, Chittibabu; Yan, Ying; Jain, Maneesh; Ganti, Apar K; Ponnusamy, Moorthy P; Batra, Surinder K

2015-08-28

Several studies have demonstrated that MUC4 is involved in progression and metastasis of pancreatic cancer (PC). Here, we report that HER3/MUC4 interaction in HER2 low cells is critical in driving pancreatic tumorigenesis. Upon HER2 knockdown, we observed elevated expression of HER3 and MUC4 and their interactions, which was confirmed by immunoprecipitation and bioinformatics analyses. In paired human PC tissues, higher percentage of HER3 positivity (10/33, 30.3%; p = 0.001) was observed than HER2 (5/33, 15.1%; p = 0.031), which was further confirmed in spontaneous mice (KPC; KrasG12D; Trp53R172H/+; Pdx-Cre) tumors of different weeks. Mechanistically, increased phosphorylation of ERK and expression of PI3K and c-Myc were observed in HER2 knockdown cells, suggesting a positive role for HER3/MUC4 in HER2 low cells. Further, HER2 knockdown resulted in increased proliferation, motility and tumorigenicity of PC cells. Consistently, transient knockdown of HER3 by siRNA in HER2 knockdown cells led to decreased proliferation. These observations led us to conclude that HER3 interacts with MUC4 to promote proliferation in HER2 low PC cells. Further, deficiency of both HER2 and HER3 leads to decreased proliferation of PC cells. Hence targeting these newly identified HER3/MUC4 signals would improve the PC patients survival by intercepting MUC4 mediated oncogenic signaling.

Novel HER3/MUC4 oncogenic signaling aggravates the tumorigenic phenotypes of pancreatic cancer cells

PubMed Central

Lakshmanan, Imayavaramban; Seshacharyulu, Parthasarathy; Haridas, Dhanya; Rachagani, Satyanarayana; Gupta, Suprit; Joshi, Suhasini; Guda, Chittibabu; Yan, Ying; Jain, Maneesh; Ganti, Apar K.; Ponnusamy, Moorthy P.; Batra, Surinder K.

2015-01-01

Several studies have demonstrated that MUC4 is involved in progression and metastasis of pancreatic cancer (PC). Here, we report that HER3/MUC4 interaction in HER2 low cells is critical in driving pancreatic tumorigenesis. Upon HER2 knockdown, we observed elevated expression of HER3 and MUC4 and their interactions, which was confirmed by immunoprecipitation and bioinformatics analyses. In paired human PC tissues, higher percentage of HER3 positivity (10/33, 30.3%; p = 0.001) was observed than HER2 (5/33, 15.1%; p = 0.031), which was further confirmed in spontaneous mice (KPC; KrasG12D; Trp53R172H/+; Pdx-Cre) tumors of different weeks. Mechanistically, increased phosphorylation of ERK and expression of PI3K and c-Myc were observed in HER2 knockdown cells, suggesting a positive role for HER3/MUC4 in HER2 low cells. Further, HER2 knockdown resulted in increased proliferation, motility and tumorigenicity of PC cells. Consistently, transient knockdown of HER3 by siRNA in HER2 knockdown cells led to decreased proliferation. These observations led us to conclude that HER3 interacts with MUC4 to promote proliferation in HER2 low PC cells. Further, deficiency of both HER2 and HER3 leads to decreased proliferation of PC cells. Hence targeting these newly identified HER3/MUC4 signals would improve the PC patients survival by intercepting MUC4 mediated oncogenic signaling. PMID:26035354

Overexpression of PHRF1 attenuates the proliferation and tumorigenicity of non-small cell lung cancer cells.

PubMed

Wang, Yadong; Wang, Haiyu; Pan, Teng; Li, Li; Li, Jiangmin; Yang, Haiyan

2016-09-27

The aim of this study was to investigate the potential role of PHRF1 in lung tumorigenesis. Western blot analysis was used to detect the expression of proteins. Quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, soft agar assay and tumor formation assay in nude mice were applied. Cell cycle distribution was analyzed by flow cytometry. The lower level of PHRF1 mRNA was observed in human lung cancer tissues than that in paracancerous tissues. The decreased expression of PHRF1 protein was observed in H1299 and H1650 cell lines than that in 16HBE and BEAS-2B cell lines. The decreased expression of PHRF1 protein was observed in malignant 16HBE cells compared to control cells. The reduced expression of PHRF1 protein was observed in mice lung tissues treated with BaP than that in control group. Overexpression of PHRF1 inhibited H1299 cell proliferation, colony formation in vitro and growth of tumor xenograft in vivo, and arrested cell cycle in G1 phase. The decreased expression of TGIF and c-Myc proteins and the increased expression of p21 protein were observed in H1299-PHRF1 cells compared with H1299-pvoid cells. In conclusion, our findings suggest that overexpression of PHRF1 attenuated the proliferation and tumorigenicity of non-small cell lung cancer cell line of H1299.

The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma

PubMed Central

Parker, Brittany C.; Annala, Matti J.; Cogdell, David E.; Granberg, Kirsi J.; Sun, Yan; Ji, Ping; Li, Xia; Gumin, Joy; Zheng, Hong; Hu, Limei; Yli-Harja, Olli; Haapasalo, Hannu; Visakorpi, Tapio; Liu, Xiuping; Liu, Chang-gong; Sawaya, Raymond; Fuller, Gregory N.; Chen, Kexin; Lang, Frederick F.; Nykter, Matti; Zhang, Wei

2013-01-01

Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3′–untranslated region (3′-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3′-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma. PMID:23298836

Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

PubMed

Santini, Roberta; Vinci, Maria C; Pandolfi, Silvia; Penachioni, Junia Y; Montagnani, Valentina; Olivito, Biagio; Gattai, Riccardo; Pimpinelli, Nicola; Gerlini, Gianni; Borgognoni, Lorenzo; Stecca, Barbara

2012-09-01

The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor. Melanomaspheres express high levels of Hedgehog (HH) pathway components and of embryonic pluripotent stem cell factors SOX2, NANOG, OCT4, and KLF4. We show that human melanomas contain a subset of cells expressing high ALDH activity (ALDH(high)), which is endowed with higher self-renewal and tumorigenic abilities than the ALDH(low) population. A good correlation between the number of ALDH(high) cells and sphere formation efficiency was observed. Notably, both pharmacological inhibition of HH signaling by the SMOOTHENED (SMO) antagonist cyclopamine and GLI antagonist GANT61 and stable expression of shRNA targeting either SMO or GLI1 result in a significant decrease in melanoma stem cell self-renewal in vitro and a reduction in the number of ALDH(high) melanoma stem cells. Finally, we show that interference with the HH-GLI pathway through lentiviral-mediated silencing of SMO and GLI1 drastically diminishes tumor initiation of ALDH(high) melanoma stem cells. In conclusion, our data indicate an essential role of the HH-GLI1 signaling in controlling self-renewal and tumor initiation of melanoma CSC/TIC. Targeting HH-GLI1 is thus predicted to reduce the melanoma stem cell compartment. Copyright © 2012 AlphaMed Press.

SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.

PubMed

Santini, R; Pietrobono, S; Pandolfi, S; Montagnani, V; D'Amico, M; Penachioni, J Y; Vinci, M C; Borgognoni, L; Stecca, B

2014-09-18

Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2 (sex-determining region Y (SRY)-Box2). Here we address the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDH(high) MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth. We show that SOX2 is regulated by HH signaling and that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI signaling, bind to the proximal promoter region of SOX2 in primary melanoma cells. In functional studies, we find that SOX2 function is required for HH-induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a critical factor for self-renewal and tumorigenicity of MICs and an important mediator of HH-GLI signaling in melanoma. These findings could provide the basis for novel therapeutic strategies based on the inhibition of SOX2 for the treatment of a subset of human melanomas.

Fabrication, Characterization, In vitro Evaluation of Solid Lipid Nanoemulsion of Flunarizine dihydrochloride for Nasal Delivery.

PubMed

Newton, Maria J; Harjot, Kaur

2017-01-01

Flunarizine dihydrochloride (FHC) is used for the prophylaxis to migraine. Flunarizine has solubility problems which is practically insoluble in water and alcohol. Nanoemulsion is the approach to increase the solubility of the insoluble drugs. Nanoemulsions of FHC was prepared which can be given through the alternate route such as nasal drug delivery for migraine. In this research work the solubility of the poorly soluble FHC was successfully improved by preparing it as a nano emulsion. Nanoemulsions can pass through the biological membrane easily so it can be delivered through nasal mucosa by which it may provide a quicker onset of action. The currently available dosage forms are in the form of tablet. The formulations were prepared by using Glycerl Monostearate (GMS), Tween 80 as surfactant and PEG 400: Ethanol as co-surfactant in the distilled water. Nanoemulsions were prepared by step by step procedure. The prepared nanoemulsions were analyzed preliminarily by Master Sizer followed by Zeta Sizer by using the technique Dynamic Photon Correlation Spectroscopy. The best nanoemulsion was subjected to Zeta Potential study. The TEM analysis was carried out on the best formulation to gain the detailed information about the formulation. The best formulation was selected based on the physical appearance, homogenecity of the preparation, Preliminary Master Sizer analysis report, Secondary Zeta Sizer analysis report with Zeta Potential and TEM. The best formulation demonstrated the size in nano range with improved solubility. The FHC nano emulsion was prepared successfully which improved the solubility of the drug. The drug release study on simulated nasal fluid revealed that the preparation is suitable to be delivered through the nasal route. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

29 CFR 2200.70 - Exhibits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION RULES OF PROCEDURE Hearings... separate file designated for rejected exhibits. (e) Return of physical exhibits. A party may on motion request the return of a physical exhibit within 30 days after expiration of the time for filing a petition...

32 CFR 705.24 - Exhibits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false Exhibits. 705.24 Section 705.24 National Defense... inform the public of the Navy's mission and operations. (2) To disseminate technical and scientific... Exhibit Center is to support local Navy recruiters. Requests for exhibits for community relations events...

32 CFR 705.24 - Exhibits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Exhibits. 705.24 Section 705.24 National Defense... inform the public of the Navy's mission and operations. (2) To disseminate technical and scientific... Exhibit Center is to support local Navy recruiters. Requests for exhibits for community relations events...

Molecular architecture of silk fibroin of Indian golden silkmoth, Antheraea assama.

PubMed

Gupta, Adarsh K; Mita, Kazuei; Arunkumar, Kallare P; Nagaraju, Javaregowda

2015-08-03

The golden silk spun by Indian golden silkmoth Antheraea assama, is regarded for its shimmering golden luster, tenacity and value as biomaterial. This report describes the gene coding for golden silk H-fibroin (AaFhc), its expression, full-length sequence and structurally important motifs discerning the underlying genetic and biochemical factors responsible for its much sought-after properties. The coding region, with biased isocodons, encodes highly repetitious crystalline core, flanked by a pair of 5' and 3' non-repetitious ends. AaFhc mRNA expression is strictly territorial, confined to the posterior silk gland, encoding a protein of size 230 kDa, which makes homodimers making the elementary structural units of the fibrous core of the golden silk. Characteristic polyalanine repeats that make tight β-sheet crystals alternate with non-polyalanine repeats that make less orderly antiparallel β-sheets, β-turns and partial α-helices. Phylogenetic analysis of the conserved N-terminal amorphous motif and the comparative analysis of the crystalline region with other saturniid H-fibroins reveal that AaFhc has longer, numerous and relatively uniform repeat motifs with lower serine content that assume tighter β-crystals and denser packing, which are speculated to be responsible for its acclaimed properties of higher tensile strength and higher refractive index responsible for golden luster.

7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 14 2012-01-01 2012-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING... Program Pt. 1980, Subpt. E, Exh. G Exhibit G to Subpart E of Part 1980 Note: The Exhibit is not published...

7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 14 2013-01-01 2013-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING... Program Pt. 1980, Subpt. E, Exh. G Exhibit G to Subpart E of Part 1980 Note: The Exhibit is not published...

7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 14 2014-01-01 2014-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING... Program Pt. 1980, Subpt. E, Exh. G Exhibit G to Subpart E of Part 1980 Note: The Exhibit is not published...

7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING... Program Pt. 1980, Subpt. E, Exh. G Exhibit G to Subpart E of Part 1980 Note: The Exhibit is not published...

7 CFR Exhibit G to Subpart E of... - Exhibit G to Subpart E of Part 1980

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 14 2011-01-01 2011-01-01 false Exhibit G to Subpart E of Part 1980 G Exhibit G to Subpart E of Part 1980 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING... Program Pt. 1980, Subpt. E, Exh. G Exhibit G to Subpart E of Part 1980 Note: The Exhibit is not published...

Assessment of the Tumorigenic Potential of Spontaneously Immortalized and hTERT-Immortalized Cultured Dental Pulp Stem Cells.

PubMed

Wilson, Ryan; Urraca, Nora; Skobowiat, Cezary; Hope, Kevin A; Miravalle, Leticia; Chamberlin, Reed; Donaldson, Martin; Seagroves, Tiffany N; Reiter, Lawrence T

2015-08-01

Dental pulp stem cells (DPSCs) provide an exciting new avenue to study neurogenetic disorders. DPSCs are neural crest-derived cells with the ability to differentiate into numerous tissues including neurons. The therapeutic potential of stem cell-derived lines exposed to culturing ex vivo before reintroduction into patients could be limited if the cultured cells acquired tumorigenic potential. We tested whether DPSCs that spontaneously immortalized in culture acquired features of transformed cells. We analyzed immortalized DPSCs for anchorage-independent growth, genomic instability, and ability to differentiate into neurons. Finally, we tested both spontaneously immortalized and human telomerase reverse transcriptase (hTERT)-immortalized DPSC lines for the ability to form tumors in immunocompromised animals. Although we observed increased colony-forming potential in soft agar for the spontaneously immortalized and hTERT-immortalized DPSC lines relative to low-passage DPSC, no tumors were detected from any of the DPSC lines tested. We noticed some genomic instability in hTERT-immortalized DPSCs but not in the spontaneously immortalized lines tested. We determined that immortalized DPSC lines generated in our laboratory, whether spontaneously or induced, have not acquired the potential to form tumors in mice. These data suggest cultured DPSC lines that can be differentiated into neurons may be safe for future in vivo therapy for neurobiological diseases. ©AlphaMed Press.

San Rafael Schools Exhibit.

ERIC Educational Resources Information Center

San Rafael City Schools, CA.

The San Rafael City Schools' exhibit which was displayed at the 1983 Marin County Fair (California) is described. The exhibit, entitled "Education - A Real Winner," consisted of 12 display panels illustrating the following aspects of the school system: (1) early history from 1861; (2) present board and administration; (3) present schools…

Maintenance of tumor initiating cells of defined genetic composition by nucleostemin.

PubMed

Okamoto, Naoko; Yasukawa, Mami; Nguyen, Christine; Kasim, Vivi; Maida, Yoshiko; Possemato, Richard; Shibata, Tatsuhiro; Ligon, Keith L; Fukami, Kiyoko; Hahn, William C; Masutomi, Kenkichi

2011-12-20

Recent work has identified a subset of cells resident in tumors that exhibit properties similar to those found in normal stem cells. Such cells are highly tumorigenic and may be involved in resistance to treatment. However, the genes that regulate the tumor initiating cell (TIC) state are unknown. Here, we show that overexpression of either of the nucleolar GTP-binding proteins nucleostemin (NS) or GNL3L drives the fraction of genetically defined tumor cells that exhibit markers and tumorigenic properties of TICs. Specifically, cells that constitutively express elevated levels of NS or GNL3L exhibit increased TWIST expression, phosphorylation of STAT3, expression of genes that induce pluripotent stem cells, and enhanced radioresistance; in addition, they form tumors even when small numbers of cells are implanted and exhibit an increased propensity to metastasize. GNL3L/NS forms a complex with the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] and the SWItch-Sucrose NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), and the expression of each of these components is necessary to facilitate the cancer stem cell state. Together, these observations define a complex composed of TERT, BRG1, and NS/GNL3L that maintains the function of TICs.

Starship 2040 Exhibit

NASA Technical Reports Server (NTRS)

2002-01-01

This photograph shows onlookers viewing displays within the Starship 2040 exhibit on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

Effects of oxyanions, natural organic matter, and bacterial cell numbers on the bioreduction of lepidocrocite ({gamma}-FeOOH) and the formation of secondary mineralization products.

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Loughlin, E. J.; Gorski, C. A.; Scherer, M. M.

Microbial reduction of Fe(III) oxides results in the production of Fe(II) and may lead to the subsequent formation of Fe(II)-bearing secondary mineralization products including magnetite, siderite, vivianite, chukanovite (ferrous hydroxy carbonate (FHC)), and green rust; however, the factors controlling the formation of specific Fe(II) phases are often not well-defined. This study examined effects of (i) a range of inorganic oxyanions (arsenate, borate, molybdate, phosphate, silicate, and tungstate), (ii) natural organic matter (citrate, oxalate, microbial extracellular polymeric substances [EPS], and humic substances), and (iii) the type and number of dissimilatory iron-reducing bacteria on the bioreduction of lepidocrocite and formation of Fe(II)-bearingmore » secondary mineralization products. The bioreduction kinetics clustered into two distinct Fe(II) production profiles. 'Fast' Fe(II) production kinetics [19-24 mM Fe(II) d-1] were accompanied by formation of magnetite and FHC in the unamended control and in systems amended with borate, oxalate, gellan EPS, or Pony Lake fulvic acid or having 'low' cell numbers. Systems amended with arsenate, citrate, molybdate, phosphate, silicate, tungstate, EPS from Shewanella putrefaciens CN32, or humic substances derived from terrestrial plant material or with 'high' cell numbers exhibited comparatively slow Fe(II) production kinetics [1.8-4.0 mM Fe(II) d-1] and the formation of green rust. The results are consistent with a conceptual model whereby competitive sorption of more strongly bound anions blocks access of bacterial cells and reduced electron-shuttling compounds to sites on the iron oxide surface, thereby limiting the rate of bioreduction.« less

Gene amplification and microsatellite instability induced in tumorigenic human bronchial epithelial cells by alpha particles and heavy ions

NASA Technical Reports Server (NTRS)

Piao, C. Q.; Hei, T. K.; Hall, E. J. (Principal Investigator)

2001-01-01

Gene amplification and microsatellite alteration are useful markers of genomic instability in tumor and transformed cell lines. It has been suggested that genomic instability contributes to the progression of tumorigenesis by accumulating genetic changes. In this study, amplification of the carbamyl-P-synthetase, aspartate transcarbamylase, dihydro-orotase (CAD) gene in transformed and tumorigenic human bronchial epithelial (BEP2D) cells induced by either alpha particles or (56)Fe ions was assessed by measuring resistance to N-(phosphonacetyl)-l-aspartate (PALA). In addition, alterations of microsatellite loci located on chromosomes 3p and 18q were analyzed in a series of primary and secondary tumor cell lines generated in nude mice. The frequency of PALA-resistant colonies was 1-3 x 10(-3) in tumor cell lines, 5-8 x 10(-5) in transformed cells prior to inoculation into nude mice, and less than 10(-7) in control BEP2D cells. Microsatellite alterations were detected in all 11 tumor cell lines examined at the following loci: D18S34, D18S363, D18S877, D3S1038 and D3S1607. No significant difference in either PALA resistance or microsatellite instability was found in tumor cell lines that were induced by alpha particles compared to those induced by (56)Fe ions.

Starship 2040 Exhibit

NASA Technical Reports Server (NTRS)

2002-01-01

This photograph shows Justin Varnadore, son of a Marshall TV employee, at the controls of one of the many displays within the Starship 2040 exhibit on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

Health-seeking behavior and medical facility choice in Samsun, Turkey.

PubMed

Dündar, Cihad

2017-09-01

Examining the factors that play a role in determining patient preferences for different healthcare institutions. This descriptive study was conducted in five family health centers (FHC) and in six hospitals in Samsun Province in Turkey. The data were collected from 1700 volunteer patients by using a structured questionnaire, while they were waiting for consultation. The average number of out-patient visits was 9.5±6.4 per person in 2012. Individuals aged less than 18 and more than 65 years old had higher preferences for FHCs, while those aged 19-64 years preferred primarily private hospitals. The order of preferences for FHC, public and private hospitals did not vary with the educational level. An increase in educational level was associated with a decrease in the preference for FHCs and in increase in the preference for private hospitals. The first three reasons given for preferring a hospital were 'the presence of a specialist', 'availability of good equipment and technology', and 'trust on the diagnosis and treatment', while 'proximity', 'receiving adequate information', and 'being treated well' were the reasons given by participants who preferred a FHC. Providing medical equipment and staff support for improving diagnostic capacity of FHCs can accommodate patient expectations and shift the demand from hospitals to FHCs. Copyright © 2017 Elsevier B.V. All rights reserved.

Exhibiting Lives

ERIC Educational Resources Information Center

Golden, Deborah; Elbaz-Luwisch, Freema

2007-01-01

This paper examines some of the dilemmas that accompany the emergence of the personal voice in scholarly work, by taking a close, grounded look at the way in which these unfolded in a specific academic course. As part of the course, entitled "A cultural approach to the life cycle", students were asked to participate in a group exhibition in which…

Museum Exhibitions: Optimizing Development Using Evaluation

NASA Astrophysics Data System (ADS)

Dusenbery, P. B.

2002-12-01

The Space Science Institute (SSI) of Boulder, Colorado, has recently developed two museum exhibits called the Space Weather Center and MarsQuest. It is currently planning to develop a third exhibit called InterActive Earth. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. The development of these exhibitions included a comprehensive evaluation plan. I will report on the important role evaluation plays in exhibit design and development using MarsQuest and InterActive Earth as models. The centerpiece of SSI's Mars Education Program is the 5,000-square-foot traveling exhibition, MarsQuest: Exploring the Red Planet, which was developed with support from the National Science Foundation (NSF), NASA, and several corporate donors. The MarsQuest exhibit is nearing the end of a highly successful, fully-booked three-year tour. The Institute plans to send an enhanced and updated MarsQuest on a second three-year tour and is also developing Destination: Mars, a mini-version of MarsQuest designed for smaller venues. They are designed to inspire and empower participants to extend the excitement and science content of the exhibitions into classrooms and museum-based education programs in an ongoing fashion. The centerpiece of the InterActive Earth project is a traveling exhibit that will cover about 4,000 square feet. The major goal of the proposed exhibit is to introduce students and the public to the complexity of the interconnections in the Earth system, and thereby, to inspire them to better understand planet Earth. Evaluation must be an integral part of the exhibition development process. For MarsQuest, a 3-phase evaluation (front end, formative and summative) was conducted by Randi Korn and Associates in close association with the development team. Sampling procedures for all three evaluation phases ensured the participation of all audiences, including family groups, students, and adults. Each phase of

Clinical and radiographic evaluation of Bio-Gen with biocollagen compared with Bio-Gen with connective tissue in the treatment of class II furcation defects: a randomized clinical trial

PubMed Central

JENABIAN, Niloofar; HAGHANIFAR, Sina; MABOUDI, Avideh; BIJANI, Ali

2013-01-01

Objective Treatment of furcation defects are thought to be challenging. The purpose of this study was to evaluate the clinical and radiographic parameters of Bio-Gen with Biocollagen compared with Bio-Gen with connective tissue in the treatment of Class II furcation defects. Material and Methods In this clinical trial, 24 patients with Class II furcation defect on a buccal or lingual mandibular molar were recruited. After oral hygiene instruction, scaling and root planing and achievement of acceptable plaque control, the patients were randomly chosen to receive either connective tissue and Bio-Gen (case group) or Biocollagen and Bio-Gen (control group). The following parameters were recorded before the first and re-entry surgery (six months later): vertical clinical attachment level (VCAL), gingival index (GI), plaque index (PI), horizontal probing depth (HPD), vertical probing depth (VPD), gingival recession (GR), furcation vertical component (FVC), furcation to alveolar crest (FAC), fornix to base of defect (FBD), and furcation horizontal component (FHC) were calculated at the time of first surgery and during re-entry. A digital periapical radiograph was taken in parallel before first surgery and re-entry. The radiographs were then analyzed by digital subtraction. The differences with p value <0.05 were considered significant. Results Only the mean changes of FAC, FHC, mean of FHC, FBD in re-entry revealed statistically significant differences between the two groups. HPD, VPD, FBD, FAC, and FHC showed statistically significant differences after 6 months in the case group. However, in the control group, statistically significant differences were found in GR and HPD. We did not observe any significant difference in radiographic changes among the two groups. Conclusion The results of this trial indicate that better clinical outcomes can be obtained with connective tissue grafts in combination with bone material compared with a resorbable barrier with bone material

KIR3DL1 interaction with HLA-B27 is altered by ankylosing spondylitis associated ERAP1 and enhanced by MHC class I cross-linking.

PubMed

Abdullah, Hasan; Zhang, Zhenbo; Yee, Kirby; Haroon, Nigil

2015-01-01

Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis of the spine and peripheral joints linked to the antigen presenting molecule HLA-B27. The risk of AS is increased in patients possessing endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphisms rs30187 and rs27044 encoding amino acid changes K528R and Q730E, respectively. Dysfunction of ERAP1 is hypothesized to cause changes in expression of HLA-B27 classical (pHLA) and non-classical (FHC) conformers on antigen presenting cells (APCs), which interact with the natural killer (NK) cell receptor KIR3DL1. Dysregulation of this pathway may be pathogenic in AS. APC cell lines expressing HLA-B27 were found to inhibit cytokine production in KIR3DL1+ NK cells due to decreased APC-NK cell adhesion, and possibly activation of receptor down-regulation. Blocking pHLA and FHC reveals that both conformers inhibit cytokine production through KIR3DL1. KIR3DL1 affinity and HLA-B27 surface expression studies suggest that ERAP1 R528 and E730 expression protects from AS by generating sub-optimal pHLA, causing reduced KIR3DL1 affinity and weaker cytokine inhibition. Secondarily we observed that KIR3DL1 binding to C1R-B27 APCs is enhanced by blocking pHLA, but not FHC, raising the possibility that antibody mediated HLA-B27 cross-linking may be important in enhancing KIR3DL1+ NK cell function. This study establishes the role of both FHC and pHLA in modulating NK cell cytokine secretion and adhesion functions by interacting with KIR3DL1. This interaction varies depending on the AS association status of the ERAP1 variant expressed in APCs. Additionally antibody cross-linking of HLA-B27 enhances KIR3DL1 binding and as such could be an important pathogenic mechanism in AS.

Science Fiction Exhibits as STEM Gateways

NASA Astrophysics Data System (ADS)

Robie, Samantha

Women continue to hold less than a quarter of all STEM jobs in the United States, prompting many museums to develop programs and exhibits with the express goal of interesting young girls in scientific fields. At the same time, a number of recent museum exhibits have harnessed the popularity of pop culture and science fiction in order to interest general audiences in STEM subject matter, as well as using the exhibits as springboards to expand or shift mission goals and focus. Because science fiction appears to be successful at raising interest in STEM fields, it may be an effective way to garner the interest of young girls in STEM in particular. This research seeks to describe the ways in which museums are currently using science fiction exhibits to interest young girls in STEM fields and careers. Research focused on four institutions across the country hosting three separate exhibits, and included staff interviews and content analysis of exhibit descriptions, promotional materials, a summative evaluation and supplementary exhibit productions. In some ways, science fiction exhibits do serve young girls, primarily through the inclusion of female role models, staff awareness, and prototype testing to ensure interactives are attractive to girls as well as to boys. However, STEM appears to be underutilized, which may be partly due to a concern within the field that the outcome of targeting a specific gender could be construed as "stereotyping".

Reaching the Public through Traveling Exhibitions

NASA Astrophysics Data System (ADS)

Dusenbery, P. B.; Harold, J. B.; Morrow, C. A.

2004-11-01

The Space Science Institute (SSI) of Boulder, Colorado has recently developed two museum exhibits called Alien Earths and MarsQuest. It has just started to develop another exhibit called Giant Planets. These exhibitions provide research scientists the opportunity to engage in a number of activities that are vital to the success of these major outreach programs. Alien Earths was developed in partnership with various research missions. The focus of the presentation will be on MarsQuest and Giant Planets. MarsQuest is a 5000 square-foot, \\$3M, traveling exhibition that is now touring the country. The exhibit's second 3-year tour will enable millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. The associated planetarium show and education program will also be described, with particular emphasis on workshops to orient museum staff (e.g. museum educators and docents) and workshops for master educators near host museums and science centers. The workshops make innovative connections between the exhibition's interactive experiences and lesson plans aligned with the National Science Education Standards. These exhibit programs are good models for actively involving scientists and their discoveries to help improve informal science education in the museum community and for forging a stronger connection between formal and informal education. The presentation will also discuss how Giant Planets, a proposed 3500 square-foot traveling exhibition on the mysteries and discoveries of the outer planets, will be able to take advantage of the connections and resources that have been developed by the MarsQuest project.

Failure of catalase to protect against aflatoxin B{sub 1}-induced mouse lung tumorigenicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guindon, Katherine A.; Foley, Julie F.; Maronpot, Robert R.

The carcinogenic mycotoxin aflatoxin B{sub 1} (AFB{sub 1}) induces 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in mouse lung, an effect that can be prevented by treatment with polyethylene glycol-conjugated catalase (PEG-CAT). G {yields} T transversion mutation in K-ras, an early event in AFB{sub 1}-induced mouse lung carcinogenesis, is thought to result from AFB{sub 1}-8,9-exo-epoxide binding to DNA to form AFB{sub 1}-N{sup 7}-guanine, but may also result from formation of 8-OHdG. Therefore, oxidative DNA damage may be important in AFB{sub 1} carcinogenicity. The objective of this study was to determine whether PEG-CAT would prevent AFB{sub 1} tumorigenicity. Mouse lung tumorigenesis was assessed following treatmentmore » of female A/J mice with 300 kU/kg PEG-CAT ip and/or 50 mg/kg AFB{sub 1}. Mice were killed 7 months post-treatment and tumors greater than 1 mm in diameter were excised. Unexpectedly, the mean number of tumors per mouse in the PEG-CAT + AFB{sub 1} group (8.81 {+-} 3.64, n = 47) was greater than that of the group treated with AFB{sub 1} alone (7.05 {+-} 3.45, n = 42) (P < 0.05). The tumors obtained from mice treated with PEG-CAT + AFB{sub 1} were larger than those from mice treated with AFB{sub 1} alone (P < 0.05). There was no difference in K-ras exon 1 mutation spectrum or in the histological diagnosis of tumors between AFB{sub 1} and PEG-CAT + AFB{sub 1} groups (P > 0.05). In vitro incubation with mouse liver catalase (CAT) resulted in conversion of [{sup 3}H]AFB{sub 1} into a DNA-binding species, a possible explanation for the results observed in vivo. These results demonstrate that PEG-CAT is not protective against AFB{sub 1} carcinogenicity in mouse lung despite preventing DNA oxidation.« less

LOX-1 activation by oxLDL triggers an epithelial mesenchymal transition and promotes tumorigenic potential in prostate cancer cells.

PubMed

González-Chavarría, I; Fernandez, E; Gutierrez, N; González-Horta, E E; Sandoval, F; Cifuentes, P; Castillo, C; Cerro, R; Sanchez, O; Toledo, Jorge R

2018-02-01

Obesity is related to an increased risk of developing prostate cancer with high malignancy stages or metastasis. Recent results demonstrated that LOX-1, a receptor associated with obesity and atherosclerosis, is overexpressed in advanced and metastatic prostate cancer. Furthermore, high levels of oxLDL, the main ligand for LOX-1, have been found in patients with advanced prostate cancer. However, the role of LOX-1 in prostate cancer has not been unraveled completely yet. Here, we show that LOX-1 is overexpressed in prostate cancer cells and its activation by oxLDL promotes an epithelial to mesenchymal transition, through of lowered expression of epithelial markers (E-cadherin and plakoglobin) and an increased expression of mesenchymal markers (vimentin, N-cadherin, snail, slug, MMP-2 and MMP-9). Consequently, LOX-1 activation by oxLDL promotes actin cytoskeleton restructuration and MMP-2 and MMP-9 activity inducing prostate cancer cell invasion and migration. Additionally, LOX-1 increased the tumorigenic potential of prostate cancer cells and its expression was necessary for tumor growth in nude mice. In conclusion, our results suggest that oxLDL/LOX-1 could be ones of mechanisms that explain why obese patients with prostate cancer have an accelerated tumor progression and a greater probability of developing metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma.

PubMed

Lee, S H; Oh, S-Y; Do, S I; Lee, H J; Kang, H J; Rho, Y S; Bae, W J; Lim, Y C

2014-11-25

Head and neck squamous cell carcinomas (HNSCCs) display cellular heterogeneity and contain cancer stem cells (CSCs). Sex-determining region Y [SRY]-box (SOX)2 is an important regulator of embryonic stem cell fate and is aberrantly expressed in several types of human tumours. Nonetheless, the role of SOX2 in HNSCC remains unclear. We created cells ectopically expressing SOX2 from previously established HNSCC cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, we knocked down SOX2 in primary spheres obtained from HNSCC tumour tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. Furthermore, we examined the clinical relevance of SOX2 expression in HNSCC patients. SOX2 is aberrantly expressed in primary tissue of HNSCC patients but not in healthy tissue. SOX2 expression correlated with tumour recurrence and poor prognosis of HNSCC patients. Ectopic expression of SOX2 induced cell proliferation via cyclin B1 expression and stemness-associated features, such as self-renewal and chemoresistance. In addition, a knockdown of SOX2 in HNSCC CSCs attenuated their self-renewal capacity, chemoresistance (through ABCG2 suppression), invasion capacity (via snail downregulation), and in vivo tumorigenicity. These results suggest that SOX2 may have important roles in the 'stemness' and progression of HNSCC. Targeting SOX2-positive tumour cells (CSCs) could be a new therapeutic strategy in HNSCCs.

Online Exhibits & Concept Maps

NASA Astrophysics Data System (ADS)

Douma, M.

2009-12-01

Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

Superconductive microstrip exhibiting negative differential resistivity

DOEpatents

Huebener, R.P.; Gallus, D.E.

1975-10-28

A device capable of exhibiting negative differential electrical resistivity over a range of values of current and voltage is formed by vapor- depositing a thin layer of a material capable of exhibiting superconductivity on an insulating substrate, establishing electrical connections at opposite ends of the deposited strip, and cooling the alloy into its superconducting range. The device will exhibit negative differential resistivity when biased in the current- induced resistive state.

Exhibitions in Sight

ERIC Educational Resources Information Center

Wasserman, Burton

1977-01-01

Today, few artists make serving vessels on a monumental scale. Here artists compete in this unique area of specialization prompted by the Campbell Museum in Camden, New Jersey, which is dedicated to collecting and exhibiting the very best in soup tureens. (Author/RK)

Genetics Home Reference: familial hypertrophic cardiomyopathy

MedlinePlus

... Savithri GR, Kumar MS, Narasimhan C, Nallari P. Molecular genetics of familial hypertrophic cardiomyopathy (FHC). J Hum Genet. ... 5(11):747. Citation on PubMed Kimura A. Molecular genetics and pathogenesis of cardiomyopathy. J Hum Genet. 2016 ...

Exhibition Spaces/Galleries.

ERIC Educational Resources Information Center

American School & University, 2003

2003-01-01

Presents educational exhibition space/galleries considered outstanding in a competition, which judged the most outstanding learning environments at educational institutions nationwide. Jurors spent two days reviewing projects, highlighting concepts and ideas that made them exceptional. For each citation, the article offers information on the firm,…

Disorder in Milk Proteins: α-Lactalbumin. Part B. A Multifunctional Whey Protein Acting as an Oligomeric Molten Globular "Oil Container" in the Anti-Tumorigenic Drugs, Liprotides.

PubMed

Uversky, Vladimir N; Permyakov, Serge E; Breydo, Leonid; Redwan, Elrashdy M; Almehdar, Hussein A; Permyakov, Eugene A

2016-07-15

This is a second part of the three-part article from a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. We continue to describe α-lactalbumin, a small globular Ca2+-binding protein, which besides being one of the two components of lactose synthase that catalyzes the final step of the lactose biosynthesis in the lactating mammary gland, possesses a multitude of other functions. In fact, recent studies indicated that some partially folded forms of this protein possess noticeable bactericidal activity and other forms might be related to induction of the apoptosis of tumor cells. In its anti-tumorigenic function, oligomeric α-lactalbumin serves as a founding member of a new family of anticancer drugs termed liprotides (for lipids and partially denatured proteins), where an oligomeric molten globular protein acts as an "oil container" or cargo for the delivery of oleic acid to the cell membranes.

Exhibitions in Sight.

ERIC Educational Resources Information Center

Wasserman, Burton

1978-01-01

Early in the eighteenth century, Pompeii was discovered, a city that had been hidden for sixteen centuries by volcanic lava. There is a traveling exhibition of the sculptures, friezes, mosaics, and paintings being shown around the United States. Described is the history and contents of "Pompeii--A.D. 79." (RK)

Assessment of the Tumorigenic Potential of Spontaneously Immortalized and hTERT-Immortalized Cultured Dental Pulp Stem Cells

PubMed Central

Wilson, Ryan; Urraca, Nora; Skobowiat, Cezary; Hope, Kevin A.; Miravalle, Leticia; Chamberlin, Reed; Donaldson, Martin; Seagroves, Tiffany N.

2015-01-01

Dental pulp stem cells (DPSCs) provide an exciting new avenue to study neurogenetic disorders. DPSCs are neural crest-derived cells with the ability to differentiate into numerous tissues including neurons. The therapeutic potential of stem cell-derived lines exposed to culturing ex vivo before reintroduction into patients could be limited if the cultured cells acquired tumorigenic potential. We tested whether DPSCs that spontaneously immortalized in culture acquired features of transformed cells. We analyzed immortalized DPSCs for anchorage-independent growth, genomic instability, and ability to differentiate into neurons. Finally, we tested both spontaneously immortalized and human telomerase reverse transcriptase (hTERT)-immortalized DPSC lines for the ability to form tumors in immunocompromised animals. Although we observed increased colony-forming potential in soft agar for the spontaneously immortalized and hTERT-immortalized DPSC lines relative to low-passage DPSC, no tumors were detected from any of the DPSC lines tested. We noticed some genomic instability in hTERT-immortalized DPSCs but not in the spontaneously immortalized lines tested. We determined that immortalized DPSC lines generated in our laboratory, whether spontaneously or induced, have not acquired the potential to form tumors in mice. These data suggest cultured DPSC lines that can be differentiated into neurons may be safe for future in vivo therapy for neurobiological diseases. Significance This study demonstrated that immortalized dental pulp stem cells (DPSCs) do not form tumors in animals and that immortalized DPSCs can be differentiated into neurons in culture. These results lend support to the use of primary and immortalized DPSCs for future therapeutic approaches to treatment of neurobiological diseases. PMID:26032749

Newly established human retinoblastoma cell lines exhibit an "immortalized" but not an invasive phenotype in vitro.

PubMed

Griegel, S; Hong, C; Frötschl, R; Hülser, D F; Greger, V; Horsthemke, B; Rajewsky, M F

1990-07-15

Retinoblastoma (RB), an intraocular childhood tumor occurring in a hereditary (mostly bilateral) or non-hereditary (unilateral) form, is associated with the inactivation of both alleles of a putative tumor suppressor gene (RB-I) located on chromosome 13q14. Both the process of RB development and the biological characteristics of RB cells are as yet poorly understood. We have established 7 new RBL lines (RBL13, RBL14, RBL18 and RBL30, derived from unilateral RB; and RBL7, RBL15 and RBL20, derived from bilateral RB). Southern blot analyses of restriction fragment length polymorphisms in DNA samples from 6 cell lines revealed loss of constitutional heterozygosity at one or several polymorphic loci on chromosome 13 in 4 cases. Gross deletions involving the RB-I locus and amplification of the N-myc gene were not detected in any of the RBL lines. The phenotypic properties of the RBL lines were analyzed in comparison with cells from the original RB tumors, with 4 RB lines established by others (RB383, RB355, RB247C3 and Y79) and with the adenovirus-EIA-transformed human retinoblast line HER-Xhol-CC2. It was found that RB tumors consist of phenotypically heterogeneous cell subpopulations with varying nutrient requirements and differentiation potential in vitro. All cell lines showed the typical characteristics of established ("immortalized") cells. In some cases, cells from original RB tumors or cell lines were able to form colonies when cell aggregates of 2-10 cells were suspended in semi-solid agar medium; however, anchorage-independent colonies never developed from single cells. Cell lines RBL13, RBL18, RB247C3, RB355, RB383 and Y79 were tested for invasion into embryonic chick heart fragments in vitro and found to be non-invasive. None of the RBL or RB lines were tumorigenic in nu/nu (T-) mice. Y79 cells (propagated in culture for many years) exhibited properties distinctly different from those of the other cell lines, and thus cannot be considered phenotypically

An Exhibit for Touching.

ERIC Educational Resources Information Center

Hunt, Susan

1979-01-01

An exhibit designed for visually handicapped persons presented by the Kalamazoo (Michigan) Institute of Art included bronze sculptures and oil paintings from the institute's permanent collection. (CL)

Evaluating the immortal strand hypothesis in cancer stem cells: symmetric/self-renewal as the relevant surrogate marker of tumorigenicity.

PubMed

Winquist, Raymond J; Hall, Amy B; Eustace, Brenda K; Furey, Brinley F

2014-09-15

Stem cells subserve repair functions for the lifetime of the organism but, as a consequence of this responsibility, are candidate cells for accumulating numerous genetic and/or epigenetic aberrations leading to malignant transformation. However, given the importance of this guardian role, stem cells likely harbor some process for maintaining their precious genetic code such as non-random segregation of chromatid strands as predicted by the Immortal Strand Hypothesis (ISH). Discerning such non-random chromosomal segregation and asymmetric cell division in normal or cancer stem cells has been complicated by methodological shortcomings but also by differing division kinetics amongst tissues and the likelihood that both asymmetric and symmetric cell divisions, dictated by local extrinsic factors, are operant in these cells. Recent data suggest that cancer stem cells demonstrate a higher incidence of symmetric versus asymmetric cell division with both daughter cells retaining self-renewal characteristics, a profile which may underlie poorly differentiated morphology and marked clonal diversity in tumors. Pathways and targets are beginning to emerge which may provide opportunities for preventing such a predilection in cancer stem cells and that will hopefully translate into new classes of chemotherapeutics in oncology. Thus, although the existence of the ISH remains controversial, the shift of cell division dynamics to symmetric random chromosome segregation/self-renewal, which would negate any likelihood of template strand retention, appears to be a surrogate marker for the presence of highly malignant tumorigenic cell populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Starship 2040 Exhibit

NASA Technical Reports Server (NTRS)

2002-01-01

This photograph shows the Starship 2040 on display at Joe Davis Stadium in Huntsville, Alabama. Developed by the Space Transportation Directorate at Marshall Space Flight Center (MSFC), the Starship 2040 exhibit is housed in a 48-ft (14.6-m) tractor and trailer rig, permitting it to travel around the Nation, demonstrating NASA's vision of what commercial spaceflight might be like 40 years from now. All the irnovations suggested aboard the exhibit (automated vehicle health monitoring systems, high-energy propulsion drive, navigational aids, and emergency and safety systems) are based on concepts and technologies now being studied at NASA Centers and partner institutions around the Nation. NASA is the Nation's premier agency for development of the space transportation system, including future-generation reusable launch vehicles. Such systems, the keys to a 'real' Starship 2040, require revolutionary advances in critical aerospace technologies, from thermal, magnetic, chemical, and propellantless propulsion systems to new energy sources such as space solar power or antimatter propulsion. These and other advances are now being studied, developed, and tested at NASA field centers and partner institutions all over the Nation.

Holy Basil Leaf Extract Decreases Tumorigenicity and Metastasis of Aggressive Human Pancreatic Cancer Cells in vitro and in vivo: Potential Role in Therapy

PubMed Central

Shimizu, Tomohiro; Torres, María P.; Chakraborty, Subhankar; Souchek, Joshua J.; Rachagani, Satyanarayana; Kaur, Sukhwinder; Macha, Muzafar; Ganti, Apar K.; Hauke, Ralph J; Batra, Surinder K.

2013-01-01

There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum (“Holy Basil”) has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future. PMID:23523869

Role of PP2Cα in cell growth, in radio- and chemosensitivity, and in tumorigenicity

PubMed Central

Lammers, Twan; Peschke, Peter; Ehemann, Volker; Debus, Jürgen; Slobodin, Boris; Lavi, Sara; Huber, Peter

2007-01-01

Background PP2Cα is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFβ-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Cα in cell growth and in radio- and chemosensitivity, wild type and PP2Cα siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Cα in tumorigenesis. Results It was found that knockdown of PP2Cα did not affect the proliferation, the clonogenic survival and the membrane integrity of MCF7 cells. In addition, it did not alter their radio- and chemosensitivity. For PP2Cα siRNA-expressing MCF7 cells, the number of cells in the G0/G1 phase of the cell cycle was reduced, the induction of the G1 block was attenuated, the number of cells in G2/M was increased, and the induction of the G2 block was enhanced. The tumorigenic potential of PP2Cα siRNA-expressing MCF7 cells was found to be higher than that of wild type MCF7 cells, and the in vivo proliferation of these cells was found to be increased. Conclusion Based on these findings, we conclude that PP2Cα is not involved in controlling cell growth and radio- and chemosensitivity in vitro. It does, however, play a role in the regulation of the cell cycle, in the induction of cell cycle checkpoints and in tumorigenesis. The latter notion implies that PP2Cα may possess tumor-suppressing properties, and it thereby sets the stage for more elaborate analyses on its involvement in the development and progression of cancer. PMID:17941990

The exploration of the exhibition informatization

NASA Astrophysics Data System (ADS)

Zhang, Jiankang

2017-06-01

The construction and management of exhibition informatization is the main task and choke point during the process of Chinese exhibition industry’s transformation and promotion. There are three key points expected to realize a breakthrough during the construction of Chinese exhibition informatization, and the three aspects respectively are adopting service outsourcing to construct and maintain the database, adopting advanced chest card technology to collect various kinds of information, developing statistics analysis to maintain good cutomer relations. The success of Chinese exhibition informatization mainly calls for mature suppliers who can provide construction and maintenance of database, the proven technology, a sense of data security, advanced chest card technology, the ability of data mining and analysis and the ability to improve the exhibition service basing on the commercial information got from the data analysis. Several data security measures are expected to apply during the process of system developing, including the measures of the terminal data security, the internet data security, the media data security, the storage data security and the application data security. The informatization of this process is based on the chest card designing. At present, there are several types of chest card technology: bar code chest card; two-dimension code card; magnetic stripe chest card; smart-chip chest card. The information got from the exhibition data will help the organizers to make relevant service strategies, quantify the accumulated indexes of the customers, and improve the level of the customer’s satisfaction and loyalty, what’s more, the information can also provide more additional services like the commercial trips, VIP ceremonial reception.

Children's Art Exhibit

ERIC Educational Resources Information Center

Roselle, Marsha L.

1973-01-01

Within the past ten years, a sufficient number of specialists in art education have been added to the faculty of the Iowa City Community Schools to relieve the classroom teacher of the responsibility of teaching elementary art classes. The resultant improvement in the quality of the elementary art program led to the creation of the exhibit series.…

The arthritis-associated HLA-B*27:05 allele forms more cell surface B27 dimer and free heavy chain ligands for KIR3DL2 than HLA-B*27:09

PubMed Central

Shaw, Jacqueline; Giles, Joanna; Hatano, Hiroko; Rysnik, Oliwia; Payeli, Sravan; McHugh, Kirsty; Dessole, Grazia; Porru, Giovanni; Desogus, Elisabetta; Fiedler, Sarah; Hölper, Soraya; Carette, Amanda; Blanco-Gelaz, Miguel Angel; Vacca, Alessandra; Piga, Matteo; Ibba, Valentina; Garau, Pietro; La Nasa, Giorgio; López-Larrea, Carlos; Mathieu, Alessandro; Renner, Christoph; Bowness, Paul; Kollnberger, Simon

2013-01-01

Objectives. HLA-B*27:05 is associated with AS whereas HLA-B*27:09 is not associated. We hypothesized that different interactions with KIR immune receptors could contribute to the difference in disease association between HLA-B*27:05 and HLAB*27:09. Thus, the objective of this study was to compare the formation of β2m-free heavy chain (FHC) including B27 dimers (B272) by HLA-B*27:05 and HLA-B*27:09 and their binding to KIR immunoreceptors. Methods. We studied the formation of HLA-B*27:05 and HLA-B*27:09 heterotrimers and FHC forms including dimers in vitro and in transfected cells. We investigated HLA-B*27:05 and HLA-B*27:09 binding to KIR3DL1, KIR3DL2 and LILRB2 by FACS staining with class I tetramers and by quantifying interactions with KIR3DL2CD3ε-reporter cells and KIR3DL2-expressing NK cells. We also measured KIR expression on peripheral blood NK and CD4 T cells from 18 HLA-B*27:05 AS patients, 8 HLA-B27 negative and 12 HLA-B*27:05+ and HLA-B*27:09+ healthy controls by FACS staining. Results. HLA-B*27:09 formed less B272 and FHC than HLA-B*27:05. HLA-B*27:05-expressing cells stimulated KIR3DL2CD3ε-reporter T cells more effectively. Cells expressing HLA-B*27:05 promoted KIR3DL2+ NK cell survival more strongly than HLA-B*27:09. HLA-B*27:05 and HLA-B*27:09 dimer tetramers stained KIR3DL1, KIR3DL2 and LILRB2 equivalently. Increased proportions of NK and CD4 T cells expressed KIR3DL2 in HLA-B*27:05+ AS patients compared with HLA-B*27:05+, HLA-B*27:09+ and HLA-B27− healthy controls. Conclusion. Differences in the formation of FHC ligands for KIR3DL2 by HLA-B*27:05 and HLA-B*27:09 could contribute to the differential association of these alleles with AS. PMID:23804219

Using Comparative Planetology in Exhibit Development

NASA Astrophysics Data System (ADS)

Dusenbery, P. B.; Harold, J. B.; Morrow, C. A.

2004-12-01

It is critically important for the public to better understand the scientific process. Museum exhibitions are an important part of informal science education that can effectively reach public audiences as well as school groups. They provide an important gateway for the public to learn about compelling scientific endeavors. The Space Science Institute (SSI) is a national leader in producing traveling science exhibitions and their associated educational programming (i.e. interactive websites, educator workshops, public talks, instructional materials). The focus of this presentation will be on three of its exhibit projects: MarsQuest (currently on tour), Alien Earths (in fabrication), and Giant Planets (in development). MarsQuest is enabling millions of Americans to share in the excitement of the scientific exploration of Mars and to learn more about their own planet in the process. Alien Earths will bring origins-related research and discoveries to students and the American public. It has four interrelated exhibit areas: Our Place in Space, Star Birth, PlanetQuest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in "habitable zones" around other stars; and finally they will be able to learn about how scientists are looking for signs of life beyond Earth. Giant Planets: Exploring the Outer Solar System will take advantage of the excitement generated by the Cassini mission and bring planetary and origins research and discoveries to students and the public. It will be organized around four thematic areas: Our Solar System; Colossal Worlds; Moons, Rings, and Fields; and Make Space for Kids. Giant Planets will open in 2007. This talk will focus on the importance of making Earth comparisons in the conceptual design of each exhibit and will show several examples of how these comparisons were manifested in

Temporary and Travelling Exhibitions. Museums and Monuments, X.

ERIC Educational Resources Information Center

Daifuku, Hiroshi; And Others

The permanent exhibition, the most typical form of museum exhibition, has failed to attract repeated visitation, since visitors quickly become familiar with the objects shown. The temporary exhibition evolved as a result for the need of repeated visitation. The temporary exhibition, set up for a period of one to six months, introduces fresh…

Communicating Complex Sciences by Means of Exhibitions

NASA Astrophysics Data System (ADS)

Schneider, S.

2011-12-01

Earth Sciences will have to take over the leading role in global sustainable policy and in discussions about climate change. Efforts to raise attention within the politically responsible communities as well as in the public are getting more and more support by executive and advisory boards all over the world. But how can you successfully communicate complex sciences? For example, to start communication about climate change, the first step is to encourage people to be concerned about climate change. After that, one has to start thinking about how to present data and how to include the presented data into an unprejudiced context. Therefore, the communication toolbox offers various methods to reach diverse audiences. The R&D programme GEOTECHNOLOGIEN conducts roving exhibitions as one of its most successful communication tools. With roving exhibitions GEOTECHNOLOGIEN is able to get in touch with different audiences at once. The main purpose and theme of these exhibitions is to convey the everyday means of climate change to the visitors. It is within the responsibility of science to communicate the effects of a phenomenon like climate change as well as the impact of research results to the everyday life of people. Currently, a GEOTECHNOLOGIEN roving exhibition on remote sensing with satellites deals with various issues of environmental research, including a chapter on climate change. By following the 3M-concept (Meaning - Memorable - Moving), exhibitions allow to connect the visitors daily environment and personal experiences with the presented issues and objects. Therefore, hands-on exhibits, exciting multimedia effects and high-tech artefacts have to be combined with interpretive text elements to highlight the daily significance of the scientific topics and the exhibition theme respectively. To create such an exhibition, strong conceptual planning has to be conducted. This includes the specification of stern financial as well as time wise milestones. In addition

Encountering Nanotechnology in an Interactive Exhibition

ERIC Educational Resources Information Center

Murriello, Sandra E.; Knobel, Marcelo

2008-01-01

This article offers findings from a learning sciences-informed evaluation of a nanoscience and nanotechnology exhibition called Nano-Aventura (NanoAdventure), based on four interactive-collaborative games and two narrated videos. This traveling exhibition was developed in Brazil by the Museu Exploratorio de Ciencias for children and teenagers…

Memory and Mourning: An Exhibit History

ERIC Educational Resources Information Center

Eberle, Scott G.

2005-01-01

Mounted by the Strong Museum in Rochester, New York, in 1993, and traveling nationally thereafter, the exhibit Memory and Mourning provided historical and contemporary perspectives to help museum guests explore their own reactions to loss and grief. In the process the exhibit's development team encountered a range of philosophical, historical,…

18 CFR 50.7 - Applications: exhibits.

Code of Federal Regulations, 2014 CFR

2014-04-01

... elements or matters contained in the exhibit. (a) Exhibit A—Articles of incorporation and bylaws. If the applicant is not an individual, a conformed copy of its articles of incorporation and bylaws, or other... following information: (i) Number of circuits, with identification as to whether the circuit is overhead or...

18 CFR 50.7 - Applications: exhibits.

Code of Federal Regulations, 2012 CFR

2012-04-01

... elements or matters contained in the exhibit. (a) Exhibit A—Articles of incorporation and bylaws. If the applicant is not an individual, a conformed copy of its articles of incorporation and bylaws, or other... following information: (i) Number of circuits, with identification as to whether the circuit is overhead or...

18 CFR 50.7 - Applications: exhibits.

Code of Federal Regulations, 2013 CFR

2013-04-01

... elements or matters contained in the exhibit. (a) Exhibit A—Articles of incorporation and bylaws. If the applicant is not an individual, a conformed copy of its articles of incorporation and bylaws, or other... following information: (i) Number of circuits, with identification as to whether the circuit is overhead or...

Soluble Suppression of Tumorigenicity-2 Predicts Hospital Mortality in Burn Patients: An Observational Prospective Cohort Pilot Study.

PubMed

Ruiz-Castilla, Mireia; Bosacoma, Pau; Dos Santos, Bruce; Baena, Jacinto; Guilabert, Patricia; Marin-Corral, Judith; Masclans, Joan R; Roca, Oriol; Barret, Juan P

2018-04-10

The IL33/ST2 pathway has been implicated in the pathogenesis of different inflammatory diseases. Our aim was to analyze whether plasma levels of biomarkers involved in the IL33/ST2 axis might help to predict mortality in burn patients. Single-center prospective observational cohort pilot study performed at the Burns Unit of the Plastic and Reconstructive Surgery Department of the Vall d'Hebron University Hospital (Barcelona). All patients aged ≥18 years old with second or third-degree burns requiring admission to the Burns Unit were considered for inclusion. Blood samples were taken to measure levels of interleukins (IL)6, IL8, IL33, and soluble suppression of tumorigenicity-2 (sST2) within 24 h of admission to the Burns Unit and at day 3. Results are expressed as medians and interquartile ranges or as frequencies and percentages. Sixty-nine patients (58 [84.1%] male, mean age 52 [35-63] years, total body surface area burned 21% [13%-30%], Abbreviated Burn Severity Index 6 [4-8]) were included. Thirteen (18.8%) finally died in the Burns Unit. Plasma levels of sST2 measured at day 3 after admission demonstrated the best prediction accuracy for survival (area under the ROC curve 0.85 [0.71-0.99]; P < 0.001). The best cutoff point for the AUROC index was estimated to be 2,561. In the Cox proportional hazards model, after adjusting for potential confounding, a plasma sST2 level ≥2,561 measured at day 3 was significantly associated with mortality (HR 6.94 [1.73-27.74]; P = 0.006). Plasma sST2 at day 3 predicts hospital mortality in burn patients.

Tumorigenic risk of human induced pluripotent stem cell explants cultured on mouse SNL76/7 feeder cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamada, Mizuna; Mitsui, Youji, E-mail: y-mitsui8310@hb.tp1.jp; Kumazaki, Tsutomu

2014-10-24

Highlights: • hiPS cell explants formed malignant tumors when SNL76/7 feeder cells were used. • Multi type tumors developed by interaction of SNL76/7 feeder cells with hiPS cells. • Tumorigenic risk occurs by co-culture of hiPS cells with SNL76/7 feeder cells. - Abstract: The potential for tumor formation from transplanted human induced pluripotent stem cell (hiPSC) derivatives represents a high risk in their application to regenerative medicine. We examined the genetic origin and characteristics of tumors, that were formed when 13 hiPSC lines, established by ourselves, and 201B7 hiPSC from Kyoto University were transplanted into severe combined immune-deficient (SCID) mice.more » Though teratomas formed in 58% of mice, five angiosarcomas, one malignant solitary fibrous tumor and one undifferentiated pleomorphic sarcoma formed in the remaining mice. Three malignant cell lines were established from the tumors, which were derived from mitomycin C (MMC)-treated SNL76/7 (MMC-SNL) feeder cells, as tumor development from fusion cells between MMC-SNL and hiPSCs was negative by genetic analysis. While parent SNL76/7 cells produced malignant tumors, neither MMC-SNL nor MMC-treated mouse embryo fibroblast (MEF) produced malignant tumors. When MMC-SNL feeder cells were co-cultured with hiPSCs, growing cell lines were generated, that expressed genes similar to the parent SNL76/7 cells. Thus, hiPSCs grown on MMC-SNL feeder cells have a high risk of generating feeder-derived malignant tumors. The possible mechanism(s) of growth restoration and the formation of multiple tumor types are discussed with respect of the interactions between MMC-SNL and hiPSC.« less

Restoration of miR-30a expression inhibits growth, tumorigenicity of medulloblastoma cells accompanied by autophagy inhibition.

PubMed

Singh, Satishkumar Vishram; Dakhole, Aditi Nigam; Deogharkar, Akash; Kazi, Sadaf; Kshirsagar, Rohan; Goel, Atul; Moiyadi, Aliasgar; Jalali, Rakesh; Sridhar, Epari; Gupta, Tejpal; Shetty, Prakash; Gadewal, Nikhil; Shirsat, Neelam Vishwanath

2017-09-30

Medulloblastoma is a highly malignant pediatric brain tumor. About 30% patients have metastasis at diagnosis and respond poorly to treatment. Those that survive, suffer long term neurocognitive, endocrine and developmental defects due to the cytotoxic treatment to developing child brain. It is therefore necessary to develop targeted treatment strategies based on underlying biology for effective treatment of medulloblastoma with minimal side effects. Medulloblastomas are believed to be the result of deregulated nervous system development as evident from the role of WNT and SHH developmental signaling pathways in pathogenesis of medulloblastomas. MicroRNAs are known to play vital roles in nervous system development as well as in cancer. MicroRNA profiling of medulloblastomas identified miR-30 family members' expression to be downregulated in medulloblastomas belonging to the four known molecular subgroups viz. WNT, SHH, Group 3 and Group 4 as compared to that in normal brain tissues. Furthermore, established medulloblastoma cell lines Daoy, D283 and D425 were also found to underexpress miR-30a. Restoration of miR-30a expression using inducible lentiviral vector inhibited proliferation, clonogenic potential and tumorigenicity of medulloblastoma cells. MiR-30a is known to target Beclin1, a mediator of autophagy. MiR-30a expression was found to downregulate Beclin1 expression and inhibit autophagy in the medulloblastoma cell lines as judged by downregulation of LC3B expression and its turnover upon chloroquine treatment and starvation induced autophagy induction. MiR-30a therefore could serve as a novel therapeutic agent for the effective treatment of medulloblastoma by inhibiting autophagy that is known to play important role in cancer cell growth, survival and malignant behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

PubMed

Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

2013-10-01

Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

PubMed Central

Olivan, M.; Rigau, M.; Colás, E.; Garcia, M.; Montes, M.; Sequeiros, T.; Regis, L.; Celma, A.; Planas, J.; Placer, J.; Reventós, J.; de Torres, I.; Doll, A.; Morote, J.

2015-01-01

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812), P < 0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155), P = 0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939), P < 0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence. PMID:25649906

Sex differences in science museum exhibit attraction

NASA Astrophysics Data System (ADS)

Arámbula Greenfield, Teresa

This study examines the relative attraction of hands-on, interactive science museum exhibits for females and males. Studies have demonstrated that such exhibits can be effective learning experiences for children, with both academic and affective benefits. Other studies have shown that girls and boys do not always experience the same science-related educational opportunities and that, even when they do, they do not necessarily receive the same benefits from them. These early differences can lead to more serious educational and professional disparities later in life. As interactive museum exhibits represent a science experience that is-readily available to both girls and boys, the question arose as to whether they were being used similarly by the two groups as well as by adult women and men. It was found that both girls and boys used all types of exhibits, but that girls were more likely than boys to use puzzles and exhibits focusing on the human body; boys were more likely than girls to use computers and exhibits illustrating physical science principles. However, this was less true of children accompanied by adults (parents) than it was of unaccompanied children on school field trips who roamed the museum more freely.Received: 16 February 1994; Revised: 3 February 1995;

Silencing of B7-H4 suppresses the tumorigenicity of the MGC-803 human gastric cancer cell line and promotes cell apoptosis via the mitochondrial signaling pathway.

PubMed

Zhou, Donghui; Zhou, Yong; Li, Chao; Yang, Lina

2018-04-01

B7-H4 is a transmembrane protein which is a member of the B7 superfamily. It is overexpressed in various types of cancer, including gastric cancer. However, the effects of B7-H4 on the tumorigenicity of gastric cancer and the underlying mechanisms have not yet been fully explored. Thus, the aim of this study was to examine the effects of B7-H4 on the tumorigenicity of gastric cancer cells and to elucidate the underlying mechanisms. For this purpose, B7-H4 expression in gastric cancer tissues was detected by immunohistochemical staining. The effects of B7-H4 on the biological behavior of the MGC-803 human gastric cancer cell line were examined by Cell Counting kit-8 (CCK-8) assay, cell cycle analysis, wound healing assay, Annexin V/propidium iodide staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Moreover, the expression levels of apoptotic markers, such as cleaved caspase‑3, cleaved caspase‑9, Bcl-2 and Bax were examined by western blot analysis. Immunohistochemical staining revealed that a high expression of B7-H4 was found in about 41.8% of tissues obtained from patients with gastric cancer. Comparative analysis revealed that B7-H4 expression significantly correlated with lymph node metastasis and the TNM stage. The results of CCK-8 assay, cell cycle analysis, wound healing assay, Annexin V/propidium iodide staining assay and TUNEL assay all demonstrated that the silencing of B7-H4 by small interfering RNA decreased cell proliferation, suppressed cell motility, and induced cell cycle arrest and the apoptosis of MGC-803 human gastric cancer cells. Furthermore, the results of western blot analysis indicated that the downregulation of B7-H4 induced the apoptosis of the MGC-803 cells via the mitochondrial signaling pathway through the activation of caspase‑3 and caspase‑9, and by altering the Bax/Bcl-2 ratio in a manner that favored apoptosis. Based on the findings on human gastric cancer cell line MGC-803, the

Biological and genetic properties of the p53 null preneoplastic mammary epithelium

NASA Technical Reports Server (NTRS)

Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

2002-01-01

The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

Suppression of AMF/PGI-mediated tumorigenic activities by ursolic acid in cultured hepatoma cells and in a mouse model.

PubMed

Shih, Wen-Ling; Yu, Feng-Ling; Chang, Ching-Dong; Liao, Ming-Huei; Wu, Hung-Yi; Lin, Ping-Yuan

2013-10-01

Our previous studies demonstrated that autocrine motility factor/phosphoglucose isomerase (AMF/PGI) possesses tumorigenic activities through the modulation of intracellular signaling. We then investigated the effects of ursolic acid (UA), oleanolic acid (OA), tangeretin, and nobiletin against AMF/PGI-mediated oncogenesis in cultured stable Huh7 and Hep3B cells expressing wild-type or mutated AMF/PGI and in a mouse model in this study. The working concentrations of the tested compounds were lower than their IC10 , which was determined by Brdu incorporation and colony formation assay. Only UA efficiently suppressed the AMF/PGI-induced Huh7 cell migration and MMP-3 secretion. Additionally, UA inhibited the AMF/PGI-mediated protection against TGF-β-induced apoptosis in Hep3B cells, whereas OA, tangeretin, and nobiletin had no effect. In Huh7 cells and tumor tissues, UA disrupted the Src/RhoA/PI 3-kinase signaling and complex formation induced by AMF/PGI. In the Hep3B system, UA dramatically suppressed AMF/PGI-induced anti-apoptotic signaling transmission, including Akt, p85, Bad, and Stat3 phosphorylation. AMF/PGI enhances tumor growth, angiogenesis, and pulmonary metastasis in mice, which is correlated with its enzymatic activity, and critically, UA intraperitoneal injection reduces the tumorigenesis in vivo, enhances apoptosis in tumor tissues and also prolongs mouse survival. Combination of sub-optimal dose of UA and cisplatin, a synergistic tumor cell-killing effects was found. Thus, UA modulates intracellular signaling and might serve as a functional natural compound for preventing or alleviating hepatocellular carcinoma. © 2012 Wiley Periodicals, Inc.

Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugimasa, Hironobu; Taniue, Kenzui; Kurimoto, Akiko

2015-03-27

Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein involved in transcription, mRNA splicing, mRNA stabilization and translation. Although hnRNP K has been suggested to play a role in the development of many cancers, its molecular function in colorectal cancer has remained elusive. Here we show that hnRNP K plays an important role in the mitotic process in HCT116 colon cancer cells. Furthermore, we demonstrate that hnRNP K directly transactivates the NUF2 gene, the product of which is a component of the NDC80 kinetochore complex and which is known to be critical for a stable spindle microtubule-kinetochore attachment. Inmore » addition, knockdown of both hnRNP K and NUF2 caused failure in metaphase chromosome alignment and drastic decrease in the growth of colon cancer cells. These results suggest that the hnRNP K-NUF2 axis is important for the mitotic process and proliferation of colon cancer cells and that this axis could be a target for the therapy of colon cancer. - Highlights: • hnRNP K is required for the tumorigenicity of colon cancer cells. • hnRNP K binds to the promoter region of NUF2 and activates its transcription. • NUF2 expression is correlated with hnRNP K expression in colorectal cancer tissue. • hnRNP K and NUF2 are required for metaphase chromosome alignment. • The hnRNP K-NUF2 axis is important for the proliferation of colon cancer cells.« less

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate.

PubMed

Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-09-27

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes.

Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate

PubMed Central

Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

2016-01-01

Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes. PMID:27557515

75 FR 3862 - Photography in Public Exhibit Space

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-25

... exhibit cases for displaying the Charters and other NAE documents to provide better clarity for viewing... documents from damaging exposure to light sources. NARA used filters in earlier exhibit cases. Although... exhibit lighting at its source to remove all ultraviolet and high energy visible light. One commenter...

Considering High-Tech Exhibits?

ERIC Educational Resources Information Center

Routman, Emily

1994-01-01

Discusses a variety of high-tech exhibit media used in The Living World, an educational facility operated by The Saint Louis Zoo. Considers the strengths and weaknesses of holograms, video, animatronics, video-equipped microscopes, and computer interactives. Computer interactives are treated with special attention. (LZ)

Utilization of preventive services by pregnant women in Jerusalem--a cross sectional study.

PubMed

Ellencweig, A Y; Ritter, M; Peleg-Olavsky, E; Tamir, D

1990-09-01

A study was made of health service utilization patterns during pregnancy of 279 young mothers, a representative sample of the Jewish population in Jerusalem. Only 47% reported that they used the municipal family health centers (FHCs) for prenatal care. Some 82% reported that they had resorted to more than one source of care during pregnancy. Sources other than the FHC were: regular Sick Fund doctor service (33%); private practitioners (25%); hospital-based services (25%). Among the FHC users, there was an unexpectedly high percentage of women of Asian-African origin and of those living in remote neighborhoods. Under-utilization was frequent among wealthy women, those with higher education and members of the Orthodox religious sector. While there was general satisfaction with the service, lower gratification was associated with higher utilization. This phenomenon may intimate that there may be a process of negative selection among women who use the service, when other alternatives are not readily available.

A Salamander Tale: Effective Exhibits and Attitude Change

ERIC Educational Resources Information Center

Rollins, Jeffrey; Watson, Sunnie Lee

2017-01-01

Little information exists regarding intention behind the design and development of Extension outreach and educational exhibits. An evaluation of response to the exhibit "A Salamander Tale" indicates that the methods used to develop the exhibit resulted in an effective way to present information to an adult audience. Survey questions were…

Asia: A Guide to Traveling Exhibitions and Displays.

ERIC Educational Resources Information Center

ASIA Society, New York, NY.

The resource guide provides information on sources of exhibitions and materials for display which depict the peoples and culture of Asia. The major portion of the booklet represents one of the original Asia Society's exhibitions. The first section suggests several organizations which offer traveling exhibitions. Under each organization the kinds…

Poster exhibitions at national conferences: education or farce?

PubMed

Salzl, Gabriele; Gölder, Stefan; Timmer, Antje; Marienhagen, Jörg; Schölmerich, Jürgen; Grossmann, Johannes

2008-02-01

The so-called poster exhibition is an established element of medical meetings which often receives little attention. The aim of this study was to analyze the organization, acceptance and value of poster exhibitions. Interview based study conducted during the annual meeting of a German specialist medical conference. A total of 247 attendees, poster authors and "poster chairpersons" were interviewed. Attendance at poster exhibitions was documented, the poster review and award process analyzed, and abstracts assessed for redundancy of presentation. Participation in poster exhibitions was very low. Despite this, their scientific value was esteemed high by young authors and the poster chairpersons. Almost a third (29.4%) of posters had been displayed at other meetings. Several attendees (55.4%) and poster presenters (49.1%) say they would welcome the opportunity for personal one-on-one discussion at the poster in addition to poster viewing. The option of additional personal discussion with the poster presenter may lead to an increase of the rather modest participation of attendees at poster exhibitions. Poster exhibitions are of value in particular for young scientists and poster chairpersons.

77 FR 31909 - Culturally Significant Objects Imported for Exhibition

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

... exhibition ``50th Anniversary Remembrance of the Tragedy at Orly,'' imported from abroad by the High Museum of Art for temporary exhibition within the United States, is of cultural significance. The object is... exhibition or display of the exhibit object at the High Museum of Art in Atlanta, Georgia from on or about...

Effect of a myosin regulatory light chain mutation K104E on actin-myosin interactions.

PubMed

Duggal, D; Nagwekar, J; Rich, R; Huang, W; Midde, K; Fudala, R; Das, H; Gryczynski, I; Szczesna-Cordary, D; Borejdo, J

2015-05-15

Familial hypertrophic cardiomyopathy (FHC) is the most common cause of sudden cardiac death in young individuals. Molecular mechanisms underlying this disorder are largely unknown; this study aims at revealing how disruptions in actin-myosin interactions can play a role in this disorder. Cross-bridge (XB) kinetics and the degree of order were examined in contracting myofibrils from the ex vivo left ventricles of transgenic (Tg) mice expressing FHC regulatory light chain (RLC) mutation K104E. Because the degree of order and the kinetics are best studied when an individual XB makes a significant contribution to the overall signal, the number of observed XBs in an ex vivo ventricle was minimized to ∼20. Autofluorescence and photobleaching were minimized by labeling the myosin lever arm with a relatively long-lived red-emitting dye containing a chromophore system encapsulated in a cyclic macromolecule. Mutated XBs were significantly better ordered during steady-state contraction and during rigor, but the mutation had no effect on the degree of order in relaxed myofibrils. The K104E mutation increased the rate of XB binding to thin filaments and the rate of execution of the power stroke. The stopped-flow experiments revealed a significantly faster observed dissociation rate in Tg-K104E vs. Tg-wild-type (WT) myosin and a smaller second-order ATP-binding rate for the K104E compared with WT myosin. Collectively, our data indicate that the mutation-induced changes in the interaction of myosin with actin during the contraction-relaxation cycle may contribute to altered contractility and the development of FHC. Copyright © 2015 the American Physiological Society.

Suppressive effects of acid-forming diet against the tumorigenic potential of pioglitazone hydrochloride in the urinary bladder of male rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Keiichiro, E-mail: Sato_Keiichiro@takeda.co.jp; Awasaki, Yasuyuki; Kandori, Hitoshi

Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonist, was administered orally for 85 weeks at 16 mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manualmore » counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats.« less

Suppressive effects of acid-forming diet against the tumorigenic potential of pioglitazone hydrochloride in the urinary bladder of male rats.

PubMed

Sato, Keiichiro; Awasaki, Yasuyuki; Kandori, Hitoshi; Tanakamaru, Zen-Yo; Nagai, Hirofumi; Baron, David; Yamamoto, Masaki

2011-03-15

Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, was administered orally for 85 weeks at 16 mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manual counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats. Copyright © 2011 Elsevier Inc. All rights reserved.

32 CFR 705.26 - Exhibit availability report.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Exhibit availability report. 705.26 Section 705.26 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES NAVY REGULATIONS AND OFFICIAL RECORDS PUBLIC AFFAIRS REGULATIONS § 705.26 Exhibit availability report. (a) A center...

Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

PubMed Central

2012-01-01

Background Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Methods Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). Conclusions We characterized a self-renewing subpopulation of CICs found among four well known human

Alan Bean Art Exhibit

NASA Image and Video Library

2009-07-19

NASA Apollo 12 Astronaut and Artist Alan Bean gives remarks at the opening of the exhibit "Alan Bean: Painting Apollo, First Artist on Another World" at the National Air and Space Museum, Monday, July 20, 2009 in Washington. The show opening coincided with the 40th anniversary celebration of Apollo. Photo Credit: (NASA/Bill Ingalls)

[Energy education exhibits for Insights El Paso Science Museum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shubinski, R.

The grant in question, DE-FG03-94ER75954, was awarded to Insights El Paso Science Museum to build key exhibits. These exhibits helped the Museum fulfill its mission to ``promote curiosity and stimulate interest by exploratory, entertaining, exciting, and participatory learning in a broad range of scientific disciplines to persons of all ages regionally and internationally.`` There are several current Board of Directors members who also were Board members during the grant period and who helped construct some of the exhibits. Through speaking with them and reviewing minutes of Board meetings during 1994, it has been determined that seven of the ten proposedmore » exhibits were constructed, with an eighth exhibit constructed as an alternative. Photos of seven of the exhibits and preliminary sketches of some are attached. Following is a list of the constructed exhibits: Hot or Cold, Give and Take, Conduction, Convection, Sources of Energy, Wind Generator, Solar Tracker, and Perpetual Motion.« less

19 CFR 212.11 - Net worth exhibit.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Net worth exhibit. 212.11 Section 212.11 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE IMPLEMENTATION OF THE EQUAL ACCESS TO JUSTICE ACT Information Required From Applicants § 212.11 Net worth exhibit...

32 CFR 705.25 - Navy Exhibit Center.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Navy Exhibit Center. 705.25 Section 705.25 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY UNITED STATES NAVY REGULATIONS AND OFFICIAL RECORDS PUBLIC AFFAIRS REGULATIONS § 705.25 Navy Exhibit Center. (a) The center is a...

Alan Bean Art Exhibit

NASA Image and Video Library

2009-07-19

Former NASA Astronaut and U.S. Senator John Glenn is seen at the opening of the exhibit "Alan Bean: Painting Apollo, First Artist on Another World" at the National Air and Space Museum, Monday, July 20, 2009 in Washington. The show opening coincided with the 40th anniversary celebration of Apollo. Photo Credit: (NASA/Carla Cioffi)

Sphere-derived tumor cells exhibit impaired metastasis by a host-mediated quiescent phenotype

PubMed Central

Bleau, Anne-Marie; Zandueta, Carolina; Redrado, Miriam; Martínez-Canarias, Susana; Larzábal, Leyre; Montuenga, Luis M.

2015-01-01

The spread of lung cancer cells to distant sites represents a common event associated with poor prognosis. A fraction of tumor cells named cancer stem cells (CSCs) have the ability to overcome therapeutic stress and remain quiescent. However, whether these CSCs have also the capacity to initiate and sustain metastasis remains unclear. Here, we used tumor sphere cultures (TSC) isolated from mouse and human lung cancer models to enrich for CSCs, and assessed their metastatic potential as compared to non-CSCs. As expected, TSC overexpressed a variety of stem cell markers and displayed chemoresistance. The CSC phenotype of TSC was confirmed by their higher growth ability in soft agar and tumorigenic potential in vivo, despite their reduced in vitro cell growth kinetics. Surprisingly, the appearance of spontaneous lung metastases was strongly delayed in mice injected with TSC as compared to non-TSC cells. Similarly, this finding was confirmed in several other models of metastasis, an effect associated with a retarded colonization activity. Interestingly, such delay correlated with a quiescent phenotype whose underlined mechanisms included an increase in p27 protein and lower phospho-ERK1/2 levels. Thus, these data suggest that cells enriched for CSC properties display an impaired metastatic activity, a finding with potential clinical implications. PMID:26318423

77 FR 14562 - Information Collection Request Sent to the Office of Management and Budget (OMB) for Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-R5-FHC-2012-N045; FXFR13340500000L4-123...; Horseshoe Crab Tagging Program AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice; request for comments. SUMMARY: We (U.S. Fish and Wildlife Service) have sent an Information Collection Request (ICR) to...

78 FR 5481 - Quagga Mussel Strategic Planning Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-HQ-FHC-2013-N008; 94140-1341-0000-N5] Quagga Mussel Strategic Planning Meeting AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of meeting. SUMMARY: This notice announces a meeting to gather information for planning an FY13 strategy to...

The Eugenides Foundation Interactive Exhibition of Science and Technology

NASA Astrophysics Data System (ADS)

Kontogiannis, Ioannis

2010-01-01

The Interactive Exhibition of Science and Technology is installed in an area of 1200 m2 at the Eugenides Foundation. 65 interactive exhibits, designed by the "Cites des Science et de l' Industrie" are organised in themes, stimulate the visitors' mind and provoke scientific thinking. Parallel activities take place inside the exhibition, such as live science demonstrations, performed by young scientists. Extra material such as news bulletins (short news, science comics and portraits), educational paths and treasure-hunting based games, all available online as well, are prepared on a monthly basis and provided along with the visit to the exhibition. Through these exhibits and activities, scientific facts are made simple and easy to comprehend using modern presentation tools. We present details on how this exhibition acts complementary to the science education provided by schools, making it a highly sophisticated educational tool.

Against the Odds Exhibition Opens

MedlinePlus

... the National Institutes of Health in Bethesda, Md. Photo courtesy of Bill Branson NIH Director Dr. Elias ... addresses visitors to the opening of the exhibition. Photo courtesy of Bill Branson Brothers Niko and Theo ...

Evolutionary Dynamics of Influenza A Viruses in US Exhibition Swine

PubMed Central

Nelson, Martha I.; Wentworth, David E.; Das, Suman R.; Sreevatsan, Srinand; Killian, Mary L.; Nolting, Jacqueline M.; Slemons, Richard D.; Bowman, Andrew S.

2016-01-01

The role of exhibition swine in influenza A virus transmission was recently demonstrated by >300 infections with influenza A(H3N2) variant viruses among individuals who attended agricultural fairs. Through active influenza A virus surveillance in US exhibition swine and whole-genome sequencing of 380 isolates, we demonstrate that exhibition swine are actively involved in the evolution of influenza A viruses, including zoonotic strains. First, frequent introduction of influenza A viruses from commercial swine populations provides new genetic diversity in exhibition pigs each year locally. Second, genomic reassortment between viruses cocirculating in exhibition swine increases viral diversity. Third, viral migration between exhibition swine in neighboring states demonstrates that movements of exhibition pigs contributes to the spread of genetic diversity. The unexpected frequency of viral exchange between commercial and exhibition swine raises questions about the understudied interface between these populations. Overall, the complexity of viral evolution in exhibition swine indicates that novel viruses are likely to continually reemerge, presenting threats to humans. PMID:26243317

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

PubMed

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R K; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-09-04

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.

Thrombomodulin reduces tumorigenic and metastatic potential of lung cancer cells by up-regulation of E-cadherin and down-regulation of N-cadherin expression.

PubMed

Zheng, Nana; Huo, Zihe; Zhang, Bin; Meng, Mei; Cao, Zhifei; Wang, Zhiwei; Zhou, Quansheng

2016-08-05

Thrombomodulin (TM) is an endothelial cell membrane protein and plays critical roles in anti-thrombosis, anti-inflammation, vascular endothelial protection, and is traditionally regarded as a "vascular protection god". In recent years, although TM has been reported to be down-regulated in a variety of malignant tumors including lung cancer, the role and mechanism of TM in lung cancer are enigmatic. In this study, we found that induction of TM overexpression by cholesterol-reducing drug atorvastatin significantly diminished the tumorigenic capability of the lung cancer cells. Moreover, we demonstrated that TM overexpression caused G0/G1 phase arrest and markedly reduced the colony forming capability of the cells. Furthermore, overexpression of TM inhibited cell migration and invasion. Consistently, depletion of TM promoted cell growth, reduced the cell population at the G0/G1 phase, and enhanced cell migratory ability. Mechanistic study revealed that TM up-regulated E-cadherin but down-regulated N-cadherin expression, resulting in reversal of epithelial-mesenchymal transition (EMT) in the lung cancer cells. Moreover, silencing TM expression led to decreased E-cadherin and increased N-cadherin. Taken together, our study suggests that TM functions as a tumor suppressive protein, providing a conceptual framework for inducing TM overexpression as a sensible strategy and approach for novel anti-lung cancer drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Two populations of double minute chromosomes harbor distinct amplicons, the MYC locus at 8q24.2 and a 0.43-Mb region at 14q24.1, in the SW613-S human carcinoma cell line.

PubMed

Guillaud-Bataille, M; Brison, O; Danglot, G; Lavialle, C; Raynal, B; Lazar, V; Dessen, P; Bernheim, A

2009-01-01

High-level amplifications observed in tumor cells are usually indicative of genes involved in oncogenesis. We report here a high resolution characterization of a new amplified region in the SW613-S carcinoma cell line. This cell line contains tumorigenic cells displaying high-level MYC amplification in the form of double minutes (DM(+) cells) and non tumorigenic cells exhibiting low-level MYC amplification in the form of homogeneously staining regions (DM(-) cells). Both cell types were studied at genomic and functional levels. The DM(+) cells display a second amplification, corresponding to the 14q24.1 region, in a distinct population of DMs. The 0.43-Mb amplified and overexpressed region contains the PLEK2, PIGH, ARG2, VTI1B, RDH11, and ZFYVE26 genes. Both amplicons were stably maintained upon in vitro and in vivo propagation. However, the 14q24.1 amplicon was not found in cells with high-level MYC amplification in the form of HSRs, either obtained after spontaneous integration of endogenous DM MYC copies or after transfection of DM(-) cells with a MYC gene expression vector. These HSR-bearing cells are highly tumorigenic. The 14q24.1 amplification may not play a role in malignancy per se but might contribute to maintaining the amplification in the form of DMs. Copyright 2009 S. Karger AG, Basel.

Repression of hTERT transcription by the introduction of chromosome 3 into human oral squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishio, Sachiyo; Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503; Ohira, Takahito

Telomerase is a ribonucleoprotein enzyme that maintains telomere length. Telomerase activity is primarily attributed to the expression of telomerase reverse transcriptase (TERT). It has been reported that introduction of an intact human chromosome 3 into the human oral squamous cell carcinoma cell line HSC3 suppresses the tumorigenicity of these cells. However, the mechanisms that regulate tumorigenicity have not been elucidated. To determine whether this reduction in tumorigenicity was accompanied by a reduction in telomerase activity, we investigated the transcriptional activation of TERT in HSC3 microcell hybrid clones with an introduced human chromosome 3 (HSC3#3). HSC#3 cells showed inhibition of hTERT transcriptionmore » compared to that of the parental HSC3 cells. Furthermore, cell fusion experiments showed that hybrids of HSC3 cells and cells of the RCC23 renal carcinoma cell line, which also exhibits suppression of TERT transcription by the introduction of human chromosome 3, also displayed suppressed TERT transcription. These results suggested that human chromosome 3 may carry functionally distinct, additional TERT repressor genes. - Highlights: • hTERT mRNA expression level decreased in the chromosome 3 introduced HSC3 clones. • hTERT mRNA expression level was tend to suppressed in HSC3 and RCC23 hybrid cells. • We provide evidence that human chromosome 3 carries at least two distinct hTERT regulatory factors.« less

[Effect of polychromatic visible light combined with infrared radiation on tumorigenicity of murine hepatoma cells and their sensitivity to lytic activity of natural killers].

PubMed

Filatova, N A; Kniazev, N A; Kosheverova, V V; Shatrova, A N; Samoĭlova, K A

2013-01-01

Tumorigenicity of murine hepatoma cells (MH22a) and their sensitivity to lysis by natural killers (NKs) have been studied after exposure to polychromatic visible and infrared light (VIS-IR, 480-3400 nm, 40 mW/cm2), similar to the terrestrial solar spectrum without its minor UV component, in order to elucidate the involvement of this important environmental and physiotherapeutic factor in regulation of the anti-tumor defense system. The MH22 cells were in vitro exposed to VIS-IR light and their sensitivity to lytic activity of NKs was evaluated. We found that sensitivity of MH22a cells to lysis by NKs after exposure to VIS-IR light at a dose of 4.8 J/cm2 increased 1.5-2 times, while it did not change after exposure to a dose of 9.6 J/cm2 at all ratios (1 : 5-1 : 50) of the number of NKs (effectors) to that of hepatoma cells (targets). The increase in the sensitivity of hepatoma cells to NKs was accompanied by structural changes of cell surface: the capability of supramembraneous glycoproteins (glycocalix) to sorb the vital dye alcian blue (AB) was significantly lower as compared with the unexposed cells of control group. However, no changes in AB sorption was revealed in hepatoma cells exposed to the light at a dose 9.6 J/cm2. Tumorigenicity of photo-irradiated MH22a cells has been studied in the in vivo experiments. Light-exposed (4.8 and 9.6 J/cm2) and intact hepatoma cells were transplanted into syngenic mice C3HA. Tumor volumes 25 days after transplantation proved to be smaller after exposure to the light at both doses than in the control group (4-4.5 times and 2.5-4 times, respectively), which correlated with the increase in the sensitivity to lisys by NKs and decrease in the AB sorption only after light exposure at dose 4.8 J/cm2. Using the flow cytometry method we could show that VIS-IR light at the applied doses did not interfere with the distribution of hepatoma cells over the cycle phases and thus deceleration of the tumor growth was not associated with

Black Holes Traveling Exhibition: This Time, It's Personal.

NASA Astrophysics Data System (ADS)

Dussault, Mary E.; Braswell, E. L.; Sunbury, S.; Wasser, M.; Gould, R. R.

2012-01-01

How can you make a topic as abstract as black holes seem relevant to the life of the average museum visitor? In 2009, the Harvard-Smithsonian Center for Astrophysics developed a 2500 square foot interactive museum exhibition, "Black Holes: Space Warps & Time Twists,” with funding from the National Science Foundation and NASA. The exhibition has been visited by more than a quarter million museum-goers, and is about to open in its sixth venue at the Reuben H. Fleet Science Center in San Diego, California. We have found that encouraging visitors to adopt a custom black hole explorer's identity can help to make the science of black holes more accessible and meaningful. The Black Holes exhibition uses networked exhibit technology that serves to personalize the visitor experience, to support learning over time including beyond the gallery, and to provide a rich quantitative source of embedded evaluation data. Visitors entering the exhibition create their own bar-coded "Black Holes Explorer's Card” which they use throughout the exhibition to collect and record images, movies, their own predictions and conclusions, and other black hole artifacts. This digital database of personal discoveries grows as visitors navigate through the gallery, and an automated web-content authoring system creates a personalized online journal of their experience that they can access once they get home. We report here on new intriguing results gathered from data generated by 112,000 visitors across five different venues. For example, an initial review of the data reveals correlations between visitors’ black hole explorer identity choices and their engagement with the exhibition. We will also discuss correlations between learning gains and personalization.

AWEA WINDPOWER 2019 Conference & Exhibition

Science.gov Websites

than go through menu items. Book a Booth Learn Exhibit Sponsor Register AWEA Wind Power May 20-23 2019 . Book Your Booth Sponsor Sponsoring AWEA WINDPOWER 2019 gives you the opportunity to broadcast your

77 FR 7174 - Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-R4-FHC-2012-N030; FVHC98130406900Y4-XXX-FF04G01000] Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and Environmental Assessment AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of availability and request...

A library synthesis of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as anti-tumor agents.

PubMed

Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

2004-09-06

As a result of a hit-to-lead program using a technique of solution-phase parallel synthesis, a highly potent (2,4-dimethoxyphenyl)-[6-(3-fluorophenyl)-4-hydroxy-3-methylbenzofuran-2-yl]methanone (15b) was synthesized as an optimized derivative of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which was discovered as a screening hit from small-molecule libraries and exhibited selective cytotoxicity against a tumorigenic cell line.

African Past: Migrant Present. A Guide to the Exhibition.

ERIC Educational Resources Information Center

Twining, Mary Arnold; Roark-Calnek, Sue

This exhibit guide describes an exhibition of African folk arts produced by seasonal migrant farmworkers in western New York State. Workers come from the American South, Haiti, Puerto Rico, and Jamaica. The exhibition pieces were collected through the BOCES Geneseo Migrant Center's Folk Arts Program and Creative Artists Migrant Program Services…

78 FR 7849 - Culturally Significant Objects Imported for Exhibition

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-04

... Century,'' imported from abroad for temporary exhibition within the United States, are of cultural... also determine that the exhibition or display of the exhibit objects at The Yale Center for British Art..., Bureau of Educational and Cultural Affairs, Department of State. [FR Doc. 2013-02401 Filed 2-1-13; 8:45...

Environment construction and bottleneck breakthrough in the improvement of wisdom exhibition

NASA Astrophysics Data System (ADS)

Zhang, Jiankang

2017-08-01

Wisdom exhibition is an inexorable trend in convention and exhibition industry in China. Information technology must be utilized by exhibition industry to achieve intelligent application and wisdom management, breaking the limitation of time as well as space, which raise the quality of exhibition service and level of operation to a totally new standard. Accordingly, exhibition industry should optimize mobile internet, a fundamental technology platform, during the advancing process of wisdom exhibition and consummate the combination among three plates including wisdom connection of information, wisdom exhibition environment and wisdom application of technology. Besides, the industry should realize the wisdom of external environment including wisdom of exhibition city, exhibition place, exhibition resource deal etc and break through bottle-neck in construction of wisdom exhibition industry, which includes construction of big data center, development of Mobile Internet application platform, promotion of information construction, innovative design of application scenarios.

CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.

PubMed

Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Naïken, Tanesha; Ilc, Karine; Ilk, Karine; Murray, Clare M; Critchlow, Susan E; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

2011-10-04

Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H(+)/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res(-)) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res(-) cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H(+) symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basigin(high) cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy.

CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors

PubMed Central

Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Ilc, Karine; Murray, Clare M.; Critchlow, Susan E.; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

2011-01-01

Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H+/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res−) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res− cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H+ symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basiginhigh cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy. PMID:21930917

Online Cultural Heritage Exhibitions: A Survey of Strategic Issues

ERIC Educational Resources Information Center

Liew, Chern Li

2006-01-01

Purpose: This paper seeks to report findings from a study that looked at a range of strategic issues faced in the development, management and maintenance of online cultural heritage exhibitions. The study examined exhibitions from different types of cultural agencies and asked questions about whether, for instance, the exhibitions are part of the…

76 FR 68808 - Culturally Significant Objects Imported for Exhibition

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... also determine that the exhibition or display of the exhibit objects at the Onassis Cultural Center... Century AD,'' imported from abroad for temporary exhibition within the United States, are of cultural... Cultural Affairs, Department of State. [FR Doc. 2011-28805 Filed 11-4-11; 8:45 am] BILLING CODE 4710-05-P ...

Cosmic Origins: A Traveling Science Exhibit and Education Program

NASA Astrophysics Data System (ADS)

Dusenbery, P. B.; Morrow, C. A.; Harold, J.

2003-12-01

The Space Science Institute of Boulder, Colorado, is developing a 3,000 square-foot traveling exhibition, called Cosmic Origins, which will bring origins-related research and discoveries to students and the American public. Cosmic Origins will have three interrelated exhibit areas: Star Formation, Planet Quest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in "habitable zones" around other stars; and finally they will be able to learn about the wide range of conditions for life on Earth and how scientists are looking for signs of life beyond Earth. Visitors will also learn about the tools scientists' use, such as space-based and ground-based telescopes, to improve our understanding of the cosmos. Exhibit content will address age-old questions that form the basis of NASA's Origins and Astrobiology programs: Where did we come from? Are we alone? In addition to the exhibit, our project will include workshops for educators and docents at host sites, as well as a public Web site that will use a virtual rendering of exhibit content. The exhibit's size will permit it to visit medium sized museums in underserved regions of the country. It will begin its 3-year tour to 9 host museums and science centers in early 2005. A second 3-year tour is also planned for 2008. The Association of Science-Technology Centers (ASTC) will manage the exhibit's national tour. Current partners in the Cosmic Origins project include ASTC, the Denver Museum of Nature and Science, Lawrence Hall of Science, NASA Astrobiology Institute, NASA missions (e.g. PlanetQuest, SIRTF, and Kepler), New York Hall of Science, the SETI Institute, and the Space Telescope Science Institute. The exhibition is supported by grants from NSF and NASA. This report will focus on the Planet Quest part of the exhibition.

Translating land use science to a museum exhibit.

PubMed

Arce-Nazario, Javier A

2016-01-01

For land use science to engage the general public it must successfully translate its concepts and conclusions and make them public outside of traditional scientific venues. Here we explore science-art exhibits, which blend artistic presentations with specific scientific data or themes, as a possible effective way of communicating scientific information and disrupting misconceptions. We describe the process of producing a science-art exhibit on remote sensing and Puerto Rican landscape history from 1937 to the present, sited at a rural Puerto Rican community museum, and examine the visitor experience and educational outcomes of the museum exhibit through analysis of survey data. The exhibit project engaged undergraduate students from a variety of academic backgrounds, introduced land use science concepts to the public in an engaging format, and was effective at reshaping visitors' misconceptions of Puerto Rico's landscape change history.

miRNA-regulated delivery of lincRNA-p21 suppresses β-catenin signaling and tumorigenicity of colorectal cancer stem cells.

PubMed

Wang, Jun; Lei, Zeng-jie; Guo, Yan; Wang, Tao; Qin, Zhong-yi; Xiao, Hua-liang; Fan, Li-lin; Chen, Dong-feng; Bian, Xiu-wu; Liu, Jia; Wang, Bin

2015-11-10

Cancer stem cells (CSCs) are key cellular targets for effective cancer therapy, due to their critical roles in cancer progression and chemo/radio-resistance. Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) are important players in the biology of cancers. However, it remains unknown whether lncRNAs could be exploited to target CSCs. We report that large intergenic non-coding RNA p21 (lincRNA-p21) is a potent suppressor of stem-like traits of CSCs purified from both primary colorectal cancer (CRC) tissues and cell lines. A novel lincRNA-p21-expressing adenoviral vector, which was armed with miRNA responsive element (MRE) of miR-451 (Ad-lnc-p21-MRE), was generated to eliminate CRC CSCs. Integration of miR-451 MREs into the adenovirus efficiently delivered lincRNA-p21 into CSCs that contained low levels of miR-451. Moreover, lincRNA-p21 inhibited the activity of β-catenin signaling, thereby attenuating the viability, self-renewal, and glycolysis of CSCs in vitro. By limiting dilution and serial tumor formation assay, we demonstrated that Ad-lnc-p21-MRE significantly suppressed the self-renewal potential and tumorigenicity of CSCs in nude mice. Importantly, application of miR-451 MREs appeared to protect normal liver cells from off-target expression of lincRNA-p21 in both tumor-bearing and naïve mice. Taken together, these findings suggest that lncRNAs may be promising therapeutic molecules to eradicate CSCs and MREs of tumor-suppressor miRNAs, such as miR-451, may be exploited to ensure the specificity of CSC-targeting strategies.

Cancer stem cells: impact, heterogeneity, and uncertainty

PubMed Central

Magee, Jeffrey A.; Piskounova, Elena; Morrison, Sean J.

2015-01-01

The differentiation of tumorigenic cancer stem cells into non-tumorigenic cancer cells confers heterogeneity to some cancers beyond that explained by clonal evolution or environmental differences. In such cancers, functional differences between tumorigenic and non-tumorigenic cells influence response to therapy and prognosis. However, it remains uncertain whether the model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells. In cancers with rapid genetic change, reversible changes in cell states, or biological variability among patients the stem cell model may not be readily testable. PMID:22439924

The Local Fair Exhibit--Still A Valuable Public Relations Tool

ERIC Educational Resources Information Center

Smith, Roswell H., Jr.

1977-01-01

Agricultural exhibits at fairs inform the public about the activities of vocational agriculture programs and Future Farmers of America chapters and are important in gaining public support for vocational agriculture. This article describes some elements involved in a fair exhibit: the exhibit committee, the exhibit design, and the use of color and…

Art exhibit focuses on African astronomy

NASA Astrophysics Data System (ADS)

Showstack, Randy

2012-07-01

Connections between Africans and astronomy are the focus of a new exhibition in the National Museum of African Art in Washington, D. C. "African Cosmos: Stellar Arts," which includes artwork, cultural items, and scientific displays from ancient to contemporary times, is the first major exhibit "that brings together arts and science focused on Africa's contribution to keen observations of the heavens over time," curator Christine Mullen Kreamer said at a 20 June news briefing. Among the exhibit's nearly 100 objects are an ancient Egyptian mummy board that includes a representation of the sky goddess Nut, sculptures by the Dogon people of Mali depicting figures in relation to the cosmos, a video that uses data from two square degrees of the Hubble Space Telescope Cosmic Evolution Survey, and a nearly floor-to-ceiling "Rainbow Serpent" constructed of plastic containers by Benin artist Hazoume. An untitled acrylic painting (Figure 1) by South African Gavin Jantjes evokes a myth of the Khoi San people of southern Africa, as it portrays a girl throwing evening fire embers into the night sky, where they remained as the Milky Way.

Effects of respirator ambient air cooling on thermophysiological responses and comfort sensations.

PubMed

Caretti, David M; Barker, Daniel J

2014-01-01

This investigation assessed the thermophysiological and subjective impacts of different respirator ambient air cooling options while wearing chemical and biological personal protective equipment in a warm environment (32.7 ± 0.4°C, 49.6 ± 6.5% RH). Ten volunteers participated in 90-min heat exposure trials with and without respirator (Control) wear and performed computer-generated tasks while seated. Ambient air cooling was provided to respirators modified to blow air to the forehead (FHC) or to the forehead and the breathing zone (BZC) of a full-facepiece air-purifying respirator using a low-flow (45 L·min(-1)) mini-blower. An unmodified respirator (APR) trial was also completed. The highest body temperatures (TTY) and least favorable comfort ratings were observed for the APR condition. With ambient cooling over the last 60 min of heat exposure, TTY averaged 37.4 ± 0.6°C for Control, 38.0 ± 0.4°C for APR, 37.8 ± 0.5°C for FHC, and 37.6 ± 0.7°C for BZC conditions independent of time. Both the FHC and BZC ambient air cooling conditions reduced facial skin temperatures, reduced the rise in body temperatures, and led to more favorable subjective comfort and thermal sensation ratings over time compared to the APR condition; however statistical differences among conditions were inconsistent. Independent of exposure time, average breathing apparatus comfort scores with BZC (7.2 ± 2.5) were significantly different from both Control (8.9 ± 1.4) and APR (6.5 ± 2.2) conditions when ambient cooling was activated. These findings suggest that low-flow ambient air cooling of the face under low work rate conditions and mild hyperthermia may be a practical method to minimize the thermophysiological strain and reduce perceived respirator discomfort.

Fuzzy clustering evaluation of the discrimination power of UV-Vis and (±) ESI-MS detection system in individual or coupled RPLC for characterization of Ginkgo Biloba standardized extracts.

PubMed

Medvedovici, Andrei; Albu, Florin; Naşcu-Briciu, Rodica Domnica; Sârbu, Costel

2014-02-01

Discrimination power evaluation of UV-Vis and (±) electrospray ionization/mass spectrometric techniques, (ESI-MS) individually considered or coupled as detectors to reversed phase liquid chromatography (RPLC) in the characterization of Ginkgo Biloba standardized extracts, is used in herbal medicines and/or dietary supplements with the help of Fuzzy hierarchical clustering (FHC). Seventeen batches of Ginkgo Biloba commercially available standardized extracts from seven manufacturers were measured during experiments. All extracts were within the criteria of the official monograph dedicated to dried refined and quantified Ginkgo extracts, in the European Pharmacopoeia. UV-Vis and (±) ESI-MS spectra of the bulk standardized extracts in methanol were acquired. Additionally, an RPLC separation based on a simple gradient elution profile was applied to the standardized extracts. Detection was made through monitoring UV absorption at 220 nm wavelength or the total ion current (TIC) produced through (±) ESI-MS analysis. FHC was applied to raw, centered and scaled data sets, for evaluating the discrimination power of the method with respect to the origins of the extracts and to the batch to batch variability. The discrimination power increases with the increase of the intrinsic selectivity of the spectral technique being used: UV-VisFHC algorithm produces better classification. However, PCA and CA may be successfully applied to discriminate between the manufacturing sources of the standardized extracts, and at some extent, to monitor the inter-batch variability. Although the chromatographic dimension sensibly contributes to the discrimination power, spectral MS data may be used as the lone powerful holistic alternative in characterization of standardized Ginkgo Biloba extracts. © 2013 Elsevier B

7 CFR Exhibit C to Subpart C of... - Checklist of Visual Exhibits and Documentation for RRH, RCH, and LH Proposals

Code of Federal Regulations, 2010 CFR

2010-01-01

... RRH, RCH, and LH Proposals C Exhibit C to Subpart C of Part 1924 Agriculture Regulations of the... REPAIR Planning and Performing Site Development Work Pt. 1924, Subpt. C, Exh. C Exhibit C to Subpart C of... the required information will be sufficient. C. Property Survey Map. A current survey map of the...

The medial prefrontal cortex exhibits money illusion

PubMed Central

Weber, Bernd; Rangel, Antonio; Wibral, Matthias; Falk, Armin

2009-01-01

Behavioral economists have proposed that money illusion, which is a deviation from rationality in which individuals engage in nominal evaluation, can explain a wide range of important economic and social phenomena. This proposition stands in sharp contrast to the standard economic assumption of rationality that requires individuals to judge the value of money only on the basis of the bundle of goods that it can buy—its real value—and not on the basis of the actual amount of currency—its nominal value. We used fMRI to investigate whether the brain's reward circuitry exhibits money illusion. Subjects received prizes in 2 different experimental conditions that were identical in real economic terms, but differed in nominal terms. Thus, in the absence of money illusion there should be no differences in activation in reward-related brain areas. In contrast, we found that areas of the ventromedial prefrontal cortex (vmPFC), which have been previously associated with the processing of anticipatory and experienced rewards, and the valuation of goods, exhibited money illusion. We also found that the amount of money illusion exhibited by the vmPFC was correlated with the amount of money illusion exhibited in the evaluation of economic transactions. PMID:19307555

Science Museum Exhibits' Summative Evaluation with Knowledge Hierarchy Method

ERIC Educational Resources Information Center

Yasar, Erkan; Gurel, Cem

2016-01-01

It is aimed in this research to measure via knowledge hierarchy the things regarding exhibit themes learned by the visitors of the exhibits and compare them with the purpose that the exhibits are designed for, thereby realizing a summative evaluation of the exhibits by knowledge hierarchy method. The research has been conducted in a children's…

18 CFR 157.14 - Exhibits.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Exhibit G—Flow diagrams showing daily design capacity and reflecting operation with and without proposed facilities added. A flow diagram showing daily design capacity and reflecting operating conditions with only existing facilities in operation. A second flow diagram showing daily design capacity and reflecting...

18 CFR 157.14 - Exhibits.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Exhibit G—Flow diagrams showing daily design capacity and reflecting operation with and without proposed facilities added. A flow diagram showing daily design capacity and reflecting operating conditions with only existing facilities in operation. A second flow diagram showing daily design capacity and reflecting...

18 CFR 157.14 - Exhibits.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Exhibit G—Flow diagrams showing daily design capacity and reflecting operation with and without proposed facilities added. A flow diagram showing daily design capacity and reflecting operating conditions with only existing facilities in operation. A second flow diagram showing daily design capacity and reflecting...

18 CFR 157.14 - Exhibits.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Exhibit G—Flow diagrams showing daily design capacity and reflecting operation with and without proposed facilities added. A flow diagram showing daily design capacity and reflecting operating conditions with only existing facilities in operation. A second flow diagram showing daily design capacity and reflecting...

18 CFR 157.14 - Exhibits.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Exhibit G—Flow diagrams showing daily design capacity and reflecting operation with and without proposed facilities added. A flow diagram showing daily design capacity and reflecting operating conditions with only existing facilities in operation. A second flow diagram showing daily design capacity and reflecting...

An Astrobiology Microbes Exhibit and Education Module

NASA Technical Reports Server (NTRS)

Lindstrom, Marilyn M.; Allen, Jaclyn S.; Stocco, Karen; Tobola, Kay; Olendzenski, Lorraine

2001-01-01

Telling the story of NASA-sponsored scientific research to the public in exhibits is best done by partnerships of scientists and museum professionals. Likewise, preparing classroom activities and training teachers to use them should be done by teams of teachers and scientists. Here we describe how we used such partnerships to develop a new astrobiology augmentation to the Microbes! traveling exhibit and a companion education module. "Additional information is contained in the original extended abstract."

International Space Station exhibit

NASA Technical Reports Server (NTRS)

2000-01-01

The International Space Station (ISS) exhibit in StenniSphere at John C. Stennis Space Center in Hancock County, Miss., gives visitors an up-close look at the largest international peacetime project in history. Step inside a module of the ISS and glimpse how astronauts will live and work in space. Currently, 16 countries contribute resources and hardware to the ISS. When complete, the orbiting research facility will be larger than a football field.

Naturally occurring glucagon-like peptide-2 (GLP-2) receptors in human intestinal cell lines.

PubMed

Sams, Anette; Hastrup, Sven; Andersen, Marie; Thim, Lars

2006-02-17

Although clinical trials with GLP-2 receptor agonists are currently ongoing, the mechanisms behind GLP-2-induced intestinal epithelial growth remain to be understood. To approach the GLP-2 mechanism of action this study aimed to identify intestinal cell lines endogenously expressing the GLP-2 receptor. Here we report the first identification of a cell line endogenously expressing functional GLP-2 receptors. The human intestinal epithelial cell line, FHC, expressed GLP-2 receptor encoding mRNA (RT-PCR) and GLP-2 receptor protein (Western blot). In cultured FHC cells, GLP-2 induced concentration dependent cAMP accumulation (pEC(50)=9.7+/-0.04 (mean+/-S.E.M., n=4)). In addition, a naturally occurring human intestinal fibroblast cell line, 18Co, endogenously expressing GLP-2 receptor encoding mRNA (RT-PCR) and protein (Western blot) was identified. No receptor functionality (binding or G-protein signalling) could be demonstrated in 18Co cells. The identified gut-relevant cell lines provide tools for future clarification of the mechanisms underlying GLP-2-induced epithelial growth.

Bringing Planetary Science to the Public through Traveling Exhibitions

NASA Astrophysics Data System (ADS)

Dusenbery, P. B.

2001-11-01

The Space Science Institute (SSI) of Boulder, Colorado has recently developed two museum exhibits called the Space Weather Center and MarsQuest. It is currently planning to develop another exhibit called Gas Giants. These exhibitions provide research scientists the opportunity to engage in a number of activities that are vital to the success of these major outreach programs. The Space Weather Center was developed in partnership with various research missions at NASA's Goddard Space Flight Center. The focus of the presentation will be on MarsQuest and Gas Giants. MarsQuest is a 5000 square-foot, 3M, traveling exhibition that is now touring the country. The exhibit's 3-year tour will enable millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. The associated planetarium show and education program will also be described, with particular emphasis on workshops to orient museum staff (e.g. museum educators and docents) and workshops for master educators near host museums and science centers. The workshops make innovative connections between the exhibitions interactive experiences and lesson plans aligned with the National Science Education Standards. These exhibit programs are good models for actively involving scientists and their discoveries to help improve informal science education in the museum community and for forging a stronger connection between formal and informal education. The presentation will also discuss how Gas Giants, a proposed 4000 square-foot traveling exhibition on the mysteries and discoveries of the outer planets, will be able to take advantage of the connections and resources that have been developed by the MarsQuest project.

The Particular Aspects of Science Museum Exhibits That Encourage Students' Engagement

NASA Astrophysics Data System (ADS)

Shaby, Neta; Assaraf, Orit Ben-Zvi; Tal, Tali

2017-06-01

This research explores learning in science museums through the most common activity in a science museum—interaction with exhibits. The goal of this study was to characterize the learning behaviors exhibited by students as they engage with interactive exhibits in order to draw insight regarding the design of the exhibits. In order to do so, we used a qualitative method of observation as well as the Visitor Engagement Framework (VEF) model, a visitor-based framework for assessing visitors' learning experiences with exhibits in a science center setting. The combined method produced a framework of nine learning behaviors exhibited during the visitors' interaction with the exhibits, grouped into three categories that reflect increasing levels of engagement and depth of the learning experience. Our research participants consisted of a total 1800 students aged 10-12 (4th, 5th, and 6th graders) who came to the museum with their class for a day visit. We observed nine exhibits, each visited by 200 students. Our observations revealed several design elements that contribute to engagement with exhibits in science museums. For example, exhibits that have familiar activation encourage visitors' interaction, exhibits that facilitate social interaction are more likely to increase engagement, and the highest levels of engagement can be found in exhibits that support large groups.

A Content-Oriented Model for Science Exhibit Engineering

ERIC Educational Resources Information Center

Achiam, Marianne Foss

2013-01-01

Recently, science museums have begun to review their educational purposes and redesign their pedagogies. At the most basic level, this entails accounting for the performance of individual exhibits, and indeed, in some cases, research indicates shortcomings in exhibit design: While often successful in prompting visitors to carry out intended…

Using Museum Exhibits: An Innovation in Experiential Learning

ERIC Educational Resources Information Center

Das, Satarupa

2015-01-01

Museum exhibits can be a tool in experiential learning. While instructors have documented various methods of experiential learning, they have not sufficiently explored such learning from museum exhibits. Museum researchers, however, have long found a satisfying cognitive component to museum visits. This paper narrates the author's design to…

The Development of Validated Museum Exhibits. Final Report.

ERIC Educational Resources Information Center

Nicol, Elizabeth H.

Exhibit development, as conceived in this report, is an evolutionary process, drawing the museum visitor into the collaborative venture of testing and improving the exhibits. The findings of contemporary learning research were put to work in the arrangement of activities and specimens that engaged children through self-instructional sequences. The…

Designing Art Exhibitions in an Educational Virtual World

ERIC Educational Resources Information Center

Julian, June; Crooks, Julian

2011-01-01

Demonstrating the multiple features of the Cerulean Gallery in Second Life, this research report showcases several exemplar exhibits created by students, artists, and museums. Located in The Educational Media Center, a Second Life teaching and social space, the Cerulean Gallery exhibits functioned as case studies that tested its effectiveness as…

DURIP - Upgrade of the Meridian ACAS-470 for Toxicological Research

DTIC Science & Technology

1990-01-18

Flow Cytometry and Fluorescence Recovery After PhotobleachIng. Scanningi Microscopy. 2 14) 21 53 -2163. Li~j. Z-Y, YMEL Sanders. and V W Hu. (1989...riinn’I.~ - correlation with increasing tumorigenicity. Northern an- alysis showed reduced levels of connexin 43 in ce!1 lines Fpi~m~iIisFP - exhibiting...cells to the curcinogenic process", In: Mouse Liver CarcinoQgnesis; 3 Mechanisms and Species Comrarisons, T.J. Slaga, Ed., Alan R. Liss, Inc., New

Evolution of Brazilian Civil-Military Relations: From Pacted Transition to Lula’s Foreign Policy Tool

DTIC Science & Technology

2011-03-01

END TO ESTADO NOVO ............................9 C. AUTHORITARIAN BRAZIL: TWENTY-ONE YEARS OF MILITARY DICTATORSHIP...Escola Superior de Guerra (Superior War College) EMFA Estado -Maior das Forcas Armadas (Joint Chiefs of Staff) FHC Fernando Henrique Cardoso MOD...Brazilian civilian-military relations literature covering the period just after the Estado Novo up to the transition to democracy. This will highlight

A Critical Appraisal of State Level Science Exhibition

ERIC Educational Resources Information Center

Nath, Baiju K.

2007-01-01

Science exhibitions are really great opportunities to students as well as teachers to disseminate knowledge that they have, and to experience a variety of new inventions and innovations that also need wide dissemination. The great significance of exhibition is that it fosters acquisition of different process skills leading to the development of…

34 CFR 101.74 - Exhibits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Exhibits. 101.74 Section 101.74 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION... objection thereto is filed prior to the hearing or unless good cause is shown at the hearing for failure to...

Relationship of follicle size and concentrations of estradiol among cows exhibiting or not exhibiting estrus during a fixed-time AI protocol

USDA-ARS?s Scientific Manuscript database

Cows exhibiting estrus near the time of fixed-time AI had greater pregnancy success than cows showing no estrus. The objective of this study was to determine the relationship between follicle size and peak estradiol concentration between cows that did or did not exhibit estrus during a fixed-time AI...

Vitamin E Protects against Lipid Peroxidation and Rescues Tumorigenic Phenotypes in Cowden/Cowden-like Patient-derived Lymphoblast Cells with Germline SDHx Variants

PubMed Central

Ni, Ying; Eng, Charis

2012-01-01

Purpose Cowden syndrome (CS), a Mendelian autosomal-dominant disorder, predisposes to breast, thyroid, and other cancers. Germline variations in succinate dehydrogenase genes (SDHx) occur in ~10% PTEN mutation-negative CS and CS-like (CSL) individuals (SDHvar+). We previously showed that SDHx variants result in elevated reactive oxygen species (ROS), disruption of nicotinamide adenine dinucleotide (NAD) equilibrium, and destabilization of p53 hence apoptosis resistance in CS/CSL patient-derived lymphoblastoid cells. In the present study, we sought to address the tumorigenic impacts of increased ROS and the potential of protecting SDHvar+ cells with antioxidants. Experimental Design We measured the lipid peroxidation levels in patient-derived SDHvar+ lymphoblastoid cells and sequenced 74 controls or SDHvar+ germline DNA samples for mitochondrial hypervariable region II (HVRII) polymorphisms. SDHvar+ lymphoblastoid cells were treated with various antioxidants to check p53 expression and SubG1 cell population with cell cycle analysis. Results We demonstrated that elevated ROS results in higher lipid peroxidation in SDHvar+ cells. Accumulation of polymorphisms in mitochondrial HVRII were observed in SDHvar+ samples. Interestingly, α-tocopherol (vitamin E) treatment, but not other antioxidants, rescued SDHvar+ cells from apoptosis resistance and protected SDHvar+ cells from oxidative damage such as decreased lipid peroxidation as well as partially recovered p53 expression and NAD/NADH levels. Conclusions We conclude that disruption of complex II due to SDHx variants leads to increased ROS generation, specifically accompanied by lipid peroxidation. The lipid soluble antioxidant α-tocopherol can selectively protect SDHxvar+ cells from oxidative damage, apoptosis resistance, and rebalance redox metabolites NAD/NADH. PMID:22829200

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer

PubMed Central

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R k; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-01-01

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors. PMID:28869585

The Use of Memories in Understanding Interactive Science and Technology Exhibits

NASA Astrophysics Data System (ADS)

Afonso, Ana S.; Gilbert, John K.

2006-10-01

Framed by a “personal constructivist” perspective, this study analyses visitors’ use of spontaneous memories in understanding different types of interactive exhibits, the nature and sources of the retrieved memories, and the way that visitors relate an exhibit analogically to memories of previous exhibits. One hundred and thirteen visitors (either alone or in groups) were observed during their interaction with exhibits and interviewed immediately afterwards. The majority of the retrieved memories were not used in understanding an exhibit; those memories used were mainly semantic and episodic in nature; and exhibits were mainly associated with memories by means of a superficial similarity between them. Suggestions for enhancing the formation of links between visitors’ memories and the understanding of an exhibit intended by the designer of it are made.

The Making of a Museum Exhibition.

ERIC Educational Resources Information Center

Bleecker, Samuel E.

1979-01-01

Discusses the preparation of the Reptile and Amphibian exhibition at the American Museum of Natural History. Various steps involved in developing the ten showcases in a six-year period are presented. (SA)

49 CFR 250.2 - Required exhibits.

Code of Federal Regulations, 2010 CFR

2010-10-01

...; number of units of locomotives, freight cars, and passenger cars owned and leased; principal commodities carried; and identification of the ten most important industries served. (6) As Exhibit 6, statement as to...

49 CFR 250.2 - Required exhibits.

Code of Federal Regulations, 2014 CFR

2014-10-01

...; number of units of locomotives, freight cars, and passenger cars owned and leased; principal commodities carried; and identification of the ten most important industries served. (6) As Exhibit 6, statement as to...

49 CFR 250.2 - Required exhibits.

Code of Federal Regulations, 2012 CFR

2012-10-01

...; number of units of locomotives, freight cars, and passenger cars owned and leased; principal commodities carried; and identification of the ten most important industries served. (6) As Exhibit 6, statement as to...

49 CFR 250.2 - Required exhibits.

Code of Federal Regulations, 2011 CFR

2011-10-01

...; number of units of locomotives, freight cars, and passenger cars owned and leased; principal commodities carried; and identification of the ten most important industries served. (6) As Exhibit 6, statement as to...

49 CFR 250.2 - Required exhibits.

Code of Federal Regulations, 2013 CFR

2013-10-01

...; number of units of locomotives, freight cars, and passenger cars owned and leased; principal commodities carried; and identification of the ten most important industries served. (6) As Exhibit 6, statement as to...

Genome-wide binding of transcription factor ZEB1 in triple-negative breast cancer cells.

PubMed

Maturi, Varun; Enroth, Stefan; Heldin, Carl-Henrik; Moustakas, Aristidis

2018-05-10

Zinc finger E-box binding homeobox 1 (ZEB1) is a transcriptional regulator involved in embryonic development and cancer progression. ZEB1 induces epithelial-mesenchymal transition (EMT). Triple-negative human breast cancers express high ZEB1 mRNA levels and exhibit features of EMT. In the human triple-negative breast cancer cell model Hs578T, ZEB1 associates with almost 2,000 genes, representing many cellular functions, including cell polarity regulation (DLG2 and FAT3). By introducing a CRISPR-Cas9-mediated 30 bp deletion into the ZEB1 second exon, we observed reduced migratory and anchorage-independent growth capacity of these tumor cells. Transcriptomic analysis of control and ZEB1 knockout cells, revealed 1,372 differentially expressed genes. The TIMP metallopeptidase inhibitor 3 and the teneurin transmembrane protein 2 genes showed increased expression upon loss of ZEB1, possibly mediating pro-tumorigenic actions of ZEB1. This work provides a resource for regulators of cancer progression that function under the transcriptional control of ZEB1. The data confirm that removing a single EMT transcription factor, such as ZEB1, is not sufficient for reverting the triple-negative mesenchymal breast cancer cells into more differentiated, epithelial-like clones, but can reduce tumorigenic potential, suggesting that not all pro-tumorigenic actions of ZEB1 are linked to the EMT. © 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

36 CFR 1284.20 - Does NARA exhibit privately-owned material?

Code of Federal Regulations, 2011 CFR

2011-07-01

... exhibition cases or other necessary fixtures; and (3) NARA has resources (such as exhibit and security staff) available to produce the special exhibit. (c) The Director of Museum Programs (NWE), in conjunction with the...) The Director of Museum Programs or director of the pertinent Presidential library will inform the...

36 CFR 1284.20 - Does NARA exhibit privately-owned material?

Code of Federal Regulations, 2014 CFR

2014-07-01

... exhibition cases or other necessary fixtures; and (3) NARA has resources (such as exhibit and security staff) available to produce the special exhibit. (c) The Director of Museum Programs (NWE), in conjunction with the...) The Director of Museum Programs or director of the pertinent Presidential library will inform the...

36 CFR 1284.20 - Does NARA exhibit privately-owned material?

Code of Federal Regulations, 2010 CFR

2010-07-01

... exhibition cases or other necessary fixtures; and (3) NARA has resources (such as exhibit and security staff) available to produce the special exhibit. (c) The Director of Museum Programs (NWE), in conjunction with the...) The Director of Museum Programs or director of the pertinent Presidential library will inform the...

36 CFR 1284.20 - Does NARA exhibit privately-owned material?

Code of Federal Regulations, 2012 CFR

2012-07-01

... exhibition cases or other necessary fixtures; and (3) NARA has resources (such as exhibit and security staff) available to produce the special exhibit. (c) The Director of Museum Programs (NWE), in conjunction with the...) The Director of Museum Programs or director of the pertinent Presidential library will inform the...

The role of exhibits in teacher workshops at science museums

NASA Astrophysics Data System (ADS)

Stein, Fred D.

Between 1986 and 1998, the Exploratorium Institute for Inquiry offered multi-week science institutes for elementary educators involving museum exhibit use during a three-day independent investigation on light and color. Many museums tend to underutilize exhibit use in their teacher education programs. This study addresses the question, "What are the contributions of exhibit use to teachers' learning of science content during a workshop at a science museum?" Data from workshops over three successive years was collected in the form of 13 case studies of participants' investigations. Pre- and post-testing of six participants showed a large (ES = 3.0 SD) and significant gain in their understanding of light and color concepts. The case studies were analyzed by coding each incident of exhibit use according to how the exhibit interaction might have helped the participant in his or her learning. Clusters of recurring themes emerged inductively from the coding process suggesting that the exhibits conferred both logistical and conceptual benefits. Logistically, the exhibits acted as "labor-saving" devices, saving participants time because they were always set up and ready to use, and saving the workshop facilitators time because facilitators could recommend that a participant visit an exhibit rather than spend time giving them individual attention or helping them construct their own investigation apparatus. Conceptually, the exhibits supported each aspect of the Piagetian conceptual change process---accommodation, assimilation, and disequilibrium. They supported accommodation of idea structures and the development of new ones by encouraging participants to ask and answer "What would happen if...?" questions which often generated ideas to explain the new experiences. They supported assimilation of experiences into recently developed idea structures or schemes (supporting and consolidating them) by providing opportunities for participants to ask and answer "Will it happen if

Repairing Hubble Exhibit Reception

NASA Image and Video Library

2014-04-23

Individuals in attendance who had a hand in the development or servicing of the Hubble Space Telescope pose for a group photo at an event unveiling a new exhibit featuring Hubble's Corrective Optics Space Telescope Axial Replacement (COSTAR) and the WFPC2 on Wednesday, April 23, 2014 at the Smithsonian National Air and Space Museum in Washington, DC. COSTAR and WFPC2 were installed in Hubble during the first space shuttle servicing mission in 1993 and returned to Earth on the fifth and final servicing mission in 2009. Photo Credit: (NASA/Joel Kowsky)

The Inside Story of Science City: An Outdoor Public Science Exhibition.

ERIC Educational Resources Information Center

Cole, Peggy Ruth; Cutting, Jennifer McGregor

1996-01-01

Discusses and compares on-site and off-site exhibition development. Argues that the development and installation of museum exhibits for public urban spaces requires skill and experience that stretches beyond the expertise of a science-technology museum exhibition staff. Focuses on Science City, an outdoor exhibition created by the New York Hall of…

Evaluating Education and Science in the KSC Visitor Complex Exhibits

NASA Technical Reports Server (NTRS)

Erickson, Lance K.

2000-01-01

The continuing development of exhibits at the Kennedy Space Center's Visitor Complex is an excellent opportunity for NASA personnel to promote science and provide insight into NASA programs and projects for the approximately 3 million visitors that come to KSC annually. Stated goals for the Visitor Complex, in fact, emphasize science awareness and recommend broadening the appeal of the displays and exhibits for all age groups. To this end, this summer project seeks to evaluate the science content of planned exhibits/displays in relation to these developing opportunities and identify specific areas for enhancement of existing or planned exhibits and displays. To help expand the educational and science content within the developing exhibits at the Visitor Complex, this project was structured to implement the goals of the Visitor Center Director. To accomplish this, the exhibits and displays planned for completion within the year underwent review and evaluation for science content and educational direction. Planning emphasis for the individual displays was directed at combining the elements of effective education with fundamental scientific integrity, within an appealing format.

75 FR 6079 - Culturally Significant Objects Imported for Exhibition

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

... DEPARTMENT OF STATE [PUBLIC NOTICE 6894] Culturally Significant Objects Imported for Exhibition Determinations: ``Compass and Rule: Architecture as Mathematical Practice in England, 1500-1750'' SUMMARY: Notice... objects to be included in the exhibition ``Compass and Rule: Architecture as Mathematical Practice in...

Final Hazard Categorization for the Remediation of the 118-D-1, 118-D-2, 118-D-3, 118-H-1, 118-H-2, and 118-H-3 Solid Waste Burial Grounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

T. J. Rodovsky

2006-12-06

This report presents the final hazard categorization (FHC) for the remediation of the 118-D-1, 118-D-2, and 118-D-3 Burial Grounds located within the 100-D/DR Area of the Hanford Site and the 118-H-1, 118-H-2, and 118-H-3 Burial Grounds located within the 100-H Area of the Hanford Site.

Final Hazard Categorization for the Remediation of the 118-D-1, 118-D-2, 118-D-3, 118-H-1, 118-H-2, and 118-H-3 Solid Waste Burial Grounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

T. J. Rodovsky

2007-04-12

This report presents the final hazard categorization (FHC) for the remediation of the 118-D-1, 118-D-2, and 118-D-3 Burial Grounds located within the 100-D/DR Area of the Hanford Site and the 118-H-1, 118-H-2, and 118-H-3 Burial Grounds located within the 100-H Area of the Hanford Site.

7 CFR Exhibit A to Subpart L of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true [Reserved] A Exhibit A to Subpart L of Part 1940 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... Funds Exhibit A to Subpart L of Part 1940 [Reserved] ...

Persistent Exposure to Porphyromonas gingivalis Promotes Proliferative and Invasion Capabilities, and Tumorigenic Properties of Human Immortalized Oral Epithelial Cells

PubMed Central

Geng, Fengxue; Liu, Junchao; Guo, Yan; Li, Chen; Wang, Hongyang; Wang, Hongyan; Zhao, Haijiao; Pan, Yaping

2017-01-01

Recent epidemiological studies revealed a significant association between oral squamous cell carcinoma (OSCC) and Porphyromonas gingivalis, a major pathogen of periodontal disease. As a keystone pathogen of periodontitis, P. gingivalis is known not only to damage local periodontal tissues, but also to evade the host immune system and eventually affect systemic health. However, its role in OSCC has yet to be defined. To explore the underlying effect of chronic P. gingivalis infection on OSCC and to identify relevant biomarkers as promising targets for therapy and prevention, we established a novel model by exposing human immortalized oral epithelial cells (HIOECs) to P. gingivalis at a low multiplicity of infection (MOI) for 5–23 weeks. The P. gingivalis infected HIOECs were monitored for tumor biological alteration by proliferation, wound healing, transwell invasion, and gelatin zymography assays. Microarray and proteomic analyses were performed on HIOECs infected with P. gingivalis for 15 weeks, and some selected data were validated by quantitative real-time PCR and (or) western blot on cells infected for 15 and 23 weeks. Persistent exposure to P. gingivalis caused cell morphological changes, increased proliferation ability with higher S phase fraction in the cell cycle, and promoted cell migratory and invasive properties. In combining results of bioinformatics analyses and validation assays, tumor-related genes such as NNMT, FLI1, GAS6, lncRNA CCAT1, PDCD1LG2, and CD274 may be considered as the key regulators in tumor-like transformation in response to long-time exposure of P. gingivalis. In addition, some useful clinical biomarkers and novel proteins were also presented. In conclusion, P. gingivalis could promote tumorigenic properties of HIOECs, indicating that chronic P. gingivalis infection may be considered as a potential risk factor for oral cancer. The key regulators detected from the present model might be used in monitoring the development of OSCC with

A phenomenological investigation of science center exhibition developers' expertise development

NASA Astrophysics Data System (ADS)

Young, Denise L.

The purpose of this study was to examine the exhibition developer role in the context of United States (U.S.) science centers, and more specifically, to investigate the way science center exhibition developers build their professional expertise. This research investigated how successfully practicing exhibition developers described their current practices, how they learned to be exhibition developers, and what factors were the most important to the developers in building their professional expertise. Qualitative data was gathered from 10 currently practicing exhibition developers from three science centers: the Exploratorium, San Francisco, California; the Field Museum, Chicago, Illinois; and the Science Museum of Minnesota, St. Paul, Minnesota. In-depth, semistructured interviews were used to collect the data. The study embraced aspects of the phenomenological tradition and sought to derive a holistic understanding of the position and how expertise was built for it. The data were methodically coded and organized into themes prior to analysis. The data analysis found that the position consisted of numerous and varied activities, but the developers' primary roles were advocating for the visitor, storytelling, and mediating information and ideas. They conducted these activities in the context of a team and relied on an established exhibition planning process to guide their work. Developers described a process of learning exhibition development that was experiential in nature. Learning through daily practice was key, though they also consulted with mentors and relied on visitor studies to gauge the effectiveness of their work. They were adept at integrating prior knowledge gained from many aspects of their lives into their practice. The developers described several internal factors that contributed to their expertise development including the desire to help others, a natural curiosity about the world, a commitment to learning, and the ability to accept critique. They

Exhibits Recognition System for Combining Online Services and Offline Services

NASA Astrophysics Data System (ADS)

Ma, He; Liu, Jianbo; Zhang, Yuan; Wu, Xiaoyu

2017-10-01

In order to achieve a more convenient and accurate digital museum navigation, we have developed a real-time and online-to-offline museum exhibits recognition system using image recognition method based on deep learning. In this paper, the client and server of the system are separated and connected through the HTTP. Firstly, by using the client app in the Android mobile phone, the user can take pictures and upload them to the server. Secondly, the features of the picture are extracted using the deep learning network in the server. With the help of the features, the pictures user uploaded are classified with a well-trained SVM. Finally, the classification results are sent to the client and the detailed exhibition’s introduction corresponding to the classification results are shown in the client app. Experimental results demonstrate that the recognition accuracy is close to 100% and the computing time from the image uploading to the exhibit information show is less than 1S. By means of exhibition image recognition algorithm, our implemented exhibits recognition system can combine online detailed exhibition information to the user in the offline exhibition hall so as to achieve better digital navigation.

Multimodal audio guide for museums and exhibitions

NASA Astrophysics Data System (ADS)

Gebbensleben, Sandra; Dittmann, Jana; Vielhauer, Claus

2006-02-01

In our paper we introduce a new Audio Guide concept for exploring buildings, realms and exhibitions. Actual proposed solutions work in most cases with pre-defined devices, which users have to buy or borrow. These systems often go along with complex technical installations and require a great degree of user training for device handling. Furthermore, the activation of audio commentary related to the exhibition objects is typically based on additional components like infrared, radio frequency or GPS technology. Beside the necessity of installation of specific devices for user location, these approaches often only support automatic activation with no or limited user interaction. Therefore, elaboration of alternative concepts appears worthwhile. Motivated by these aspects, we introduce a new concept based on usage of the visitor's own mobile smart phone. The advantages in our approach are twofold: firstly the Audio Guide can be used in various places without any purchase and extensive installation of additional components in or around the exhibition object. Secondly, the visitors can experience the exhibition on individual tours only by uploading the Audio Guide at a single point of entry, the Audio Guide Service Counter, and keeping it on her or his personal device. Furthermore, since the user usually is quite familiar with the interface of her or his phone and can thus interact with the application device easily. Our technical concept makes use of two general ideas for location detection and activation. Firstly, we suggest an enhanced interactive number based activation by exploiting the visual capabilities of modern smart phones and secondly we outline an active digital audio watermarking approach, where information about objects are transmitted via an analog audio channel.

Editor's Highlight: Complete Attenuation of Mouse Lung Cell Proliferation and Tumorigenicity in CYP2F2 Knockout and CYP2F1 Humanized Mice Exposed to Inhaled Styrene for up to 2 Years Supports a Lack of Human Relevance.

PubMed

Cruzan, George; Bus, James S; Banton, Marcy I; Sarang, Satinder S; Waites, Robbie; Layko, Debra B; Raymond, James; Dodd, Darol; Andersen, Melvin E

2017-10-01

Styrene is a mouse-specific lung carcinogen, and short-term mode of action studies have demonstrated that cytotoxicity and/or cell proliferation, and genomic changes are dependent on CYP2F2 metabolism. The current study examined histopathology, cell proliferation, and genomic changes in CD-1, C57BL/6 (WT), CYP2F2(-/-) (KO), and CYP2F2(-/-) (CYP2F1, 2B6, 2A13-transgene) (TG; humanized) mice following exposure for up to 104 weeks to 0- or 120-ppm styrene vapor. Five mice per treatment group were sacrificed at 1, 26, 52, and 78 weeks. Additional 50 mice per treatment group were followed until death or 104 weeks of exposure. Cytotoxicity was present in the terminal bronchioles of some CD-1 and WT mice exposed to styrene, but not in KO or TG mice. Hyperplasia in the terminal bronchioles was present in CD-1 and WT mice exposed to styrene, but not in KO or TG mice. Increased cell proliferation, measured by KI-67 staining, occurred in CD-1 and WT mice exposed to styrene for 1 week, but not after 26, 52, or 78 weeks, nor in KO or TG mice. Styrene increased the incidence of bronchioloalveolar adenomas and carcinomas in CD-1 mice. No increase in lung tumors was found in WT despite clear evidence of lung toxicity, or, KO or TG mice. The absence of preneoplastic lesions and tumorigenicity in KO and TG mice indicates that mouse-specific CYP2F2 metabolism is responsible for both the short-term and chronic toxicity and tumorigenicity of styrene, and activation of styrene by CYP2F2 is a rodent MOA that is neither quantitatively or qualitatively relevant to humans. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

TGF-β Tumor Suppression Through A Lethal EMT

PubMed Central

David, Charles J.; Huang, Yun-Han; Chen, Mo; Su, Jie; Zou, Yilong; Bardeesy, Nabeel; Iacobuzio-Donahue, Christine A.; Massagué, Joan

2016-01-01

TGF-β signaling can be pro-tumorigenic or tumor suppressive. We investigated this duality in pancreatic ductal adenocarcinoma (PDA), which, with other gastrointestinal cancers, exhibits frequent inactivation of the TGF-β mediator Smad4. We show that TGF-β induces an epithelial-mesenchymal transition (EMT), generally considered a pro-tumorigenic event. However, in TGF-β sensitive PDA cells, EMT becomes lethal by converting TGF-β-induced Sox4 from an enforcer of tumorigenesis into a promoter of apoptosis. This is the result of an EMT-linked remodeling of the cellular transcription factor landscape, including the repression of the gastrointestinal lineage-master regulator Klf5. Klf5 cooperates with Sox4 in oncogenesis and prevents Sox4-induced apoptosis. Smad4 is required for EMT but dispensable for Sox4 induction by TGF-β. TGF-β-induced Sox4 is thus geared to bolster progenitor identity, while simultaneous Smad4-dependent EMT strips Sox4 of an essential partner in oncogenesis. Our work demonstrates that TGF-β tumor suppression functions through an EMT-mediated disruption of a lineage-specific transcriptional network. PMID:26898331

76 FR 61472 - Culturally Significant Objects Imported for Exhibition

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... DEPARTMENT OF STATE [Public Notice: 7634] Culturally Significant Objects Imported for Exhibition Determinations: ``The Game of Kings: Medieval Ivory Chessmen From the Isle of Lewis'' SUMMARY: Notice is hereby... objects to be included in the exhibition ``The Game of Kings: Medieval Ivory Chessmen from the Isle of...

14 CFR 77.59 - Subpoenas of witnesses and exhibits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 77.59 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... for any witness or exhibit that he determines may be material and relevant to the issues of the... witnesses and exhibits, he shall advise the presiding officer far enough in advance that the presiding...

14 CFR 77.59 - Subpoenas of witnesses and exhibits.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Section 77.59 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... issue subpoenas for any witness or exhibit that he determines may be material and relevant to the issues... his necessary witnesses and exhibits, he shall advise the presiding officer far enough in advance that...

7 CFR Exhibit G to Subpart G of... - [Reserved

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 2009-01-01 true [Reserved] G Exhibit G to Subpart G of Part 1940 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) GENERAL Environmental Program Exhibit G to Subpart G of Part 1940...

7 CFR Exhibit G to Subpart G of... - [Reserved

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 13 2012-01-01 2012-01-01 false [Reserved] G Exhibit G to Subpart G of Part 1940 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) GENERAL Environmental Program Exhibit G to Subpart G of Part 1940...

7 CFR Exhibit G to Subpart G of... - [Reserved

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 13 2013-01-01 2013-01-01 false [Reserved] G Exhibit G to Subpart G of Part 1940 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) GENERAL Environmental Program Exhibit G to Subpart G of Part 1940...

7 CFR Exhibit G to Subpart G of... - [Reserved

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 13 2014-01-01 2013-01-01 true [Reserved] G Exhibit G to Subpart G of Part 1940 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) GENERAL Environmental Program Exhibit G to Subpart G of Part 1940...

7 CFR Exhibits A-B to Subpart G... - [Reserved

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 12 2013-01-01 2013-01-01 false [Reserved] A Exhibits A-B to Subpart G to Part 1822 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS..., Procedures, and Authorizations Exhibits A-B to Subpart G to Part 1822 [Reserved] ...

7 CFR Exhibit G to Subpart G of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true [Reserved] G Exhibit G to Subpart G of Part 1940 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) GENERAL Environmental Program Exhibit G to Subpart G of Part 1940...

46 CFR 169.805 - Exhibition of merchant mariner credentials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Exhibition of merchant mariner credentials. 169.805 Section 169.805 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Operations § 169.805 Exhibition of merchant mariner credentials. Officers on any vessel...

46 CFR 169.805 - Exhibition of merchant mariner credentials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Exhibition of merchant mariner credentials. 169.805 Section 169.805 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Operations § 169.805 Exhibition of merchant mariner credentials. Officers on any vessel...

Alien Earths: A Traveling Science Exhibit and Education Program

NASA Astrophysics Data System (ADS)

Dusenbery, P. B.; Morrow, C. A.; Harold, J.

2004-05-01

Where did we come from? Are we alone? These age-old questions form the basis of NASA's Origins Program, a series of missions spanning the next twenty years that will use a host of space- and ground-based observatories to understand the origin and development of galaxies, stars, planets, and the conditions necessary to support life. The Space Science Institute in Boulder, CO, is developing a 3,000 square-foot traveling exhibition, called Alien Earths, which will bring origins-related research and discoveries to students and the American public. Alien Earths will have four interrelated exhibit areas: Our Place in Space, Star Birth, PlanetQuest, and Search for Life. Exhibit visitors will explore the awesome events surrounding the birth of stars and planets; they will join scientists in the hunt for planets outside our solar system including those that may be in "habitable zones" around other stars; and finally they will be able to learn about the wide range of conditions for life on Earth and how scientists are looking for signs of life beyond Earth. Visitors will also learn about the tools scientists use, such as space-based and ground-based telescopes, to improve our understanding of the cosmos. The exhibit's size will permit it to visit medium sized museums in all regions of the country. It will begin its 3-year tour to 9 host museums and science centers in early 2005 at the Lawrence Hall of Science in Berkeley, California. The Association of Science-Technology Centers (ASTC) will manage the exhibit's national tour. In addition to the exhibit, the project includes workshops for educators and docents at host sites, as well as a public website that will use exhibit content to delve deeper into origins research. Current partners in the Alien Earths project include ASTC, Denver Museum of Nature and Science, Lawrence Hall of Science, NASA Astrobiology Institute, NASA missions (Navigator, SIRTF, and Kepler), the SETI Institute, and the Space Telescope Science Institute

STEM promotion through museum exhibits on cardiac monitoring & cardiac rhythm management.

PubMed

Countryman, Jordan D; Dow, Douglas E

2014-01-01

Formal education in science, technology, engineering and math (STEM) does not successfully engage all of the students who have potential to become skilled in STEM activities and careers. Museum exhibits may be able to reach and engage a broader range of the public. STEM Exhibits that are both understandable and capture the imagination of viewers may contribute toward increased interest in STEM activities. One such topic for such an exhibit could be cardiac pacemakers and cardioverter defibrillators that sustain life. Although museums have existed for centuries, the available types of exhibit designs has dramatically increased in recent decades due to innovations in technology. Science and technology museums have especially taken advantage of the progression of exhibit design to developed new ways to communicate to their viewers. These novel presentation tools allow museums to more effectively convey to and engage viewers. This paper examines the techniques employed by museums in exhibits and considers the practices of several museums with exhibits related to cardiac monitoring (CM) and cardiac rhythm management (CRM).

The Nature of Exhibits About Acoustics in Science and Technology Centres

NASA Astrophysics Data System (ADS)

Afonso, Ana S.; Gilbert, John K.

2008-11-01

This is a study of the opportunities currently provided by interactive science and technology centres for visitors’ engagement in the field of acoustics. E-mails, requesting a description of exhibits on acoustics (sound and hearing) in use, were sent to members of staff of interactive science and technology centres around the world as well as to companies that design and sell exhibits. Eighty-seven descriptions of distinctive interactive exhibits were received and analysed. Results show that: there are few analogy-based exhibits concerning the more complex aspects of acoustics; narratives involving visitors’ everyday lives, that might provide continuity between and beyond the situations presented by exhibits, are not generally provided; science is emphasised at the expense of technology; the risks, benefits and ethical implications of relevant technological artefacts are rarely mentioned; the majority of the exhibits are concerned with the fields of fundamental acoustics, hearing, and psychoacoustics. It is suggested that interactive science and technology centres need to rethink the design of exhibits about acoustics if their mission includes some appreciation of this important branch of science and technology.

7 CFR Exhibit A to Subpart B of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false [Reserved] A Exhibit A to Subpart B of Part 1900 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS GENERAL Adverse Decisions and Administrative Appeals Exhibit A to Subpart B of Part 1900 [Reserved] ...

7 CFR Exhibit C to Subpart N of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true [Reserved] C Exhibit C to Subpart N of Part 1944 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) HOUSING Housing Preservation Grants Exhibit C to Subpart N of Part 1944...

27 CFR 7.42 - Exhibiting certificates to Government officials.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exhibiting certificates to Government officials. 7.42 Section 7.42 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... certificate of label approval shall, upon demand exhibit such certificate to a duly authorized representative...

7 CFR Exhibit A to Subpart C of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false [Reserved] A Exhibit A to Subpart C of Part 1924 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS CONSTRUCTION AND REPAIR Planning and Performing Site Development Work Exhibit A to Subpart C of...

7 CFR Exhibit C to Subpart N of... - [Reserved

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 2009-01-01 true [Reserved] C Exhibit C to Subpart N of Part 1944 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) HOUSING Housing Preservation Grants Exhibit C to Subpart N of Part 1944...

7 CFR Exhibit C to Subpart N of... - [Reserved

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 13 2012-01-01 2012-01-01 false [Reserved] C Exhibit C to Subpart N of Part 1944 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) HOUSING Housing Preservation Grants Exhibit C to Subpart N of Part 1944...

Informing the Development of Science Exhibitions through Educational Research

ERIC Educational Resources Information Center

Laherto, Antti

2013-01-01

This paper calls for greater use of educational research in the development of science exhibitions. During the past few decades, museums and science centres throughout the world have placed increasing emphasis on their educational function. Although exhibitions are the primary means of promoting visitors' learning, educational research is not…

27 CFR 4.51 - Exhibiting certificates to Government officials.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exhibiting certificates to Government officials. 4.51 Section 4.51 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND... approval or a certificate of exemption shall, upon demand, exhibit such certificate to a duly authorized...

A coarse-grained model to study calcium activation of the cardiac thin filament

NASA Astrophysics Data System (ADS)

Zhang, Jing; Schwartz, Steven

2015-03-01

Familial hypertrophic cardiomyopathy (FHC) is one of the most common heart disease caused by genetic mutations. Cardiac muscle contraction and relaxation involve regulation of crossbridge binding to the cardiac thin filament, which regulates actomyosin interactions through calcium-dependent alterations in the dynamics of cardiac troponin (cTn) and tropomyosin (Tm). An atomistic model of cTn complex interacting with Tm has been studied by our group. A more realistic model requires the inclusion of the dynamics of actin filament, which is almost 6 times larger than cTn and Tm in terms of atom numbers, and extensive sampling of the model becomes very resource-demanding. By using physics-based protein united-residue force field, we introduce a coarse-grained model to study the calcium activation of the thin filament resulting from cTn's allosteric regulation of Tm dynamics on actin. The time scale is much longer than that of all-atom molecular dynamics simulation because of the reduction of the degrees of freedom. The coarse-grained model is a good template for studying cardiac thin filament mutations that cause FHC, and reduces the cost of computational resources.

Collaborative virtual environments art exhibition

NASA Astrophysics Data System (ADS)

Dolinsky, Margaret; Anstey, Josephine; Pape, Dave E.; Aguilera, Julieta C.; Kostis, Helen-Nicole; Tsoupikova, Daria

2005-03-01

This panel presentation will exhibit artwork developed in CAVEs and discuss how art methodologies enhance the science of VR through collaboration, interaction and aesthetics. Artists and scientists work alongside one another to expand scientific research and artistic expression and are motivated by exhibiting collaborative virtual environments. Looking towards the arts, such as painting and sculpture, computer graphics captures a visual tradition. Virtual reality expands this tradition to not only what we face, but to what surrounds us and even what responds to our body and its gestures. Art making that once was isolated to the static frame and an optimal point of view is now out and about, in fully immersive mode within CAVEs. Art knowledge is a guide to how the aesthetics of 2D and 3D worlds affect, transform, and influence the social, intellectual and physical condition of the human body through attention to psychology, spiritual thinking, education, and cognition. The psychological interacts with the physical in the virtual in such a way that each facilitates, enhances and extends the other, culminating in a "go together" world. Attention to sharing art experience across high-speed networks introduces a dimension of liveliness and aliveness when we "become virtual" in real time with others.

The Invisible Universe: A Tactile and Braille Exhibit of Astronomical Images

NASA Astrophysics Data System (ADS)

Arcand, Kimberly; Lestition, K.; Watzke, M.; Steel, S.

2010-01-01

As part of the "From Earth to the Universe" (FETTU) project, a NASA-funded tactile exhibit for the visually impaired community was launched in July 2009 at the Martin Luther King Library in D.C. The exhibit is part of the global FETTU exhibit, a project of the International Year of Astronomy 2009. The science content of the exhibit includes explanations of our Sun, Eta Carinae, Crab Nebula, Whirlpool Galaxy, and the electromagnetic spectrum, and was adapted from the NASA-funded Braille/tactile book Touch the Invisible Sky. Multiple geographic locations and venue types have been targeted for the displays. The FETTU-tactile exhibit opens a wider door to experiencing and understanding astronomy, bridging a gap in learning. This exhibit is based upon work supported by the National Aeronautics and Space Administration under proposal 08-EPO08-0068 issued through the Science Mission Directorate.

18 CFR 50.7 - Applications: exhibits.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Applications: exhibits. 50.7 Section 50.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS FOR PERMITS TO SITE INTERSTATE...

18 CFR 50.7 - Applications: exhibits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Applications: exhibits. 50.7 Section 50.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS FOR PERMITS TO SITE INTERSTATE...

18 CFR 153.8 - Required exhibits.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Office of Energy Projects, 888 First Street, NE., Washington, DC 20426; (6) Exhibit E-1. If the LNG... Technical Information Service or the Commission's Office of Energy Projects, 888 First Street, NE....8 Section 153.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION...

18 CFR 153.8 - Required exhibits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Office of Energy Projects, 888 First Street, NE., Washington, DC 20426; (6) Exhibit E-1. If the LNG... Technical Information Service or the Commission's Office of Energy Projects, 888 First Street, NE....8 Section 153.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION...

18 CFR 153.8 - Required exhibits.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Office of Energy Projects, 888 First Street, NE., Washington, DC 20426; (6) Exhibit E-1. If the LNG... Technical Information Service or the Commission's Office of Energy Projects, 888 First Street, NE....8 Section 153.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION...

18 CFR 153.8 - Required exhibits.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Office of Energy Projects, 888 First Street, NE., Washington, DC 20426; (6) Exhibit E-1. If the LNG... Technical Information Service or the Commission's Office of Energy Projects, 888 First Street, NE....8 Section 153.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION...

18 CFR 153.8 - Required exhibits.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Office of Energy Projects, 888 First Street, NE., Washington, DC 20426; (6) Exhibit E-1. If the LNG... Technical Information Service or the Commission's Office of Energy Projects, 888 First Street, NE....8 Section 153.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION...

Science on a Sphere exhibit

NASA Image and Video Library

2009-03-31

Students from Xavier University Preparatory School in New Orleans view the newest exhibit at StenniSphere, the visitor center at NASA's John C. Stennis Space Center - Science on a Sphere, a 68-inch global presentation of planetary data. StenniSphere is only the third NASA visitor center to offer the computer system, which uses four projectors to display data on a globe and present a dynamic, revolving, animated view of Earth and other planets.

Science on a Sphere exhibit

NASA Technical Reports Server (NTRS)

2009-01-01

Students from Xavier University Preparatory School in New Orleans view the newest exhibit at StenniSphere, the visitor center at NASA's John C. Stennis Space Center - Science on a Sphere, a 68-inch global presentation of planetary data. StenniSphere is only the third NASA visitor center to offer the computer system, which uses four projectors to display data on a globe and present a dynamic, revolving, animated view of Earth and other planets.

Outreach to Science Faculty and Students through Research Exhibitions

ERIC Educational Resources Information Center

Chan, Tina; Hebblethwaite, Chris

2014-01-01

Penfield Library at the State University of New York at Oswego (SUNY Oswego) has a gallery exhibit space near the front entrance that is used to showcase student-faculty research and art class projects. This article features the library's outreach efforts to science faculty and students through research exhibitions. The library held an exhibition…

4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

PubMed

Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

2004-01-19

Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

The Use of Memories in Understanding Interactive Science and Technology Exhibits

ERIC Educational Resources Information Center

Afonso, Ana S.; Gilbert, John K.

2006-01-01

Framed by a "personal constructivist" perspective, this study analyses visitors' use of spontaneous memories in understanding different types of interactive exhibits, the nature and sources of the retrieved memories, and the way that visitors relate an exhibit analogically to memories of previous exhibits. One hundred and thirteen…

Cancer (stem) cell differentiation: An inherent or acquired property?

PubMed

Mohr, Marieke; Zänker, Kurt S; Dittmar, Thomas

2015-12-01

There is a growing list of data indicating that cancer (stem) cells could functionally adapt foreign tissue features, such as endothelial-like cells or neuroendocrine cells, express lineage markers or could differentiate into various lineages in response to appropriate differentiation criteria. The finding that cancer (stem) cells may possess some kind of differentiation capacity poses the question whether this might be an inherent or acquired property. Cancer stem cells share stem cell characteristics and may thus possess an inherent differentiation capacity enabling the cells to respond to various differentiation stimuli. Considering the plasticity of cancer (stem) cells, even non-tumorigenic (and putatively non-differentiable) tumor cells could give rise to tumorigenic tumor stem cells, exhibiting stem cell characteristics including an inherent differentiation capacity. On the contrary, cancer (stem) cells may have acquired differentiation capacity as a consequence of a previous cell fusion event with cell types exhibiting differentiation potential and being fusogenic, such as macrophages or stem cells. Of pivotal interest in a tumor context are macrophages, which chiefly foster the chronically inflamed tumor microenvironment. Because chronically inflamed tissue is a well-known trigger for cell fusion and both macrophages and stem cells are highly fusogenic we conclude that cell fusion events between these cell types and cancer (stem) cells should frequently occur, thereby giving rise to hybrid cells exhibiting not only novel properties, like an enhanced metastatogenic phenotype, but also parental characteristics, such as differentiation capacity. Conceivably, the combination of both properties might be advantageous for metastasizing cancer (stem) cells to adapt better and faster to a foreign organ tissue environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

36 CFR § 1284.20 - Does NARA exhibit privately-owned material?

Code of Federal Regulations, 2013 CFR

2013-07-01

... exhibition cases or other necessary fixtures; and (3) NARA has resources (such as exhibit and security staff) available to produce the special exhibit. (c) The Director of Museum Programs (NWE), in conjunction with the...) The Director of Museum Programs or director of the pertinent Presidential library will inform the...

Modelling the Future: Exhibitions and the Materiality of Education

ERIC Educational Resources Information Center

Lawn, Martin, Ed.

2009-01-01

The role of World Exhibitions in the 19th and early 20th centuries was to confirm a relation between the nation state and modernity. As a display about industries, inventions and identities, the Exhibition, in a sense, put entire nations into an elevated, viewable space. It is a significant element in modernity as comparisons can be made, progress…

Data Collection Methods for Evaluating Museum Programs and Exhibitions

ERIC Educational Resources Information Center

Nelson, Amy Crack; Cohn, Sarah

2015-01-01

Museums often evaluate various aspects of their audiences' experiences, be it what they learn from a program or how they react to an exhibition. Each museum program or exhibition has its own set of goals, which can drive what an evaluator studies and how an evaluation evolves. When designing an evaluation, data collection methods are purposefully…

Toxicity profiles in rats treated with tumorigenic and nontumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

PubMed

Wolf, Douglas C; Allen, James W; George, Michael H; Hester, Susan D; Sun, Guobin; Moore, Tanya; Thai, Sheau-Fung; Delker, Don; Winkfield, Ernest; Leavitt, Sharon; Nelson, Gail; Roop, Barbara C; Jones, Carlton; Thibodeaux, Julie; Nesnow, Stephen

2006-01-01

Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. The particular mode of toxic and tumorigenic action for these compounds is not known, however it has been proposed that triadimefon-induced rat thyroid tumors arise through the specific mechanism of increased TSH. The present study was designed to identify commonalities of effects across the different conazoles and to determine unique features of the tissue responses that suggest a toxicity pathway and a mode of action for the observed thyroid response for triadimefon. Male Wistar/Han rats were treated with triadimefon (100, 500, 1800 ppm), propiconazole (100, 500, 2500 ppm), or myclobutanil (100, 500, 2000 ppm) in feed for 4, 30, or 90 days. The rats were evaluated for clinical signs, body and liver weight, histopathology of thyroid and liver, hepatic metabolizing enzyme activity, and serum T3, T4, TSH, and cholesterol levels. There was a dose-dependent increase in liver weight but not body weight for all treatments. The indication of cytochrome induction, pentoxyresorufin O-dealkylation (PROD) activity, had a dose-related increase at all time points for all conazoles. Uridine diphopho-glucuronosyl transferase (UDPGT), the T4 metabolizing enzyme measured as glucuronidation of 1-naphthol, was induced to the same extent after 30 and 90 days for all three conazoles. Livers from all high dose treated rats had centrilobular hepatocyte hypertrophy after 4 days, while only triadimefon and propiconazole treated rats had hepatocyte hypertrophy after 30 days, and only triadimefon treated rats had hepatocyte hypertrophy after 90 days. Thyroid follicular cell hypertrophy, increased follicular cell proliferation, and colloid depletion were

7 CFR Exhibit C to Subpart B of... - Cooperative Agreement (Example)

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Cooperative Agreement (Example) C Exhibit C to Subpart B of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING... Exhibit C to Subpart B of Part 1955—Cooperative Agreement (Example) Editorial Note: Exhibit C is not...

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

PubMed

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

2016-12-06

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

Is having a family member with chronic health concerns bad for young people's health? Cross-sectional evidence from a national survey of young Australians.

PubMed

Moffat, Anna K; Redmond, Gerry

2017-01-06

Young people's perspectives on the association between having a family member with a chronic health concern (FHC) and their own health are under-researched. This study used young people's reports to assess the prevalence of FHCs and their association with negative health outcomes, with an aim of identifying potential inequalities between marginalised and non-marginalised young people. Family cohesion was examined as a moderating factor. Cross-sectional data from the Australian Child Wellbeing Project survey were used. Respondents were asked whether someone in their family experienced one or more FHCs (disability, mental illness or drug/alcohol addiction). In addition, their experience of different psychosomatic symptoms (headache, sleeplessness, irritability, etc), aspects of family relationships and social and economic characteristics (disability, materially disadvantaged and Indigenous) were documented. Nationally representative Australian sample. 1531 students in school years 4 and 6 and 3846 students in year 8. A quarter of students reported having an FHC (years 4 and 6: 23.96% (95% CI 19.30% to 28.62%); year 8: 25.35% (95% CI 22.77% to 27.94%)). Significantly, more students with FHCs than those without reported experiencing 2 or more negative health symptoms at least weekly (OR=1.78; 95% CI 1.19 to 2.65; p<0.01). However, an independent relationship between FHCs and symptom load was only found in the case of FHC-drug/alcohol addiction. Marginalised students and students reporting low family cohesion had an increased prevalence of FHCs and notably higher symptom loads where FHCs were present. Level of family cohesion did not impact the relationship between FHCs and symptom load. The burden of FHCs is inequitably distributed between marginalised and non-marginalised groups, and between young people experiencing different levels of family cohesion. More work is required regarding appropriate targets for community and family-level interventions to support young

7 CFR Exhibit C to Subpart B of... - Cooperative Agreement (Example)

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 14 2012-01-01 2012-01-01 false Cooperative Agreement (Example) C Exhibit C to... Pt. 1955, Subpt. B, Note Exhibit C to Subpart B of Part 1955—Cooperative Agreement (Example) Editorial Note: Exhibit C is not published in the Code of Federal Regulations. It is available in any FmHA...

7 CFR Exhibit C to Subpart B of... - Cooperative Agreement (Example)

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 14 2011-01-01 2011-01-01 false Cooperative Agreement (Example) C Exhibit C to... Pt. 1955, Subpt. B, Note Exhibit C to Subpart B of Part 1955—Cooperative Agreement (Example) Editorial Note: Exhibit C is not published in the Code of Federal Regulations. It is available in any FmHA...

7 CFR Exhibit C to Subpart B of... - Cooperative Agreement (Example)

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 14 2014-01-01 2014-01-01 false Cooperative Agreement (Example) C Exhibit C to... Pt. 1955, Subpt. B, Note Exhibit C to Subpart B of Part 1955—Cooperative Agreement (Example) Editorial Note: Exhibit C is not published in the Code of Federal Regulations. It is available in any FmHA...

Chromosome copy number variation in telomerized human bone marrow stromal cells; insights for monitoring safe ex-vivo expansion of adult stem cells.

PubMed

Burns, Jorge S; Harkness, Linda; Aldahmash, Abdullah; Gautier, Laurent; Kassem, Moustapha

2017-12-01

Adult human bone marrow stromal cells (hBMSC) cultured for cell therapy require evaluation of potency and stability for safe use. Chromosomal aberrations upsetting genomic integrity in such cells have been contrastingly described as "Limited" or "Significant". Previously reported stepwise acquisition of a spontaneous neoplastic phenotype during three-year continuous culture of telomerized cells (hBMSC-TERT20) didn't alter a diploid karyotype measured by spectral karyotype analysis (SKY). Such screening may not adequately monitor abnormal and potentially tumorigenic hBMSC in clinical scenarios. We here used array comparative genomic hybridization (aCGH) to more stringently compare non-tumorigenic parental hBMSC-TERT strains with their tumorigenic subcloned populations. Confirmation of a known chromosome 9p21 microdeletion at locus CDKN2A/B, showed it also impinged upon the adjacent MTAP gene. Compared to reference diploid human fibroblast genomic DNA, the non-tumorigenic hBMSC-TERT4 cells had a copy number variation (CNV) in at least 14 independent loci. The pre-tumorigenic hBMSC-TERT20 cell strain had further CNV including 1q44 gain enhancing SMYD3 expression and 11q13.1 loss downregulating MUS81 expression. Bioinformatic analysis of gene products reflecting 11p15.5 CNV gain in tumorigenic hBMSC-TERT20 cells highlighted networks implicated in tumorigenic progression involving cell cycle control and mis-match repair. We provide novel biomarkers for prospective risk assessment of expanded stem cell cultures. Copyright © 2017. Published by Elsevier B.V.

Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1): A potential biomarker for coronary artery disease in patients with obstructive sleep apnea

PubMed Central

Matsumura, Takuma; Kinoshita, Taku; Sakurai, Yoriko; Yahaba, Misuzu; Tsushima, Kenji; Sakao, Seiichiro; Nagashima, Kengo; Ozaki, Toshinori; Kobayashi, Yoshio; Hiwasa, Takaki; Tatsumi, Koichiro

2018-01-01

Objective Although severe obstructive sleep apnea (OSA) is an important risk factor for atherosclerosis-related diseases including coronary artery disease (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This study aimed to test our hypothesis that circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the prevalence of CAD in patients with OSA. Methods Eighty-two adults diagnosed with OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples were collected from patients with OSA at diagnostic polysomnography and from patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified luminescence proximity homogeneous assay and its association with clinical variables related to atherosclerosis was evaluated. Results NBL1-Ab level was significantly elevated in patients with both OSA and ACS compared with HVs. Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with severe OSA and OSA patients with a history of CAD. Weak associations were observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO2 and arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA patients with a history of CAD than in those without a history of CAD. Sensitivity analysis using a logistic regression model also demonstrated that increased NBL1-Ab levels were associated with the previous history of CAD in patients with OSA. Conclusions Elevated NBL1-Ab levels may be associated with the prevalence of CAD in patients with OSA, which needs to be confirmed further. PMID:29596467

Graduation by Exhibition: Assessing Genuine Achievement.

ERIC Educational Resources Information Center

McDonald, Joseph P.; And Others

This book describes a strategy for school reform, "planning backwards from exhibitions," which is a collective invention of the Coalition of Essential Schools. The strategy is based on the principle that graduation from high school should be based on genuine achievement. The first article, by Joseph P. McDonald, explains that the purpose of…

Interactive Exhibits Foster Partnership and Engage Diverse Learners at Their Local Libraries

NASA Astrophysics Data System (ADS)

LaConte, K.; Dusenbery, P.; Fitzhugh, G.; Harold, J. B.; Holland, A.

2016-12-01

Learners frequently need to access increasingly complex information to help them understand our changing world. More and more libraries are transforming themselves into places where learners not only access STEM information, but interact with professionals and undertake hands-on learning. Libraries are beginning to position themselves as part of learning ecosystems that contribute to a collective impact on the community. Traveling STEM exhibits are catalyzing these partnerships and engaging students, families, and adults in repeat visits through an accessible venue: their public library. The impact of the STAR Library Education Network's (STAR_Net) Discover Earth: A Century of Change exhibit on partnerships, the circulation of STEM resources, and the engagement of learners was studied by an external evaluation team. The STAR_Net project's summative evaluation utilized mixed methods to investigate project implementation and its outcomes. Methods included pre- and post-exhibit surveys administered to staff from each library that hosted the exhibits; interviews with staff from host libraries; patron surveys; exhibit-related circulation records; web metrics regarding the online STAR_Net community of practice; and site visits. A subset of host libraries recruited professionals, who delivered programming that connected Earth systems science, weather, climate, and conservation themes from the exhibit to local issues. Library patrons improved their knowledge about STEM topics presented in the exhibits and associated programming, and patrons viewing the exhibit reflected the demographics of their communities. In a follow-up survey, patrons reported spending an average of 60 minutes looking at the exhibit over their cumulative visits to the library. In contrast, visitors might visit a museum only once to look at a comparably-sized traveling exhibit due to barriers such as cost and distance. Exhibit host libraries reported an increase in the circulation of Earth science

Loss of tumorigenic potential by human lung tumor cells in the presence of antisense RNA specific to the ectopically synthesized alpha subunit of human chorionic gonadotropin.

PubMed

Rivera, R T; Pasion, S G; Wong, D T; Fei, Y B; Biswas, D K

1989-06-01

A clonal strain of human lung tumor cells in culture (ChaGo), derived from a bronchogenic carcinoma, synthesizes and secretes large amounts of alpha (alpha) and a comparatively lower level of beta (beta) subunit of the glycoprotein hormone, human chorionic gonadotropin (HCG). ChaGo cells lost their characteristic anchorage-independent growth phenotype in the presence of anti-alpha-HCG antibody. The effect of the antibody was partially reversed by addition of alpha-HCG to the culture medium. ChaGo cells were transfected with an expression vector (pRSV-anti-alpha-HCG), that directs synthesis of RNA complementary to alpha-HCG mRNA. The transfectants produced alpha-HCG antisense RNA which was associated with the reduced level of alpha-HCG. Transfectants also displayed several altered phenotypic properties, including altered morphology, less mitosis, reduced growth rate, loss of anchorage-independent growth, and loss of tumorigenicity in nude mice. Treatment of transfectants with 8,bromo-cAMP resulted in increased accumulation of alpha-HCG mRNA, no change in the level of alpha-HCG antisense RNA, release of the inhibition of [3H]thymidine incorporation, and restoration of anchorage-independent growth phenotype. The overexpression of c-myc, observed in ChaGo cells, was unaffected by the reduced level of alpha-HCG. These results suggest that ectopic synthesis of the alpha subunit of HCG plays a functional role in the transformation of these human lung cells.

Heroes and Legends Exhibit

NASA Image and Video Library

2016-11-07

Inside the Heroes and Legends attraction at the Kennedy Space Center Visitor Complex, the Sigma 7 Mercury spacecraft in this exhibit was piloted by astronaut Wally Schirra during his six-orbit mission on Oct. 3, 1962. For display purposes, it is shown here attached to a Redstone launch vehicle like the one that boosted astronauts Alan Shepard and Gus Grissom on sub-orbital flights in 1961. Schirra's capsule was actually launched by the more powerful Atlas rocket in order to reach orbit. The new facility looks back to the pioneering efforts of Mercury, Gemini and Apollo. It sets the stage by providing the background and context for space exploration and the legendary men and women who pioneered the nation's journey into space.

Exhibition of stochastic resonance in vestibular tilt motion perception.

PubMed

Galvan-Garza, R C; Clark, T K; Mulavara, A P; Oman, C M

2018-04-03

Stochastic Resonance (SR) is a phenomenon broadly described as "noise benefit". The application of subsensory electrical Stochastic Vestibular Stimulation (SVS) via electrodes behind each ear has been used to improve human balance and gait, but its effect on motion perception thresholds has not been examined. This study investigated the capability of subsensory SVS to reduce vestibular motion perception thresholds in a manner consistent with a characteristic bell-shaped SR curve. We measured upright, head-centered, roll tilt Direction Recognition (DR) thresholds in the dark in 12 human subjects with the application of wideband 0-30 Hz SVS ranging from ±0-700 μA. To conservatively assess if SR was exhibited, we compared the proportions of both subjective and statistical SR exhibition in our experimental data to proportions of SR exhibition in multiple simulation cases with varying underlying SR behavior. Analysis included individual and group statistics. As there is not an established mathematical definition, three humans subjectively judged that SR was exhibited in 78% of subjects. "Statistically significant SR exhibition", which additionally required that a subject's DR threshold with SVS be significantly lower than baseline (no SVS), was present in 50% of subjects. Both percentages were higher than simulations suggested could occur simply by chance. For SR exhibitors, defined by subjective or statistically significant criteria, the mean DR threshold improved by -30% and -39%, respectively. The largest individual improvement was -47%. At least half of the subjects were better able to perceive passive body motion with the application of subsensory SVS. This study presents the first conclusive demonstration of SR in vestibular motion perception. Copyright © 2018 Elsevier Inc. All rights reserved.

Exploring the Invisible Universe: A Tactile and Braille Exhibit of Astronomical Images

NASA Astrophysics Data System (ADS)

Arcand, K. K.; Watzke, M.; de Pree, C.

2010-06-01

A tactile/Braille exhibit for the visually impaired community in the USA was launched in July 2009. The exhibit is part of the global From Earth to the Universe (FETTU) project, a Cornerstone of the International Year of Astronomy 2009. The science content of the travelling tactile/Braille exhibit includes explanations of our Sun, Eta Carinae, the Crab Nebula, the Whirlpool Galaxy and the electromagnetic spectrum, and was adapted from the tactile/Braille book Touch the Invisible Sky. We present some of the early observations and findings on the tactile/Braille FETTU exhibit. The new exhibit opens a wider door to experiencing and understanding astronomy for the underserved visually impaired population.

An Interactive Exhibition about Animal Skeletons: Did the Visitors Learn Any Zoology?

ERIC Educational Resources Information Center

Tunnicliffe, Sue Dale; Laterveer-de Beer, Manon

2002-01-01

Explores museum visitors' understanding of skeleton exhibits and whether such exhibits increase their understanding of the zoology displayed. The exhibition under study focused on the diversity of vertebrae skeletons which were arranged according to the mode of locomotion. (DDR)

"Wenn die Erde bebt", an educational public exhibition in Vienna

NASA Astrophysics Data System (ADS)

Parithusta, Rizkita; Brueckl, Ewald; Heuer, Rudolf; Mitterbauer, Ulrike

2010-05-01

Natural disasters can cause the loss of human lives, an economic crisis and also the loss of irreplaceable cultural heritage. Earthquakes can mean instantaneous destruction without warning, causing extensive and often irreparable damage to our heritage. An exhibition with the title "Wenn die Erde bebt" (i.e. "When the Earth shakes") which was held at the Natural History Museum, Vienna; in an effort to introduce understanding, awareness, and preparedness to the public, facing earthquake phenomenon. The exhibition compiled and classified examples of large earthquakes and introduces into the basic principles of seismology. It further addresses earthquake impact and how to live with earthquakes, giving access to the most suitable procedure of safety education. The idea of the exhibition is communicated by the means of posters, videos, and physical models which support the understanding of seismometry, elastic rebound theory and earthquake resistant construction. The exhibition is an Austrian contribution to IYPE - International Year of Planet Earth and is now on tour through Austria.

Exhibit of School Architecture, 1996. Special Section.

ERIC Educational Resources Information Center

Texas Architect, 1997

1997-01-01

Presents selected winners of the Texas 1996 Exhibit of School Architecture Design Competition. The Caudill and honor award-winning projects are listed along with facility photos, brief descriptions, project credits, and the names of the construction companies used. (GR)

Exhibit of School Architecture, 1997. Special Section.

ERIC Educational Resources Information Center

Texas Architect, 1998

1998-01-01

Presents selected winners of the Texas 1997 Exhibit of School Architecture Design Competition. The Caudill and honor award winning projects are listed along with facility photos, brief descriptions, project credits, and the names of the construction companies used. (GR)

46 CFR 167.60-10 - Exhibition of certificate of inspection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PUBLIC NAUTICAL SCHOOL SHIPS Certificates of Inspection § 167.60-10 Exhibition of certificate of inspection. On every nautical school ship, the original certificate of inspection shall be framed under glass... 46 Shipping 7 2010-10-01 2010-10-01 false Exhibition of certificate of inspection. 167.60-10...

Perspectives on ... Multiculturalism and Library Exhibits: Sites of Contested Representation

ERIC Educational Resources Information Center

Reece, Gwendolyn J.

2005-01-01

This article analyzes a multicultural library exhibit presenting the Palestinian/Israeli conflict as a site of contested representation. Qualitative methodology is used to interrogate the exhibit and its audience reception. Drawing on insights from critical pedagogy, implications for libraries arising from this case study are given and suggestions…

SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer

PubMed Central

Zhou, Xiaorong; Comerford, Sarah A.; York, Brian; O’Donnell, Kathryn A.

2017-01-01

Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis. To determine if genetic loss of SRC-2 is sufficient to accelerate MYC-mediated liver tumorigenesis, we bred Src-2-/- mice with a MYC-induced liver tumor model and observed a significant increase in liver tumor burden. RNA sequencing of liver tumors and in vivo chromatin immunoprecipitation assays revealed a set of direct target genes that are bound by SRC-2 and exhibit downregulated expression in Src-2-/- liver tumors. We demonstrate that activation of SHP (Small Heterodimer Partner), DKK4 (Dickkopf-4), and CADM4 (Cell Adhesion Molecule 4) by SRC-2 suppresses tumorigenesis in vitro and in vivo. These studies suggest that SRC-2 may exhibit oncogenic or tumor suppressor activity depending on the target genes and nuclear receptors that are expressed in distinct tissues and illuminate the mechanisms of tumor suppression by SRC-2 in liver. PMID:28273073

Enhancing Nontraditional Informal Programs Using Exhibitions: a case study of MarsQuest

NASA Astrophysics Data System (ADS)

Dusenbery, P. B.

2001-12-01

The Space Science Institute (SSI) of Boulder, Colorado has recently developed a large traveling exhibition called MarsQuest. The 5,000 square foot exhibition will enable millions of Americans to share in the excitement of the scientific exploration of Mars and learn more about their own planet in the process. A large exhibition, like MarsQuest, can provide a memorable experience for visitors, but it does not have to end there. A variety of nontraditional informal activities can tie into such informal science education projects to enhance and extend their impact. I will first discuss the MarsQuest exhibition that features compelling hands-on displays, updateable computer stations, and models that offer memorable experiences for visitors of all ages. The MarsQuest Education Program includes a professional development workshop for teachers, a museum staff orientation, web resources, and a public talk by a Mars scientist. By surrounding visitors with vivid Mars images, the planetarium show, narrated by Patrick Stewart, expands on the exhibition's main themes and allows visitors to delve deeper into the mysteries of Mars. The MarsQuest exhibition is proving to be extraordinarily successful. The exhibit's three-year tour is already fully booked (a second 3-year tour is planned), and the exhibit has been met with tremendous amounts of publicity and press coverage at its venues to date. The MarsQuest experience will be used to explore how a large exhibition can enhance nontraditional informal programs such as public talks by scientists, mall science events, camp-ins, public demonstrations, interactive web events, and the creation of mini versions that can travel to smaller venues in underserved regions of the country. I will then discuss how these activities can best piggyback on the media attention and public awareness that is generated by a large exhibition.

Mediating the Message: The Team Approach to Developing Interdisciplinary Science Exhibitions

NASA Astrophysics Data System (ADS)

Stauffer, B. W.; Starrs, S. K.

2005-05-01

Museum exhibition developers can take advantage of a wide range of methods and media for delivering scientific information to a general audience. But, determining what information to convey and which medium is the best means of conveying it can be an arduous process. How do you design an exhibition so a visiting fifth grade school group learns basic scientific concepts while an amateur naturalist finds enough rich content to warrant coming back in a few months? How much or how little media should be included? What forms of media are most appropriate? Answering these questions requires intensive and iterative collaboration and compromise among a team of educators, scientists and designers. The National Museum of Natural History's Forces of Change Program uses a unique team approach that includes scientific, exhibit design, and education experts to create interdisciplinary science exhibitions. Exhibit topics have explored the dynamics of a grasslands ecosystem, global impacts of El Nino, climate change in the Arctic, the functions of the atmosphere, and soil composition. Exhibition-related products include publications, scavenger hunts, interactive computer kiosks, educational CD-ROMs, animated cartoons, web sites, and school group activities. Team members will describe the team process and the iterative discussions involved in developing these products so they are as scientifically sound and engaging as possible.

Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT

PubMed Central

2011-01-01

Background The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. Methods The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. Results The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar. Conclusions We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment. PMID:21943074

Application of Glass Fiber Reinforced Cement in Exhibition Decoration Project

NASA Astrophysics Data System (ADS)

Wang, Yao

2018-02-01

Through the study of GRC material and its application field, the aesthetic characteristics and functional characteristics of GRC materials are demonstrated. The decorative application and technology of GRC material in an art exhibition center are highlighted. The design, application and construction technology of GRC curtain wall and ceiling board in the interior and exterior decoration of art exhibition hall are discussed in detail. The unique advantages of GRC materials in exhibition engineering decoration are fully reflected. In practical design application, the application principle and method are summarized, and an application procedure is formed. The research proves that GRC materials in the art of building decoration engineering has an underrated advantage.

One exhibition, many goals. Combining scientific research and risk communication

NASA Astrophysics Data System (ADS)

Charrière, Marie; Bogaard, Thom; Junier, Sandra; Malet, Jean-Philippe; Mostert, Erik

2015-04-01

How effective is visual communication to increase awareness of natural hazards and risks? To answer this research question, we developed a research design that was at the same time an experimental setting and an actual communication effort. Throughout the full length of the 2-years project held in the Ubaye valley (southeastern France), we collaborated with local and regional stakeholders (politicians and technicians). During a consultation phase, the communication context was determined, the audience of the project was defined and finally the testing activity-communication effort was determined. We were offered the opportunity to design an exhibition for the local public library. In a consultation phase that corresponded to the design of the exhibition, the stakeholders contributed to its content as well as helping with the funding of the exhibition. Finally, during the experimentation phase, the stakeholders participated in advertising the activity, gathering of participants and designing the scientific survey. In order to assess the effects of the exhibition on risk awareness, several groups of children, teenagers and adults were submitted to a research design, consisting of 1) a pre-test, 2) the visit of the exhibition and 3) a post-test similar to the pre-test. In addition, the children answered a second post-test 3 months after the visit. Close ended questions addressed the awareness indicators mentioned in the literature, i.e. worry level, previous experiences with natural hazards events, exposure to awareness raising, ability to mitigate/respond/prepare, attitude to risk, and demographics. In addition, the post-test included several satisfaction questions concerning the visual tools displayed in the exhibition. A statistical analysis of the changes between the pre- and post- tests (paired t-test, Wilcoxon signed-rank test and bootstrapping) allowed to verify whether the exhibition had an impact on risk awareness or not. In order to deduce which variable

45 CFR 13.7 - Studies, exhibits, analyses, engineering reports, tests and projects.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Studies, exhibits, analyses, engineering reports... Studies, exhibits, analyses, engineering reports, tests and projects. The reasonable cost (or the reasonable portion of the cost) for any study, exhibit, analysis, engineering report, test, project or...

45 CFR 13.7 - Studies, exhibits, analyses, engineering reports, tests and projects.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Studies, exhibits, analyses, engineering reports... Studies, exhibits, analyses, engineering reports, tests and projects. The reasonable cost (or the reasonable portion of the cost) for any study, exhibit, analysis, engineering report, test, project or...

45 CFR 13.7 - Studies, exhibits, analyses, engineering reports, tests and projects.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Studies, exhibits, analyses, engineering reports... Studies, exhibits, analyses, engineering reports, tests and projects. The reasonable cost (or the reasonable portion of the cost) for any study, exhibit, analysis, engineering report, test, project or...

45 CFR 13.7 - Studies, exhibits, analyses, engineering reports, tests and projects.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Studies, exhibits, analyses, engineering reports... Studies, exhibits, analyses, engineering reports, tests and projects. The reasonable cost (or the reasonable portion of the cost) for any study, exhibit, analysis, engineering report, test, project or...

45 CFR 13.7 - Studies, exhibits, analyses, engineering reports, tests and projects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Studies, exhibits, analyses, engineering reports... Studies, exhibits, analyses, engineering reports, tests and projects. The reasonable cost (or the reasonable portion of the cost) for any study, exhibit, analysis, engineering report, test, project or...

Online Cultural Heritage Exhibitions: A Survey of Information Retrieval Features

ERIC Educational Resources Information Center

Liew, Chern Li

2005-01-01

Purpose: What kinds of online cultural heritage exhibitions are now available on the internet? How far have these cultural heritage institutions voyaged in terms of harnessing the power of information and communication technology and the interactivity of multimedia systems to exhibit cultural heritage resources? This study aims to highlight the…

7 CFR Exhibit B to Subpart B of... - Servicing Company

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 12 2013-01-01 2013-01-01 false Servicing Company B Exhibit B to Subpart B of Part 1806 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL... GENERAL REGULATIONS INSURANCE National Flood Insurance Pt. 1806, Subpt. B, Exh. B Exhibit B to Subpart B...

7 CFR Exhibit B to Subpart B of... - Servicing Company

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 12 2014-01-01 2013-01-01 true Servicing Company B Exhibit B to Subpart B of Part 1806 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL... GENERAL REGULATIONS INSURANCE National Flood Insurance Pt. 1806, Subpt. B, Exh. B Exhibit B to Subpart B...

7 CFR Exhibit B to Subpart B of... - Servicing Company

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 12 2012-01-01 2012-01-01 false Servicing Company B Exhibit B to Subpart B of Part 1806 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL... GENERAL REGULATIONS INSURANCE National Flood Insurance Pt. 1806, Subpt. B, Exh. B Exhibit B to Subpart B...

7 CFR Exhibit B to Subpart B of... - Servicing Company

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 12 2011-01-01 2011-01-01 false Servicing Company B Exhibit B to Subpart B of Part 1806 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL... GENERAL REGULATIONS INSURANCE National Flood Insurance Pt. 1806, Subpt. B, Exh. B Exhibit B to Subpart B...

7 CFR Exhibit B to Subpart B of... - Servicing Company

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Servicing Company B Exhibit B to Subpart B of Part 1806 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL... GENERAL REGULATIONS INSURANCE National Flood Insurance Pt. 1806, Subpt. B, Exh. B Exhibit B to Subpart B...

7 CFR Exhibit A to Subpart Jj of... - Agreement Form

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 15 2014-01-01 2014-01-01 false Agreement Form A Exhibit A to Subpart JJ of Part 2045.... A Exhibit A to Subpart JJ of Part 2045—Agreement Form for utilization of employees of (official... Agreement, date ___ between, , a (political subdivision), (educational), (charitable), (or nonprofit) an...

7 CFR Exhibit A to Subpart Jj of... - Agreement Form

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 15 2011-01-01 2011-01-01 false Agreement Form A Exhibit A to Subpart JJ of Part 2045.... A Exhibit A to Subpart JJ of Part 2045—Agreement Form for utilization of employees of (official... Agreement, date ___ between, , a (political subdivision), (educational), (charitable), (or nonprofit) an...

19 CFR 146.52 - Manipulation, manufacture, exhibition or destruction; Customs Form 216.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Manipulation, manufacture, exhibition or... Merchandise in a Zone § 146.52 Manipulation, manufacture, exhibition or destruction; Customs Form 216. (a... application) on Customs Form 216 for permission to manipulate, manufacture, exhibit, or destroy merchandise in...

76 FR 17425 - Agency Information Collection Activities: Entry of Articles for Exhibition

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-29

... Activities: Entry of Articles for Exhibition AGENCY: U.S. Customs and Border Protection, Department of... of Articles for Exhibition (19 CFR 147.11(c)). This is a proposed extension of an information... other technological techniques or other forms of information. Title: Entry of Articles for Exhibition...

37 CFR 1.94 - Return of models, exhibits or specimens.

Code of Federal Regulations, 2010 CFR

2010-07-01

... business before the Office and will be returned, applicant must arrange for the return of the model... model, exhibit or specimen is no longer necessary for the conduct of business before the Office. (b... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Return of models, exhibits or...

Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells

PubMed Central

Li, Luyuan; Paz, Ana C.; Wilky, Breelyn A.; Johnson, Britt; Galoian, Karina; Rosenberg, Andrew; Hu, Guozhi; Tinoco, Gabriel; Bodamer, Olaf; Trent, Jonathan C.

2015-01-01

Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas. PMID:26368816

76 FR 4929 - Agency Information Collection Activities: Entry of Articles for Exhibition.

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

... Activities: Entry of Articles for Exhibition. AGENCY: U.S. Customs and Border Protection (CBP), Department of... requirement concerning the Entry of Articles for Exhibition (19 CFR 147.11(c)). This request for comment is...: Title: Entry of Articles for Exhibition. OMB Number: 1651-0037. Form Number: None. Abstract: Goods...

Crows spontaneously exhibit analogical reasoning.

PubMed

Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

2015-01-19

Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

7 CFR Exhibit G to Subpart A of... - Performance Bond

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 12 2013-01-01 2013-01-01 false Performance Bond G Exhibit G to Subpart A of Part 1924 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL.... 1924, Subpt. A, Exh. G Exhibit G to Subpart A of Part 1924—Performance Bond KNOW ALL PERSONS BY THESE...

39 CFR 955.23 - Copies of papers, withdrawal of exhibits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Copies of papers, withdrawal of exhibits. 955.23... SERVICE BOARD OF CONTRACT APPEALS § 955.23 Copies of papers, withdrawal of exhibits. (a) When books, records, papers, or documents have been received in evidence, a true copy thereof or of such part thereof...

Induced PTF1a expression in pancreatic ductal adenocarcinoma cells activates acinar gene networks, reduces tumorigenic properties, and sensitizes cells to gemcitabine treatment.

PubMed

Jakubison, Brad L; Schweickert, Patrick G; Moser, Sarah E; Yang, Yi; Gao, Hongyu; Scully, Kathleen; Itkin-Ansari, Pamela; Liu, Yunlong; Konieczny, Stephen F

2018-05-02

Pancreatic acinar cells synthesize, package, and secrete digestive enzymes into the duodenum to aid in nutrient absorption and meet metabolic demands. When exposed to cellular stresses and insults, acinar cells undergo a dedifferentiation process termed acinar-ductal metaplasia (ADM). ADM lesions with oncogenic mutations eventually give rise to pancreatic ductal adenocarcinoma (PDAC). In healthy pancreata, the basic helix-loop-helix (bHLH) factors MIST1 and PTF1a coordinate an acinar-specific transcription network that maintains the highly developed differentiation status of the cells, protecting the pancreas from undergoing a transformative process. However, when MIST1 and PTF1a gene expression is silenced, cells are more prone to progress to PDAC. In this study, we tested whether induced MIST1 or PTF1a expression in PDAC cells could (i) re-establish the transcriptional program of differentiated acinar cells and (ii) simultaneously reduce tumor cell properties. As predicted, PTF1a induced gene expression of digestive enzymes and acinar-specific transcription factors, while MIST1 induced gene expression of vesicle trafficking molecules as well as activation of unfolded protein response components, all of which are essential to handle the high protein production load that is characteristic of acinar cells. Importantly, induction of PTF1a in PDAC also influenced cancer-associated properties, leading to a decrease in cell proliferation, cancer stem cell numbers, and repression of key ATP-binding cassette efflux transporters resulting in heightened sensitivity to gemcitabine. Thus, activation of pancreatic bHLH transcription factors rescues the acinar gene program and decreases tumorigenic properties in pancreatic cancer cells, offering unique opportunities to develop novel therapeutic intervention strategies for this deadly disease. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

"Technology: Chance or Choice?"--A Museum Exhibit on the Impact of Technology.

ERIC Educational Resources Information Center

Ucko, David A.

1983-01-01

The Museum of Science and Industry (Chicago) has created a new exhibit, "Technology: Chance or Choice?," which emphasizes the human impact on technology. Development of and techniques used in the exhibit are discussed. The latter include microcomputers placed throughout the exhibit to pose questions about critical issues raised by particular…

Inside active volcanoes; an exhibit on the move!

USGS Publications Warehouse

Fiske, R.S.

1990-01-01

All of us are aware of the emphasis currently being placed in the United States on science education and public understanding of science. Most of this emphasis is directed toward mass audiences through book publications, school curricula, and television programs; sadly, most of it deals with non-earth science topics. In an effort to take advantage of this awakened consciousness and to highlight the earth sciences, the Smithsonian Institution and the U.S Geological Survey joined forces to prepare a traveling exhibit on volcanoes that is currently touring the country. This note will serve to bring you up to date on the progress of this exhibit as it reaches the mid-point of its tour. 

EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer.

PubMed

Dong, Y U; Ren, Weihong; Qi, Jun; Jin, B O; Li, Ying; Tao, Huiqing; Xu, Ren; Li, Yanqing; Zhang, Qinxian; Han, Baohui

2016-04-01

Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies

Space Research Institute (IKI) Exhibition as an Educational Project

NASA Astrophysics Data System (ADS)

Sadovski, Andrei; Antonenko, Elena

2016-07-01

The Exhibition "Space Science: Part and Future" in Space Research Institute (IKI) was opened in 2007 in commemoration of the 50th anniversary of the first man-made satellite launch. It covers the latest and the most important findings in space research, shows instruments which are used in space exploration, and presents past, current, and future Russian science missions. Prototypes of space instruments developed by Russian specialists and mockups of spacecraft and spaceships flown to space are displayed, together with information posters, describing space missions, their purposes and results. The Exhibition takes a great part in school space education. Its stuff actively works with schoolchildren, undergraduate students and also makes a great contribution in popularization of space researches. Moreover the possibility to learn about scientific space researches first-hand is priceless. We describe the main parts of the Exhibition and forms of it work and also describe the collaboration with other museums and educational organizations.

7 CFR Exhibit G to Subpart A of... - Performance Bond

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 12 2012-01-01 2012-01-01 false Performance Bond G Exhibit G to Subpart A of Part.... 1924, Subpt. A, Exh. G Exhibit G to Subpart A of Part 1924—Performance Bond KNOW ALL PERSONS BY THESE... and faithful performance of the CONTRACT as so amended. The term “Amendment”, wherever used in this...

7 CFR Exhibit G to Subpart A of... - Performance Bond

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Performance Bond G Exhibit G to Subpart A of Part.... 1924, Subpt. A, Exh. G Exhibit G to Subpart A of Part 1924—Performance Bond KNOW ALL PERSONS BY THESE... and faithful performance of the CONTRACT as so amended. The term “Amendment”, wherever used in this...

7 CFR Exhibit G to Subpart A of... - Performance Bond

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 12 2011-01-01 2011-01-01 false Performance Bond G Exhibit G to Subpart A of Part.... 1924, Subpt. A, Exh. G Exhibit G to Subpart A of Part 1924—Performance Bond KNOW ALL PERSONS BY THESE... and faithful performance of the CONTRACT as so amended. The term “Amendment”, wherever used in this...

7 CFR Exhibit G to Subpart A of... - Performance Bond

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 12 2014-01-01 2013-01-01 true Performance Bond G Exhibit G to Subpart A of Part 1924.... A, Exh. G Exhibit G to Subpart A of Part 1924—Performance Bond KNOW ALL PERSONS BY THESE PRESENTS... and faithful performance of the CONTRACT as so amended. The term “Amendment”, wherever used in this...

TGF-β Tumor Suppression through a Lethal EMT.

PubMed

David, Charles J; Huang, Yun-Han; Chen, Mo; Su, Jie; Zou, Yilong; Bardeesy, Nabeel; Iacobuzio-Donahue, Christine A; Massagué, Joan

2016-02-25

TGF-β signaling can be pro-tumorigenic or tumor suppressive. We investigated this duality in pancreatic ductal adenocarcinoma (PDA), which, with other gastrointestinal cancers, exhibits frequent inactivation of the TGF-β mediator Smad4. We show that TGF-β induces an epithelial-mesenchymal transition (EMT), generally considered a pro-tumorigenic event. However, in TGF-β-sensitive PDA cells, EMT becomes lethal by converting TGF-β-induced Sox4 from an enforcer of tumorigenesis into a promoter of apoptosis. This is the result of an EMT-linked remodeling of the cellular transcription factor landscape, including the repression of the gastrointestinal lineage-master regulator Klf5. Klf5 cooperates with Sox4 in oncogenesis and prevents Sox4-induced apoptosis. Smad4 is required for EMT but dispensable for Sox4 induction by TGF-β. TGF-β-induced Sox4 is thus geared to bolster progenitor identity, whereas simultaneous Smad4-dependent EMT strips Sox4 of an essential partner in oncogenesis. Our work demonstrates that TGF-β tumor suppression functions through an EMT-mediated disruption of a lineage-specific transcriptional network. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of silk sericin on the proliferation and apoptosis of colon cancer cells.

PubMed

Kaewkorn, Waraporn; Limpeanchob, Nanteetip; Tiyaboonchai, Waree; Pongcharoen, Sutatip; Sutheerawattananonda, Manote

2012-01-01

Sericin is a silk protein woven from silkworm cocoons (Bombyx mori). In animal model, sericin has been reported to have anti-tumoral action against colon cancer. The mechanisms underlying the activity of sericin against cancer cells are not fully understood. The present study investigated the effects of sericin on human colorectal cancer SW480 cells compared to normal colonic mucosal FHC cells. Since the size of the sericin protein may be important for its activity, two ranges of molecular weight were tested. Sericin was found to decrease SW480 and FHC cell viability. The small sericin had higher anti-proliferative effects than that of the large sericin in both cell types. Increased apoptosis of SW480 cells is associated with increased caspase-3 activity and decreased Bcl-2 expression. The anti-proliferative effect of sericin was accompanied by cell cycle arrest at the S phase. Thus, sericin reduced SW480 cell viability by inducing cell apoptosis via caspase-3 activation and down-regulation of Bcl-2 expression. The present study provides scientific data that support the protective effect of silk sericin against cancer cells of the colon and suggests that this protein may have significant health benefits and could potentially be developed as a dietary supplement for colon cancer prevention.

Kinetics of a single cross-bridge in familial hypertrophic cardiomyopathy heart muscle measured by reverse Kretschmann fluorescence

PubMed Central

Mettikolla, Prasad; Calander, Nils; Luchowski, Rafal; Gryczynski, Ignacy; Gryczynski, Zygmunt; Borejdo, Julian

2010-01-01

Familial hypertrophic cardiomyopathy (FHC) is a serious heart disease that often leads to a sudden cardiac death of young athletes. It is believed that the alteration of the kinetics of interaction between actin and myosin causes FHC by making the heart to pump blood inefficiently. We set out to check this hypothesis ex vivo. During contraction of heart muscle, a myosin cross-bridge imparts periodic force impulses to actin. The impulses are analyzed by fluorescence correlation spectroscopy (FCS) of fluorescently labeled actin. To minimize observation volume and background fluorescence, we carry out FCS measurements in surface plasmon coupled emission mode in a reverse Kretschmann configuration. Fluorescence is a result of near-field coupling of fluorophores excited in the vicinity of the metal-coated surface of a coverslip with the surface plasmons propagating in the metal. Surface plasmons decouple on opposite sides of the metal film and emit in a directional manner as far-field p-polarized radiation. We show that the rate of changes of orientation is significantly faster in contracting cardiac myofibrils of transgenic mice than wild type. These results are consistent with the fact that mutated heart muscle myosin translates actin faster in in vitro motility assays. PMID:20210485

48 CFR 6101.17 - Exhibits [Rule 17].

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Exhibits [Rule 17]. 6101.17 Section 6101.17 Federal Acquisition Regulations System CIVILIAN BOARD OF CONTRACT APPEALS, GENERAL... before the commencement of the hearing in order, for example, to eliminate the introduction of additional...

Analysis of the mutations induced by conazole fungicides in vivo.

PubMed

Ross, Jeffrey A; Leavitt, Sharon A

2010-05-01

The mouse liver tumorigenic conazole fungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue transgenic mutation assay when administered in feed at tumorigenic doses, whereas the non-tumorigenic conazole myclobutanil was not mutagenic. DNA sequencing of the mutants recovered from each treatment group as well as from animals receiving control diet was conducted to gain additional insight into the mode of action by which tumorigenic conazoles induce mutations. Relative dinucleotide mutabilities (RDMs) were calculated for each possible dinucleotide in each treatment group and then examined by multivariate statistical analysis techniques. Unsupervised hierarchical clustering analysis of RDM values segregated two independent control groups together, along with the non-tumorigen myclobutanil. The two tumorigenic conazoles clustered together in a distinct grouping. Partitioning around mediods of RDM values into two clusters also groups the triadimefon and propiconazole together in one cluster and the two control groups and myclobutanil together in a second cluster. Principal component analysis of these results identifies two components that account for 88.3% of the variability in the points. Taken together, these results are consistent with the hypothesis that propiconazole- and triadimefon-induced mutations do not represent clonal expansion of background mutations and support the hypothesis that they arise from the accumulation of reactive electrophilic metabolic intermediates within the liver in vivo.

Science Exhibitions Promote College and Community Interaction.

ERIC Educational Resources Information Center

Stout, Dorothy LaLonde

1991-01-01

Science exhibitions presented by college students at local elementary schools foster goodwill in the community; give college students an opportunity to share their science as role models; provide elementary school children with a positive, enjoyable approach to science; and can be organized rather easily following guidelines that outline…

Using NLM exhibits and events to engage library users and reach the community.

PubMed

Auten, Beth; Norton, Hannah F; Tennant, Michele R; Edwards, Mary E; Stoyan-Rosenzweig, Nina; Daley, Matthew

2013-01-01

In an effort to reach out to library users and make the library a more relevant, welcoming place, the University of Florida's Health Science Center Library hosted exhibits from the National Library of Medicine's (NLM) Traveling Exhibition Program. From 2010 through 2012, the library hosted four NLM exhibits and created event series for each. Through reflection and use of a participant survey, lessons were learned concerning creating relevant programs, marketing events, and forming new partnerships. Each successive exhibit added events and activities to address different audiences. A survey of libraries that have hosted NLM exhibits highlights lessons learned at those institutions.

Galaxy Makers Exhibition: Re-engagement, Evaluation and Content Legacy through an Online Component

NASA Astrophysics Data System (ADS)

Borrow, J.; Harrison, C.

2017-09-01

For the Royal Society Summer Science Exhibition 2016, Durham University's Institute of Computational Cosmology created the Galaxy Makers exhibit to communicate our computational cosmology and astronomy research. In addition to the physical exhibit we created an online component to foster re-engagement, create a permanent home for our content and allow us to collect important information about participation and impact. Here we summarise the details of the exhibit and the degree of success attached to the online component. We also share suggestions for further uses and improvements that could be implemented for the online components of other science exhibitions.

The Making of the Fathers of Astronomy Exhibit

NASA Astrophysics Data System (ADS)

Graney, C. M.

2010-10-01

The International Year of Astronomy 2009 stretched a few days into 2010 here in Louisville, Kentucky - the Fathers of Astronomy exhibit at the Frazier International History Museum did not close until 3 January 2010. Fathers of Astronomy, which was open for five months, told the story of Galileo through authentic original editions of three books - the 1493 Nuremberg Chronicle, Nicolas Copernicus's 1543 On the Revolutions of Heavenly Spheres, and Galileo Galilei's 1632 Dialogue Concerning the two Chief World Systems. The success of "Fathers" resulted from three very different partners coming together and combining resources to produce a history-themed IYA2009 programme of the highest quality at minimal cost. Lessons learned from the exhibit may be of value to people interested in communicating astronomy to the public.

14 CFR 14.11 - Net worth exhibit.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Net worth exhibit. 14.11 Section 14.11 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES RULES IMPLEMENTING THE EQUAL ACCESS TO JUSTICE ACT OF 1980 Information Required From Applicants § 14.11 Net worth...

14 CFR 14.11 - Net worth exhibit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Net worth exhibit. 14.11 Section 14.11 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES RULES IMPLEMENTING THE EQUAL ACCESS TO JUSTICE ACT OF 1980 Information Required From Applicants § 14.11 Net worth...

14 CFR 14.11 - Net worth exhibit.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Net worth exhibit. 14.11 Section 14.11 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES RULES IMPLEMENTING THE EQUAL ACCESS TO JUSTICE ACT OF 1980 Information Required From Applicants § 14.11 Net worth...

14 CFR 14.11 - Net worth exhibit.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Net worth exhibit. 14.11 Section 14.11 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES RULES IMPLEMENTING THE EQUAL ACCESS TO JUSTICE ACT OF 1980 Information Required From Applicants § 14.11 Net worth...

14 CFR 14.11 - Net worth exhibit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Net worth exhibit. 14.11 Section 14.11 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES RULES IMPLEMENTING THE EQUAL ACCESS TO JUSTICE ACT OF 1980 Information Required From Applicants § 14.11 Net worth...

76 FR 29286 - Culturally Significant Objects Imported for Exhibition Determinations: “Pissarro's People”

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... DEPARTMENT OF STATE [Public Notice 7462] Culturally Significant Objects Imported for Exhibition Determinations: ``Pissarro's People'' SUMMARY: Notice is hereby given of the following determinations: Pursuant... the exhibition ``Pissarro's People,'' imported from abroad for temporary exhibition within the United...

77 FR 52783 - Culturally Significant Objects Imported for Exhibition Determinations: “Federico Barocci...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... DEPARTMENT OF STATE [Public Notice 8001] Culturally Significant Objects Imported for Exhibition Determinations: ``Federico Barocci: Renaissance Master'' SUMMARY: Notice is hereby given of the following... exhibition ``Federico Barocci: Renaissance Master,'' imported from abroad for temporary exhibition within the...

Comic Strips to Accompany Science Museum Exhibits

ERIC Educational Resources Information Center

Chung, Beom Sun; Park, Eun-mi; Kim, Sang-Hee; Cho, Sook-kyoung; Chung, Min Suk

2016-01-01

Science museums make the effort to create exhibits with amusing explanations. However, existing explanation signs with lengthy text are not appealing, and as such, visitors do not pay attention to them. In contrast, conspicuous comic strips composed of simple drawings and humors can attract science museum visitors. This study attempted to reveal…

49 CFR 1016.202 - Net worth exhibit.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Net worth exhibit. 1016.202 Section 1016.202... BY PARTIES TO BOARD ADJUDICATORY PROCEEDINGS Information Required From Applicants § 1016.202 Net... worth of the applicant and any affiliates (as defined in § 1016.105(f) of this part) when the proceeding...

49 CFR 1016.202 - Net worth exhibit.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Net worth exhibit. 1016.202 Section 1016.202... BY PARTIES TO BOARD ADJUDICATORY PROCEEDINGS Information Required From Applicants § 1016.202 Net... worth of the applicant and any affiliates (as defined in § 1016.105(f) of this part) when the proceeding...

Smoking and Health Experiments, Demonstrations, and Exhibits.

ERIC Educational Resources Information Center

Center for Disease Control (DHEW/PHS), Atlanta, GA.

This booklet of experiments was compiled from various teachers' guides in response to the many requests from students for help in preparing smoking demonstrations and exhibits. The booklet is divided into three sections. Part 1 illustrates a number of experiments, most of which require some laboratory equipment. Part 2 includes a number of…

Do Online Students Exhibit Different Learning Styles

ERIC Educational Resources Information Center

Hausler, Joel; Sanders, John W.; Young, Barbara

2007-01-01

We examined the relationship between learning styles and student type. This research seeks to examine if online students exhibit different learning styles from onsite students; and, if so, what accommodations relating to learning style differences may be made for online students? Students (N = 80) were asked to complete an online survey in order…

Using NLM Exhibits and Events to Engage Library Users and Reach the Community

PubMed Central

Auten, Beth; Norton, Hannah F.; Tennant, Michele R.; Edwards, Mary E.; Stoyan-Rosenzweig, Nina; Daley, Matthew

2013-01-01

In an effort to reach out to library users and make the library a more relevant, welcoming place, the University of Florida’s Health Science Center Library hosted exhibits from the National Library of Medicine’s (NLM) Traveling Exhibition Program. From 2010 through 2012, the library hosted four NLM exhibits and created event series for each. Through reflection and use of a participant survey, lessons were learned concerning creating relevant programs, marketing events, and forming new partnerships. Each successive exhibit added events and activities to address different audiences. A survey of libraries that have hosted NLM exhibits highlights lessons learned at those institutions. PMID:23869634

Naval Meteorology and Oceanography Command exhibit

NASA Technical Reports Server (NTRS)

2000-01-01

Designed to entertain while educating, StenniSphere at the John C. Stennis Space Center in Hancock County, Miss., includes informative displays and exhibits from NASA and other agencies located at Stennis, such as this one from the Naval Meteorology and Oceanography Command. Visitors can 'travel' three-dimensionally under the sea and check on the weather back home in the Weather Center. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.

Witnessing Each Other: An Intersubjective Stance for Exhibitions Relating to Substance Use and Abuse.

PubMed

Hennes, Tom

2015-01-01

Most exhibitions are conceived to convey information the experts making the exhibition believe other people need or want. But the notion that the intended exhibition public will cooperate with the exhibition organizers. intent disregards the reasons people come to exhibitions and the way they use them. While the author contends that an exhibition cannot use facts to convince someone to abstain from substances they crave, exhibitions can nonetheless make a difference in lives complicated by substance use by providing representation for voices that are rarely heard and building empathy between witness and witnessed. The purpose of such an endeavor is not to change attitudes or behaviors toward a pre-determined outcome, but to facilitate a witnessing of others. The uniquely intersubjective medium of exhibition can thus succeed in this field by opening the potential of mutual, humanizing recognition among people with varied life experience of substance use and abuse.

Uranium mining wastes, garden exhibition and health risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, Gerhard; Schmidt, Peter; Hinz, Wilko

2007-07-01

Available in abstract form only. Full text of publication follows: For more than 40 years the Soviet-German stockholding company SDAG WISMUT mined and milled Uranium in the East of Germany and became up to 1990 the world's third largest Uranium producer. After reunification of Germany, the new found state own company Wismut GmbH was faced with the task of decommissioning and rehabilitation of the mining and milling sites. One of the largest mining areas in the world, that had to be cleaned up, was located close to the municipality of Ronneburg near the City of Gera in Thuringia. After closingmore » the operations of the Ronneburg underground mine and at the 160 m deep open pit mine with a free volume of 84 Mio.m{sup 3}, the open pit and 7 large piles of mine waste, together 112 Mio.m{sup 3} of material, had to be cleaned up. As a result of an optimisation procedure it was chosen to relocate the waste rock piles back into the open pit. After taking this decision and approval of the plan the disposal operation was started. Even though the transport task was done by large trucks, this took 16 years. The work will be finished in 2007, a cover consisting of 40 cm of uncontaminated material will be placed on top of the material, and the re-vegetation of the former open pit area will be established. When in 2002 the City of Gera applied to host the largest garden exhibition in Germany, Bundesgartenschau (BUGA), in 2007, Wismut GmbH supported this plan by offering parts of the territory of the former mining site as an exhibition ground. Finally, it was decided by the BUGA organizers to arrange its 2007 exhibition on grounds in Gera and in the valley adjacent to the former open pit mine, with parts of the remediated area within the fence of the exhibition. (authors)« less

Exhibition of Monogamy Relations between Entropic Non-contextuality Inequalities

NASA Astrophysics Data System (ADS)

Zhu, Feng; Zhang, Wei; Huang, Yi-Dong

2017-06-01

We exhibit the monogamy relation between two entropic non-contextuality inequalities in the scenario where compatible projectors are orthogonal. We show the monogamy relation can be exhibited by decomposing the orthogonality graph into perfect induced subgraphs. Then we find two entropic non-contextuality inequalities are monogamous while the KCBS-type non-contextuality inequalities are not if the orthogonality graphs of the observable sets are two odd cycles with two shared vertices. Supported by 973 Programs of China under Grant Nos. 2011CBA00303 and 2013CB328700, Basic Research Foundation of Tsinghua National Laboratory for Information Science and Technology (TNList)

Maintaining Students' Speaking Fluency through Exhibition Examination in Sociolinguistic Studies

ERIC Educational Resources Information Center

Yuliatuty, Khusnul Qhotimah

2013-01-01

Using exhibition for the final project in Sociolinguistic study is really interesting for Universitas Siswa Bangsa Internasional students, especially for 2011 English Department students. Exhibition becomes interesting because this is the new thing to conduct the final project for English Department students' cohort 2011 at Universitas Siswa…

``From Earth to the Solar System'' Traveling Exhibit Visits Puerto Rico

NASA Astrophysics Data System (ADS)

Pantoja, C. A.; Lebrón, M. E.; Isidro, G. M.

2013-04-01

Puerto Rico was selected as one of the venues for the exhibit “From Earth to the Solar System” (FETTSS) during the month of October 2011. A set of outreach activities were organized to take place during the month of October aligned with the FETTSS themes. These activities included the following: 1) Main Exhibit, 2) Guided tours for school groups, 3) Planet Festival, 4) Film Festival and 5) Astronomy Conferences. We describe this experience and in particular the work with a group of undergraduate students from the University of Puerto Rico (UPR) that assisted in the outreach events. Among this group were three blind students. The FETTSS exhibit included a set of tactile and Braille images for the blind and visually impaired. A special exhibit was prepared with additional adapted materials for the visually impaired. This allowed blind visitors to participate and the general public to become more aware of the needs of this population.

Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

PubMed Central

Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

2009-01-01

The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E2). With these LTEE cells and with parallel control cells cultured without E2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E2-dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E2. PMID:19619570

Preventing Youth Pregnancy: Dialogue and Deliberation in a Science Museum Exhibit

ERIC Educational Resources Information Center

Navas-Iannini, Ana Maria; Pedretti, Erminia

2017-01-01

In this article, we explore how visitors engage with a science museum exhibit that displays controversial topics. Through a case study methodology, we focus on the Brazilian exhibit "Preventing Youth Pregnancy" that delves into teen pregnancy, sexual practices, and sexually transmitted diseases. Using the lens of science communication…

22 CFR 224.22 - Exchange of witness lists, statements, and exhibits.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Exchange of witness lists, statements, and exhibits. 224.22 Section 224.22 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT IMPLEMENTATION OF THE PROGRAM FRAUD CIVIL REMEDIES ACT § 224.22 Exchange of witness lists, statements, and exhibits. (a...

22 CFR 224.22 - Exchange of witness lists, statements, and exhibits.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Exchange of witness lists, statements, and exhibits. 224.22 Section 224.22 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT IMPLEMENTATION OF THE PROGRAM FRAUD CIVIL REMEDIES ACT § 224.22 Exchange of witness lists, statements, and exhibits. (a...

22 CFR 224.22 - Exchange of witness lists, statements, and exhibits.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Exchange of witness lists, statements, and exhibits. 224.22 Section 224.22 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT IMPLEMENTATION OF THE PROGRAM FRAUD CIVIL REMEDIES ACT § 224.22 Exchange of witness lists, statements, and exhibits. (a...

22 CFR 224.22 - Exchange of witness lists, statements, and exhibits.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Exchange of witness lists, statements, and exhibits. 224.22 Section 224.22 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT IMPLEMENTATION OF THE PROGRAM FRAUD CIVIL REMEDIES ACT § 224.22 Exchange of witness lists, statements, and exhibits. (a...

22 CFR 224.22 - Exchange of witness lists, statements, and exhibits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Exchange of witness lists, statements, and exhibits. 224.22 Section 224.22 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT IMPLEMENTATION OF THE PROGRAM FRAUD CIVIL REMEDIES ACT § 224.22 Exchange of witness lists, statements, and exhibits. (a...

After Terror Charges, Artist Exhibits Academic Freedom

ERIC Educational Resources Information Center

Wilson, Robin

2008-01-01

Steven Kurtz, a professor of visual studies at the State University of New York, has been working with various bacteria as part of his counterculture exhibit artworks for nearly 20 years. Four years ago, federal agents raided his home in a bioterrorism investigation. The federal agents had been called to the house by local police officers…

The "Gravity-Powered Calculator," a Galilean Exhibit

ERIC Educational Resources Information Center

Cerreta, Pietro

2014-01-01

The Gravity-Powered Calculator is an exhibit of the Exploratorium in San Francisco. It is presented by its American creators as an amazing device that extracts the square roots of numbers, using only the force of gravity. But if you analyze his concept construction one can not help but recall the research of Galileo on falling bodies, the inclined…

University of Maryland MRSEC - NanoFabulous Exhibit

Science.gov Websites

NanoFabulous, an exciting interactive museum exhibition designed to help children and their families understand we can engage children, the more likely they are to develop a life-long interest in STEM," says with Nano is to present nanoscience to children in a fun and engaging way that they can understand, and

History and the Culture Wars: The Case of the Smithsonian Institution's Enola Gay Exhibition.

ERIC Educational Resources Information Center

Kohn, Richard H.

1995-01-01

Presents an excellent summation of the controversy over the Smithsonian's Enola Gay exhibit. Delineates the preparation of the exhibit, nature and origins of the objections raised, subsequent revisions in the text, and the decision to cancel the exhibit. Includes textual passages from the most disputed sections of the exhibit. (MJP)

Reduction of virion-associated σ1 fibers on oncolytic reovirus variants promotes adaptation toward tumorigenic cells.

PubMed

Mohamed, Adil; Teicher, Carmit; Haefliger, Sarah; Shmulevitz, Maya

2015-04-01

Wild-type mammalian orthoreovirus serotype 3 Dearing (T3wt) is nonpathogenic in humans but preferentially infects and kills cancer cells in culture and demonstrates promising antitumor activity in vivo. Using forward genetics, we previously isolated two variants of reovirus, T3v1 and T3v2, with increased infectivity toward a panel of cancer cell lines and improved in vivo oncolysis in a murine melanoma model relative to that of T3wt. Our current study explored how mutations in T3v1 and T3v2 promote infectivity. Reovirions contain trimers of σ1, the reovirus cell attachment protein, at icosahedral capsid vertices. Quantitative Western blot analysis showed that purified T3v1 and T3v2 virions had ∼ 2- and 4-fold-lower levels of σ1 fiber than did T3wt virions. Importantly, using RNA interference to reduce σ1 levels during T3wt production, we were able to generate wild-type reovirus with reduced levels of σ1 per virion. As σ1 levels were reduced, virion infectivity increased by 2- to 5-fold per cell-bound particle, demonstrating a causal relationship between virion σ1 levels and the infectivity of incoming virions. During infection of tumorigenic L929 cells, T3wt, T3v1, and T3v2 uncoated the outer capsid proteins σ3 and μ1C at similar rates. However, having started with fewer σ1 molecules, a complete loss of σ1 was achieved sooner for T3v1 and T3v2. Distinct from intracellular uncoating, chymotrypsin digestion, as a mimic of natural enteric infection, resulted in more rapid σ3 and μ1C removal, unique disassembly intermediates, and a rapid loss of infectivity for T3v1 and T3v2 compared to T3wt. Optimal infectivity toward natural versus therapeutic niches may therefore require distinct reovirus structures and σ1 levels. Wild-type reovirus is currently in clinical trials as a potential cancer therapy. Our molecular studies on variants of reovirus with enhanced oncolytic activity in vitro and in vivo now show that distinct reovirus structures promote