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Sample records for promote neoplastic transformation

  1. Promoting effect of bile acids on neoplastic transformation of x-irradiated 10T1/2 cells

    International Nuclear Information System (INIS)

    Han, A.; Hill, C.K.

    1984-01-01

    Experimental studies have raised a concern about a role of bile acids in colo-rectal carcinogenesis. Studies in vivo suggest that bile acids may act as tumor promoters. Using 10T1/2 mouse cells as a model system, the authors explored the effects of cholic and cheno-deoxycholic acid on x-ray-induced neoplastic transformation in these cells. Addition of either cheno-deoxycholic acid or cholic acid to 10T1/2 cells, 24 hours after exposure to x-rays (50kv) increases significantly the frequencies of transformation. The compounds were present in the medium throughout the entire postirradiation refeeding period. At the concentrations used (0.5μg/ml), neither acid was cytotoxic and did not have any effect on cell survival. The enhancement of radiation-induced transformation seems to be greater in the presence of cholic acid, as compared to the effect of cheno-deoxycholic acid. Increase in transformation was relatively greater after low compared to high doses of radiation. The effect of bile acids on transformation of 10T1/2 cells is similar to that of a known tumor promoter TPA. The authors' observations support the conclusion that promotional effect of bile acids is not because of their specific effect on colonic epithelium, but rather due to their general properties as tumor promoters

  2. STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells.

    Science.gov (United States)

    Liu, Yi; Luo, Fei; Wang, Bairu; Li, Huiqiao; Xu, Yuan; Liu, Xinlu; Shi, Le; Lu, Xiaolin; Xu, Wenchao; Lu, Lu; Qin, Yu; Xiang, Quanyong; Liu, Qizhan

    2016-01-01

    Although microRNA (miRNA) enclosed in exosomes can mediate intercellular communication, the roles of exosomal miRNA and angiogenesis in lung cancer remain unclear. We investigated functions of STAT3-regulated exosomal miR-21 derived from cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells in the angiogenesis of CSE-induced carcinogenesis. miR-21 levels in serum were higher in smokers than those in non-smokers. The medium from transformed HBE cells promoted miR-21 levels in normal HBE cells and angiogenesis of human umbilical vein endothelial cells (HUVEC). Transformed cells transferred miR-21 into normal HBE cells via exosomes. Knockdown of STAT3 reduced miR-21 levels in exosomes derived from transformed HBE cells, which blocked the angiogenesis. Exosomes derived from transformed HBE cells elevated levels of vascular endothelial growth factor (VEGF) in HBE cells and thereby promoted angiogenesis in HUVEC cells. Inhibition of exosomal miR-21, however, decreased VEGF levels in recipient cells, which blocked exosome-induced angiogenesis. Thus, miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of HBE cells. These results, demonstrating the function of exosomal miR-21 from transformed HBE cells, provide a new perspective for intervention strategies to prevent carcinogenesis of lung cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Neoplastic transformation induced by carbon ions.

    Science.gov (United States)

    Bettega, Daniela; Calzolari, Paola; Hessel, Petra; Stucchi, Claudio G; Weyrather, Wilma K

    2009-03-01

    The objective of this experiment was to compare the oncogenic potential of carbon ion beams and conventional photon beams for use in radiotherapy. The HeLa X human skin fibroblast cell line CGL1 was irradiated with carbon ions of three different energies (270, 100, and 11.4 MeV/u). Inactivation and transformation data were compared with those for 15 MeV photons. Inactivation and transformation frequencies for the 270 MeV/u carbon ions were similar to those for 15-MeV photons. The maximal relative biologic effectiveness (RBE(alpha)) values for 100MeV/u and 11.4 MeV/u carbon ions, respectively, were as follows: inactivation, 1.6 +/- 0.2 and 6.7 +/- 0.7; and transformation per surviving cell, 2.5 +/- 0.6 and 12 +/- 3. The curve for dose-transformation per cell at risk exhibited a maximum that was shifted toward lower doses at lower energies. Transformation induction per cell at risk for carbon ions in the entrance channel was comparable to that for photons, whereas for the lower energies, 100 MeV/u and 11 MeV/u, which are representative of the energies delivered to the tumor margins and volume, respectively, the probability of transformation in a single cell was greater than it was for photons. In addition, at isoeffective doses with respect to cell killing, the 11.4-MeV/u beam was more oncogenic than were photons.

  4. Snail family members unequally trigger EMT and thereby differ in their ability to promote the neoplastic transformation of mammary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Baptiste Gras

    Full Text Available By fostering cell commitment to the epithelial-to-mesenchymal transition (EMT, SNAIL proteins endow cells with motility, thereby favoring the metastatic spread of tumor cells. Whether the phenotypic change additionally facilitates tumor initiation has never been addressed. Here we demonstrate that when a SNAIL protein is ectopically produced in non-transformed mammary epithelial cells, the cells are protected from anoikis and proliferate under low-adherence conditions: a hallmark of cancer cells. The three SNAIL proteins show unequal oncogenic potential, strictly correlating with their ability to promote EMT. SNAIL3 especially behaves as a poor EMT-inducer comforting the concept that the transcription factor functionally diverges from its two related proteins.

  5. Mechanisms of radiation-induced neoplastic cell transformation

    International Nuclear Information System (INIS)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

  6. Mechanisms of radiation-induced neoplastic cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T.C.H.; Tobias, C.A.

    1984-04-01

    Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

  7. Depleted uranium induces neoplastic transformation in human lung epithelial cells.

    Science.gov (United States)

    Xie, Hong; LaCerte, Carolyne; Thompson, W Douglas; Wise, John Pierce

    2010-02-15

    Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and noncombatants is frequent and widespread. Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion. However, there is limited research information on the potential carcinogenicity of DU in human bronchial cells. Accordingly, we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells (BEP2D). We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h. We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU. Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype. These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype.

  8. X-ray-induced in vitro neoplastic transformation of human diploid cells

    International Nuclear Information System (INIS)

    Borek, C.

    1980-01-01

    Techniques have recently been developed to identify and score quantitatively neoplastic transformation caused by x-rays in cultured cells derived from rodents. The present report describes for the first time the neoplastic transformation in vitro of human diploid cells by x-ray irradiation into cells which can progress in vitro into advanced stages of neoplastic development, namely, to form colonies in agar and give rise to tumors when injected into nude mice

  9. Low Dose Suppression of Neoplastic Transformation in Vitro

    Energy Technology Data Exchange (ETDEWEB)

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  10. X-ray-induced in vitro neoplastic transformation of human diploid cells

    International Nuclear Information System (INIS)

    Borek, C.

    1980-01-01

    The neoplastic transformation, in vitro, of human diploid cells by x-ray irradiation into cells which can progress, in vitro, into advanced stages of neoplastic development is described. The cells are shown to form colonies in agar and to give rise to tumours when injected into nude mice. (U.K.)

  11. SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts.

    Science.gov (United States)

    Ray, F A; Peabody, D S; Cooper, J L; Cram, L S; Kraemer, P M

    1990-01-01

    To define the role of SV40 large T antigen in the transformation and immortalization of human cells, we have constructed a plasmid lacking most of the unique coding sequences of small t antigen as well as the SV40 origin of replication. The promoter for T antigen, which lies within the origin of replication, was deleted and replaced by the Rous sarcoma virus promoter. This minimal construct was co-electroporated into normal human fibroblasts of neonatal origin along with a plasmid containing the neomycin resistance gene (neo). Three G418-resistant, T antigen-positive clones were expanded and compared to three T antigen-positive clones that received the pSV3neo plasmid (capable of expressing large and small T proteins and having two origins of replication). Autonomous replication of plasmid DNA was observed in all three clones that received pSV3neo but not in any of the three origin minus clones. Immediately after clonal expansion, several parameters of neoplastic transformation were assayed. Low percentages of cells in T antigen-positive populations were anchorage independent or capable of forming colonies in 1% fetal bovine serum. The T antigen-positive clones generally exhibited an extended lifespan in culture but rarely became immortalized. Large numbers of dead cells were continually generated in all T antigen-positive, pre-crisis populations. Ninety-nine percent of all T antigen-positive cells had numerical or structural chromosome aberrations. Control cells that received the neo gene did not have an extended life span, did not have noticeable numbers of dead cells, and did not exhibit karyotype instability. We suggest that the role of T antigen protein in the transformation process is to generate genetic hypervariability, leading to various consequences including neoplastic transformation and cell death.

  12. Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

    Science.gov (United States)

    Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

    1989-01-01

    Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

  13. Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

    DEFF Research Database (Denmark)

    Haugen, A; Laerum, O D; Bock, E

    1981-01-01

    of gestation. The brains of the treated fetuses were transferred to cell culture and underwent neoplastic transformation with a characteristic sequence of phenotypic alterations which could be divided into five different stages. During the first 40 days after explantation (stage I & II) BE induced...

  14. Characteristics of radiation-induced neoplastic transformation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B.

    1986-01-01

    Data are presented to support the hypothesis that the initial step in the morphologic transformation of irradiated rodent (BALB/3T3) cells is a frequent cellular event involving a large fraction of the irradiated population. This process appears to involve DNA damage, but not to represent a targeted mutation in specific structural gene(s). Morphologic transformation and immortalization appear to be distinct steps in the overall process of transformation. In contradistinction to rodent cells, immortalization is a very rare event in human diploid cells which is induced at extremely low frequencies. The hypothesis is presented that immortality develops among clones of cells bearing stable chromosomal rearrangements which emerge during the proliferation of a population of radiation damaged cells.

  15. Some characteristics of neoplastic cell transformation in transgenic mice.

    Science.gov (United States)

    Shvemberger, I N; Ermilov, A N

    1996-01-01

    The role of the expression of different cellular genes and viral oncogenes in malignant cell transformation is discussed. We pay special attention to the role of the genes for growth factors and their receptors and homeobox genes in oncogenesis. Based on both the literature and our own data, specific features of tumors developed in transgenic mice are discussed. All of these data are used to analyze current theories of multistep oncogenesis and the stochastic component in this process. We suggest that all known evidence about the mechanisms of oncogenesis be used in studying the problem at various structural and functional levels in an organism. The chapter shows that transgenic mice are a most suitable model for studying various aspects of malignant transformation from the molecular to the organismal and populational levels.

  16. Neoplastic transformation of hamster embryo cells irradiated in utero and assayed in vitro

    International Nuclear Information System (INIS)

    Borek, C.; Pain, C.; Mason, H.

    1977-01-01

    It is stated that induction of neoplastic transformation in vitro by x-rays and neutrons has been reported, and the authors had previously found that transformation by x-rays could be detected at doses as low as 1 R and the rate of transformation increased with dose, reaching a peak of 1% between 150 and 300 R. This frequency of neoplastic transformation in vitro is much higher than the frequency of radiation induced tumors observed after exposing animals to similar doses of radiation. Studies are here reported showing that malignant transformed cells can be obtained from embryos irradiated in utero and assayed in vitro, and that the frequency of transformation is at least tenfold lower than when the irradiations are performed in vitro, and thus closer to the incidence in animals. Hamster embryo cells were used for the studies. Questions that arise are as follows: does the host mediate in modulating transformation by radiation; is there a repair of transforming events before they can be expressed; and how significant is the state of cells during irradiation in determining the rate of transformation. It is known from in vitro studies that cell replication is required for fixation of the transformation. With the in vitro technique cells are seeded as single cells with ample opportunity to divide. In addition they are not in contact with one another, and constitute a mixture of cell types from many tissues. In utero the situation is quite different; the embryonic cells are irradiated as tissues where there is cell to cell contact in tissue-specific arrangements, and where the rate of cell replication varies with the tissue. It remains to be seen which of these factors, if any, is responsible for the lowered yield of transformed cells characteristic of in utero as opposed to in vitro irradiation. (U.K.)

  17. Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

    Science.gov (United States)

    Russo, Francesco; Linsalata, Michele; Orlando, Antonella

    2014-10-07

    Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.

  18. Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Alam Hunain

    2012-01-01

    Full Text Available Abstract Background Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC. Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. Methods To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131 using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. Results Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041, increased lymph node metastasis (P = 0.001, less differentiation (P = 0.005, increased recurrence (P = 0.038 and shorter survival (P = 0.004 of the patients. Conclusion In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and

  19. Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Alam, Hunain; Kannanl, Sadhna; Gude, Rajiv; Kane, Shubhada; Dalal, Sorab N; Vaidya, Milind M; Bhate, Amruta V; Gangadaran, Prakash; Sawant, Sharda S; Salot, Shimul; Sehgal, Lalit; Dange, Prerana P; Chaukar, Devendra A; D'cruz, Anil K

    2012-01-01

    Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients. In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC

  20. Mechanisms of chemical modification of neoplastic cell transformation by ionizing radiation

    International Nuclear Information System (INIS)

    Yang, T.C.; Tobias, C.A.

    1985-01-01

    During space travel, astronauts will be continuously exposed to ionizing radiation; therefore, it is necessary to minimize the radiation damage by all possible means. The authors' studies show that DMSO (when present during irradiation) can protect cells from being killed and transformed by X rays and that low concentration of DMSO can reduce the transformation frequency significantly when it is applied to cells, even many days after irradiation. The process of neoplastic cell transformation is a complicated one and includes at least two different stages: induction and expression. DMSO apparently can modify the radiation damage during both stages. There are several possible mechanisms for the DMSO effect: (1) changing the cell membrane structure and properties; (2) inducing cell differentiation by acting on DNA; and (3) scavanging free radicals in the cell. Recent studies with various chemical agents, e.g., 5-azacytidine, dexamethane, rhodamin-123, etc., indicate that the induction of cell differentiation by acting on DNA may be an important mechanism for the suppression of expression of neoplastic cell transformation by DMSO

  1. Speeding through cell cycle roadblocks: Nuclear cyclin D1-dependent kinase and neoplastic transformation

    Directory of Open Access Journals (Sweden)

    Diehl J Alan

    2008-09-01

    Full Text Available Abstract Mitogenic induction of cyclin D1, the allosteric regulator of CDK4/6, is a key regulatory event contributing to G1 phase progression. Following the G1/S transition, cyclin D1 activation is antagonized by GSK3β-dependent threonine-286 (Thr-286 phosphorylation, triggering nuclear export and subsequent cytoplasmic degradation mediated by the SCFFbx4-αBcrystallin E3 ubiquitin ligase. Although cyclin D1 overexpression occurs in numerous malignancies, overexpression of cyclin D1 alone is insufficient to drive transformation. In contrast, cyclin D1 mutants refractory to phosphorylation-dependent nuclear export and degradation are acutely transforming. This raises the question of whether overexpression of cyclin D1 is a significant contributor to tumorigenesis or an effect of neoplastic transformation. Significantly, recent work strongly supports a model wherein nuclear accumulation of cyclin D1-dependent kinase during S-phase is a critical event with regard to transformation. The identification of mutations within SCFFbx4-αBcrystallin ligase in primary tumors provides mechanistic insight into cyclin D1 accumulation in human cancer. Furthermore, analysis of mouse models expressing cyclin D1 mutants refractory to degradation indicate that nuclear cyclin D1/CDK4 kinase triggers DNA re-replication and genomic instability. Collectively, these new findings provide a mechanism whereby aberrations in post-translational regulation of cyclin D1 establish a cellular environment conducive to mutations that favor neoplastic growth.

  2. Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation

    Directory of Open Access Journals (Sweden)

    Yiannis Drosos

    2016-03-01

    Full Text Available The current paradigm of pancreatic neoplastic transformation proposes an initial step whereby acinar cells convert into acinar-to-ductal metaplasias, followed by progression of these lesions into neoplasias under sustained oncogenic activity and inflammation. Understanding the molecular mechanisms driving these processes is crucial to the early diagnostic and prevention of pancreatic cancer. Emerging evidence indicates that transcription factors that control exocrine pancreatic development could have either, protective or facilitating roles in the formation of preneoplasias and neoplasias in the pancreas. We previously identified that the homeodomain transcription factor Prox1 is a novel regulator of mouse exocrine pancreas development. Here we investigated whether Prox1 function participates in early neoplastic transformation using in vivo, in vitro and in silico approaches. We found that Prox1 expression is transiently re-activated in acinar cells undergoing dedifferentiation and acinar-to-ductal metaplastic conversion. In contrast, Prox1 expression is largely absent in neoplasias and tumors in the pancreas of mice and humans. We also uncovered that Prox1-heterozygosis markedly increases the formation of acinar-to-ductal-metaplasias and early neoplasias, and enhances features associated with inflammation, in mouse pancreatic tissues expressing oncogenic Kras. Furthermore, we discovered that Prox1-heterozygosis increases tissue damage and delays recovery from inflammation in pancreata of mice injected with caerulein. These results are the first demonstration that Prox1 activity protects pancreatic cells from acute tissue damage and early neoplastic transformation. Additional data in our study indicate that this novel role of Prox1 involves suppression of pathways associated with inflammatory responses and cell invasiveness.

  3. KRAS Mutation and Epithelial-Macrophage Interplay in Pancreatic Neoplastic Transformation.

    Science.gov (United States)

    Bishehsari, Faraz; Zhang, Lijuan; Barlass, Usman; Preite, Nailliw; Turturro, Sanja; Najor, Matthew S; Shetuni, Brandon B; Zayas, Janet P; Mahdavinia, Mahboobeh; Abukhdeir, Abde M; Keshavarzian, Ali

    2018-05-14

    Pancreatic ductal adenocarcinoma (PDA) is characterized by epithelial mutations in KRAS and prominent tumor-associated inflammation, including macrophage infiltration. But knowledge of early interactions between neoplastic epithelium and macrophages in PDA carcinogenesis is limited. Using a pancreatic organoid model, we found that the expression of mutant KRAS in organoids increased i) ductal to acinar gene expression ratios, ii) epithelial cells proliferation, and iii) colony formation capacity in vitro, and endowed pancreatic cells with the ability to generate neoplastic tumors in vivo. KRAS mutations induced a pro-tumorigenic phenotype in macrophages. Altered macrophages decreased epithelial Pigment Epithelial Derived Factor (PEDF) expression and induced a cancerous phenotype. We validated our findings using annotated patient samples from The Cancer Genome Atlas (TCGA) as well as in our human PDA specimens. Epithelium-macrophage cross talk occurs early in pancreatic carcinogenesis where KRAS directly induces cancer-related phenotypes in epithelium, and also promotes a pro-tumorigenic phenotype in macrophages, in turn augmenting neoplastic growth. This article is protected by copyright. All rights reserved. © 2018 UICC.

  4. Adaptive Response Against Spontaneous Neoplastic Transformation In Vitro Induced by Ionizing Radiation

    International Nuclear Information System (INIS)

    Redpath, J. Leslie

    2003-01-01

    The goal of this project was to establish a dose response curve for radiation-induced neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro under experimental conditions were an adaptive response, if it were induced, would have an opportunity to be expressed. During the first two years of the grant an exhaustive series of experiments were performed and the resulting data were reported at the 2000 Annual Meeting of the Radiation Research Society and then Subsequently published. The data showed that an adaptive response against spontaneous neoplastic transformation was seen up to doses of 10cGy of Cs-137 gamma rays. At dose of 30, 50 and 100 cGy the transformation frequencies were above background. This indicated that for this system, under the specific experimental conditions used, there was a threshold of somewhere between 10 and 30 cGy. The results also indicated some unexpected, though very interesting, correlations with relative risk estimates made from human epidemiologic studies

  5. Possible error-prone repair of neoplastic transformation induced by fission-spectrum neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Hill, C K; Han, A; Elkind, M M

    1948-01-01

    An examination was made of the effect of fission-spectrum neutrons from the JANUS reactor at Argonne National Laboratory, delivered either as acute or protracted irradiation, on the incidence of neoplastic transformation in the C3H 10T1/2 mouse embryo cell line. Acute exposures were delivered at 10-38 cGy min/sup -1/, protracted exposures at 0.086 or 0.43 cGy min/sup -1/. The total doses for both ranged from 2.4 to 350 cGy. In the low dose region (2.4-80 cGy), there was a large enhancement in transformation frequency when the neutrons were delivered at the low dose rates compared with the high dose rates, but the survival of the cells was not significantly different between the two exposures conditions. Analysis of the intial parts of the curves shows that the regression line for protracted doses is about 9 times steeper than that for single acute exposures. Finally, the possibility is discussed that an ''error-prone'' repair process may be causing the enhanced transformation frequency by protracted neutron exposures.

  6. Ozone acts alone and synergistically with ionizing radiation to induce in vitro neoplastic transformation

    Energy Technology Data Exchange (ETDEWEB)

    Borek, C; Zaider, M; Ong, A; Mason, H; Witz, G

    1986-09-01

    Ozone, a major chemical oxidant in the atmosphere, is an environmental air pollutant whose ability to act as a direct carcinogen is unclear. Using in vitro transformation, a technique which permits the study of oncogenesis in the absence of host specific effects, it is reported for the first time that ozone (5 p.p.m. for 5 min) induces neoplastic transformation in vitro in both primary hamster embryo cells and mouse fibroblast cultures (C3H/10-1/2). Exposure of the hamster and mouse cells to ozone also results in enhanced levels of free radical-mediated lipid peroxidation products. The carcinogenic interaction between ozone and ionizing radiation is also reported. Exposure of the cells to 3 or 4 Gy of ..gamma..-rays, 2 h prior to O/sub 3/ treatment, results in markedly enhanced rates of transformation, statistically consistent with a synergistic interaction between the agents. The results demonstrate that O/sub 3/ acts as a direct carcinogen and co-carcinogen on susceptible cells, therefore having important consequences for public health.

  7. Genes that cooperate with tumor promoters in transformation

    International Nuclear Information System (INIS)

    Colburn, N.H.; Smith, B.M.

    1988-01-01

    Tumor-promoting phorbol esters, like growth factors, elicit pleiotropic responses involving biochemical pathways that lead to different biological responses. Genetic variant cell lines that are resistant to mitogenic, differentiation, or transformation responses to tumor promoters have been valuable tools for understanding the molecular bases of these responses. Studies using the mouse epidermal JB6 cell lines that are sensitive or resistant to tumor promoter-induced transformation have yielded new understanding of genetic and signal transduction events involved in neoplastic transformation. The isolation and characterization of cloned mouse promotion sensitivity genes pro-1 and pro-2 is reviewed. A new activity of pro-1 has been identified: when transfected into human cancer prone basal cell nevus syndrome fibroblasts but not normal fibroblasts mouse pro-1 confers lifespan extension of these cells. Recently, we have found tat a pro-1 homolog from a library of nasopharyngeal carcinoma, but not the homolog from a normal human library, is activated for transferring promotion sensitivity. The many genetic variants for responses to tumor promoters have also proved valuable for signal transduction studies. JPB P- cells fail to show the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced syntheses of two proteins of 15 and 16 kD seen in P+ cells. P-, P+, and TPA transformed cells show a progressive decrease in both basal and TPA-inducible levels of a protein kinase C substrate of 80 kD. P- cells are relatively resistant both to anchorage-independent transformation and to a protein band shift induced by the calcium analog lanthanum. It appears that one or more calcium-binding proteins and one or more pro genes may be critical determinants of tumor promoter-induced neoplastic transformation

  8. Mobile phone base station radiation does not affect neoplastic transformation in BALB/3T3 cells.

    Science.gov (United States)

    Hirose, H; Suhara, T; Kaji, N; Sakuma, N; Sekijima, M; Nojima, T; Miyakoshi, J

    2008-01-01

    A large-scale in vitro study focusing on low-level radiofrequency (RF) fields from mobile radio base stations employing the International Mobile Telecommunication 2000 (IMT-2000) cellular system was conducted to test the hypothesis that modulated RF fields affect malignant transformation or other cellular stress responses. Our group previously reported that DNA strand breaks were not induced in human cells exposed to 2.1425 GHz Wideband Code Division Multiple Access (W-CDMA) radiation up to 800 mW/kg from mobile radio base stations employing the IMT-2000 cellular system. In the current study, BALB/3T3 cells were continuously exposed to 2.1425 GHz W-CDMA RF fields at specific absorption rates (SARs) of 80 and 800 mW/kg for 6 weeks and malignant cell transformation was assessed. In addition, 3-methylcholanthrene (MCA)-treated cells were exposed to RF fields in a similar fashion, to assess for effects on tumor promotion. Finally, the effect of RF fields on tumor co-promotion was assessed in BALB/3T3 cells initiated with MCA and co-exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA). At the end of the incubation period, transformation dishes were fixed, stained with Giemsa, and scored for morphologically transformed foci. No significant differences in transformation frequency were observed between the test groups exposed to RF signals and the sham-exposed negative controls in the non-, MCA-, or MCA plus TPA-treated cells. Our studies found no evidence to support the hypothesis that RF fields may affect malignant transformation. Our results suggest that exposure to low-level RF radiation of up to 800 mW/kg does not induce cell transformation, which causes tumor formation. (c) 2007 Wiley-Liss, Inc.

  9. Neoplastic transformation in vitro by low doses of ionizing radiation: Role of adaptive response and bystander effects

    International Nuclear Information System (INIS)

    Ko, M.; Lao, X.-Y.; Kapadia, R.; Elmore, E.; Redpath, J.L.

    2006-01-01

    The shape of the dose-response curve for cancer induction by low doses of ionizing radiation is of critical importance to the assessment of cancer risk at such doses. Epidemiologic analyses are limited by sensitivity to doses typically greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the examination of lower doses using cancer-relevant endpoints. One such endpoint is neoplastic transformation in vitro. It is known that this endpoint is responsive to both adaptive response and bystander effects. The relative balance of these processes is likely to play an important role in determining the shape of the dose-response curve at low doses. A factor that may influence this balance is cell density at time of irradiation. The findings reported in this paper indicate that the transformation suppressive effect of low doses previously seen following irradiation of sub-confluent cultures, and attributed to an adaptive response, is reduced for irradiated confluent cultures. However, even under these conditions designed to optimize the role of bystander effects the data do not fit a linear no-threshold model and are still consistent with the notion of a threshold dose for neoplastic transformation in vitro by low LET radiation

  10. RET/PTC1-Driven Neoplastic Transformation and Proinvasive Phenotype of Human Thyrocytes Involve Met Induction and β-Catenin Nuclear Translocation

    Directory of Open Access Journals (Sweden)

    Giuliana Cassinelli

    2009-01-01

    Full Text Available Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC. We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, β-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and β-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of β-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated β-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes β-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs.

  11. RET/PTC1-Driven Neoplastic Transformation and Proinvasive Phenotype of Human Thyrocytes Involve Met Induction and β-Catenin Nuclear Translocation1

    Science.gov (United States)

    Cassinelli, Giuliana; Favini, Enrica; Degl'Innocenti, Debora; Salvi, Alessandro; De Petro, Giuseppina; Pierotti, Marco A; Zunino, Franco; Borrello, Maria Grazia; Lanzi, Cinzia

    2009-01-01

    Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC). We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, β-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and β-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F) devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of β-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated β-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes β-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs. PMID:19107227

  12. Neoplastic progression of rat tracheal epithelial cells involves resistance to transforming growth factor beta

    International Nuclear Information System (INIS)

    Hubbs, A.F.; Hahn, F.F.; Thomassen, D.G.

    1988-01-01

    Primary, transformed, and tumor-derived rat tracheal epithelial (RTE) cells were grown in serum-free medium containing 0 to 300 pg/mL transforming growth factor beta (TGFβ) markedly inhibited the growth of primary RTE cells with a 50% drop in the efficiency of colony formation seen at TGFβ concentrations between 10 and 30 pg/ mL. The effect of TGFβ on preneoplastic RTE cells was similar to the effect on normal primary RTE cells. Cell lines established from tumors produced by inoculation of transformed RTE cells into nude mice were relatively resistant to -TGFβ-induced growth inhibition. Resistance to TGFβ-induced growth inhibition, therefore, appears to be a late event in the development of neoplasia. (author)

  13. In vitro neoplastic transformation of plant callus tissue by γ-radiation

    International Nuclear Information System (INIS)

    Pandey, K.N.; Sabharwal, P.S.

    1979-01-01

    Tumours have been induced by γ-radiation in callus tissue derived from a monocotyledonous flowering plant, Haworthia mirabilis Haw. The transformed tissue exhibited compact texture, excessive cell proliferation and loss of capacity for organogenesis. Tumors were characterized by their ability to undergo continuous autonomous growth on minimal media in the subsequent 4 generations of subculture. In contrast, the nonirradiated control tissue grew with friable texture, required inositol or growth hormones and showed prolific differentiation of vegetative buds. (Auth.)

  14. Age-Related DNA Methylation Changes and Neoplastic Transformation of the Human Prostate

    Science.gov (United States)

    2009-07-01

    associated CpG island to be d ifferentially hyp ermethylated in th e L NCaP cell line and 25 unique promoter associated CpG island s to b e dif ferentially h...ypomethylated in the L NCaP cell line . Several of these differentially m ethylated genes have been previously reported. Novel methylated genes of

  15. Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Amie L. Holmes

    2013-11-01

    Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

  16. Enhanced sensitivity to neoplastic transformation by 137Cs γ-rays of cells in the G2-/M-phase age interval

    International Nuclear Information System (INIS)

    Cao, J.; Wells, R.L.; Elkind, M.M.

    1992-01-01

    C3H mouse 10T1/2 cells, exposed to low doses of fission-spectrum neutrons, have an enhanced frequency of neoplastic transformation if protracted exposures are used (Hill et al. 1982, 1984a, 1985). To explain this anormaly, a biophysical model was proposed (Elkind 1991 a,b). The unique shape and radiobiological properties of cells in and around mitosis, led to the proposal that the sensitive window is mitosis and possible cells just preceding or just following M phase (Elkind 1991a,b). This study was undertaken using 137 Cs γ-rays. The authors found that late G 2- to M-phase 10T1/2 cells have a maximal sensitivity to neoplastic transformation as well as to killing by 137 Cs γ-rays. (author)

  17. Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang

    Directory of Open Access Journals (Sweden)

    Mandy M. Liu

    2017-03-01

    Full Text Available Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT, comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women’s diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT’s activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(aanthracene (DMBA. In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in ‘Sensitivity to Carcinogenesis’ (SENCAR mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA, and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB.

  18. In vitro study of the influence of alpha particles irradiation on the pre-neoplastic transformation of rat trachea epithelial cells

    International Nuclear Information System (INIS)

    Kugel, C.

    2001-12-01

    Intern contamination by actinide oxide inhalation is potentially one health hazard during the nuclear fuel fabrication process. The aerosol particles can induce pulmonary lesions, such as epithelial cancers in particular. Their toxicity is mainly due to radiotoxicity of α irradiation. The aim of this work was to contribute, by an in vitro model, to the study of the apparition of pre-neoplastic states on epithelial cells after high LET irradiation. Primary cultures of rat tracheal epithelial cells were used. Two rat strain cells, SD TR for Sprague Dawley rats and WF TR for Wistar Furth I Fischer F344 rats, were compared after exposure to a dose range from 0 to 5 Gy. Reproductive cell death, i.e. senescent death, seems to be the main lethal way induced by α and γ irradiations. The nuclear volume of WF TR cells is higher than that of SD TR ones, explaining the higher α radiation-induced lethality of these cells. These WF TR cells are also much sensitive to dose rate and α particles energy. In the same manner, pre-neoplastic transformation rate of the cells seems to depend on the physical parameters of irradiation. But, it mainly varies as a function of cell radiosensitivity, that means cell death. In fact, the transformation rate of sensitive WF TR cells is lower than that of SD TR ones. In term of transformation for SD TR cells, dose-effect relationship fits to a linear and infra linear function after α irradiation, whereas the curve fits to linear and quadratic function after γ irradiation. The Relative Biological Efficiency (RBE) of α particles for lethality and pre-neoplastic transformation were determined for several levels of dose. A constant value of about 3 was found for RBE of lethality whatever the α dose. By contrast, the RBE of transformation has a value of about 10 up to 0.5 Gy and gradually decreases at higher doses to reach a value of 1 at 5 Gy. Similar shapes of dose-effect relationship can be observed for malignant lung tumour induction after

  19. Loss of a putative tumor suppressor locus after gamma-ray-induced neoplastic transformation of HeLa x Skin fibroblast human cell hybrids

    International Nuclear Information System (INIS)

    Mendonca, M.S.; Redpath, J.L.; Fasching, C.L.

    1995-01-01

    The nontumorigenic HeLa x skin fibroblast hybrid cell line, CGL1, can be induced to re-express HeLa tumor-associated cell surface antigen, p75-IAP (intestinal alkaline phosphatase), with resulting neoplastic transformation, by exposure to γ radiation. This has allowed the human hybrid system to be developed into a quantitative in vitro model for radiation-induced neoplastic transformation of human cells. Recently, several γ-ray-induced IAP-expression mutants (GIMs) of the nontumorigenic HeLa x skin fibroblast hybrid CGL1 were isolated and all were tumorigenic when injected subcutaneously into nude mice. Control cell lines which were negative for p75-IAP (CONs) were also isolated from irradiated populations, and none were found to be tumorigenic. We have now begun to investigate the molecular basis of radiation-induced neoplastic transformation in this system by studying the potential genetic linkage between p75/IAP expression, tumorigenicity and damage to a putative tumor suppressor locus on fibroblast chromosome 11. Previous analysis of rare spontaneous segregants has indicated that this locus is involved in the regulation of tumorigenicity and in the expression of the HeLa tumor-associated cell surface marker intestinal alkaline phosphatase (p75-IAP) in this system. Therefore, analysis by restriction fragment length polymorphism and chromosome painting have been performed for chromosome 11, and for chromosome 13 as a control, for the p75/IAP-positive GIM and p75/IAP-negative CON cell lines. We report that in five of eight of the GIMs large-scale damage to the fibroblast chromosome 11's is evident (four GIMs have lost one complete copy of a fibroblast chromosome 11 heavily damaged). None of the CONs, however (0/5), have lost a complete copy of either fibroblast chromosome 11. No large-scale damage to the control chromosome 13's was detected in the GIMs or CONs. 49 refs., 3 figs., 2 tabs

  20. Focus formation and neoplastic transformation by herpes simplex virus type 2 inactivated intracellularly by 5-bromo-2'-deoxyuridine and near UV light

    International Nuclear Information System (INIS)

    Manak, M.M.; Aurelian, L.; Ts'o, P.O.

    1981-01-01

    The induction of focus formation in low serum and of neoplastic transformation of Syrian hamster embryo cells was examined after the expression of herpes simplex virus type 2 functions. Syrian hamster embryo cells infected at a high multiplicity (5 PFU/cell) with 5-bromo-2'-deoxyuridine-labeled herpes simplex virus type 2 (11% substitution of thymidine residues) were exposed to near UV light irradiation at various times postinfection. This procedure specifically inactivated the viral genome, while having little, if any, effect on the unlabeled cellular DNA. Focus formation in 1% serum and neoplastic transformation were observed in cells exposed to virus inactivated before infection, but the frequency was enhanced (15- to 27-fold) in cells in which the virus was inactivated at 4 to 8 h postinfection. Only 2 to 45 independently isolated foci were capable of establishing tumorigenic lines. The established lines exhibited phenotypic alterations characteristic of a transformed state, including reduced serum requirement, anchorage-independent growth, and tumorigenicity. They retained viral DNA sequences and, even at relatively late passage, expressed viral antigens, including ICP 10

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

    International Nuclear Information System (INIS)

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-01-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As 2 O 3

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-01

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

  3. [Neoplastic transformation of mouse fibroblasts under the influence of high-energy protons and gamma-rays].

    Science.gov (United States)

    Voskanian, K Sh

    2004-01-01

    Oncoginic transformations of mouse fibroblasts C3H10T1/2 after exposure to proton energies 150 and 584 MeV were compared with fibroblast effects of gamma-radiation. Prior to exposure, cell populations (2.7 x 10(3) cells/cm2) were inoculated in plastic vials with the surface area of 75 cm2 and cultivated 11 days. Survivability was determined by comparing the number of cell colonies in irradiated and non-irradiated (control) vials. Transformation rate was calculated by dividing the total transformation focus number by the number of survived cells in a vial. Rate of oncogenic transformations after gamma- and proton (584 MeV) irradiation was essentially identical, i.e. the parameter grew rapidly at the doses 1 Gy. In the dose interval between 1 and 5 Gy, transformation rate for proton energy 150 MeV was found low compared with gamma-radiation and proton energy 584 MeV. It is hypothesized that the different transformation rate after exposure to proton energy 150 MeV is linked with the high linear energy transfer as compared with the proton energy of 584 MeV and gamma-radiation.

  4. A Microbiomic Analysis in African Americans with Colonic Lesions Reveals Streptococcus sp.VT162 as a Marker of Neoplastic Transformation

    Directory of Open Access Journals (Sweden)

    Hassan Brim

    2017-11-01

    Full Text Available Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis (CRC. To detect bacterial markers of colorectal cancer in African Americans a metabolomic analysis was performed on fecal water extracts. DNA from stool samples of adenoma and healthy subjects and from colon cancer and matched normal tissues was analyzed to determine the microbiota composition (using 16S rDNA and genomic content (metagenomics. Metagenomic functions with discriminative power between healthy and neoplastic specimens were established. Quantitative Polymerase Chain Reaction (q-PCR using primers and probes specific to Streptococcus sp. VT_162 were used to validate this bacterium association with neoplastic transformation in stool samples from two independent cohorts of African Americans and Chinese patients with colorectal lesions. The metabolomic analysis of adenomas revealed low amino acids content. The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. Cross-mapping of metagenomic data led to 9 markers with significant discriminative power between normal and diseased specimens. These markers identified with Streptococcus sp. VT_162. Q-PCR data showed a statistically significant presence of this bacterium in advanced adenoma and cancer samples in an independent cohort of CRC patients. We defined metagenomic functions from Streptococcus sp. VT_162 with discriminative power among cancers vs. matched normal and adenomas vs. healthy subjects’ stools. Streptococcus sp. VT_162 specific 16S rDNA was validated in an independent cohort. These findings might facilitate non-invasive screening for colorectal cancer.

  5. Promoting Transformational Leadership Through Air Force Culture

    Science.gov (United States)

    2013-03-01

    transformational leadership styles . Transformational leaders lead through social exchange, help followers grow, and empower their organization by aligning goals...Transformational leadership will truly allow the USAF to do more with less, as it improves productivity. This paper examines leadership styles and...analyzing and evaluating the effectiveness of various leadership styles , the transformational leadership theory is quickly becoming a choice approach.10

  6. Multistep process of neoplastic transformation of normal human fibroblasts by 60Co gamma rays and Harvey sarcoma viruses

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-15

    As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma-ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST-6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha-MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha-MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha-MSV-transformed KMST-6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma-ray-transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha-MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.

  7. Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins

    DEFF Research Database (Denmark)

    Salcini, A E; McGlade, J; Pelicci, G

    1994-01-01

    The mammalian SHC gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are phosphorylated on tyrosine by a variety of receptor and cytoplasmic tyrosine kinases. Phosphorylated Shc proteins form a complex with the SH2-SH3 containing Grb2 protein which...... of Grb2 to Shc proteins requires phosphorylation of Shc at Tyr317, which lies within the high affinity binding motif for the Grb2 SH2 domain, pYVNV, where Asn at the +2 position is crucial for complex formation. In vivo, Tyr317 is the major, but not the only, site for Shc phosphorylation, and is the sole...... aminoterminal deletion, but retain the Tyr317 site and the SH2 domain conserve the capacity to be phosphorylated, to bind to Grb2 and to induce cell transformation. These data indicate that the formation of the Shc-Grb2 complex is a crucial event in the transformation induced by overexpression of Shc...

  8. Mutation induction and neoplastic transformation in human and human-hamster hybrid cells: dependence on photon energy and modulation in the low-dose range

    Energy Technology Data Exchange (ETDEWEB)

    Frankenberg, D.; Frankenberg-Schwager, M.; Garg, I.; Pralle, E. [Abt. Klin. Strahlenbiologie und Klin. Strahlenphysik, Universitaet Goettingen, Goettingen (Germany); Uthe, D.; Greve, B.; Severin, E.; Goehde, W. [Institut fuer Strahlenbiologie, Universitaet Muenster, Munster (Germany)

    2002-09-01

    Mutation induction in the HPRT gene of human fibroblasts after irradiation with mammography-like 29 kVp or 200 kVp x-rays shows radiohypersensitivity for doses smaller than {approx}0.5 Gy. Similarly, mutation induction in the CD 59 gene on human chromosome 11 in A{sub L} cells shows radiohypersensitivity for doses smaller than {approx}0.5 Gy after exposure to 200 kVp x-rays, but not after irradiation with low-filtered 30 kVp x-rays. The RBE values of 29 and 30 kVp x-rays relative to 200 kVp x-rays are strongly dose dependent. For neoplastic transformation of human hybrid (CGL1) cells after irradiation with 29 or 200 kVp x-rays or {sup 60}Co gamma rays a linear-quadratic dose relationship was observed with RBE values of approximately four and eight for mammography relative to 200 kVp x-rays and {sup 60}Co gamma rays, respectively. (author)

  9. Regulation of the pituitary tumor transforming gene by insulin-like-growth factor-I and insulin differs between malignant and non-neoplastic astrocytes

    International Nuclear Information System (INIS)

    Chamaon, Kathrin; Kirches, Elmar; Kanakis, Dimitrios; Braeuninger, Stefan; Dietzmann, Knut; Mawrin, Christian

    2005-01-01

    The reasons for overexpression of the oncogene pituitary tumor transforming gene (PTTG) in tumors are still not fully understood. A possible influence of the insulin-like growth factor I (Igf-I) may be of interest, since enhanced Igf-I signalling was reported in various human tumors. We examined the influence of Igf-I and insulin on PTTG expression in human astrocytoma cells in comparison to proliferating non-neoplastic rat embryonal astrocytes. PTTG mRNA expression and protein levels were increased in malignant astrocytes treated with Igf-I or insulin, whereas in rat embryonic astrocytes PTTG expression and protein levels increased only when cells were exposed to Igf-I. Enhanced transcription did not occur after treatment with inhibitors of phosphoinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), blocking the two basic signalling pathways of Igf-I and insulin. In addition to this transcriptional regulation, both kinases directly bind to PTTG, suggesting a second regulatory route by phosphorylation. However, the interaction of endogenous PTTG with MAPK and PI3K, as well as PTTG phosphorylation were independent from Igf-I or insulin. The latter results were also found in human testis, which contains high PTTG levels as well as in nonneoplastic astrocytes. This suggest, that PI3K and MAPK signalling is involved in PTTG regulation not only in malignant astrocytomas but also in non-tumorous cells

  10. Enhanced neoplastic transformation by mammography X rays relative to 200 kVp X rays: indication for a strong dependence on photon energy of the RBE(M) for various end points.

    Science.gov (United States)

    Frankenberg, D; Kelnhofer, K; Bär, K; Frankenberg-Schwager, M

    2002-01-01

    The fundamental assumption implicit in the use of the atomic bomb survivor data to derive risk estimates is that the gamma rays of Hiroshima and Nagasaki are considered to have biological efficiencies equal to those of other low-LET radiations up to 10 keV/microm, including mammography X rays. Microdosimetric and radiobiological data contradict this assumption. It is therefore of scientific and public interest to evaluate the efficiency of mammography X rays (25-30 kVp) to induce cancer. In this study, the efficiency of mammography X rays relative to 200 kVp X rays to induce neoplastic cell transformation was evaluated using cells of a human hybrid cell line (CGL1). For both radiations, a linear-quadratic dose-effect relationship was observed for neoplastic transformation of CGL1 cells; there was a strong linear component for the 29 kVp X rays. The RBE(M) of mammography X rays relative to 200 kVp X rays was determined to be about 4 for doses energies of transformation of CGL1 cells. Both the data available in the literature and the results of the present study strongly suggest an increase of RBE(M) for carcinogenesis in animals, neoplastic cell transformation, and clastogenic effects with decreasing photon energy or increasing LET to an RBE(M) approximately 8 for mammography X rays relative to 60Co gamma rays.

  11. Reduced temperature (22 degrees C) results in enhancement of cell killing and neoplastic transformation in noncycling HeLa x skin fibroblast human hybrid cells irradiated with low-dose-rate gamma radiation

    International Nuclear Information System (INIS)

    Redpath, J.L.; Antoniono, R.J.

    1995-01-01

    The effect of reduced temperature (22 degrees C) or serum deprivation during low-dose-rate (0.66 cGy/min) γ irradiation on cell killing and neoplastic transformation has been examined using the HeLa x skin fibroblast human hybrid cell system. The reduced temperature stops progression of these cells through the cell cycle while serum deprivation slows down cell turnover markedly. The data demonstrate an enhancement in both of the end points when cells are held at 22 degrees C compared to parallel experiments done at 37 degrees C. In operational terms, the decreased survival and increased neoplastic transformation are consistent with our earlier hypothesis of a higher probability of misrepair at reduced temperature. The interpretation that this damage enhancement was associated with the reduced temperature, and not the fact that the cells were noncycling, was supported by the results of experiments performed with cells cultured at 37 degrees C in serum-free medium for 35 h prior to and then during the 12.24 h low-dose-rate radiation exposure. Under these conditions, cell cycle progression, as shown by reduction in growth rate and dual-parameter flow cytometric analysis, was considerable inhibited (cell cycle time increased from 20 h to 40 h), and there was no significant enhancement of cell killing or neoplastic transformation. 23 refs., 2 figs., 1 tab

  12. TPA-inducible proteins may account for sensitivity to promotion of transformation

    International Nuclear Information System (INIS)

    Hirano, K.; Smith, B.; Colburn, N.H.

    1986-01-01

    The preneoplastic JB6 mouse epidermal cell system includes cell lines sensitive (P + ) or resistant (P - ) to tumor promoter induced neoplastic transformation. The authors investigated whether a difference in TPA-inducible proteins may explain this differential sensitivity. The synthesis of a 39 Kd cytoplasmic protein (Major Excreted Protein) was TPA-inducible, but to a similar extent in both P + and P - cells. TPA stimulated phosphorylation but not synthesis of the previously described stress protein pp80 in both P + and P - cells from 1 to 5 hr after treatment. Pulse labelling of P + and P - cells with 35 S-methionine revealed a TPA dependent P + specific transient increase in the synthesis of 58Kd protein. Induction was observed at 1 hr, and returned to basal levels by 4 hr and 20 hr, in nuclear and cytoplasmic fractions, respectively. This protein is not phosphorylated in response to TPA treatment. P + cells differ from P - cells in one or more genes that specify sensitivity to promotion of transformation, designated pro genes. Antibodies to three peptides representing the pro-1 open reading frame were used in immunoprecipitation and Western blotting to isolate the pro-1 gene product. A 43 Kd protein was immunologically responsive to the pro-1 peptide antibodies, and showed an increased signal 40 min after TPA treatment. Since the predicted molecular weight of a pro-1 gene product is only 7 Kd, the possibility of a modification of the protein by poly(ADP-ribosylation) or glycosylation is being investigated

  13. The effect of postirradiation holding at 22 degrees C on the repair of sublethal, potentially lethal and potentially neoplastic transforming damage in gamma-irradiated HeLa x skin fibroblast human hybrid cells

    International Nuclear Information System (INIS)

    Redpath, J.L.; Antoniono, R.J.; Mendonca, M.S.; Sun, C.

    1994-01-01

    The effect of postirradiation holding at 22 degrees C on cell growth, progression of cells through the cell cycle, and the repair of sublethal, potentially lethal and potentially neoplastic transforming damage in γ-irradiated HeLa x skin fibroblast human hybrid cells has been examined. Cell growth and cell cycle progression were essentially stopped at this reduced temperature. Cell survival was dramatically reduced by holding confluent cultures for 6 h at 22 degrees C, as opposed to 37 degrees C, after 7.5 Gy γ radiation delivered at a rate of 2 Gy/min. Return of the cells to 37 degrees C for 6 h after holding at 22 degrees C did not result in increased survival. A similar effect was obtained when the cells were held at 22 degrees C between split-dose irradiation of log-phase cultures where no increase in survival was observed over a split-dose interval of 4 h. In this case a partial increase in survival was observed upon returning the cells to 37 degrees C for 3 h after holding at 22 degrees C for the first 3 h of the split-dose interval. Neoplastic transformation frequency was not enhanced by holding confluent cultures for 6 h at 22 degrees C after 7.5 Gy γ radiation. This is consistent with previous observations that misrepair of potentially neoplastic transforming damage already occurs at 37 degrees C. The overall results are interpreted in terms of the reduced temperature favoring misrepair, rather than inhibition of repair, of sublethal, potentially lethal and potentially transforming radiation damage. 24 refs., 5 figs., 3 tabs

  14. Cellular transformation by radiation: induction, promotion, and inhibition

    International Nuclear Information System (INIS)

    Borek, C.

    1981-01-01

    Radiation oncogenesis induced in utero in hamsters is expressed at a lower frequency than that induced in vitro. Quantitative studies carried out on hamster embryo cells indicate that neutrons are more effective in their carcinogenic potential than x-rays but also more toxic, that splitting the dose of x-rays at low doses leads to enhanced transformation, but that at high doses protracted radiation has a sparing effect. At all dose ranges survival was increased by protracting the radiation dose, thus suggesting that different repair processes must be involved for survival and transformation. In our qualitative studies, once cells are transformed by radiation, they exhibit a wide range of structural and functional phenotypic changes, some of which are membrane-associated and are expressed within days after induction. Our current studies on nutritional and hormonal influences on radiation transformation indicate the following: Pyrolysate products from broiled protein foods act in synergism with radiation to produce transformation, whereas vitamin A analogs are powerful, preventive agents. Retinoids inhibit both x-ray-induced transformation and its promotion by TPA; these modifications (enhancement by TPA, inhibition by retinoids) are not reflected in sister chromatid exchanges, but are reflected in the level of membrane associated enzymes Na/K ATPase. Whereas retinoids modify late events (expression, promotion), we find that thyroid hormone plays a crucial role in the early phases of radiation and chemically induced transformation. Our recent success in transforming human skin fibroblasts will enable quantitative and qualitative studies of radiation carcinogenesis in a system relevant to man

  15. Late biological effects of ionizing radiation as influenced by dose, dose rate, age at exposure and genetic sensitivity to neoplastic transformation

    International Nuclear Information System (INIS)

    Spalding, J.F.; Prine, J.R.; Tietjen, G.L.

    1978-01-01

    A most comprehensive investigation is in progress at the Los Alamos Scientific Laboratory to study the late biological effects of whole-body exposure to gamma irradiation as they may be influenced by total dose, dose rate, age at exposure and genetic background. Strain C57B1/6J mice of four age groups (newborn, 2, 6 and l5 months) were given five doses (20, 60, 180, 540, and 1620 rads) of gamma rays, with each dose being delivered at six dose rates (0.7, 2.1, 6.3, 18.9, 56.7 rads/day and 25 rads/min). Forty to sixty mice were used in each of the approximately 119 dose/dose-rate and age combinations. The study was done in two replications with an equal number of mice per replicaton. Strain RF/J mice were used in a companion study to investigate the influence of genetic background on the type and magnitude of effect. Results of the first and second replications of the l5-month-old age group and data on the influence of genetic background on biological response have been completed, and the results show no significant life shortening within the dose and dose-rate range used. It was also concluded that radiaton-induced neoplastic transformaton was significantly greater in mice with a known genetic sensitivity to neoplastic disease than in mammals which do not normally have a significant incidence of tumours. (author)

  16. A Professionalism Curricular Model to Promote Transformative Learning Among Residents.

    Science.gov (United States)

    Foshee, Cecile M; Mehdi, Ali; Bierer, S Beth; Traboulsi, Elias I; Isaacson, J Harry; Spencer, Abby; Calabrese, Cassandra; Burkey, Brian B

    2017-06-01

    Using the frameworks of transformational learning and situated learning theory, we developed a technology-enhanced professionalism curricular model to build a learning community aimed at promoting residents' self-reflection and self-awareness. The RAPR model had 4 components: (1) R ecognize : elicit awareness; (2) A ppreciate : question assumptions and take multiple perspectives; (3) P ractice : try new/changed perspectives; and (4) R eflect : articulate implications of transformed views on future actions. The authors explored the acceptability and practicality of the RAPR model in teaching professionalism in a residency setting, including how residents and faculty perceive the model, how well residents carry out the curricular activities, and whether these activities support transformational learning. A convenience sample of 52 postgraduate years 1 through 3 internal medicine residents participated in the 10-hour curriculum over 4 weeks. A constructivist approach guided the thematic analysis of residents' written reflections, which were a required curricular task. A total of 94% (49 of 52) of residents participated in 2 implementation periods (January and March 2015). Findings suggested that RAPR has the potential to foster professionalism transformation in 3 domains: (1) attitudinal, with participants reporting they viewed professionalism in a more positive light and felt more empathetic toward patients; (2) behavioral, with residents indicating their ability to listen to patients increased; and (3) cognitive, with residents indicating the discussions improved their ability to reflect, and this helped them create meaning from experiences. Our findings suggest that RAPR offers an acceptable and practical strategy to teach professionalism to residents.

  17. Transcription profiling of human MCF10A cells subjected to ionizing radiation and treatment with transforming growth factor beta-1

    Data.gov (United States)

    National Aeronautics and Space Administration — Transforming growth factor beta-1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis but it can switch to a tumor promoter during neoplastic...

  18. Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells

    Directory of Open Access Journals (Sweden)

    Saikali Melody

    2012-07-01

    Full Text Available Abstract Background Sesquiterpene lactones (SL are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-β-methoxy-iso-seco-tanapartholide (β-tan isolated from Achillea falcata and salograviolide A (Sal A isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how β-tan and Sal A modulate their signaling pathways in JB6P + cells. Methods The effects of β-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes. Results β-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways. Conclusions These results highlight the anti-tumor promoting properties of β-tan and Sal A. These SL molecules isolated from two plant species native to

  19. Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells.

    Science.gov (United States)

    Saikali, Melody; Ghantous, Akram; Halawi, Racha; Talhouk, Salma N; Saliba, Najat A; Darwiche, Nadine

    2012-07-09

    Sesquiterpene lactones (SL) are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-β-methoxy-iso-seco-tanapartholide (β-tan) isolated from Achillea falcata and salograviolide A (Sal A) isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how β-tan and Sal A modulate their signaling pathways in JB6P + cells. The effects of β-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes. β-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways. These results highlight the anti-tumor promoting properties of β-tan and Sal A. These SL molecules isolated from two plant species native to the Middle East may provide opportunities for complementary

  20. Management of neoplastic meningitis.

    Science.gov (United States)

    Roth, Patrick; Weller, Michael

    2015-06-01

    Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.

  1. The human T-lymphotropic virus type I tax gene can cooperate with the ras oncogene to induce neoplastic transformation of cells.

    Science.gov (United States)

    Pozzatti, R; Vogel, J; Jay, G

    1990-01-01

    Epidemiologic studies have linked infection by the human T-lymphotropic virus type I (HTLV-I) with the development of adult T-cell leukemia. The low penetrance of the virus and the long latency for disease manifestation are factors that obscure the role of HTLV-I infection in oncogenesis. We have used an in vitro transformation assay system to determine directly whether the HTLV-I tax gene has transformation potential. Transfection of the tax gene alone into early-passage rat embryo fibroblasts did not induce morphological alterations. However, cotransfection of tax with the selectable marker plasmid pRSVneo gave rise to G418-resistant colonies that could be established as immortalized cell lines. Cotransfection of tax with the ras oncogene into rat embryo fibroblasts gave rise to foci of transformed cells that were highly tumorigenic in nude mice. These data represent a direct demonstration of the oncogenic potential of the tax gene in nonlymphoid cells and establish HTLV-I as a transforming virus.

  2. Phosphorylation of stress protein pp80 is related to promotion of transformation

    International Nuclear Information System (INIS)

    Smith, B.M.; Gindhart, T.D.; Hirano, K.; Colburn, N.H.

    1986-01-01

    The JB6 mouse epidermal cell system is an in vitro model of late stage promotion, and includes cell lines sensitive (P+) or resistant (P-) to phorbol ester-induced anchorage independent transformation, and transformed (T/sub x/) lines. Certain promoter-induced changes in phosphoproteins, identified by gel electrophoresis, are unique to cells of one phenotype, and occur only with specific promoters. An 80Kd protein is inversely correlated with phenotype: P- cells have a constitutively higher level (p 35 S-methionine. pp80 shares properties with the 80Kd heat stress protein: molecular weight relative abundance, and isoelectric point (4.5). Pharmacological analogs of calcium, the lanthanides, promote transformation of JB6 cells, but have no effect on phosphorylation of the 80Kd protein. If pp80 is on the promotion pathway, it is limited to a specific subset of transformation promoters

  3. Promoting structural transformation: Strategic diversification vs laissez-faire approach

    NARCIS (Netherlands)

    Freire Junior, Clovis

    2017-01-01

    Economic development is associated with structural transformation and the increase of complexity of production and exports. This paper examines whether strategic diversification is required to increase economic complexity or whether market incentives would be sufficient to drive this process of

  4. Modeling mechanical effects on promotion and retardation of martensitic transformation

    Energy Technology Data Exchange (ETDEWEB)

    Maalekian, Mehran, E-mail: mehran.maalekian@ubc.ca [Department of Materials Engineering, University of British Columbia, 309-6350 Stores Road, Vancouver, B.C. V61Z4 (Canada); Kozeschnik, Ernst [Christian Doppler Laboratory for ' Early Stages of Precipitation' , Institute of Materials Science and Technology, Vienna University of Technology (Austria)

    2011-01-25

    Research highlights: {yields} Compressive elastic stresses up to 250 MPa are applied in continuous cooling. {yields} Using the thermodynamic data and maximum value of the mechanical driving force the predicted increase in M{sub s} ({approx}0.1 K/MPa) is in agreement with experiment {yields} Austenite was deformed plastically at different temperatures (800 deg. C-1100 deg. C). {yields} High deformation temperature (i.e. 1100 deg. C) as well as low plastic strain (i.e. {epsilon}{sub ave} {approx} 30%) do not affect martensite transformation noticeably, whereas lower deformation temperature (e.g. 900 deg. C) and large plastic strain (i.e. {epsilon}{sub ave} {approx} 70%) retards martensite transformation. {yields} The theory of mechanical stabilization predicts the depression of M{sub s}. - Abstract: The influence of compressive stress and prior plastic deformation of austenite on the martensite transformation in a eutectoid steel is studied both experimentally and theoretically. It is demonstrated that martensite formation is assisted by stress but it is retarded when transformation occurs from deformed austenite. With the quantitative modeling of the problem based on the theory of displacive shear transformation, the explanation of the two opposite roles of mechanical treatment prior to or simultaneously to martensite transformation is presented.

  5. Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

    OpenAIRE

    Andrzej Eljaszewicz; Małgorzata Wiese; Anna Helmin-Basa; Michal Jankowski; Lidia Gackowska; Izabela Kubiszewska; Wojciech Kaszewski; Jacek Michalkiewicz; Wojciech Zegarski

    2013-01-01

    Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages...

  6. Transforming lives: microcredit promotes renewable energy in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Urmee, Tania; Wimmer, Nancy [Grameen Shakti, Dhaka (Bangladesh)

    1999-07-01

    Outlines the work of Grameen Shakti in Bangladesh in promoting the use of renewable energy, in particular the marketing strategy aimed at popularising PV systems. Challenges to the success of its strategy such as cost and competition are outlined. Biomass and wind power are briefly mentioned.

  7. Transformational leadership to promote cross-generational retention.

    Science.gov (United States)

    Lobo, Vanessa M

    2010-05-01

    As the current nursing shortage intensifies under the weight of an aging population, retention of front-line staff is becoming paramount. Studies have consistently demonstrated that the leadership style of nurse managers plays a significant role to this end. This paper describes some of the challenges that managers encounter in their dealings with the contemporary multigenerational workforce - including the baby boomers, generation X and generation Y (the "millennials"). A review of research findings suggests the insufficiency of a single leadership approach to nurse management compared to more tailored generational strategies. Application of the transformational leadership model provides the background and tenets from which solutions are proposed for multigenerational management.

  8. Non-neoplastic gliotic cerebellar cysts

    International Nuclear Information System (INIS)

    Weisberg, L.A.

    1982-01-01

    The clinical and CT findings in 3 patients with non-neoplastic gliotic cerebellar cyst are described. CT does not permit accurate preoperative differentiation of these lesions from neoplastic disorders. (orig.)

  9. The effect of transformational leadership and job autonomy on promotive and prohibitive voice

    DEFF Research Database (Denmark)

    Svendsen, Mari; Unterrainer, Christine; Jønsson, Thomas Faurholt

    2018-01-01

    Although there is a vast amount of research on leadership and improvement-oriented voice behavior, the amount of cross-lagged research on leadership that also incorporates more challenging forms of voice is sparse. This paper reports on a two-wave study of white-collar workers in a Norwegian...... medical technology company, investigating the relationship among employees’ perceived transformational leadership behaviors, job autonomy, and promotive and prohibitive voice. Testing our results cross-lagged, we demonstrate that perceived transformational leadership is significantly related...... to prohibitive voice over time, whereas this effect worked in the opposite direction for promotive voice. We also explore the boundary conditions of transformational leadership, demonstrating that perceived job autonomy strengthens the effect of transformational leadership on prohibitive voice. Implications...

  10. NEOPLASTIC LESIONS OF THE APPENDIX

    Directory of Open Access Journals (Sweden)

    Piotr Bryk

    2013-11-01

    Full Text Available The aim of the research was to present the clinical observations of neoplastic lesions of the appendix (one carcinoid and two mucous cysts and to discuss various manners of treatment and prognosis. Material and methods: The authors of the following paper present a description of three cases of appendix tumours, two patients with a mucous cyst and a patient with carcinoid, against the background of all the appendectomies performed at the Clinical Department of General, Endocrine and Oncological Surgery of the Provincial Polyclinical Hospital in Kielce in the years 2005–2011. Results : Within the 7-year period, a total of 11 719 surgical operations have been performed, where 834 (7.1% were that of appendectomy. Among all of the removed vermiform appendixes, neoplastic lesions occurred in three cases constituting a mere 0.3% of all of the appendectomies performed within that period. In two of the cases there was a suspicion of mucous cysts before the surgical operation. In none of the above-mentioned cases was is possible to ultimately establish the diagnosis before the operation. The patients were subjected to a simple appendectomy. The patients are in good clinical health, with no signs of relapse. Conclusions : The presented cases of patients with appendix tumours illustrate the difficulty of preoperative detection of a neoplastic lesion. This is mainly due to a scantily symptomatic course or symptoms typical of appendicitis. In light of this, histopathological examination of each appendix should be treated as obligatory.

  11. Gender-transformative health promotion for women: a framework for action.

    Science.gov (United States)

    Pederson, Ann; Greaves, Lorraine; Poole, Nancy

    2015-03-01

    Gender inequity is a pervasive global challenge to health equity. Health promotion, as a field, has paid only limited attention to gender inequity to date, but could be an active agent of change if gender equity became an explicit goal of health promotion research, policy and programmes. As an aspect of gendered health systems, health promotion interventions may maintain, exacerbate or reduce gender-related health inequities, depending upon the degree and quality of gender-responsiveness within the programme or policy. This article introduces a framework for gender-transformative health promotion that builds on understanding gender as a determinant of health and outlines a continuum of actions to address gender and health. Gender-transformative health promotion interventions could play a significant role in improving the lives of millions of girls and women worldwide. Gender-related principles of action are identified that extend the core principles of health promotion but reflect the significance of attending to gender in the development and use of evidence, engagement of stakeholders and selection of interventions. We illustrate the framework with examples from a range of women's health promotion activities, including cardiovascular disease prevention, tobacco control, and alcohol use. The literature suggests that gender-responsiveness will enhance the acceptance, relevance and effectiveness of health promotion interventions. By moving beyond responsiveness to transformation, gender-transformative health promotion could enhance both health and social outcomes for large numbers of women and men, girls and boys. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. The chromatin remodeling BAP complex limits tumor-promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in Drosophila epithelia

    DEFF Research Database (Denmark)

    Song, Shilin; Herranz, Héctor; Cohen, Stephen M.

    2017-01-01

    Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are mutated in many human cancers. In this article, we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit...

  13. Radiation-induced irreparable heritable changes in cells promoting their tumoral transformation

    International Nuclear Information System (INIS)

    Kuzin, A.M.; Vagabova, M.Eh.; Yurov, S.S.

    1988-01-01

    In experiments with model plant tumors (Kalanchoe-ti plasmid Agrobat. tumefaciens C-58D) it was shown that exposure of the recepient plant to low-level γ-radiation of Gy induced changes in cells that were not repaired over two months promoting tumoral transformations in them. Those changes were shown to persist in the offspring of the exposed somatic cells

  14. Collaborating with the enemy: function of macrophages in the development of neoplastic disease.

    Science.gov (United States)

    Eljaszewicz, Andrzej; Wiese, Małgorzata; Helmin-Basa, Anna; Jankowski, Michal; Gackowska, Lidia; Kubiszewska, Izabela; Kaszewski, Wojciech; Michalkiewicz, Jacek; Zegarski, Wojciech

    2013-01-01

    Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, "cooperate" with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

  15. Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

    Directory of Open Access Journals (Sweden)

    Andrzej Eljaszewicz

    2013-01-01

    Full Text Available Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc., neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect, induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc., and support invasion and metastases formation. Tumor-associated macrophages (TAMs, a predominant component of leukocytic infiltrate, “cooperate” with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

  16. A comparison study of Agrobacterium-mediated transformation methods for root-specific promoter analysis in soybean.

    Science.gov (United States)

    Li, Caifeng; Zhang, Haiyan; Wang, Xiurong; Liao, Hong

    2014-11-01

    Both in vitro and in vivo hairy root transformation systems could not replace whole plant transformation for promoter analysis of root-specific and low-P induced genes in soybean. An efficient genetic transformation system is crucial for promoter analysis in plants. Agrobacterium-mediated transformation is the most popular method to produce transgenic hairy roots or plants. In the present study, first, we compared the two different Agrobacterium rhizogenes-mediated hairy root transformation methods using either constitutive CaMV35S or the promoters of root-preferential genes, GmEXPB2 and GmPAP21, in soybean, and found the efficiency of in vitro hairy root transformation was significantly higher than that of in vivo transformation. We compared Agrobacterium rhizogenes-mediated hairy root and Agrobacterium tumefaciens-mediated whole plant transformation systems. The results showed that low-phosphorous (P) inducible GmEXPB2 and GmPAP21 promoters could not induce the increased expression of the GUS reporter gene under low P stress in both in vivo and in vitro transgenic hairy roots. Conversely, GUS activity of GmPAP21 promoter was significantly higher at low P than high P in whole plant transformation. Therefore, both in vitro and in vivo hairy root transformation systems could not replace whole plant transformation for promoter analysis of root-specific and low-P induced genes in soybean.

  17. Promoting energy-efficient products: GEF experience and lessons for market transformation in developing countries

    International Nuclear Information System (INIS)

    Birner, Sabrina; Martinot, Eric

    2005-01-01

    The Global Environment Facility (GEF) has allocated more than $90 million over the past 10 years to eight projects promoting energy-efficient products in developing and transition countries. We review the early experience from these projects and suggest lessons relevant to market transformation programs. Based on GEF project designs, we also propose a menu of generic supply-side and demand-side interventions useful for designing and analyzing market transformation programs. Experience suggests that institutional and policy changes, leading to sustained price reductions and higher market volumes, are important outcomes for market transformation; that market impacts can appear early in programs due to increased expectations and awareness; and that projects can have a catalytic effect. We recommend eight principles for designers of future projects but caution that no single approach guarantees success

  18. Amelogenin Affects Brushite Crystal Morphology and Promotes Its Phase Transformation to Monetite

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Dongni; Ruan, Qichao; Tao, Jinhui; Lo, Jonathan; Nutt, Steven; Moradian-Oldak, Janet

    2016-09-07

    Amelogenin protein is involved in organized apatite crystallization during enamel formation. Brushite (CaHPO4·2H2O), which is one of the precursors for hydroxyapatite in in vitro mineralization, has been used for fabrication of biomaterials for hard tissue repair. In order to explore its potential application in biomimetic material synthesis, we studied the influence of amelogenin on brushite morphology and phase transformation to monetite. Our results show that amelogenin can adsorb onto surface of brushite, leading to the formation of layered structures on the (010) face. Amelogenin promoted the phase transformation of brushite into monetite (CaHPO4) in the dry state, presumably by interacting with crystalline water layers in brushite unit cell. Changes to the crystal morphology by amelogenin continued even after the phase transformation to monetite forming an organized nanotextured structure of nano-sticks resembling the bundle structure in enamel.

  19. Seismic data two-step recovery approach combining sparsity-promoting and hyperbolic Radon transform methods

    International Nuclear Information System (INIS)

    Wang, Hanchuang; Chen, Shengchang; Ren, Haoran; Liang, Donghui; Zhou, Huamin; She, Deping

    2015-01-01

    In current research of seismic data recovery problems, the sparsity-promoting method usually produces an insufficient recovery result at the locations of null traces. The HRT (hyperbolic Radon transform) method can be applied to problems of seismic data recovery with approximately hyperbolic events. Influenced by deviations of hyperbolic characteristics between real and ideal travel-time curves, some spurious events are usually introduced and the recovery effect of intermediate and far-offset traces is worse than that of near-offset traces. Sparsity-promoting recovery is primarily dependent on the sparsity of seismic data in the sparse transform domain (i.e. on the local waveform characteristics), whereas HRT recovery is severely affected by the global characteristics of the seismic events. Inspired by the above conclusion, a two-step recovery approach combining sparsity-promoting and time-invariant HRT methods is proposed, which is based on both local and global characteristics of the seismic data. Two implementation strategies are presented in detail, and the selection criteria of the relevant strategies is also discussed. Numerical examples of synthetic and real data verify that the new approach can achieve a better recovery effect by simultaneously overcoming the shortcomings of sparsity-promoting recovery and HRT recovery. (paper)

  20. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khin, Sann Sanda [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Pathology Research Unit, Department of Medical Research (Central Myanmar), Naypyitaw, Union of (Myanmar); Kitazawa, Riko [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Haraguchi, Ryuma [Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Mori, Kiyoshi [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Kitazawa, Sohei, E-mail: kitazawa@m.ehime-u.ac.jp [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan)

    2011-03-03

    Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.

  1. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

    International Nuclear Information System (INIS)

    Khin, Sann Sanda; Kitazawa, Riko; Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo; Haraguchi, Ryuma; Mori, Kiyoshi; Kitazawa, Sohei

    2011-01-01

    Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression

  2. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β Signaling in Cancer

    Directory of Open Access Journals (Sweden)

    Kiyoshi Mori

    2011-03-01

    Full Text Available Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β, induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.

  3. Neoplastic causes of abnormal puberty.

    Science.gov (United States)

    Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

    2014-04-01

    Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

  4. Non-neoplastic disorders of the esophagus

    International Nuclear Information System (INIS)

    Hong, Min Ji; Kim, Young Tong

    2013-01-01

    Non-neoplastic disorders of the esophagus include esophagitis, esophageal diverticulum, esophageal injury, foreign body, fistulous formation between the esophagus and the surrounding structures and mucocele. Since these disorders have variable symptoms and radiologic findings, it needs to differentiated from other disorders other than esophageal diseases. Being knowledgeable of CT findings suggest that these disorders can help diagnose non-neoplastic disorders of the esophagus. The purpose of this pictorial essay is to review the CT appearance of non-neoplastic disorders of the esophagus.

  5. Capsule endoscopy in neoplastic diseases

    Science.gov (United States)

    Pennazio, Marco; Rondonotti, Emanuele; de Franchis, Roberto

    2008-01-01

    Until recently, diagnosis and management of small-bowel tumors were delayed by the difficulty of access to the small bowel and the poor diagnostic capabilities of the available diagnostic techniques. An array of new methods has recently been developed, increasing the possibility of detecting these tumors at an earlier stage. Capsule endoscopy (CE) appears to be an ideal tool to recognize the presence of neoplastic lesions along this organ, since it is non-invasive and enables the entire small bowel to be visualized. High-quality images of the small-bowel mucosa may be captured and small and flat lesions recognized, without exposure to radiation. Recent studies on a large population of patients undergoing CE have reported small-bowel tumor frequency only slightly above that reported in previous surgical series (range, 1.6%-2.4%) and have also confirmed that the main clinical indication to CE in patients with small-bowel tumors is obscure gastrointestinal (GI) bleeding. The majority of tumors identified by CE are malignant; many were unsuspected and not found by other methods. However, it remains difficult to identify pathology and tumor type based on the lesion’s endoscopic appearance. Despite its limitations, CE provides crucial information leading in most cases to changes in subsequent patient management. Whether the use of CE in combination with other new diagnostic (MRI or multidetector CT enterography) and therapeutic (Push-and-pull enteroscopy) techniques will lead to earlier diagnosis and treatment of these neoplasms, ultimately resulting in a survival advantage and in cost savings, remains to be determined through carefully-designed studies. PMID:18785274

  6. Total gastrectomy for non-neoplastic diseases

    DEFF Research Database (Denmark)

    Bjorn, Niels; Ainsworth, Alan Patrick; Mortensen, Michael Bau

    2017-01-01

    Background: The aim of this study was to describe patients who had total gastrectomy for non-neoplastic diseases within a well-defined geographical area. Material and Methods: Retrospective study of patients who had gastrectomy for a non-neoplastic disease at the Department of Surgery, Odense...... University Hospital from 1 January 2005 to 31 December 2014. Results: A total of 268 gastrectomies were performed with the 10-year period. Of these, ten (4%) were done for non-neoplastic diseases. Two were men and eight women with a median age of 51 years (range 31 to 96 years). Six had emergency surgery...... of 10 and 2 of 10, respectively. Histology of the resected specimens showed: Oedema, inflammation and/or necrosis (n=6), Menetrier's disease (n=2) and perforation (n=2). Conclusions: Gastrectomy for non-neoplastic diseases accounts for less than 5% of all gastrectomies. The majority of these cases...

  7. Degradation of type IV collagen by neoplastic human skin fibroblasts

    International Nuclear Information System (INIS)

    Sheela, S.; Barrett, J.C.

    1985-01-01

    An assay for the degradation of type IV (basement membrane) collagen was developed as a biochemical marker for neoplastic cells from chemically transformed human skin fibroblasts. Type IV collagen was isolated from basement membrane of Syrian hamster lung and type I collagen was isolated from rat tails; the collagens were radioactively labelled by reductive alkylation. The abilities of normal (KD) and chemically transformed (Hut-11A) human skin fibroblasts to degrade the collagens were studied. A cell-associated assay was performed by growing either normal or transformed cells in the presence of radioactively labelled type IV collagen and measuring the released soluble peptides in the medium. This assay also demonstrated that KD cells failed to synthesize an activity capable of degrading type IV collagen whereas Hut-11A cells degraded type IV collagen in a linear manner for up to 4 h. Human serum at very low concentrations, EDTA and L-cysteine inhibited the enzyme activity, whereas protease inhibitors like phenylmethyl sulfonyl fluoride, N-ethyl maleimide or soybean trypsin inhibitor did not inhibit the enzyme from Hut-11A cells. These results suggest that the ability to degrade specifically type IV collagen may be an important marker for neoplastic human fibroblasts and supports a role for this collagenase in tumor cell invasion

  8. The induction and regulation of radiogenic transformation in vitro: Cellular and molecular mechanisms

    International Nuclear Information System (INIS)

    Borek, C.

    1987-01-01

    Rodent and human cells in culture, transformed in vitro by ionizing radiation, ultraviolet light, or chemicals into malignant cells afford us the opportunity to probe into early and late events in the neoplastic process at a cellular and molecular level. Transformation can be regarded as an abnormal expression of cellular genes. The initiating agents disrupt the integrity of the genetic apparatus altering DNA in ways that result in the activation of cellular transforming genes (oncogenes) during some stage of the neoplastic process. Events associated with initiation and promotion may overlap to some degree, but in order for them to occur, cellular permissive conditions must prevail. Permissive factors include thyroid and steroid hormones, specific states of differentiation, certain stages in the cell cycle, specific genetic impairment, and inadequate antioxidants. Genetically susceptible cells require physiological states conducive to transformation. These may differ with age, tissue, and species and in part may be responsible for the observed lower sensitivity of human cells to transformation

  9. Transformation mechanism of benzophenone-4 in free chlorine promoted chlorination disinfection.

    Science.gov (United States)

    Xiao, Ming; Wei, Dongbin; Yin, Junxia; Wei, Guohua; Du, Yuguo

    2013-10-15

    The UV-filter BP-4 (2-hydroxy-4-methoxybenzophenone-5-sulfonic acid) has been frequently observed in the environment, showing high potentials to invade drinking water, swimming water, or wastewater reclamation treatment systems. With the help of high performance liquid chromatography-high resolution mass spectrometry and nuclear magnetic resonance spectroscopy, 10 new products from free chlorine-promoted BP-4 disinfection have been disclosed and their possible transformation routes have been investigated. The first route is chlorine substitution of BP-4 and its transformation products, forming mono-, di-, and tri-chlorinated BP-4 analogs. The second is Baeyer-Villiger-Type oxidation, converting diphenyl ketone to phenyl ester derivatives. The third is ester hydrolysis, generating corresponding phenolic and benzoic products. The fourth is decarboxylation, replacing the carboxyl group by chloride in the benzoic-type intermediate. The fifth is desulfonation, degrading the sulfonic group through an alternative chlorine substitution on the benzene ring. Orthogonal experiments have been established to investigate the species transformed from BP-4 at different pH values and free available chlorine (FAC) dosages. The reaction pathways are strongly dependent on pH conditions, while an excessive amount of FAC eliminates BP-4 to the smaller molecules. The initial transformation of BP-4 in chlorination system follows pseudo-first-order kinetics, and its half-lives ranged from 7.48 s to 1.26 × 10(2) s. More importantly, we have observed that the FAC-treated BP-4 aqueous solution might increase the genotoxic potentials due to the generation of chlorinated disinfection by-products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Cell-to-cell transformation in Escherichia coli: a novel type of natural transformation involving cell-derived DNA and a putative promoting pheromone.

    Directory of Open Access Journals (Sweden)

    Rika Etchuuya

    Full Text Available Escherichia coli is not assumed to be naturally transformable. However, several recent reports have shown that E. coli can express modest genetic competence in certain conditions that may arise in its environment. We have shown previously that spontaneous lateral transfer of non-conjugative plasmids occurs in a colony biofilm of mixed E. coli strains (a set of a donor strain harbouring a plasmid and a plasmid-free recipient strain. In this study, with high-frequency combinations of strains and a plasmid, we constructed the same lateral plasmid transfer system in liquid culture. Using this system, we demonstrated that this lateral plasmid transfer was DNase-sensitive, indicating that it is a kind of transformation in which DNase-accessible extracellular naked DNA is essential. However, this transformation did not occur with purified plasmid DNA and required a direct supply of plasmid from co-existing donor cells. Based on this feature, we have termed this transformation type as 'cell-to-cell transformation'. Analyses using medium conditioned with the high-frequency strain revealed that this strain released a certain factor(s that promoted cell-to-cell transformation and arrested growth of the other strains. This factor is heat-labile and protease-sensitive, and its roughly estimated molecular mass was between ∼9 kDa and ∼30 kDa, indicating that it is a polypeptide factor. Interestingly, this factor was effective even when the conditioned medium was diluted 10(-5-10(-6, suggesting that it acts like a pheromone with high bioactivity. Based on these results, we propose that cell-to-cell transformation is a novel natural transformation mechanism in E. coli that requires cell-derived DNA and is promoted by a peptide pheromone. This is the first evidence that suggests the existence of a peptide pheromone-regulated transformation mechanism in E. coli and in Gram-negative bacteria.

  11. Mechanical Properties of Human Cells Change during Neoplastic Processes

    Science.gov (United States)

    Guthold, Martin; Guo, Xinyi; Bonin, Keith; Scarpinato, Karin

    2014-03-01

    Using an AFM with a spherical probe of 5.3 μm, we determined mechanical properties of individual human mammary epithelial cells that have progressed through four stages of neoplastic transformation: normal, immortal, tumorigenic, and metastatic. Measurements on cells in all four stages were taken over both the nucleus and the cytoplasm. Moreover, the measurements were made for cells outside of a colony (isolated), on the periphery of a colony, and inside a colony. By fitting the AFM force vs. indentation curves to a Hertz model, we determined the Young's modulus, E. We found a distinct contrast in the influence a cell's colony environment has on its stiffness depending on whether the cells are normal or cancer cells. We also found that cells become softer as they advance to the tumorigenic stage and then stiffen somewhat in the final step to metastatic cells. For cells averaged over all locations the stiffness values of the nuclear region for normal, immortal, tumorigenic, and metastatic cells were (mean +/- sem) 880 +/- 50, 940+/-50, 400 +/- 20, and 600 +/-20 Pa respectively. Cytoplasmic regions followed a similar trend. These results point to a complex picture of the mechanical changes that occur as cells undergo neoplastic transformation. This work is supported by NSF Materials and Surface Engineering grant CMMI-1152781.

  12. The value of the indirect immunoradiometric assay of serum alpha - fetoprotein in detecting liver regeneration and neoplastic transformation in chronic liver disease. Part of a coordinated programme on in vitro assay techniques

    International Nuclear Information System (INIS)

    Voiculetz, N.

    1979-07-01

    To investigate the concentration of alphafetoprotein AFP in different liver diseases and above all in liver cancer the immunoradiometric assay was utilized. The results of AFP studies were compared with regeneration index, blastic T lymphocytes transformation as well as other morphological and biochemical data. The results of the investigations indicated that: 38% of chronic benign hepatopathies displayed the values of serum AFP in normal ranges, 54% were in the range of 41 - 200ng/ml, and 8% showed 200 and more ng/ml. The most important conclusion from the work performed was that the elevation of serum AFP level in the evaluation of chronic hepatopathies, especially in cirrhoses, appears as an index of malignancy

  13. Neoplastic pericardial disease. Analysis of 26 patients

    Directory of Open Access Journals (Sweden)

    Helena Nogueira Soufen

    1999-01-01

    Full Text Available PURPOSE: To characterize patients with neoplastic pericardial disease diagnosed by clinical presentation, complementary test findings, and the histological type of tumor. METHODS: Twenty-six patients with neoplastic pericardial disease were retrospectively analyzed. RESULTS: Clinical manifestations and abnormalities in chest roentgenograms and electrocardiograms were frequent, but were not specific. Most patients underwent surgery. There was a high positivity of the pericardial biopsy when associated with the cytological analysis of the pericardial liquid used to determine the histological type of the tumor, particularly when the procedure was performed with the aid of pericardioscopy. CONCLUSION: The correct diagnosis of neoplastic pericardial disease involves suspicious but nonspecific findings during clinical examination and in screen tests. The suspicious findings must be confirmed through more invasive diagnostic approaches, in particular pericardioscopy with biopsy and cytological study.

  14. Imaging of limbic para-neoplastic encephalitis

    International Nuclear Information System (INIS)

    Rimmelin, A.; Sellat, F.; Morand, G.; Quoix, E.; Clouet, P.L.; Dietemann, J.L.

    1997-01-01

    Para-neoplastic limbic encephalitis is a rare syndrome mostly associated with small cell lung cancer. We present the case of a 69-year-old man with selective amnesia suggesting limbic encephalitis. A neuroendocrine cell lung cancer was found, confirming the diagnostics of para-neoplastic limbic encephalitis. Contrast-enhanced cerebral CT was normal whether magnetic resonance imaging showed signal abnormalities of the medial part of temporal lobes and hippocampal regions. Because neurologic improvement may follow treatment of the primary tumor, early diagnosis is important. (authors)

  15. Complex Systems Analysis of Cell Cycling Models in Carcinogenesis:II. Cell Genome and Interactome, Neoplastic Non-random Transformation Models in Topoi with Lukasiewicz-Logic and MV Algebras

    CERN Document Server

    Baianu, I C

    2004-01-01

    Quantitative Biology, abstract q-bio.OT/0406045 From: I.C. Baianu Dr. [view email] Date (v1): Thu, 24 Jun 2004 02:45:13 GMT (164kb) Date (revised v2): Fri, 2 Jul 2004 00:58:06 GMT (160kb) Complex Systems Analysis of Cell Cycling Models in Carcinogenesis: II. Authors: I.C. Baianu Comments: 23 pages, 1 Figure Report-no: CC04 Subj-class: Other Carcinogenesis is a complex process that involves dynamically inter-connected modular sub-networks that evolve under the influence of micro-environmentally induced perturbations, in non-random, pseudo-Markov chain processes. An appropriate n-stage model of carcinogenesis involves therefore n-valued Logic treatments of nonlinear dynamic transformations of complex functional genomes and cell interactomes. Lukasiewicz Algebraic Logic models of genetic networks and signaling pathways in cells are formulated in terms of nonlinear dynamic systems with n-state components that allow for the generalization of previous, Boolean or "fuzzy", logic models of genetic activities in vivo....

  16. Building Health Promotion into the Job of Home Care Aides: Transformation of the Workplace Health Environment

    Directory of Open Access Journals (Sweden)

    Naoko Muramatsu

    2017-04-01

    Full Text Available Home care aides (HCAs, predominantly women, constitute one of the fastest growing occupations in the United States. HCAs work in clients’ homes that lack typical workplace resources and benefits. This mixed-methods study examined how HCAs’ work environment was transformed by a pilot workplace health promotion program that targeted clients as well as workers. The intervention started with training HCAs to deliver a gentle physical activity program to their older clients in a Medicaid-funded home care program. Older HCAs aged 50+ reported increased time doing the types of physical activity that they delivered to their clients (stretching or strengthening exercise (p = 0.027. Almost all (98% HCAs were satisfied with the program. These quantitative results were corroborated by qualitative data from open-ended survey questions and focus groups. HCAs described how they exercised with clients and how the psychosocial work environment changed with the program. Building physical activity into HCAs’ job is feasible and can effectively promote HCAs’ health, especially among older HCAs.

  17. Building Health Promotion into the Job of Home Care Aides: Transformation of the Workplace Health Environment.

    Science.gov (United States)

    Muramatsu, Naoko; Yin, Lijuan; Lin, Ting-Ti

    2017-04-05

    Home care aides (HCAs), predominantly women, constitute one of the fastest growing occupations in the United States. HCAs work in clients' homes that lack typical workplace resources and benefits. This mixed-methods study examined how HCAs' work environment was transformed by a pilot workplace health promotion program that targeted clients as well as workers. The intervention started with training HCAs to deliver a gentle physical activity program to their older clients in a Medicaid-funded home care program. Older HCAs aged 50+ reported increased time doing the types of physical activity that they delivered to their clients (stretching or strengthening exercise) ( p = 0.027). Almost all (98%) HCAs were satisfied with the program. These quantitative results were corroborated by qualitative data from open-ended survey questions and focus groups. HCAs described how they exercised with clients and how the psychosocial work environment changed with the program. Building physical activity into HCAs' job is feasible and can effectively promote HCAs' health, especially among older HCAs.

  18. Leukaemia virus infection promotes fibroblast transformation by normal BALB/c mouse DNA

    NARCIS (Netherlands)

    Krump-Konvalinkova, V.; Berg, K.J. van den

    1980-01-01

    All normal cells are thought to carry genetic information for oncogenic transformation, which, on activation to continuous expression. might make the cell cancerous. The presently known transforming retroviruses contain transforming genes which were probably derived by recombination of a slow

  19. BAG3 promotes the phenotypic transformation of primary rat vascular smooth muscle cells via TRAIL.

    Science.gov (United States)

    Fu, Yao; Chang, Ye; Chen, Shuang; Li, Yuan; Chen, Yintao; Sun, Guozhe; Yu, Shasha; Ye, Ning; Li, Chao; Sun, Yingxian

    2018-05-01

    Under normal physiological condition, the mature vascular smooth muscle cells (VSMCs) show differentiated phenotype. In response to various environmental stimuluses, VSMCs convert from the differentiated phenotype to dedifferentiated phenotype characterized by the increased ability of proliferation/migration and the reduction of contractile ability. The phenotypic transformation of VSMCs played an important role in atherosclerosis. Both Bcl-2-associated athanogene 3 (BAG3) and tumor necrosis factor-related apopt-osis inducing ligand (TRAIL) involved in apoptosis. The relationship between BAG3 and TRAIL and their effects the proliferation and migration in VSMCs are rarely reported. This study investigated the effects of BAG3 on the phenotypic modulation and the potential underlying mechanisms in primary rat VSMCs. Primary rat VSMCs were extracted and cultured in vitro. Cell proliferation was detected by cell counting, real-time cell analyzer (RTCA) and EdU incorporation. Cell migration was detected by wound healing, Transwell and RTCA. BAG3 and TRAIL were detected using real-time PCR and western blotting and the secreted proteins in the cultured media by dot blot. The expression of BAG3 increased with continued passages in cultured primary VSMCs. BAG3 promoted the proliferation and migration of primary rat VSMC in a time-dependent manner. BAG3 significantly increased the expression of TRAIL while had no effects on its receptors. TRAIL knockdown or blocking by neutralizing antibody inhibited the proliferation of VSMCs induced by BAG3. TRAIL knockdown exerted no obvious influence on the migration of VSMCs. Based on this study, we report for the first time that BAG3 was expressed in cultured primary rat VSMCs and the expression of BAG3 increased with continued passages. Furthermore, BAG3 promoted the proliferation of VSMCs via increasing the expression of TRAIL. In addition, we also demonstrated that BAG3 promoted the migration of VSMCs independent of TRAIL

  20. Transformation

    DEFF Research Database (Denmark)

    Bock, Lars Nicolai

    2011-01-01

    Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi.......Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi....

  1. TRANSFORMATION

    Energy Technology Data Exchange (ETDEWEB)

    LACKS,S.A.

    2003-10-09

    Transformation, which alters the genetic makeup of an individual, is a concept that intrigues the human imagination. In Streptococcus pneumoniae such transformation was first demonstrated. Perhaps our fascination with genetics derived from our ancestors observing their own progeny, with its retention and assortment of parental traits, but such interest must have been accelerated after the dawn of agriculture. It was in pea plants that Gregor Mendel in the late 1800s examined inherited traits and found them to be determined by physical elements, or genes, passed from parents to progeny. In our day, the material basis of these genetic determinants was revealed to be DNA by the lowly bacteria, in particular, the pneumococcus. For this species, transformation by free DNA is a sexual process that enables cells to sport new combinations of genes and traits. Genetic transformation of the type found in S. pneumoniae occurs naturally in many species of bacteria (70), but, initially only a few other transformable species were found, namely, Haemophilus influenzae, Neisseria meningitides, Neisseria gonorrheae, and Bacillus subtilis (96). Natural transformation, which requires a set of genes evolved for the purpose, contrasts with artificial transformation, which is accomplished by shocking cells either electrically, as in electroporation, or by ionic and temperature shifts. Although such artificial treatments can introduce very small amounts of DNA into virtually any type of cell, the amounts introduced by natural transformation are a million-fold greater, and S. pneumoniae can take up as much as 10% of its cellular DNA content (40).

  2. TRANSFORMER

    Science.gov (United States)

    Baker, W.R.

    1959-08-25

    Transformers of a type adapted for use with extreme high power vacuum tubes where current requirements may be of the order of 2,000 to 200,000 amperes are described. The transformer casing has the form of a re-entrant section being extended through an opening in one end of the cylinder to form a coaxial terminal arrangement. A toroidal multi-turn primary winding is disposed within the casing in coaxial relationship therein. In a second embodiment, means are provided for forming the casing as a multi-turn secondary. The transformer is characterized by minimized resistance heating, minimized external magnetic flux, and an economical construction.

  3. Morphological spectrum of non‑neoplastic lesions of the uterine ...

    African Journals Online (AJOL)

    Background: The uterine cervix is a gateway to several non‑neoplastic and neoplastic gynecological lesions. Most of these non‑neoplastic lesions are commonly found in women of reproductive age. These lesions constitute a source of morbidity and mortality in women worldwide hence the need to analyze them to provide ...

  4. Multistep change in epidermal growth factor receptors during spontaneous neoplastic progression in Chinese hamster embryo fibroblasts

    International Nuclear Information System (INIS)

    Wakshull, E.; Kraemer, P.M.; Wharton, W.

    1985-01-01

    Whole Chinese hamster embryo lineages have been shown to undergo multistep spontaneous neoplastic progression during serial passage in culture. The authors have studied the binding, internalization, and degradation of 125 I-labeled epidermal growth factor at four different stages of transformation. The whole Chinese hamster embryo cells lost cell surface epidermal growth factor receptors gradually during the course of neoplastic progression until only 10% of the receptor number present in the early-passage cells (precrisis) were retained in the late-passage cells (tumorigenic). No differences in internalization rates, chloroquine sensitivity, or ability to degrade hormone between the various passage levels were seen. No evidence for the presence in conditioned medium of transforming growth factors which might mask or down-regulate epidermal growth factor receptor was obtained. These results suggest that a reduction in cell surface epidermal growth factor receptor might be an early event during spontaneous transformation in whole Chinese hamster embryo cells

  5. A study on mast cell variation in neoplastic and non neoplastic disease of uterine cervix

    Directory of Open Access Journals (Sweden)

    N Mainali

    2014-09-01

    Full Text Available Background: Mast cells are heterogeneous group of immune cells involved in multiple biological events. The significance of mast cells in uterine tumor surveillance has been studied with conflicting results. The presence of mast cell in tumor has been described as evidence of a host immunologic anti tumor response and if they are abundant the prognosis is good. However in other studies, with the help of different granules of mast cell, it is said to be very closely related with angiogenesis and tumor invasion. The study aims to analyze the histomorphologic changes with special reference to mast cells in different neoplastic and non neoplastic disease of uterine cervix, and also the relationship of the mast cell population with degree of anaplasia and mitotic figures.Materials and methods: Cervical biopsies received in the department of Pathology for HPE were stained with H& E stain and toludine blue for the identification of mast cellResult: Out of a total of 100 cases, 82 were non neoplastic cases with the mean mast cell count of 83.73 and mean age of patient being 44.30 year. Eighteen neoplastic cases were included which had mean mast cell count of 13.5 and mean age of 49.5 year.Conclusion: Mast cell was found to be highest in non Neoplastic lesion with increase count in polypoidal cervicitis. There was a statistical significance variation between mast cell count in neoplastic and non Neoplastic disease of the cervix. However,role of age in mast cell count was least significant.DOI: http://dx.doi.org/10.3126/jpn.v4i8.11594 Journal of Pathology of Nepal; Vol.4,No. 8 (2014 658-662

  6. Organoids as Models for Neoplastic Transformation | Office of Cancer Genomics

    Science.gov (United States)

    Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines.

  7. Somatic mutation and cell differentiation in neoplastic transformation

    International Nuclear Information System (INIS)

    Huberman, E.; Collart, F.R.

    1987-01-01

    In brief, the authors suggest that tumor formation may result from continuous expression of growth facilitating genes that, as a result of irreversible changes during the initiation step, are placed under the control of genes expressed during normal differentiation. Thus, to understand carcinogenesis, we must decipher the processes that lead to the acquisition of a mature phenotype in both normal and tumor cells and characterize the growth dependency of tumor cells to inducers of cell differentiation. Furthermore, the growth of a variety of tumors may be controlled through the use of inducers of maturation that activate genes located beyond the gene that is altered during tumor initiation. 22 refs., 3 figs

  8. Mechanistic studies of neoplastic cell transformation by ionizing radiation

    International Nuclear Information System (INIS)

    Yang, T.C.; Craise, L.M.; Tobias, C.A.

    1982-01-01

    As part of the Biology and Medicine heavy-ion radiation program, we are systematically investigating the potential carcinogenic and mutagenic effects of high- and low-linear energy transfer (LET) radiation at the cellular level. From these studies, we anticipate additional insight into the molecular and cellular mechanisms of radiation carcinogenesis. Such results should provide quantitative information useful for assessing the undesirable biological effects of cosmic rays in space. Some of our recent experimental results are presented here

  9. Damages to DNA that result in neoplastic transformation

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1975-01-01

    Some topics discussed are: correlation between carcinogens and mutagens; defective DNA repair in uv-damaged xeroderma pigmentosum cells; analysis of nucleotide damage to DNA following exposure to chemicals or radiations; photoreactivation in uv-irradiated Escherichia coli; tumor development in fish; excision repair as an aid in identifying damage; detection of excision repair; role of endonucleases in repair of uv damage; and alkylation products and tumors

  10. [The risk of neoplastic processes transformation in cervix uteri].

    Science.gov (United States)

    Kiseleva, V I; Krikunova, L I; Mkrtchian, L S; Liubina, L V; Beziaeva, G P; Panarina, L V; Zamuliaeva, I A

    2014-01-01

    There was performed a comparative analysis of quantitative load and physical status of human papillomavirus (HPV) type 16 in groups of patients with cervical intraepithelial neoplasia (CIN)--25 people and cervical cancer (CC)--85 people. According to the analysis there were selected criteria appropriate to a combination of adverse factors that characterized HPV- infection and at the same time estimated both quantitative load and physical status of the virus: high viral load (> 6,5 lg copies of HPV DNA per 100000 cells) in episomal form or low load (< 6,5 lg copies of HPV DNA per 100000 cells) in integrated form of the virus. According to calculations a relative chance of appearing of CC in CIN patients with unfavorable combination of factors was 7,5 times higher than in other patients.

  11. RTVP-1 promotes mesenchymal transformation of glioma via a STAT-3/IL-6-dependent positive feedback loop

    Science.gov (United States)

    Giladi, Nis David; Ziv-Av, Amotz; Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Ben-Asher, Hiba Waldman; deCarvalho, Ana; Mikkelsen, Tom; Poisson, Laila; Brodie, Chaya

    2015-01-01

    Glioblastomas (GBMs), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. We explored the role of RTVP-1, a glioma-associated protein that promotes glioma cell migration, in the mesenchymal transformation of GBM. Analysis of The Cancer Genome Atlas (TCGA) demonstrated that RTVP-1 expression was higher in mesenchymal GBM and predicted tumor recurrence and poor clinical outcome. ChiP analysis revealed that the RTVP-1 promoter binds STAT3 and C/EBPβ, two master transcription factors that regulate mesenchymal transformation of GBM. In addition, IL-6 induced RTVP-1 expression in a STAT3-dependent manner. RTVP-1 increased the migration and mesenchymal transformation of glioma cells. Similarly, overexpression of RTVP-1 in human neural stem cells induced mesenchymal differentiation, whereas silencing of RTVP-1 in glioma stem cells (GSCs) decreased the mesenchymal transformation and stemness of these cells. Silencing of RTVP-1 also increased the survival of mice bearing GSC-derived xenografts. Using gene array analysis of RTVP-1 silenced glioma cells we identified IL-6 as a mediator of RTVP-1 effects on the mesenchymal transformation and migration of GSCs, therefore acting in a positive feedback loop by upregulating RTVP-1 expression via the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM. PMID:26267319

  12. Transforming doctor-patient relationships to promote patient-centered care: lessons from palliative care.

    Science.gov (United States)

    Yedidia, Michael J

    2007-01-01

    Palliative care was studied for its potential to yield lessons for transforming doctor-patient relationships to promote patient-centered care. Examination of patient and provider experiences of the transition from curative to palliative care promises valuable insights about establishing and maintaining trust as the goals of care shift and about addressing a broad spectrum of patient needs. The study was guided by a conceptual framework grounded in existing models to address five dimensions of doctor-patient relationships: range of needs addressed, source of authority, maintenance of trust, emotional involvement, and expression of authenticity. Data collection included observation of the care of 40 patients in the inpatient hospice unit and at home, interviews with patients and family members, and in-depth interviews with 22 physicians and two nurses providing end-of-life care. Standard qualitative procedures were used to analyze the data, incorporating techniques for maximizing the validity of the results and broadening their relevance to other contexts. Findings provide evidence for challenging prominent assumptions about possibilities for doctor-patient relationships: questioning the merits of the prohibition on emotional involvement, dependence on protocols for handling difficult communication issues, unqualified reliance on consumer empowerment to assure that care is responsive to patients' needs, and adoption of narrowly defined boundaries between medical and social service systems in caring for patients. Medical education can play a role in preparing doctors to assume new roles by openly addressing management of emotions in routine clinical work, incorporating personal awareness training, facilitating reflection on interactions with patients through use of standardized patients and videotapes, and expanding capacity to effectively address a broad range of needs through teamwork training.

  13. Role of free radicals in the initiation and promotion of radiation transformation in vitro

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Troll, W.; Little, J.B.

    1984-01-01

    We have studied the effects of superoxide dismutase (SOD), catalase, Cu(II) (3,5-diisopropylsalicylate)2 (CuDIPS) and other copper compounds on radiation transformation in vitro using C3H 10T1/2 cells. When present only during irradiation, high concentrations of SOD in the medium enhanced transformation, while catalase, inactivated SOD (autoclaved), CuDIPS, cupric chloride and cuprous chloride inhibited the initiation phase of radiation transformation. SOD, catalase and CuDIPS did not affect the expression phase of radiation transformation. Suppression of the TPA enhancement of transformation by catalase was a highly significant effect, while the suppression by SOD was not of statistical significance. Our results suggest that hydrogen peroxide (H 2 O 2 ) may be important in the cellular damage leading to malignant transformation

  14. Role of free radicals in the initiation and promotion of radiation transformation in vitro

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Little, J.B.; Troll, W.

    1984-01-01

    The effects of superoxide dismutase (SOD), catalase, Cu(II) (3,5-diisopropylsalicylate) 2 (CuDIPS) and other copper compounds on radiation transformation in vitro have been studied using C3H 10T1/2 cells. When present only during irradiation, high concentrations of SOD in the medium enhanced transformation, while catalase, inactivated SOD (autoclaved), CuDIPS, cupric chloride and cuprous chloride inhibited the initiation phase of radiation transformation. SOD, catalase and CuDIPS did not affect the expression phase of radiation transformation. Suppression of the TPA enhancement of transformation by catalase was a highly significant effect, while the suppression by SOD was not of statistical significance. These results suggest that hydrogen peroxide (H 2 O 2 ) may be important in the cellular damage leading to malignant transformation. (author)

  15. Insect cell transformation vectors that support high level expression and promoter assessment in insect cell culture

    Science.gov (United States)

    A somatic transformation vector, pDP9, was constructed that provides a simplified means of producing permanently transformed cultured insect cells that support high levels of protein expression of foreign genes. The pDP9 plasmid vector incorporates DNA sequences from the Junonia coenia densovirus th...

  16. Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT

    International Nuclear Information System (INIS)

    Xu, Hanwen; Pirisi, Lucia; Creek, Kim E.

    2015-01-01

    Previous studies in our laboratory discovered that SIX1 mRNA expression increased during in vitro progression of HPV16-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we explored the role of Six1 at early stages of HPV16-mediated transformation by overexpressing Six1 in HKc/HPV16. We found that Six1 overexpression in HKc/HPV16 increased cell proliferation and promoted cell migration and invasion by inducing epithelial–mesenchymal transition (EMT). Moreover, the overexpression of Six1 in HKc/HPV16 resulted in resistance to serum and calcium-induced differentiation, which is the hallmark of the HKc/DR phenotype. Activation of MAPK in HKc/HPV16 overexpressing Six1 is linked to resistance to calcium-induced differentiation. In conclusion, this study determined that Six1 overexpression resulted in differentiation resistance and promoted EMT at early stages of HPV16-mediated transformation of human keratinocytes. - Highlights: • Six1 expression increases during HPV16-mediated transformation. • Six1 overexpression causes differentiation resistance in HPV16-immortalized cells. • Six1 overexpression in HPV16-immortalized keratinocytes activates MAPK. • Activation of MAPK promotes EMT and differentiation resistance. • Six1 overexpression reduces Smad-dependent TGF-β signaling

  17. Ca2+ promoted the low transformation efficiency of plasmid DNA exposed to PAH contaminants.

    Directory of Open Access Journals (Sweden)

    Fuxing Kang

    Full Text Available The effects of interactions between genetic materials and polycyclic aromatic hydrocarbons (PAHs on gene expression in the extracellular environment remain to be elucidated and little information is currently available on the effect of ionic strength on the transformation of plasmid DNA exposed to PAHs. Phenanthrene and pyrene were used as representative PAHs to evaluate the transformation of plasmid DNA after PAH exposure and to determine the role of Ca(2+ during the transformation. Plasmid DNA exposed to the test PAHs demonstrated low transformation efficiency. In the absence of PAHs, the transformation efficiency was 4.7 log units; however, the efficiency decreased to 3.72-3.14 log units with phenanthrene/pyrene exposures of 50 µg · L(-1. The addition of Ca(2+ enhanced the low transformation efficiency of DNA exposed to PAHs. Based on the co-sorption of Ca(2+ and phenanthrene/pyrene by DNA, we employed Fourier-transform infrared spectroscopy (FTIR, X-ray photoelectron spectroscopy (XPS, and mass spectrometry (MS to determine the mechanisms involved in PAH-induced DNA transformation. The observed low transformation efficiency of DNA exposed to either phenanthrene or pyrene can be attributed to a broken hydrogen bond in the double helix caused by planar PAHs. Added Ca(2+ formed strong electrovalent bonds with "-POO(--" groups in the DNA, weakening the interaction between PAHs and DNA based on weak molecular forces. This decreased the damage of PAHs to hydrogen bonds in double-stranded DNA by isolating DNA molecules from PAHs and consequently enhanced the transformation efficiency of DNA exposed to PAH contaminants. The findings provide insight into the effects of anthropogenic trace PAHs on DNA transfer in natural environments.

  18. Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-beta.

    Science.gov (United States)

    Calonge, María Julia; Seoane, Joan; Massagué, Joan

    2004-05-28

    A critical component of the epidermal basement membrane, collagen type VII, is produced by keratinocytes and fibroblasts, and its production is stimulated by the cytokine transforming growth factor-beta (TGF-beta). The gene, COL7A1, is activated by TGF-beta via Smad transcription factors in cooperation with AP1. Here we report a previously unsuspected level of complexity in this regulatory process. We provide evidence that TGF-beta may activate the COL7A1 promoter by two distinct inputs operating through a common region of the promoter. One input is provided by TGF-beta-induced Smad complexes via two Smad binding elements that function redundantly depending on the cell type. The second input is provided by relieving the COL7A1 promoter from chicken ovalbumin upstream promoter transcription factor (COUP-TF)-mediated transcriptional repression. We identified COUP-TFI and -TFII as factors that bind to the TGF-beta-responsive region of the COL7A1 promoter in an expression library screening. COUP-TFs bind to a site between the two Smad binding elements independently of Smad or AP1 and repress the basal and TGF-beta-stimulated activities of this promoter. We provide evidence that endogenous COUP-TF activity represses the COL7A1 promoter. Furthermore, we show that TGF-beta addition causes a rapid and profound down-regulation of COUP-TF expression in keratinocytes and fibroblasts. The results suggest that TGF-beta signaling may exert tight control over COL7A1 by offsetting the balance between opposing Smad and COUP-TFs.

  19. Experimental control of neoplastic progression in cell populations: Foulds' rules revisited.

    OpenAIRE

    Rubin, H

    1994-01-01

    Foulds introduced six rules of tumor progression based on his observations of spontaneous mammary cancer in mice and generalized them to all forms of neoplasia [Foulds, L. (1954) Cancer Res. 14, 327-339 and Foulds, L. (1969) Neoplastic Development (Academic, New York), Vol. 1, preface and pp. 72-74.] Rules III, IV, and V are considered controversial, and research in animals seems inadequate to resolve the controversies. A subline of NIH 3T3 cells undergoes progressive transformation to produc...

  20. Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study.

    Science.gov (United States)

    D'Silva, Shaloom; Sumathi, M K; Balaji, N; Shetty, Nisha K N; Pramod, K M; Cheeramelil, Jacob

    2013-12-01

    Calretinin a 29-kDa calcium binding protein is expressed widely in normal human tissue and tumours including amelobastoma. The objective of this study was to determine calretinin expression in heamatoxylin and eosin diagnosed cases of ameloblastoma and non-neoplastic odontogenic cysts. The lining epithelium in 3 cases of radicular cysts, 5 cases of odontogenic keratocysts, 5 cases of dentigerous cysts and 11 cases of ameloblastomas were examined for expression of calretinin. No positive epithelial staining was observed in radicular and dentigerous cysts. In comparison, however 100% of cases of ameloblastomas and 40% of cases of odontogenic karatocysts showed positive calretinin expression. Calretinin may be a specific immunohistochemical marker for ameloblastoma. If there is any possible relation between calretinin expression and neural origin of the odontogenic epithelium and its neoplastic transformation and if calretinin could be used as an early marker to predict the tendency of neoplastic change of odontogenic epithelium could be answered through further researches. How to cite this article: D'Silva S, Sumathi MK, Balaji N, Shetty NK, Pramod KM, Cheeramelil J. Evaluation of Calretinin expression in Ameloblastoma and Non-Neoplastic Odontogenic Cysts - An immunohistochemical study. J Int Oral Health 2013; 5(6):42-8 .

  1. Development of an Agrobacterium-Mediated Transformation Method and Evaluation of Two Exogenous Constitutive Promoters in Oleaginous Yeast Lipomyces starkeyi.

    Science.gov (United States)

    Lin, Xinping; Liu, Sasa; Bao, Ruiqi; Gao, Ning; Zhang, Sufang; Zhu, Rongqian; Zhao, Zongbao Kent

    2017-11-01

    Oleaginous yeast Lipomyces starkeyi, a promising strain of great biotechnical importance, is able to accumulate over 60% of its cell biomass as triacylglycerols (TAGs). It is promising to directly produce the derivatives of TAGs, such as long-chain fatty acid methyl esters and alkanes, in L. starkeyi. However, techniques for genetic modification of this oleaginous yeast are lacking, thus, further research is needed to develop genetic tools and functional elements. Here, we used two exogenous promoters (pGPD and pPGK) from oleaginous yeast Rhodosporidium toruloides to establish a simpler Agrobacterium-mediated transformation (AMT) method for L. starkeyi. Hygromycin-resistant transformants were obtained on antibiotic-contained plate. Mitotic stability test, genotype verification by PCR, and protein expression confirmation all demonstrated the success of this method. Furthermore, the strength of these two promoters was evaluated at the phenotypic level on a hygromycin-gradient plate and at the transcriptional level by real-time quantitative PCR. The PGK promoter strength was 2.2-fold as that of GPD promoter to initiate the expression of the hygromycin-resistance gene. This study provided an easy and efficient genetic manipulation method and elements of the oleaginous yeast L. starkeyi for constructing superior strains to produce advanced biofuels.

  2. An exploration of stereotypical beliefs about leadership styles: Is transformational leadership a route to women's promotion?

    NARCIS (Netherlands)

    Vinkenburg, C.J.; van Engen, M.L.; Eagly, A.H.; Johannesen-Schmidt, M.C.

    2011-01-01

    Two experimental studies examined whether gender stereotypes about the transformational, transactional, and laissez-faire leadership styles constitute an advantage or an impediment for women's access to leadership positions in organizations. The first study investigated the accuracy of descriptive

  3. Canine tracheal epithelial cells are more sensitive than rat tracheal epithelial cells to transforming growth factor beta induced growth inhibition

    International Nuclear Information System (INIS)

    Hubbs, A.F.; Hahn, F.F.; Kelly, G.; Thomassen, D.G.

    1988-01-01

    Transforming growth factor beta (TGFβ) markedly inhibited growth of canine tracheal epithelial (CTE) cells. Reduced responsiveness to TGFβ-induced growth inhibition accompanied neoplastic progression of these cells from primary to transformed to neoplastic. This was similar to the relationship between neoplastic progression and increased resistance to TGFβ-induced growth inhibition seen for rat tracheal epithelial (RTE) cells. The canine cells were more sensitive than rat cells to TGFβ-induced growth inhibition at all stages in the neoplastic process. (author)

  4. HTLV-1 tax stabilizes MCL-1 via TRAF6-dependent K63-linked polyubiquitination to promote cell survival and transformation.

    Directory of Open Access Journals (Sweden)

    Young Bong Choi

    2014-10-01

    Full Text Available The human T-cell leukemia virus type 1 (HTLV-1 Tax protein hijacks the host ubiquitin machinery to activate IκB kinases (IKKs and NF-κB and promote cell survival; however, the key ubiquitinated factors downstream of Tax involved in cell transformation are unknown. Using mass spectrometry, we undertook an unbiased proteome-wide quantitative survey of cellular proteins modified by ubiquitin in the presence of Tax or a Tax mutant impaired in IKK activation. Tax induced the ubiquitination of 22 cellular proteins, including the anti-apoptotic BCL-2 family member MCL-1, in an IKK-dependent manner. Tax was found to promote the nondegradative lysine 63 (K63-linked polyubiquitination of MCL-1 that was dependent on the E3 ubiquitin ligase TRAF6 and the IKK complex. Tax interacted with and activated TRAF6, and triggered its mitochondrial localization, where it conjugated four carboxyl-terminal lysine residues of MCL-1 with K63-linked polyubiquitin chains, which stabilized and protected MCL-1 from genotoxic stress-induced degradation. TRAF6 and MCL-1 played essential roles in the survival of HTLV-1 transformed cells and the immortalization of primary T cells by HTLV-1. Therefore, K63-linked polyubiquitination represents a novel regulatory mechanism controlling MCL-1 stability that has been usurped by a viral oncogene to precipitate cell survival and transformation.

  5. HTLV-1 Tax Stabilizes MCL-1 via TRAF6-Dependent K63-Linked Polyubiquitination to Promote Cell Survival and Transformation

    Science.gov (United States)

    Choi, Young Bong; Harhaj, Edward William

    2014-01-01

    The human T-cell leukemia virus type 1 (HTLV-1) Tax protein hijacks the host ubiquitin machinery to activate IκB kinases (IKKs) and NF-κB and promote cell survival; however, the key ubiquitinated factors downstream of Tax involved in cell transformation are unknown. Using mass spectrometry, we undertook an unbiased proteome-wide quantitative survey of cellular proteins modified by ubiquitin in the presence of Tax or a Tax mutant impaired in IKK activation. Tax induced the ubiquitination of 22 cellular proteins, including the anti-apoptotic BCL-2 family member MCL-1, in an IKK-dependent manner. Tax was found to promote the nondegradative lysine 63 (K63)-linked polyubiquitination of MCL-1 that was dependent on the E3 ubiquitin ligase TRAF6 and the IKK complex. Tax interacted with and activated TRAF6, and triggered its mitochondrial localization, where it conjugated four carboxyl-terminal lysine residues of MCL-1 with K63-linked polyubiquitin chains, which stabilized and protected MCL-1 from genotoxic stress-induced degradation. TRAF6 and MCL-1 played essential roles in the survival of HTLV-1 transformed cells and the immortalization of primary T cells by HTLV-1. Therefore, K63-linked polyubiquitination represents a novel regulatory mechanism controlling MCL-1 stability that has been usurped by a viral oncogene to precipitate cell survival and transformation. PMID:25340740

  6. HK2 Recruitment to Phospho-BAD Prevents Its Degradation, Promoting Warburg Glycolysis by Theileria-Transformed Leukocytes.

    Science.gov (United States)

    Haidar, Malak; Lombès, Anne; Bouillaud, Frédéric; Kennedy, Eileen J; Langsley, Gordon

    2017-03-10

    Theileria annulata infects bovine leukocytes, transforming them into invasive, cancer-like cells that cause the widespread disease called tropical theileriosis. We report that in Theileria-transformed leukocytes hexokinase-2 (HK2) binds to B cell lymphoma-2-associated death promoter (BAD) only when serine (S) 155 in BAD is phosphorylated. We show that HK2 recruitment to BAD is abolished by a cell-penetrating peptide that acts as a nonphosphorylatable BAD substrate that inhibits endogenous S155 phosphorylation, leading to complex dissociation and ubiquitination and degradation of HK2 by the proteasome. As HK2 is a critical enzyme involved in Warburg glycolysis, its loss forces Theileria-transformed macrophages to switch back to HK1-dependent oxidative glycolysis that down-regulates macrophage proliferation only when they are growing on glucose. When growing on galactose, degradation of HK2 has no effect on Theileria-infected leukocyte proliferation, because metabolism of this sugar is independent of hexokinases. Thus, targeted disruption of the phosphorylation-dependent HK2/BAD complex may represent a novel approach to control Theileria-transformed leukocyte proliferation.

  7. Promotion of TNF-α on malignant transformation of syrian hamster embryo cells irradiated with α-particles

    International Nuclear Information System (INIS)

    Zhu Maoxiang; Guo Renfeng; Yang Zhihua; GongYifen

    1999-01-01

    Objective: To illustrate the role of tumor necrosis factor-α (TNF-α) in radiation-induced cancer and regulatory mechanism of protein tyrosine phosphorylation. Methods: Taking Syrian hamster embryo cells exposed to 0.5 Gy α-particles as the target, an array of biological indicators such as cell growth curve, transformation frequency (TF), colony formation efficiency (CFE) and tumor formation in nude mice were observed, and the activities of protein tyrosine kinases and protein tyrosine phosphatases were measured. Results: Neither 0.5 Gy α-particle irradiation nor TNF-α alone could induce transformation of SHE cells morphologically, but the TF, CFE and levels of protein tyrosine phosphorylation were obviously increased in SHE cells treated with 600 U/ml TNF-α after exposure to 0.5 Gy α-particles, and malignant transformation was proved by tumorigenicity assays. Conclusion: TNF-α promotes significantly the transformation of SHE cells induced by α-particles, and protein tyrosine phosphorylation is probably involved in regulation of the process

  8. Organizational Transformation to Promote Knowledge Transfer at Universities and R&D Institutions in Sonora, Mexico

    Science.gov (United States)

    Balderrama, Jorge Ines Leon; Lopez, Lydia Venecia Gutierrez; Lafarga, Cuitlahuac Valdez

    2013-01-01

    Using the results of an empirical study in the State of Sonora, Mexico, this paper reports on an attempt to identify trends and transformations that have taken place in the way knowledge transfer activities are organized and structured in higher education institutions and research centres. The research was designed to provide a characterization of…

  9. Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

    International Nuclear Information System (INIS)

    Walker, C.; Nettesheim, P.; Barrett, J.C.; Gilmer, T.M.

    1987-01-01

    Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injected into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of ≅ 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor

  10. Photodynamic therapy and the treatment of neoplastic and non-neoplastic diseases of the larynx

    International Nuclear Information System (INIS)

    Biel, M.A.

    1992-01-01

    Approximately 12000 new cases of laryngeal carcinoma are reported yearly in the united States. Early carcinomas of the larynx (Tis, T1 and T2) are presently treated with either radiation therapy or surgery alone. Five year cure rates achieved with this therapy are 75-85%. Radiation therapy has the advantage of preserving physical integrity of the larynx, thereby preserving voice. Radiation therapy, however, has significant disadvantages even when small laryngeal fields of radiation are used. These disadvantages include discomfort and mucositis during and for potential prolonged periods after therapy, permanently altered voice quality, dysphagia, chondroradionecrosis of the larynx and trachea, and the prolonged length of therapy (6-7 weeks). This report presents the results of 10 patients treated with PDT for neo-plastic and non-neoplastic diseases of the larynx and tracheobronchial tree. (author). 12 refs., 1 tab

  11. A nine - year retrospective study of avian neoplastic diseases in ...

    African Journals Online (AJOL)

    Avian neoplastic diseases have been identified as one of the leading causes of mortality and production losses in commercial chickens in Nigeria. Although available reports described the trend of Marek's disease in Zaria, Kaduna state, they did not take cognizance of other neoplastic diseases of poultry hence the need for ...

  12. Comparative tumor promotion assessment of e-cigarette and cigarettes using the in vitro Bhas 42 cell transformation assay.

    Science.gov (United States)

    Breheny, Damien; Oke, Oluwatobiloba; Pant, Kamala; Gaça, Marianna

    2017-05-01

    In vitro cell transformation assays (CTA) are used to assess the carcinogenic potential of chemicals and complex mixtures and can detect nongenotoxic as well as genotoxic carcinogens. The Bhas 42 CTA has been developed with both initiation and promotion protocols to distinguish between these two carcinogen classes. Cigarette smoke is known to be carcinogenic and is positive in in vitro genotoxicity assays. Cigarette smoke also contains nongenotoxic carcinogens and is a tumour promoter and cocarcinogen in vivo. We have combined a suite of in vitro assays to compare the relative biological effects of new categories of tobacco and nicotine products with traditional cigarettes. The Bhas promotion assay has been included in this test battery to provide an in vitro surrogate for detecting tumor promoters. The activity of an electronic cigarette (e-cigarette; Vype ePen) was compared to that of a reference cigarette (3R4F) in the promotion assay, using total particulate matter (TPM)/aerosol collected matter (ACM) and aqueous extracts (AqE) of product aerosol emissions. 3R4F TPM was positive in this assay at concentrations ≥6 µg/mL, while e-cigarette ACM did not have any promoter activity. AqE was found to be a lesssuitable test matrix in this assay due to high cytotoxicity. This is the first study to use the Bhas assay to compare tobacco and nicotine products and demonstrates the potential for its future application as part of a product assessment framework. These data add to growing evidence suggesting that e-cigarettes may provide a safer alternative to traditional cigarettes. Environ. Mol. Mutagen. 58:190-198, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation.

    Directory of Open Access Journals (Sweden)

    Christian Berrios

    2016-11-01

    Full Text Available Merkel cell polyomavirus (MCPyV is an etiological agent of Merkel cell carcinoma (MCC, a highly aggressive skin cancer. The MCPyV small tumor antigen (ST is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dynamically alters the cellular transcriptome with increased levels of glycolytic genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1. Extracellular flux analysis revealed increased lactate export reflecting elevated aerobic glycolysis in ST expressing cells. Inhibition of MCT1 activity suppressed the growth of MCC cell lines and impaired MCPyV-dependent transformation of IMR90 cells. Both NF-κB and MYC have been shown to regulate MCT1 expression. While MYC was required for MCT1 induction, MCPyV-induced MCT1 levels decreased following knockdown of the NF-κB subunit RelA, supporting a synergistic activity between MCPyV and MYC in regulating MCT1 levels. Several MCC lines had high levels of MYCL and MYCN but not MYC. Increased levels of MYCL was more effective than MYC or MYCN in increasing extracellular acidification in MCC cells. Our results demonstrate the effects of MCPyV ST on the cellular transcriptome and reveal that transformation is dependent, at least in part, on elevated aerobic glycolysis.

  14. Transformation of lacZ using different promoters in the commercially ...

    African Journals Online (AJOL)

    Yomi

    2012-01-26

    Jan 26, 2012 ... forced growth under unnatural conditions. In order to ... yezoensis include the gluc, cat, GUS and GFP genes. (Cheney et al. ... bacterial lacZ gene encodes the β-galactosidase enzyme which is capable of .... Table 1. Effect of viral promoters on transient β-galactosidase activity in microparticle bombarded G.

  15. Teachers as researchers: a narrative pedagogical approach to transforming a graduate family and health promotion course.

    Science.gov (United States)

    Brykczynski, Karen A

    2012-01-01

    Scholarship of teaching in nursing is illustrated by describing the development, implementation, evaluation, and revision of a family and health promotion course for graduate family nurse practitioner students. A narrative pedagogical approach that combines conventional pedagogy with action research is used. The work, an example of curriculum as dialogue, illustrates how teachers can incorporate research, evaluation, and reflection into their daily teaching practice. Given adequate support, these evaluation and research activities could constitute part of the scholarship of teaching, and, as such, would warrant allocation of time in faculty workloads and formal acknowledgment in annual performance evaluations and promotion and tenure decisions. The importance of increasing the clinical relevance of the scholarship of teaching in a practice discipline such as nursing is also emphasized.

  16. Mid-market transformation programs: programs to promote best practices in system specification and installation

    International Nuclear Information System (INIS)

    Rosenberg, Mitchell

    2003-01-01

    This paper summarizes the experience of programs designed to promote the adoption of best practices in equipment specification and installation among distributors and installation contractors in the residential central air conditioning and industrial compressed air equipment markets. For each of those markets, the paper identifies the current understanding of best practices, characterizes energy savings available from their adoption, assesses the nature of barriers to their adoption, and describes the operations and accomplishments of programs designed to address those barriers

  17. Arsenic transformation and plant growth promotion characteristics of As-resistant endophytic bacteria from As-hyperaccumulator Pteris vittata.

    Science.gov (United States)

    Xu, Jia-Yi; Han, Yong-He; Chen, Yanshan; Zhu, Ling-Jia; Ma, Lena Q

    2016-02-01

    The ability of As-resistant endophytic bacteria in As transformation and plant growth promotion was determined. The endophytes were isolated from As-hyperaccumulator Pteris vittata (PV) after growing for 60 d in a soil containing 200 mg kg(-1) arsenate (AsV). They were isolated in presence of 10 mM AsV from PV roots, stems, and leaflets, representing 4 phyla and 17 genera. All endophytes showed at least one plant growth promoting characteristics including IAA synthesis, siderophore production and P solubilization. The root endophytes had higher P solubilization ability than the leaflet (60.0 vs. 18.3 mg L(-1)). In presence of 10 mM AsV, 6 endophytes had greater growth than the control, suggesting As-stimulated growth. Furthermore, root endophytes were more resistant to AsV while the leaflet endophytes were more tolerant to arsenite (AsIII), which corresponded to the dominant As species in PV tissues. Bacterial As resistance was positively correlated to their ability in AsV reduction but not AsIII oxidation. The roles of those endophytes in promoting plant growth and As resistance in P. vittata warrant further investigation. Published by Elsevier Ltd.

  18. Matrix Metalloproteinases in Non-Neoplastic Disorders

    Science.gov (United States)

    Tokito, Akinori; Jougasaki, Michihisa

    2016-01-01

    The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action. PMID:27455234

  19. Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.

    Science.gov (United States)

    McCoy, Sara S; Reed, Tamra J; Berthier, Celine C; Tsou, Pei-Suen; Liu, Jianhua; Gudjonsson, Johann E; Khanna, Dinesh; Kahlenberg, J Michelle

    2017-11-01

    SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  20. Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

    DEFF Research Database (Denmark)

    Brakebusch, C; Wennerberg, K; Krell, H W

    1999-01-01

    To investigate the role of beta1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding beta1A integrin resulted in beta1A......, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta1 integrin expression. The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1......-deficient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of fibronectin, laminin-1...

  1. Transforming EFL Classroom Practices and Promoting Students’ Empowerment: Collaborative Learning From a Dialogical Approach

    Directory of Open Access Journals (Sweden)

    Janeth Juliana Contreras León

    2017-07-01

    Full Text Available This study investigates the impact of implementing collaborative learning from a social and dialogical perspective on seventh graders’ interaction in an English as a foreign language classroom at a public school in Bogotá, Colombia. Thirty students participated in this action research where field notes, questionnaires, semi-structured interviews, and artifacts of students’ work were used to collect data during a complete academic year. Results show that taking a critical approach to language education and understanding collaborative learning as a social construction of knowledge can ignite opportunities for changing traditional teaching and learning practices where both the teacher and students take different roles, thus balancing classroom relations and interaction among participants and also promoting students’ empowerment.

  2. Transforming the culture of surgical education: promoting teacher identity through human factors training.

    Science.gov (United States)

    Cahan, Mitchell A; Starr, Susan; Larkin, Anne C; Litwin, Demetrius E M; Sullivan, Kate M; Quirk, Mark E

    2011-07-01

    Promoting a culture of teaching may encourage students to choose a surgical career. Teaching in a human factors (HF) curriculum, the nontechnical skills of surgery, is associated with surgeons' stronger identity as teachers and with clinical students' improved perception of surgery and satisfaction with the clerkship experience. To describe the effects of an HF curriculum on teaching culture in surgery. Surgeons and educators developed an HF curriculum including communication, teamwork, and work-life balance. Teacher identity, student interest in a surgical career, student perception of the HF curriculum, and teaching awards. Ninety-two of 123 faculty and residents in a single program (75% of total) completed a survey on teacher identity. Fifteen of the participants were teachers of HF. Teachers of HF scored higher than control participants on the total score for teacher identity (P < .001) and for subcategories of global teacher identity (P = .001), intrinsic satisfaction (P = .001), skills and knowledge (P = .006), belonging to a group of teachers (P < .001), feeling a responsibility to teach (P = .008), receiving rewards (P =.01), and HF (P = .02). Third-year clerks indicated that they were more likely to select surgery as their career after the clerkship and rated the curriculum higher when it was taught by surgeons than when taught by educators. Of the teaching awards presented to surgeons during HF years, 100% of those awarded to attending physicians and 80% of those awarded to residents went to teachers of HF. Curricular focus on HF can strengthen teacher identity, improve teacher evaluations, and promote surgery as a career choice.

  3. Selfish third parties act as peacemakers by transforming conflicts and promoting cooperation.

    Science.gov (United States)

    Halevy, Nir; Halali, Eliran

    2015-06-02

    The tremendous costs of conflict have made humans resourceful not only at warfare but also at peacemaking. Although third parties have acted as peacemakers since the dawn of history, little is known about voluntary, informal third-party intervention in conflict. Here we introduce the Peacemaker Game, a novel experimental paradigm, to model and study the interdependence between disputants and third parties in conflict. In the game, two disputants choose whether to cooperate or compete and a third party chooses whether or not to intervene in the conflict. Intervention introduces side payments that transform the game disputants are playing; it also introduces risk for the third party by making it vulnerable to disputants' choices. Six experiments revealed three robust effects: (i) The mere possibility of third-party intervention significantly increases cooperation in interpersonal and intergroup conflicts; (ii) reducing the risk to third parties dramatically increases intervention rates, to everyone's benefit; and (iii) disputants' cooperation rates are consistently higher than third parties' intervention rates. These findings explain why, how, and when self-interested third parties facilitate peaceful conflict resolution.

  4. Transformation of Food Habits through Promotion of Under-Utilized Cereals in High Hills of Nepal

    International Nuclear Information System (INIS)

    Koirala, Pramod; Bajracharya, Keshari; Chalise, Ananda

    2014-01-01

    Full text: Malnutrition is a persistent social setback in Nepal. High hills in Nepal is considered as the headquarter of the malnourished people as it holds almost the twice of stunted children than the national average. Food insecurity is the major causes of malnutrition as there is low agriculture production followed by difficult terrain and poor road connectivity. Nevertheless, there are several types of locally produced cereals that are under-utilized because of the traditional food-habit of eating rice. In order to bring a change in local food habit by the high-hill residents, attempts were made in processing of under-utilized cereals. Six different cereals were processed into super flour, porridge, cookies, flakes and traditional sweets for which locally accessible home level processing technology was used. Sorghum (Sorghum bicolor), Foxtail Millet (Setaria italica), Porso Millet (Panicum miliaceum), Buck Wheat (Fagopyrum esculentum), Amaranth (Amaranth caudatus) and Naked Barley (Hordeum vulgare) were processed into diverse products that suit to the local taste. The processing steps were standardized and laboratory analysis was carried out. It was then distributed to local development partners through trainers' training. Now, local people have started processing and consuming these products. It is anticipated that processed products promotion helps in solving food insecurity to some extent, and contributes in reducing malnutrition for the children below two. (author)

  5. Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis

    Science.gov (United States)

    Gao, Yang; Vincent, David F.; Davis, Anna Jane; Sansom, Owen J.; Bartholin, Laurent; Li, Qinglei

    2016-01-01

    Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies. PMID:27344183

  6. Using Fourier transform infrared spectroscopy to evaluate biological effects induced by photodynamic therapy.

    Science.gov (United States)

    Lima, Cassio A; Goulart, Viviane P; Correa, Luciana; Zezell, Denise M

    2016-07-01

    Vibrational spectroscopic methods associated with multivariate statistical techniques have been succeeded in discriminating skin lesions from normal tissues. However, there is no study exploring the potential of these techniques to assess the alterations promoted by photodynamic effect in tissue. The present study aims to demonstrate the ability of Fourier Transform Infrared (FTIR) spectroscopy on Attenuated total reflection (ATR) sampling mode associated with principal component-linear discriminant analysis (PC-LDA) to evaluate the biochemical changes caused by photodynamic therapy (PDT) in skin neoplastic tissue. Cutaneous neoplastic lesions, precursors of squamous cell carcinoma (SCC), were chemically induced in Swiss mice and submitted to a single session of 5-aminolevulinic acid (ALA)-mediated PDT. Tissue sections with 5 μm thickness were obtained from formalin-fixed paraffin-embedded (FFPE) and processed prior to the histopathological analysis and spectroscopic measurements. Spectra were collected in mid-infrared region using a FTIR spectrometer on ATR sampling mode. Principal Component-Linear Discriminant Analysis (PC-LDA) was applied on preprocessed second derivatives spectra. Biochemical changes were assessed using PCA-loadings and accuracy of classification was obtained from PC-LDA . Sub-bands of Amide I (1,624 and 1,650 cm(-1) ) and Amide II (1,517 cm(-1) ) indicated a protein overexpression in non-treated and post-PDT neoplastic tissue compared with healthy skin, as well as a decrease in collagen fibers (1,204, 1,236, 1,282, and 1,338 cm(-1) ) and glycogen (1,028, 1,082, and 1,151 cm(-1) ) content. Photosensitized neoplastic tissue revealed shifted peak position and decreased β-sheet secondary structure of proteins (1,624 cm(-1) ) amount in comparison to non-treated neoplastic lesions. PC-LDA score plots discriminated non-treated neoplastic skin spectra from post-PDT cutaneous lesions with accuracy of 92.8%, whereas non-treated neoplastic

  7. Melanocytic nevi and non-neoplastic hyperpigmentations.

    Science.gov (United States)

    Clemente, C

    2017-06-01

    This is the first of three chapters that will be progressively published on Pathologica as updating activity of the Italian Study Group of Dermatopathology (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will address the topics of dysplastic nevus, borderline and low malignant potential melanocytic proliferations and the third melanoma in its variants and differential diagnoses with a supplement on the immunohistochemistry and molecular support to diagnostic and prognostic definition of nevi and melanomas. Although we believe that great advances were made in the application of ancillary genetic, immunohistochemical and molecular techniques, for the diagnosis and biological characterization of melanocytic tumors the morphology still remains the gold standard. These chapters are not intended as substitutes or even claim to be compared to the numerous and valuable texts that are also recently published, but they want to present, concisely and quickly available, all of those traits that we believe essential to the histopathological evaluation of a melanocytic lesion. No morphological parameter is exclusive and individually sufficient to make the correct diagnosis of nevus or melanoma but to reach a final conclusive and appropriate interpretation a set of morphological characters must be evaluated and compared. I was lucky enough to be able to examine several thousand cases and to draw lessons from each of these increasing my diagnostic experience. I had a great lesson by my teacher and good friend Prof. Martin C. Mihm Jr of Boston, dermato-pathologist with undisputed international reputation, who, with great passion, patience and friendship, transferred me much of his experience and knowledge and for which I always thank him. Special thanks I would like to address Dr. Agostino Crupi, dermatologist, skin-oncologist and brilliant dermatoscopist who taught me how the

  8. A HISTOPATHOLOGICAL STUDY OF NON-NEOPLASTIC AND NEOPLASTIC LESIONS OF KIDNEY FOR A PERIOD OF TWO YEARS

    Directory of Open Access Journals (Sweden)

    Jagadeeswari Suvvari

    2018-01-01

    Full Text Available BACKGROUND Nephrectomy is a common procedure in surgical practice. There are many indications for nephrectomy, non-neoplastic and neoplastic conditions. The common conditions being chronic pyelonephritis and renal tumours. A detailed and meticulous histopathological examination is essential to establish the diagnosis of lesions of kidney. MATERIALS AND METHODS It is a retrospective study for a period of two years from January 2015 to December 2016 at a tertiary care centre. 34 cases of nephrectomy specimens were analysed and data recorded. RESULTS Non-neoplastic lesions were constituting 47.05% (16 of cases and 52.94% (18 cases were neoplastic lesions. Lesions were more common in females with male:female ratio of 1:1.4. Both the lesions were common in age group of 41-50 years. CONCLUSION The prevalence of neoplastic lesions was more common than non-neoplastic lesions. The commonest indication for nephrectomy was chronic pyelonephritis followed by renal tumours. Histopathological examination in correlation with clinical and radiological features plays a great role in subcategorisation of lesions accurately to ensure better therapy.

  9. Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase*S⃞

    Science.gov (United States)

    Kang, Nam Joo; Lee, Ki Won; Lee, Dong Eun; Rogozin, Evgeny A.; Bode, Ann M.; Lee, Hyong Joo; Dong, Zigang

    2008-01-01

    Cocoa was shown to inhibit chemically induced carcinogenesis in animals and exert antioxidant activity in humans. However, the molecular mechanisms of the chemopreventive potential of cocoa and its active ingredient(s) remain unknown. Here we report that cocoa procyanidins inhibit neoplastic cell transformation by suppressing the kinase activity of mitogen-activated protein kinase kinase (MEK). A cocoa procyanidin fraction (CPF) and procyanidin B2 at 5 μg/ml and 40 μm, respectively, inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ mouse epidermal (JB6 P+) cells by 47 and 93%, respectively. The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-κB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2. In vitro and ex vivo kinase assay data demonstrated that CPF or procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation. In contrast, theobromine (up to 80 μm) had no effect on TPA-induced transformation, cyclooxygenase-2 expression, the transactivation of activator protein-1 or nuclear factor-κB, or MEK. Notably, procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity and neoplastic cell transformation. PMID:18519570

  10. The A-myb transcription factor in neoplastic and normal B cells.

    Science.gov (United States)

    Golay, J; Facchinetti, V; Ying, G; Introna, M

    1997-07-01

    The myb family of transcription factors has been strongly implicated in the regulation of cell growth and differentiation in the haematopoietic system. The v-myb oncogene, carried by avian defective retroviruses, causes leukaemias in the chicken and transforms haematopoietic cells in vitro. Its normal cellular equivalent c-myb, has been shown to promote the proliferation and block the differentiation of haematopoietic cells in several experimental models and is required for fetal haematopoiesis. Two other members of the family have been cloned more recently, A-myb and B-myb, which show sequence homology with c-myb in several domains, of which the DNA binding domain as well as other regulatory domains. Both have been shown to be transcription factors. B-myb is also involved in the control of proliferation and differentiation, but, unlike c-myb, it is expressed in many cell types. The third member of the family, A-myb, shows the most restricted pattern of expression, suggesting a very specific role for this transcription factor. A-myb is expressed in a subpopulation of normal B lymphocytes activated in vivo and localised in the germinal center of peripheral lymphoid organs and is not detected at significant levels in all other mature or immature haematopoietic populations studied, including bone marrow cells, T lymphocytes, granulocytes, monocytes, either at rest or after in vitro activation. These studies indicate that A-myb plays a role during a narrow window of normal B cell differentiation. A-myb expression has also been studied in a wide range of neoplastic B cells, representing the whole spectrum of B cell differentiation. A-myb is strongly expressed in Burkitt's lymphomas (BL) and slg+ B-acute lymphoblastic leukaemias (B-ALL) and not in all other leukaemias/lymphomas tested, with the exception of a subset of CLL (about 25% of cases). It is intriguing that the A-myb genome has been localised relatively close to the c-myc gene on chromosome 8, suggesting that

  11. The cell cycle regulator ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells.

    Science.gov (United States)

    Bele, Aditya; Mirza, Sameer; Zhang, Ying; Ahmad Mir, Riyaz; Lin, Simon; Kim, Jun Hyun; Gurumurthy, Channabasavaiah Basavaraju; West, William; Qiu, Fang; Band, Hamid; Band, Vimla

    2015-01-01

    The mammalian ortholog of Drosophila ecdysoneless (Ecd) gene product regulates Rb-E2F interaction and is required for cell cycle progression. Ecd is overexpressed in breast cancer and its overexpression predicts shorter survival in patients with ErbB2-positive tumors. Here, we demonstrate Ecd knock down (KD) in human mammary epithelial cells (hMECs) induces growth arrest, similar to the impact of Ecd Knock out (KO) in mouse embryonic fibroblasts. Furthermore, whole-genome mRNA expression analysis of control vs. Ecd KD in hMECs demonstrated that several of the top 40 genes that were down-regulated were E2F target genes. To address the role of Ecd in mammary oncogenesis, we overexpressed Ecd and/or mutant H-Ras in hTERT-immortalized hMECs. Cell cycle analyses revealed hMECs overexpressing Ecd+Ras showed incomplete arrest in G1 phase upon growth factor deprivation, and more rapid cell cycle progression in growth factor-containing medium. Analyses of cell migration, invasion, acinar structures in 3-D Matrigel and anchorage-independent growth demonstrated that Ecd+Ras-overexpressing cells exhibit substantially more dramatic transformed phenotype as compared to cells expressing vector, Ras or Ecd. Under conditions of nutrient deprivation, Ecd+Ras-overexpressing hMECs exhibited better survival, with substantial upregulation of the autophagy marker LC3 both at the mRNA and protein levels. Significantly, while hMECs expressing Ecd or mutant Ras alone did not form tumors in NOD/SCID mice, Ecd+Ras-overexpressing hMECs formed tumors, clearly demonstrating oncogenic cooperation between Ecd and mutant Ras. Collectively, we demonstrate an important co-oncogenic role of Ecd in the progression of mammary oncogenesis through promoting cell survival.

  12. Glycaemic adverse drug reactions from anti-neoplastics used in ...

    African Journals Online (AJOL)

    235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

  13. Corneal Structural Changes in Nonneoplastic and Neoplastic Monoclonal Gammopathies.

    Science.gov (United States)

    Aragona, Pasquale; Allegra, Alessandro; Postorino, Elisa Imelde; Rania, Laura; Innao, Vanessa; Wylegala, Edward; Nowinska, Anna; Ieni, Antonio; Pisani, Antonina; Musolino, Caterina; Puzzolo, Domenico; Micali, Antonio

    2016-05-01

    To investigate corneal confocal microscopic changes in nonneoplastic and neoplastic monoclonal gammopathies. Three groups of subjects were considered: group 1, twenty normal subjects; group 2, fifteen patients with monoclonal gammopathy of undetermined significance (MGUS); group 3, eight patients with smoldering multiple myeloma and eight patients with untreated multiple myeloma. After hematologic diagnosis, patients underwent ophthalmologic exam and in vivo confocal microscopic study. The statistical analysis was performed using ANOVA and Student-Newman-Keuls tests and receiver operating characteristic (ROC) curve analysis. Epithelial cells of gammopathic patients showed significantly higher reflectivity than controls, demonstrated by optical density (P < 0.001). Subbasal nerve density, branching, and beading were significantly altered in gammopathic patients (P = 0.01, P = 0.02, P = 0.02, respectively). The number of keratocytes was significantly reduced in neoplastic patients (P < 0.001 versus both normal and MGUS) in the anterior, medium, and posterior stroma. The ROC curve analysis showed good sensitivity and specificity for this parameter. Group 2 and 3 keratocytes showed higher nuclear and cytoplasmatic reflectivity in the medium and posterior stroma. Endothelial cells were not affected. Patients with neoplastic gammopathies showed peculiar alterations of the keratocyte number, which appeared significantly reduced. A follow-up with corneal confocal microscopy of patients with MGUS is suggested as a useful tool to identify peripheral tissue alterations linked to possible neoplastic disease development.

  14. Non-neoplastic surgical diseases of the lung and pleura

    International Nuclear Information System (INIS)

    Walter, P.A.

    1987-01-01

    Non-neoplastic diseases of the bronchi, pulmonary parenchyma, mediastinum, and pleura that are amenable to surgical management represent a wide range of unrelated etiopathogenic conditions that usually have a focal distribution. The author discusses the presurgical clinical, radiographic, and laboratory assessment and prognoses, and addresses therapeutic recommendations

  15. Enteroclysis of non-neoplastic disorders of the small intestine

    International Nuclear Information System (INIS)

    Nolan, D.J.

    2000-01-01

    Enteroclysis is now widely used for examining the jejunum and ileum. The technique is ideal for demonstrating the extent and severity of disorders that cause morphological changes to the small intestine. In this review many non-neoplastic small intestinal disorders as demonstrated by enteroclysis are described and illustrated. (orig.)

  16. Knowledge on neoplastic diseases among young rural inhabitants

    Directory of Open Access Journals (Sweden)

    Anna Lewandowska

    2017-09-01

    According to self-assessment, every third respondent stated having a low or average level of knowledge. The most frequently used source of knowledge was the Internet, and much more rarely a doctor or a nurse. Very few of the respondents could enumerate the tests applied in the early detection of neoplastic diseases.

  17. 2-[(aminopropyl)amino]ethanethiol (WR1065) is anti-neoplastic and anti-mutagenic when given during 60Coγ-ray irradiation

    International Nuclear Information System (INIS)

    Hill, C.K.; Nagy, B.; Peraino, C.; Grdina, D.

    1986-01-01

    The effect of 2[(aminopropyl)amino]ethanethiol (WR1065) has been studied on the induction of neoplastic transformation using 10T1/2 cells and on mutation of the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus using Chinese hamster V79 cells. The first observations that treatment of 10T1/2 cells with 1 mM WR1065 for a total of 35 min during irradiation with 60 C γ-rays significantly reduces the incidence of neoplastic transformation while having no effect on cell viability are reported. In a similar experiment with V79 cells in which 4mM WR1065 was used, a significant reduction in mutation frequency at the HGPRT locus and significant protection against cell killing was found. These results suggest that WR1965 acts to modulate both acute damage and sub-lethal processes that lead to mutation and neoplastic transformation. Beyond the purely mechanistic approach of these studies, the potential application of these agents to minimizing the long-term neoplastic effects of radiation or chemotherapeutic agents currently in use for treating potentially curable cancer patients should be further investigated. (author)

  18. Extracellular matrix in tumours as a source of additional neoplastic lesions - a review

    Directory of Open Access Journals (Sweden)

    Madej Janusz A.

    2014-03-01

    Full Text Available The review describes the role of cells of extracellular matrix (ECM as a source of neoplastic outgrowths additional to the original tumour. The cells undergo a spontaneous transformation or stimulation by the original tumour through intercellular signals, e.g. through Shh protein (sonic hedgehog. Additionally, cells of an inflammatory infiltrate, which frequently accompany malignant tumours and particularly carcinomas, may regulate tumour cell behaviour. This is either by restricting tumour proliferation or, inversely, by induction and stimulation of the proliferation of another tumour cell type, e.g. mesenchymal cells. The latter type of tumour may involve formation of histologically differentiated stromal tumours (GIST, which probably originate from interstitial cells of Cajal in the alimentary tract. Occasionally, e.g. in gastric carcinoma, proliferation involves lymphoid follicles and lymphocytes of GALT (gut-associated lymphoid tissue, which gives rise to lymphoma. The process is preceded by the earlier stage of intestinal metaplasia, or is induced by gastritis alone. This is an example of primary involvement of inflammatory infiltrate cells in neoplastic progression. Despite the numerous histogenetic classifications of tumours (zygotoma benignum et zygotoma malignum, or mesenchymomata maligna et mesenchymomata benigna, currently in oncological diagnosis the view prevails that the direction of tumour differentiation and its degree of histologic malignancy (grading are more important factors than the histogenesis of the tumour.

  19. Biological Characteristics of Caspase-14 and Its Expression in Neoplastic Diseases in the View of Translational Medicine

    Directory of Open Access Journals (Sweden)

    Kang-sheng LIU

    2016-06-01

    Full Text Available Caspase-14, a member of caspase family, only exists in mammals. As the most divergent member in the family of mammalian caspases, caspase-14 displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. At present, it has been found that caspase-14 is functionally different from the inflammatory reaction group of typical caspase family members. It exerts a certain effect in the promotion of final differentiation of epidermal cells and hydration of stratum corneum so as to maintain the steady state of skin barrier. In recent years, caspase-14 expression has been discovered in neoplastic diseases. Translational medicine integrates experimental research results and clinical guidance into the optimal implementation criteria for promoting the prediction, prevention and treatment of diseases. Via human genomics and molecular biology, translational medicine offers a possibility of screening molecular markers so that it can be used to diagnose the neoplastic diseases. In this article, the biological characteristics and substrates of caspase-14 as well as its expression in embryonic period and neoplastic diseases were reviewed.

  20. Upstream CREs participate in the basal activity of minute virus of mice promoter P4 and in its stimulation in ras-transformed cells.

    Science.gov (United States)

    Perros, M; Deleu, L; Vanacker, J M; Kherrouche, Z; Spruyt, N; Faisst, S; Rommelaere, J

    1995-01-01

    The activity of the P4 promoter of the parvovirus minute virus of mice (prototype strain MVMp) is stimulated in ras-transformed FREJ4 cells compared with the parental FR3T3 line. This activation may participate in the oncolytic effect of parvoviruses, given that P4 drives a transcriptional unit encoding cytotoxic nonstructural proteins. Our results suggest that the higher transcriptional activity of promoter P4 in FREJ4 cells is mediated at least in part by upstream CRE elements. Accordingly, mutations in the CRE motifs impair P4 function more strongly in the FREJ4 derivative than in its FR3T3 parent. Further evidence that these elements contribute to hyperactivity of the P4 promoter in the ras transformant is the fact that they form distinct complexes with proteins from FREJ4 and FR3T3 cell extracts. This difference can be abolished by treating the FREJ4 cell extracts with cyclic AMP-dependent protein kinase (PKA) or treating original cultures with a PKA activator. These findings can be linked with two previously reported features of ras-transformed cells: the activation of a PKA-inhibited protein kinase cascade and the reduction of PKA-induced protein phosphorylation. In keeping with these facts, P4-directed gene expression can be up- or downmodulated in vivo by exposing cells to known inhibitors or activators of PKA, respectively. PMID:7636996

  1. Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

    Directory of Open Access Journals (Sweden)

    Laghi Luigi

    2006-04-01

    Full Text Available Abstract Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia, dysplastic (large regenerative, low and high grade dysplastic nodules and neoplastic (hepatocellular adenoma and carcinoma growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis to hepatocellular nodules (p RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly methylated, that this condition takes place as an age-related phenomenon and that the early setting and spreading over time of an epigenetically methylated hepatocyte subpopulation, might be related to liver tumorigenesis.

  2. Non-neoplastic conditions presenting as soft-tissue tumours

    Energy Technology Data Exchange (ETDEWEB)

    Crundwell, N. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); O' Donnell, P. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); Saifuddin, A. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom)]. E-mail: asif.saifuddin@rnoh.nhs.uk

    2007-01-15

    Review of referrals to our unit over the last 7 years showed that of approximately 750 cases referred as soft-tissue tumours, 132 were subsequently diagnosed as non-neoplastic lesions. The imaging characteristics of these lesions are presented to differentiate them from neoplasms. The most common diagnoses were myositis ossificans, ganglion cyst, abscess/infection, bursitis and synovitis. The imaging features of other rarer conditions will also be discussed.

  3. Non-neoplastic conditions presenting as soft-tissue tumours

    International Nuclear Information System (INIS)

    Crundwell, N.; O'Donnell, P.; Saifuddin, A.

    2007-01-01

    Review of referrals to our unit over the last 7 years showed that of approximately 750 cases referred as soft-tissue tumours, 132 were subsequently diagnosed as non-neoplastic lesions. The imaging characteristics of these lesions are presented to differentiate them from neoplasms. The most common diagnoses were myositis ossificans, ganglion cyst, abscess/infection, bursitis and synovitis. The imaging features of other rarer conditions will also be discussed

  4. The influence of theosophy on Mondrian's neoplastic work

    OpenAIRE

    Bris Marino, Pablo

    2014-01-01

    (ENG)The influence of Theosophy in the symbolist painting of Mondrian (1908-1911) has been unanimously recognized. There is not, however, the same consensus with respect to the influence of theosophy in his neoplastic period. There is a relationship between Mondrian’s theoretical writing and his practical work, but no proportionality. Mondrian’s theoretical discourse is not limited to painting and touches on other arts and disciplines (architecture,...

  5. Neoplastic stem cells: current concepts and clinical perspectives.

    Science.gov (United States)

    Schulenburg, Axel; Brämswig, Kira; Herrmann, Harald; Karlic, Heidrun; Mirkina, Irina; Hubmann, Rainer; Laffer, Sylvia; Marian, Brigitte; Shehata, Medhat; Krepler, Clemens; Pehamberger, Hubert; Grunt, Thomas; Jäger, Ulrich; Zielinski, Christoph C; Valent, Peter

    2010-11-01

    Neoplastic stem cells have initially been characterized in myeloid leukemias where NOD/SCID mouse-repopulating progenitors supposedly reside within a CD34+/Lin- subset of the malignant clone. These progenitors are considered to be self-renewing cells responsible for the in vivo long-term growth of neoplastic cells in leukemic patients. Therefore, these cells represent an attractive target of therapy. In some lymphoid leukemias, NOD/SCID mouse-repopulating cells were also reported to reside within the CD34+/Lin- subfraction of the clone. More recently, several attempts have been made to transfer the cancer stem cell concept to solid tumors and other non-hematopoietic neoplasms. In several of these tumors, the cell surface antigens AC133 (CD133) and CD44 are considered to indicate the potential of a cell to initiate permanent tumor formation in vivo. However, several questions concerning the phenotype, self-renewal capacity, stroma-dependence, and other properties of cancer- or leukemia-initiating cells remain to be solved. The current article provides a summary of our current knowledge on neoplastic (cancer) stem cells, with special emphasis on clinical implications and therapeutic options as well as a discussion about conceptual and technical limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

    International Nuclear Information System (INIS)

    Benson, M.D.; Cohen, A.S.

    1979-01-01

    Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. High SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease

  7. Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression.

    Science.gov (United States)

    Chen, Yan; Huang, Shai; Wu, Bo; Fang, Jiankai; Zhu, Minsheng; Sun, Li; Zhang, Lifeng; Zhang, Yongsheng; Sun, Maomin; Guo, Lingling; Wang, Shouli

    2017-07-25

    Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1. Moreover, transforming growth factor-β1-mediated inhibition of microRNA -196a-3p and activation of neuropilin-2were required for transforming growth factor-β1-induced migration and invasion of breast cancer cells. In addition, neuropilin-2 expression was suppressed in breast tumors, particularly in triple-negative breast cancers. Collectively, our findings strongly indicate that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and patient survival and a potential therapeutic target in metastatic breast cancer.

  8. Promoting safety voice with safety-specific transformational leadership: the mediating role of two dimensions of trust.

    Science.gov (United States)

    Conchie, Stacey M; Taylor, Paul J; Donald, Ian J

    2012-01-01

    Although safety-specific transformational leadership is known to encourage employee safety voice behaviors, less is known about what makes this style of leadership effective. We tested a model that links safety-specific transformational leadership to safety voice through various dimensions of trust. Data from 150 supervisor-employee dyads from the United Kingdom oil industry supported our predictions that the effects of safety-specific transformational leadership are sequentially mediated by affect-based trust beliefs and disclosure trust intentions. Moreover, we found that reliance trust intentions moderated the effect of disclosure: employees' disclosure intentions mediated the effects of affect-based trust on safety voice behaviors only when employees' intention to rely on their leader was moderate to high. These findings suggest that leaders seeking to encourage safety voice behaviors should go beyond "good reason" arguments and develop affective bonds with their employees.

  9. Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes.

    Science.gov (United States)

    Suliman, Salwa; Mustafa, Kamal; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Osdal, Tereza; Hamza, Amani O; Sun, Yang; Parajuli, Himalaya; Waag, Thilo; Nickel, Joachim; Johannessen, Anne Christine; McCormack, Emmet; Costea, Daniela Elena

    2016-07-01

    This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK(Luc)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK(Luc) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK(Luc) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK(Luc) both in vitro in 3D-OT and in vivo in xenografts formed by DOK(Luc) alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK(Luc) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK(Luc), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Promoter deletions are essential for transformation of lettuce by the T-cyt gene: the phenotypes of transgenic plants

    NARCIS (Netherlands)

    Curtis, H.E.C.; Jordi, W.; Davelaar, E.; Power, J.B.; Laat, de A.M.M.; Davey, M.R.

    1999-01-01

    The Agrobacterium T- cyt gene was transferred into lettuce, Latuca sativa‘Saladin’ using a genotype-independent transformation procedure employing a supervirulent Agrobacterium tumefaciens strain carrying the binary vector pMOG23. Kanamycin-resistant shoots were initiated from inoculated explants

  11. Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function

    DEFF Research Database (Denmark)

    Mirastschijski, Ursula; Schnabel, Reinhild; Claes, Juliane

    2010-01-01

    applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-beta1 (TGF-beta1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined......, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP...... and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-beta1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound...

  12. Transforming Bloom's Taxonomy into Classroom Practice: A Practical yet Comprehensive Approach to Promote Critical Reading and Student Participation

    Science.gov (United States)

    Mulcare, Daniel M.; Shwedel, Allan

    2017-01-01

    This article presents the Critical Reading Topics approach, a pedagogical method employed to promote deep thinking in a variety of politics courses. Derived from principles articulated in active learning, critical thinking, backward design, and flipped classroom literature, this method utilizes Bloom's Taxonomy as the scaffolding for students to…

  13. FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

    International Nuclear Information System (INIS)

    Chiappetta, Gennaro; Pierantoni, Giovanna Maria; Fusco, Alfredo; Ferraro, Angelo; Botti, Gerardo; Monaco, Mario; Pasquinelli, Rosa; Vuttariello, Emilia; Arnaldi, Liliane; Di Bonito, Maurizio; D'Aiuto, Giuseppe

    2007-01-01

    Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples. The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders

  14. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

    Science.gov (United States)

    Beger, Hans G; Schwarz, Michael; Poch, Bertram

    2012-11-01

    Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment. The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment. Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed. Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

  15. Curcumin and Turmeric Modulate the Tumor-Promoting Effects of Iron In Vitro.

    Science.gov (United States)

    Messner, Donald J; Robinson, Todd; Kowdley, Kris V

    2017-04-01

    Free or loosely chelated iron has tumor-promoting properties in vitro. Curcumin, a polyphenol derived from the food spice turmeric (Curcuma longa), is a potent antioxidant that binds iron. The primary aim of this study was to investigate whether curcuminoids prevent tumor-promoting effects of iron in T51B cells, a non-neoplastic rat liver epithelial cell line. Purified curcuminoids (curcumin) or a standardized turmeric extract similarly reduced oxidative stress and cytotoxicity associated with iron overload (IC 50 values near 10 μM, P turmeric for 16 wk in culture; subsequently assayed by soft agar colony formation) was nearly complete at 20 μM of total curcuminoids (P turmeric extract were taken up better by cells, had a longer half-life, and appeared more effective in blocking tumor promotion (P < 0.01), suggesting enhanced curcuminoid delivery to cells in culture. The primary finding that curcuminoids can inhibit tumor promotion caused by iron in T51B cells is tempered by evidence for an underlying increase in neoplastic transformation at lower concentrations.

  16. Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1987-01-01

    The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same

  17. Genetic biomarkers for neoplastic colorectal cancer in peripheral lymphocytes.

    Science.gov (United States)

    Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

    2011-04-01

    Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer.

  18. Neoplastic and proliferative disorders of the perinephric space

    International Nuclear Information System (INIS)

    Heller, M.T.; Haarer, K.A.; Thomas, E.; Thaete, F.L.

    2012-01-01

    The perinephric space is a well-marginated central compartment of the retroperitoneum, located between the anterior and posterior pararenal spaces. Various neoplastic and proliferative disorders can affect the perinephric space, and there is a wide array of imaging findings. Although many perinephric lesions may extend directly from the kidney and adrenal gland, other lesions occur in the perinephric space due to haematogenous spread, as part of a systemic disease, or by extension from an adjacent retroperitoneal compartment. Imaging plays a pivotal role in the diagnosis of perinephric diseases, as many of the disease processes affecting this space will not result in clinical signs or symptoms until the disease is at an advanced stage. Despite the often shared non-specific clinical and imaging findings among these disease processes, application of a categorical differential diagnosis based on the imaging characteristics will serve to narrow the differential diagnosis and direct further evaluation and treatment. In this article, the lesions have been categorized as soft-tissue rind [nephroblastomatosis, fibrosis, Erdheim–Chester disease (ECD), extramedullary haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions (extension of renal or adrenal malignancies, melanoma metastases, treated lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and cystic lesions (lymphangiomas, abscesses). The aim of this article is to demonstrate and describe the key imaging features of several neoplastic and proliferative disorders that affect the perinephric space.

  19. Increased sensitivity of transforming growth factor (TGF) beta 1 null cells to alkylating agents reveals a novel link between TGFbeta signaling and O(6)-methylguanine methyltransferase promoter hypermethylation.

    Science.gov (United States)

    Yamada, H; Vijayachandra, K; Penner, C; Glick, A

    2001-06-01

    Inactivation of the transforming growth factor beta (TGFbeta)-signaling pathway and gene silencing through hypermethylation of promoter CpG islands are two frequent alterations in human and experimental cancers. Here we report that nonneoplastic TGFbeta1-/- keratinocyte cell lines exhibit increased sensitivity to cell killing by alkylating agents, and this is due to lack of expression of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT). In TGFbeta1-/- but not TGFbeta1+/- cell lines, the CpG dinucleotides in the MGMT promoter are hypermethylated, as measured by restriction enzyme analysis and methylation specific polymerase chain reaction. In one unstable TGFbeta1+/- cell line, loss of the wild type TGFbeta1 allele correlates with the appearance of methylation in the MGMT promoter. Bisulfite sequencing shows that in the KO3 TGFbeta1-/- cell line nearly all of the 28 CpG sites in the MGMT promoter 475 base pairs upstream of the start site of transcription are methylated, whereas most are unmethylated in the H1 TGFbeta1+/- line. Treatment of the TGFbeta1-/- cell lines with 5-azacytidine causes reexpression of MGMT mRNA and demethylation of CpG islands in the promoter. Analysis of the time course of methylation using methylation-specific polymerase chain reaction shows a lack of methylation in primary TGFbeta1-/- keratinocytes and increasing methylation with passage number of immortalized clones. Subcloning of early passage clones reveals a remarkable heterogeneity and instability of the methylation state in the TGFbeta1-/- keratinocytes. Thus, the TGFbeta1-/- genotype does not directly regulate MGMT methylation but predisposes cells to immortalization-associated MGMT hypermethylation.

  20. Latent Transforming Growth Factor-beta1 Functionalised Electrospun Scaffolds Promote Human Cartilage Differentiation: Towards an Engineered Cartilage Construct

    Directory of Open Access Journals (Sweden)

    Erh-Hsuin Lim

    2013-11-01

    Full Text Available BackgroundTo overcome the potential drawbacks of a short half-life and dose-related adverse effects of using active transforming growth factor-beta 1 for cartilage engineering, a cell-mediated latent growth factor activation strategy was developed incorporating latent transforming growth factor-β1 (LTGF into an electrospun poly(L-lactide scaffold.MethodsThe electrospun scaffold was surface modified with NH3 plasma and biofunctionalised with LTGF to produce both random and orientated biofunctionalised electrospun scaffolds. Scaffold surface chemical analysis and growth factor bioavailability assays were performed. In vitro biocompatibility and human nasal chondrocyte gene expression with these biofunctionalised electrospun scaffold templates were assessed. In vivo chondrogenic activity and chondrocyte gene expression were evaluated in athymic rats.ResultsChemical analysis demonstrated that LTGF anchored to the scaffolds was available for enzymatic, chemical and cell activation. The biofunctionalised scaffolds were non-toxic. Gene expression suggested chondrocyte re-differentiation after 14 days in culture. By 6 weeks, the implanted biofunctionalised scaffolds had induced highly passaged chondrocytes to re-express Col2A1 and produce type II collagen.ConclusionsWe have demonstrated a proof of concept for cell-mediated activation of anchored growth factors using a novel biofunctionalised scaffold in cartilage engineering. This presents a platform for development of protein delivery systems and for tissue engineering.

  1. Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

    Science.gov (United States)

    Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

    2016-03-01

    BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

  2. Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

    Science.gov (United States)

    Di Gioia, Sonia; Bianchi, Paolo; Destro, Annarita; Grizzi, Fabio; Malesci, Alberto; Laghi, Luigi; Levrero, Massimo; Morabito, Alberto; Roncalli, Massimo

    2006-01-01

    Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia), dysplastic (large regenerative, low and high grade dysplastic nodules) and neoplastic (hepatocellular adenoma and carcinoma) growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC) we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis) to hepatocellular nodules (p < 0.01) to HCC (p < 0.001). In the non-hepatitic liver a consistent pattern of gene methylation was also found in both lesional (focal nodular hyperplasia and hepatocellular adenoma) and non-lesional tissue. Specifically, hepatocellular adenomas (HA) showed a methylation index significantly higher than that detected in focal nodular hyperplasia (FNH) (p < 0.01) and in non-lesional tissue (p < 0.001). In non-lesional liver also the methylation index gradually increased by ageing (p = 0.002), suggesting a progressive spreading of methylated cells over time. As opposed to RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly

  3. HLA‐G modulates the radiosensitivity of human neoplastic cells

    International Nuclear Information System (INIS)

    Michelin, Severino; Gallegos, Cristina; Baffa Trasci, Sofía; Dubner, Diana; Favier, B.; Carosella, E.D.

    2011-01-01

    Tumor cells show a very broad range of radiosensitivities. The differential radiosensitivity may depend on many factors, being the efficiency to recognize and/or repair the DNA lesion, and the cell cycle control mechanisms, the most important (Jeggo and Lavin, 2009; Kumala et al., 2003). Human leukocyte antigen‐G (HLA‐G) is a non‐classical HLA class I molecule involved in fetus protection form the maternal immune system, transplant tolerance, and viral and tumoral immune escape (Carosella et al., 2008). It has been determined that gamma radiation modulates HLA‐G expression at the plasma membrane of human melanoma cells. However, its role in tumoral radiosensitivity has not been demonstrated yet. The objective of this work was to determine if the radiosensitivity of human neoplastic cell lines cultured in vitro was mediated by HLA‐G expression. (authors)

  4. Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

    OpenAIRE

    Camara, Geni NL; Cerqueira, Daniela M; Oliveira, Ana PG; Silva, Evandro O; Carvalho, Luciano GS; Martins, Cláudia RF

    2003-01-01

    As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using c...

  5. Superconducting transformer

    International Nuclear Information System (INIS)

    Murphy, J.H.

    1982-01-01

    A superconducting transformer having a winding arrangement that provides for current limitation when subjected to a current transient as well as more efficient utilization of radial spacing and winding insulation. Structural innovations disclosed include compressed conical shaped winding layers and a resistive matrix to promote rapid switching of current between parallel windings

  6. Nuclear Division Index may Predict Neoplastic Colorectal Lesions.

    Science.gov (United States)

    Ionescu, Mirela E; Ciocirlan, Mihai; Becheanu, Gabriel; Nicolaie, Tudor; Ditescu, Cristina; Teiusanu, Adriana G; Gologan, Serban I; Arbanas, Tudor; Diculescu, Mircea M

    2011-07-01

    Colorectal cancer (CRC) develops by accumulation of multiple genetic damages leading to genetic instability that can be evaluated by cytogenetic methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in peripheral lymphocytes of patients with CRC and polyps versus patients with normal colonoscopy. Blood samples were collected from patients after informed consent. By CBMN technique we assessed the proportion of mono-nucleated, bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate NDI. Data were statistically analyzed using the SPSS 11.0 package. 45 patients were available for analysis, 23 men and 22 women, with a mean age of 58.7±13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean NDI values were significantly smaller for patients with CRC or polyps than in patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference persisted for patients with neoplastic lesions (adenomas and carcinomas) when compared with patients with normal colonoscopy or non neoplastic (hyperplastic) polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81% specificity of lower values (p=0.019). The NDI cut off value to predict the presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and a specificity of 82.8% (p=0.048). NDI may be useful in screening strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic biomarker.

  7. The claudin gene family: expression in normal and neoplastic tissues

    International Nuclear Information System (INIS)

    Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J

    2006-01-01

    The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4

  8. Ionizing Radiation Promotes Migration and Invasion of Cancer Cells Through Transforming Growth Factor-Beta–Mediated Epithelial–Mesenchymal Transition

    International Nuclear Information System (INIS)

    Zhou Yongchun; Liu Junye; Li Jing; Zhang Jie; Xu Yuqiao; Zhang Huawei; Qiu Lianbo; Ding Guirong; Su Xiaoming; Mei Shi; Guo Guozhen

    2011-01-01

    Purpose: To examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-β)–mediated epithelial–mesenchymal transition (EMT). Methods and Materials: Six cancer cell lines originating from different human organs were irradiated by 60 Co γ-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-β in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-β signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. Results: After irradiation with γ-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-β were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-β signaling. Conclusions: These results suggest that EMT mediated by TGF-β plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.

  9. Ionizing Radiation Promotes Migration and Invasion of Cancer Cells Through Transforming Growth Factor-Beta-Mediated Epithelial-Mesenchymal Transition

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yongchun [Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi' an (China); Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China); Liu Junye; Li Jing; Zhang Jie [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China); Xu Yuqiao [Department of Pathology, Xijing Hospital Fourth Military Medical University, Xi' an (China); Zhang Huawei; Qiu Lianbo; Ding Guirong [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China); Su Xiaoming [Department of Radiation Oncology, 306th Hospital of PLA, Beijing (China); Mei Shi [Department of Radiation Oncology, Xijing Hospital Fourth Military Medical University, Xi' an (China); Guo Guozhen, E-mail: guozhenguo@hotmail.com [Department of Radiation Medicine, College of Preventive Medicine, Xijing Hospital Fourth Military Medical University, Xi' an (China)

    2011-12-01

    Purpose: To examine whether ionizing radiation enhances the migratory and invasive abilities of cancer cells through transforming growth factor (TGF-{beta})-mediated epithelial-mesenchymal transition (EMT). Methods and Materials: Six cancer cell lines originating from different human organs were irradiated by {sup 60}Co {gamma}-ray at a total dose of 2 Gy, and the changes associated with EMT, including morphology, EMT markers, migration and invasion, were observed by microscope, Western blot, immunofluorescence, scratch assay, and transwell chamber assay, respectively. Then the protein levels of TGF-{beta} in these cancer cells were detected by enzyme-linked immunosorbent assay, and the role of TGF-{beta} signaling pathway in the effect of ionizing radiation on EMT was investigate by using the specific inhibitor SB431542. Results: After irradiation with {gamma}-ray at a total dose of 2 Gy, cancer cells presented the mesenchymal phenotype, and compared with the sham-irradiation group the expression of epithelial markers was decreased and of mesenchymal markers was increased, the migratory and invasive capabilities were strengthened, and the protein levels of TGF-{beta} were enhanced. Furthermore, events associated with EMT induced by IR in A549 could be reversed through inhibition of TGF-{beta} signaling. Conclusions: These results suggest that EMT mediated by TGF-{beta} plays a critical role in IR-induced enhancing of migratory and invasive capabilities in cancer cells.

  10. The spectrum of non- neoplastic skin lesions in Ibadan, Nigeria: a ...

    African Journals Online (AJOL)

    The other common specific skin lesions were lichen planus/lichenoid dermatitis 27(12.9% of 209 cases), verruca vulgaris 25 (12% of 209 cases). Conclusion: The number of histologically diagnosed non-neoplastic skin lesions is relatively small. There is a very wide spectrum of non-neoplastic skin lesions diagnosed within ...

  11. Cell surface response of chemically transformed, malignant mouse embryonal fibroblasts and human colon cancer cells to the maturation-promoting agent, N,N-dimethylformamide

    International Nuclear Information System (INIS)

    Marks, M.E.

    1985-01-01

    The lactoperoxidase/ 125 I radioiodination procedure was used to probe the cell surface of normal, nontransformed AKR-2B mouse embryo fibroblasts and malignant, permanently methylcholanthrene-transformed AKR-2B (AKR-MCA) cells to establish the relationship between cell surface changes and transformation/differentiation in this call system. AKR-MCA cells displayed surface alterations secondary to N,N-dimethylformamide (DFM)-promoted differentiation. Growth of AKR-MCA cells in DMF virtually eliminated the 85,000 and 63,000 molecular weight surface proteins susceptible to radioiodination and increased surface material of ∼200,000 molecular weight. Thus, surface profiles of DFM-treated AKR-MCA cells were essentially identical to those of nontransformed AKR-2B cells. Experimentation was extended to a cultured human colon cancer cell line (HCT MOSER). HCT MOSER cells exposed to DMF manifested marked, reversible morphological and surface changes which occurred as a function of time of growth in DMF and DMF concentration. Interestingly, material reactive with anti-fibronectin was found on the surfaces and in the culture medium of DFM-treated HCT MOSER cells

  12. "互联网+"开启酒店业转型升级%"Internet+ " Promotes the Transformation and Upgrading of the Hotel Industry

    Institute of Scientific and Technical Information of China (English)

    陈莉

    2015-01-01

    Nowadays, China's hotel industry has entered a period of new normal. The hotel industry is facing tremendous pressure of industry transformation. It becomes a significant task of hotels as to how to improve the marketing, channel, communication, payment, and consumer experience, ensure the long-term competitive advantages under the circumstances of increasingly severe market competition. This article attempts to explore, in the background of the " Internet+," how to promote the transformation and upgrading of the hotel industry .%当前,中国酒店业正面临国内外经济发展新常态和行业转型的双重压力,行业竞争异常激烈.酒店业正在从营销、渠道、传播、支付、消费者体验等环节,重新定义行业的运营模式和发展模式,越来越多的传统酒店纷纷融入"互联网+"大潮,以开放共享的用户思维全面进入转型阶段.

  13. Joint approach based on clinical and imaging features to distinguish non-neoplastic from neoplastic pituitary stalk lesions.

    Directory of Open Access Journals (Sweden)

    Ji Ye Lee

    Full Text Available Distinguishing non-neoplastic pituitary stalk lesions (non-NPSLs from neoplastic pituitary stalk lesions (NPSLs is a major concern in guiding treatment for a thickened pituitary stalk. Our study aimed to aid provide preoperative diagnostic assistance by combining clinical and magnetic resonance imaging (MRI findings to distinguish non-NPSLs from NPSLs.We recruited 158 patients with thickened pituitary stalk lesions visible on MRI. Laboratory findings included hypopituitarism, diabetes insipidus (DI, and hyperprolactinemia. MR images were assessed for anterior-posterior thickness (mm, diffuse pituitary stalk thickening, cystic changes, a high T1 signal, and glandular or extrasellar involvement. A diagnostic model was developed using a recursive partitioning logistic regression analysis. The model was validated in an independent dataset comprising 63 patients, and its diagnostic performance was compared with that of the original radiological reports.A univariate analysis found significant associations of DI (P = 0.006, absence of extrasellar involvement (P = 0.002, and lower stalk thickness (P = 0.031 with non-NPSLs. A diagnostic model was created using the following parameters (in order of priority: 1 lack of extrasellar involvement, 2 stalk thickness < 5.3 mm, and 3 presence of DI. The diagnostic performance (area under the curve; AUC of this model in the independent set was 0.813, representing a significant improvement over the original radiological reports (AUC: 0.713, P = 0.029.The joint diagnostic approach based on clinical and imaging-based factors robustly distinguished non-NPSLs from NPSLs. This approach could guide treatment strategies and prevent unnecessary surgery in patients with non-NPSL.

  14. Cell-cell adhesion mediated by binding of membrane-anchored transforming growth factor α to epidermal growth factor receptors promotes cell proliferation

    International Nuclear Information System (INIS)

    Anklesaria, P.; Greenberger, J.S.; Teixido, J.; Laiho, M.; Massague, J.; Pierce, J.H.

    1990-01-01

    The precursor for transforming growth factor α, pro-TGF-α, is a cell surface glycoprotein that can establish contact with epidermal growth factor (EGF) receptors on adjacent cells. To examine whether the pro-TGF-α/EGF receptor pair can simultaneously mediate cell adhesion and promote cell proliferation, the authors have expressed pro-TGF-α in a bone marrow stromal cell line labeled with [ 35 S] cysteine. Expression of pro-TGF-α allows these cells to support long-term attachment of an EGF/interleukin-3-dependent hematopoietic progenitor cell line that expresses EGF receptors but is unable to adhere to normal stroma. This interaction is inhibited by soluble EGF receptor ligands. Further, the hematopoietic progenitor cells replicate their DNA while they are attached to the stromal cell layer and become foci of sustained cell proliferation. Thus, pro-TGF-α and the EGF receptor can function as mediators of intercellular adhesion and this interaction may promote a mitogenic response. They propose the term juxtacrine to designate this form of stimulation between adjacent cells

  15. Ultraviolet-x-ray interaction: mutation and transformation

    International Nuclear Information System (INIS)

    Han, A.; Elkind, M.M.; Suzuki, F.; Dainko, J.L.; Buess, E.

    1981-01-01

    The overall long-range objectives of the proposed research are to: (1) determine whether ionizing and nonionizing radiations interact in the induction of mutation and neoplastic transformation; (2) identify the nature of the interaction; (3) establish the possible relationship between the repair processes and the expression of interactive damage related to mutation and neoplastic transformation. Principal methods were used to assess survival, mutation, and neoplastic transformation of mammalian cells in culture. Cells were exposed to the following radiations: 50-kV x-rays; light from a germicidal lamp, uv-C (254 nm); light from unfiltered sun lamps, uv-B (290 to 345 nm); and light from sun lamps filtered by polystyrene dish covers

  16. Transforming Growth Factor-β and Interleukin-1β Signaling Pathways Converge on the Chemokine CCL20 Promoter.

    Science.gov (United States)

    Brand, Oliver J; Somanath, Sangeeta; Moermans, Catherine; Yanagisawa, Haruhiko; Hashimoto, Mitsuo; Cambier, Stephanie; Markovics, Jennifer; Bondesson, Andrew J; Hill, Arthur; Jablons, David; Wolters, Paul; Lou, Jianlong; Marks, James D; Baron, Jody L; Nishimura, Stephen L

    2015-06-05

    CCL20 is the only chemokine ligand for the chemokine receptor CCR6, which is expressed by the critical antigen presenting cells, dendritic cells. Increased expression of CCL20 is likely involved in the increased recruitment of dendritic cells observed in fibroinflammatory diseases such as chronic obstructive pulmonary disease (COPD). CCL20 expression is increased by the proinflammatory cytokine IL-1β. We have determined that IL-1β-dependent CCL20 expression is also dependent on the multifunctional cytokine TGF-β. TGF-β is expressed in a latent form that must be activated to function, and activation is achieved through binding to the integrin αvβ8 (itgb8). Here we confirm correlative increases in αvβ8 and IL-1β with CCL20 protein in lung parenchymal lysates of a large cohort of COPD patients. How IL-1β- and αvβ8-mediated TGF-β activation conspire to increase fibroblast CCL20 expression remains unknown, because these pathways have not been shown to directly interact. We evaluate the 5'-flanking region of CCL20 to determine that IL-1β-driven CCL20 expression is dependent on αvβ8-mediated activation of TGF-β. We identify a TGF-β-responsive element (i.e. SMAD) located on an upstream enhancer of the human CCL20 promoter required for efficient IL-1β-dependent CCL20 expression. By chromatin immunoprecipitation, this upstream enhancer complexes with the p50 subunit of NF-κB on a NF-κB-binding element close to the transcriptional start site of CCL20. These interactions are confirmed by electromobility shift assays in nuclear extracts from human lung fibroblasts. These data define a mechanism by which αvβ8-dependent activation of TGF-β regulates IL-1β-dependent CCL20 expression in COPD. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Activated Hepatic Stellate Cells Induce Tumor Progression of Neoplastic Hepatocytes in a TGF-β Dependent Fashion

    Science.gov (United States)

    MIKULA, M.; PROELL, V.; FISCHER, A.N.M.; MIKULITS, W.

    2010-01-01

    The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells. For both tumorigenesis and hepatic fibrogenesis, transforming growth factor (TGF)-β signaling executes key roles and therefore is considered as a hallmark of these pathological events. By employing cellular transplantation we show that the interaction of neoplastic MIM-R hepatocytes with the tumor microenvironment, containing either activated hepatic stellate cells (M1-4HSCs) or myofibroblasts derived thereof (M-HTs), induces progression in malignancy. Cotransplantation of MIM-R hepatocytes with M-HTs yielded strongest MIM-R generated tumor formation accompanied by nuclear localization of Smad2/3 as well as of β-catenin. Genetic interference with TGF-β signaling by gain of antagonistic Smad7 in MIM-R hepatocytes diminished epithelial dedifferentiation and tumor progression upon interaction with M1-4HSCs or M-HTs. Further analysis showed that tumors harboring disrupted Smad signaling are devoid of nuclear β-catenin accumulation, indicating a crosstalk between TGF-β and β-catenin signaling. Together, these data demonstrate that activated HSCs and myofibroblasts directly govern hepatocarcinogenesis in a TGF-β dependent fashion by inducing autocrine TGF-β signaling and nuclear β-catenin accumulation in neoplastic hepatocytes. These results indicate that intervention with TGF-β signaling is highly promising in liver cancer therapy. PMID:16883581

  18. Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

    Directory of Open Access Journals (Sweden)

    Eugen Dhimolea

    Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

  19. Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation.

    Science.gov (United States)

    Jackson, Laura E; Kulkarni, Sucheta; Wang, Huabo; Lu, Jie; Dolezal, James M; Bharathi, Sivakama S; Ranganathan, Sarangarajan; Patel, Mulchand S; Deshpande, Rahul; Alencastro, Frances; Wendell, Stacy G; Goetzman, Eric S; Duncan, Andrew W; Prochownik, Edward V

    2017-11-01

    Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels of glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion to acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response to complex energetic, enzymatic, and metabolic cues. Here we utilized a mouse model of hepatocyte-specific PDC inactivation to determine the need for this metabolic link during normal hepatocyte regeneration and malignant transformation. In PDC "knockout" (KO) animals, the long-term regenerative potential of hepatocytes was unimpaired, and growth of aggressive experimental hepatoblastomas was only modestly slowed in the face of 80%-90% reductions in AcCoA and significant alterations in the levels of key tricarboxylic acid (TCA) cycle intermediates and amino acids. Overall, oxphos activity in KO livers and hepatoblastoma was comparable with that of control counterparts, with evidence that metabolic substrate abnormalities were compensated for by increased mitochondrial mass. These findings demonstrate that the biochemical link between glycolysis and the TCA cycle can be completely severed without affecting normal or neoplastic proliferation, even under the most demanding circumstances. Cancer Res; 77(21); 5795-807. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. SMAD family proteins: the current knowledge on their expression and potential role in neoplastic diseases

    Directory of Open Access Journals (Sweden)

    Magdalena Witkowska

    2014-03-01

    Full Text Available Transforming growth factor beta (TGF-β plays a crucial role and takes part in many processes in the human body both in physiology and pathology. This cytokine is involved in angiogenesis, regulates apoptosis and stimulates divisions of cells, such as hepatocytes, lymphocytes or hematopoietic cells. SMAD proteins family is a unique group of particles responsible for transducting the signal induced by TGF-β into the nucleus. This molecules, after receiving a signal from activated TGF-β, act on transcription factors in the nucleus, leading directly to the expression of the corresponding genes. According to current knowledge, disturbances in the functioning of SMAD proteins are present in a number of diseases. The reduced expression was observed, for example in cardiovascular diseases such as primary pulmonary hypertension or myocardial infarction, autoimmune diseases for instance systemic lupus erythematosus and multiple sclerosis, Alzheimer’s disease or osteoporosis. The latest clinical data showed the presence of mutations in SMAD proteins in cancerogenesis. Mutation of SMAD-4 protein can be detected in half of the patients with pancreatic cancer, 20% of patients with colorectal cancer and 10% of patients with lung cancer. However, mutation in SMAD-2 protein was observed in 7% of both patients with colorectal cancer and lung cancer. On the basis of numerous works, SMAD protein expression would be valuable prognostic factor in some of neoplastic diseases.

  1. Age-Related DNA Methylation Changes and Neoplastic Transformation of the Human Prostate

    Science.gov (United States)

    2011-07-01

    Toyota M, Ho C, Ahuja N, et al. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification...hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received 12/23/2009; revised 05/07/2010; accepted 05...Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB, Herman JG (2000

  2. Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer

    International Nuclear Information System (INIS)

    Merritt, Melissa A; Parsons, Peter G; Newton, Tanya R; Martyn, Adam C; Webb, Penelope M; Green, Adèle C; Papadimos, David J; Boyle, Glen M

    2009-01-01

    The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression. Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes. We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity. These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis

  3. Overexpression of Pax5 is not sufficient for neoplastic transformation of mouse neuroectoderm

    Czech Academy of Sciences Publication Activity Database

    Steinbach, P. J.; Kozmik, Zbyněk; Pfeffer, P.; Aguzzi, A.

    2001-01-01

    Roč. 93, č. 4 (2001), s. 459-467 ISSN 0020-7136 Institutional research plan: CEZ:AV0Z5052915 Keywords : Pax5 * retrovirus * transgenic mice Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.233, year: 2001

  4. Mechanism of Integrim-Mediated Growth Control in Normal, Transformed, and Neoplastic Breast Cells

    National Research Council Canada - National Science Library

    Wayner, Elizabeth

    1999-01-01

    .... The primary cell adhesion receptors that mediate binding to extracellular matrix proteins are integrins Our data suggest that alpha 3 beta 1 and alpha 6 beta 4 are the primary integrins responsible...

  5. DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome).

    Science.gov (United States)

    Findling, James W; Raff, Hershel

    2017-05-01

    Endogenous hypercortisolism (Cushing's syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing's syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing's syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing's syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing's syndrome). © 2017 European Society of Endocrinology.

  6. Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

    International Nuclear Information System (INIS)

    Badylak, S.F.; Babbs, C.F.

    1984-01-01

    The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

  7. Neoplastic changes in freshwater fishes: Correlation with oil refining

    International Nuclear Information System (INIS)

    Ostrander, G.K.

    1993-01-01

    Traditionally, oil pollution has been viewed as single event, large scale disasters such as the Exxon Valdez spill in Alaska. However, it is becoming increasingly apparent that by products and anthropogenic contaminants resulting from oil exploration, extraction, recovery, refining, and the manufacture and use of oil and oil-based products are negatively impacting the environment. Potential problems of freshwater pollution by oil contaminants are increasing in many parts of the world from both active and abandoned oil production facilities. In the USA many ''Superfund'' sites have been designated for cleanup under the Comprehensive Environmental Response, Compensation and Liability Act of 1980; primarily because of waste discharged on to the sites by the oil industry. Pollution of surface and groundwater from these sites has already occurred and in some cases has led to deleterious effects on the complex aquatic and terrestrial ecosystems on and near these sites. The effect of oil and oil related products on aquatic organisms will be reviewed. Specifically, the discussion will focus on preneoplastic and neoplastic changes in fishes with a primary endpoint of cancer. Finally, a summary of current studies of feral fishes residing on and near an abandoned oil refinery in Oklahoma will be presented

  8. Inhibition of mitogen-activated protein kinase kinase, DNA methyltransferase, and transforming growth factor-β promotes differentiation of human induced pluripotent stem cells into enterocytes.

    Science.gov (United States)

    Kodama, Nao; Iwao, Takahiro; Kabeya, Tomoki; Horikawa, Takashi; Niwa, Takuro; Kondo, Yuki; Nakamura, Katsunori; Matsunaga, Tamihide

    2016-06-01

    We previously reported that small-molecule compounds were effective in generating pharmacokinetically functional enterocytes from human induced pluripotent stem (iPS) cells. In this study, to determine whether the compounds promote the differentiation of human iPS cells into enterocytes, we investigated the effects of a combination of mitogen-activated protein kinase kinase (MEK), DNA methyltransferase (DNMT), and transforming growth factor (TGF)-β inhibitors on intestinal differentiation. Human iPS cells cultured on feeder cells were differentiated into endodermal cells by activin A. These endodermal-like cells were then differentiated into intestinal stem cells by fibroblast growth factor 2. Finally, the cells were differentiated into enterocyte cells by epidermal growth factor and small-molecule compounds. After differentiation, mRNA expression levels and drug-metabolizing enzyme activities were measured. The mRNA expression levels of the enterocyte marker sucrase-isomaltase and the major drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 were increased by a combination of MEK, DNMT, and TGF-β inhibitors. The mRNA expression of CYP3A4 was markedly induced by 1α,25-dihydroxyvitamin D3. Metabolic activities of CYP1A1/2, CYP2B6, CYP2C9, CYP2C19, CYP3A4/5, UDP-glucuronosyltransferase, and sulfotransferase were also observed in the differentiated cells. In conclusion, MEK, DNMT, and TGF-β inhibitors can be used to promote the differentiation of human iPS cells into pharmacokinetically functional enterocytes. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  9. Role of thyroid in x-ray-induced oncogenic transformation in cell culture

    International Nuclear Information System (INIS)

    Borek, C.

    1982-01-01

    This paper examines the role of thyroid hormones in x-ray-induced neoplastic transformation of C3H/10 T 1/2 cells. In addition, the delineation of the time when transformation is sensitive to T3, the dependence of transformation on T3 concentration, and the involvement of protein synthesis are studied. The results indicate that thyroid hormone plays a key role in the initiation of x-ray-induced neoplastic transformation and that induction of protein synthesis may mediate this response

  10. Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function.

    Science.gov (United States)

    Wang, Yanyan; Huang, Gonghua; Vogel, Peter; Neale, Geoffrey; Reizis, Boris; Chi, Hongbo

    2012-02-07

    Homeostatic control of dendritic cell (DC) survival is crucial for adaptive immunity, but the molecular mechanism is not well defined. Moreover, how DCs influence immune homeostasis under steady state remains unclear. Combining DC-specific and -inducible deletion systems, we report that transforming growth factor beta-activated kinase 1 (TAK1) is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c(+) cells induced markedly elevated apoptosis, leading to the depletion of DC populations, especially the CD8(+) and CD103(+) DC subsets in lymphoid and nonlymphoid tissues, respectively. TAK1 also contributed to DC development by promoting the generation of DC precursors. Prosurvival signals from Toll-like receptors, CD40 and receptor activator of nuclear factor-κB (RANK) are integrated by TAK1 in DCs, which in turn mediated activation of downstream NF-κB and AKT-Foxo pathways and established a gene-expression program. TAK1 deficiency in DCs caused a myeloid proliferative disorder characterized by expansion of neutrophils and inflammatory monocytes, disrupted T-cell homeostasis, and prevented effective T-cell priming and generation of regulatory T cells. Moreover, TAK1 signaling in DCs was required to prevent myeloid proliferation even in the absence of lymphocytes, indicating a previously unappreciated regulatory mechanism of DC-mediated control of myeloid cell-dependent inflammation. Therefore, TAK1 orchestrates a prosurvival checkpoint in DCs that affects the homeostasis and function of the immune system.

  11. Telomere length in normal and neoplastic canine tissues.

    Science.gov (United States)

    Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

    2007-12-01

    To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

  12. Role of nuclear medicine in pulmonary neoplastic processes

    International Nuclear Information System (INIS)

    Waxman, A.D.

    1986-01-01

    It has been demonstrated that the single most important factor in determining survival in patients with bronchogenic carcinoma is the extent of spread of metastasis from the primary lesion. This explains the extensive efforts in developing accurate staging tests for pulmonary tumors, both primary and metastatic, with special emphasis on the determination of pulmonary hilar and mediastinal spread of disease. Continued improvements in nuclear medicine instrumentation along with the development of tumor specific radiopharmaceuticals, as well as agents that have the capability of tracking tumor viability, have changed the orientation of scintigraphic techniques in the evaluation of pulmonary neoplastic processes. Gallium scintigraphy is no longer considered as a primary imaging modality in the staging of pulmonary tumors, and in most institutions has been replaced by computed tomography (CT) for this purpose. It has been demonstrated that gallium, relative to other imaging modalities, is a sensitive indicator of hilar spread of tumor. However, because of the normally high background activity within the sternum and spine, mediastinal abnormalities are poorly detected. Since most pulmonary tumors metastasize via regional nodes to the pulmonary hilum and then to the mediastinum, the high sensitivity for the detection of pulmonary hilar abnormalities and the high specificity for mediastinal lesion detection suggest that gallium scintigraphy is a valuable adjunctive test when used appropriately. Thallium 201 as a tumor agent is being studied by several institutions. Preliminary results indicate a high degree of sensitivity for the detection of pulmonary hilar and mediastinal lesions and there are early indications that thallium is a promising agent to evaluate tumor viability. 52 references

  13. Evaluation of Neoplastic Nature of Keratocystic Odontogenic Tumor Versus Ameloblastoma

    International Nuclear Information System (INIS)

    KHALIFA, Gh.A.; SMOKIER, H.M.; ABO-HAGER, E.A.

    2010-01-01

    Although most of odontogenic tumors are benign, some of them will show locally destructive behavior, as keratocystic odontogenic tumor (KCOT) is now known as a benign but aggressive odontogenic neoplasm. The neoplastic characteristics in KCOT have been suggested from clinical as well as pathologic aspects. Matrix metalloproteinase-2 (MMP-2) is a gelatinase form of the MMPs family, which is a group of proteolytic enzymes that degrade many types of collagen. Cysteine aspartic acid-specific protease-3 (caspase-3) is the most downstream enzyme in the apoptosis-inducing protease pathway and is probably the most clearly associated with cell death. The aim of this study is to evaluate and compare the extracellular degradation potentiality (MMP-2) and apoptosis (caspase-3) of the epithelial lining in KCOT versus radicular cysts and ameloblastoma, in order to reinforce its classification as an odontogenic tumor. Material and Methods: Twenty-six surgical specimens including keratocyst odontogenic tumor (KCOT; n=l 1), ameloblastoma (AB; n=8) and radicular cysts (RC; n=7) were examined for expression of MMP-2 and caspase-3 using the immunohistochemical method. Results: For MMP-2 immuno expression, AB showed the statistically significant highest mean area percentage, followed by KCOT, while RC showed the statistically significant lowest mean area percentage. As for caspase-3, there was no statistically significant difference between KCOT and AB, while RC showed the statistically significantly lowest mean area percentage. Conclusion: Overexpression of MMP-2 protein related to growth and progression of lesions analyzed and may be one of the factors enhancing the recurrence of KCOT and invasion of AB. In addition, the epithelial lining of KCOT showed a high cell turnover reinforcing its classification as an odontogenic tumor

  14. 78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

    Science.gov (United States)

    2013-12-17

    ... include updating the medical terminology in the listings. For example, we would replace the term ``Hodgkin... Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases); Proposed Rule #0;#0...

  15. Chondroblastoma and chondromyxoid fibroma : disentangling the neoplastic chondrogenesis of two rare cartilaginous tumours

    NARCIS (Netherlands)

    Romeo, Salvatore

    2010-01-01

    The scope of this study was to disentangle neoplastic chondrogenesis in two rare cartilaginous tumours: chondroblastoma and chondromyxoid fibroma. It was addressed: 1 The spectrum of phenotypic differentiation in chondroblastoma and chondromyxoid fibroma, 2 The signalling pathways driving

  16. The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

    Science.gov (United States)

    Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

    2006-01-15

    The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate

  17. Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

    International Nuclear Information System (INIS)

    Kuwert, T.; Morgenroth, C.; Woesler, B.; Matheja, P.; Palkovic, S.; Vollet, B.; Samnick, S.; Maasjosthusmann, U.; Lerch, H.; Gildehaus, F.J.; Wassmann, H.; Schober, O.

    1996-01-01

    Using single-photon emission tomography (SPET), the radiopharmaceutical L-3-iodine-123-α-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating higc-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. (orig.)

  18. Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

    Directory of Open Access Journals (Sweden)

    Ana Paula Cleto Marolla

    2016-01-01

    Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.

  19. Simian virus 40 small t antigen is not required for the maintenance of transformation but may act as a promoter (cocarcinogen) during establishment of transformation in resting rat cells.

    Science.gov (United States)

    Seif, R; Martin, R G

    1979-12-01

    Simian virus 40 deletion mutants affecting the 20,000-dalton (20K) t antigen and tsA mutants rendering the 90K T antigen temperature sensitive, as well as double mutants containing both mutations, induced host DNA synthesis in resting rat cells at the restrictive temperature. Nonetheless, the deletion mutants and double mutants did not induce transformation in resting cells even at the permissive temperature. On the other hand, the deletion mutants did induce full transformants when actively growing rat cells were infected; the transformants grew efficiently in agar and to high saturation densities on platic. The double mutants did not induce T-antigen-independent (temperature-insensitive) transformants which were shown previously to arise preferentially from resting cells. Thus, small t antigen was dispensable for the maintenance of the transformed phenotype in T-antigen-dependent rat transformants (transformants derived from growing cells) and may play a role in the establishment of T-antigen-independent transformants. We attempt to establish a parallel between transformation induced by chemical carcinogens and simian virus 40-induced transformation.

  20. Diffusion tensor imaging in inflammatory and neoplastic intramedullary spinal cord lesions: Focusing on fiber tracking

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Jin; Lee, Joon Woo; Lee, Eugene; Kim, Sung Gon; Kang, Yu Suhn; Ahn, Joong Mo; Kang, Heung Sik [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2017-02-15

    Inflammatory and neoplastic intramedullary spinal cord lesions have overlapping clinical features, and it is occasionally difficult to distinguish one from the other on conventional magnetic resonance imaging. We aimed to compare diffusion tensor imaging findings between inflammatory and neoplastic intramedullary spinal cord lesions, with a specific focus on patterns of fiber tracking. Diffusion tensor imaging was performed in patients with either inflammatory or neoplastic intramedullary spinal cord lesions. The fiber tracking patterns (categorized as “intact,” “displaced,” or “interrupted”) were compared between these two groups. Eight patients were included in the study: 5 patients with pathologically or clinically confirmed inflammatory lesions and 3 patients with pathologically or clinically confirmed neoplastic lesions. Among the 5 patients with inflammatory lesions, 2 patients exhibited the displaced pattern and 3 patients exhibited the intact pattern. Among the 3 patients with neoplastic lesions, 1 patient exhibited the intact pattern, 1 patient exhibited the displaced pattern, and 1 patient exhibited the interrupted pattern. In this study, inflammatory and neoplastic intramedullary spinal cord lesions were not clearly differentiated by fiber tracking; both conditions can present with overlapping features such as displaced fibers. The exclusion of inflammatory conditions based on the presence of displaced fibers in fiber tracking images should be avoided.

  1. A cluster-randomized controlled trial to reduce sedentary behavior and promote physical activity and health of 8-9 year olds: The Transform-Us! Study

    Directory of Open Access Journals (Sweden)

    Ball Kylie

    2011-10-01

    Full Text Available Abstract Background Physical activity (PA is associated with positive cardio-metabolic health and emerging evidence suggests sedentary behavior (SB may be detrimental to children's health independent of PA. The primary aim of the Transform-Us! study is to determine whether an 18-month, behavioral and environmental intervention in the school and family settings results in higher levels of PA and lower rates of SB among 8-9 year old children compared with usual practice (post-intervention and 12-months follow-up. The secondary aims are to determine the independent and combined effects of PA and SB on children's cardio-metabolic health risk factors; identify the factors that mediate the success of the intervention; and determine whether the intervention is cost-effective. Methods/design A four-arm cluster-randomized controlled trial (RCT with a 2 × 2 factorial design, with schools as the unit of randomization. Twenty schools will be allocated to one of four intervention groups, sedentary behavior (SB-I, physical activity (PA-I, combined SB and PA (SB+PA-I or current practice control (C, which will be evaluated among approximately 600 children aged 8-9 years in school year 3 living in Melbourne, Australia. All children in year 3 at intervention schools in 2010 (8-9 years will receive the intervention over an 18-month period with a maintenance 'booster' delivered in 2012 and children at all schools will be invited to participate in the evaluation assessments. To maximize the sample and to capture new students arriving at intervention and control schools, recruitment will be on-going up to the post-intervention time point. Primary outcomes are time spent sitting and in PA assessed via accelerometers and inclinometers and survey. Discussion To our knowledge, Transform-Us! is the first RCT to examine the effectiveness of intervention strategies for reducing children's overall sedentary time, promoting PA and optimizing health outcomes. The integration

  2. Onconeuronal and antineuronal antibodies in patients with neoplastic and non-neoplastic pulmonary pathologies and suspected for paraneoplastic neurological syndrome

    Directory of Open Access Journals (Sweden)

    Michalak S

    2009-12-01

    Full Text Available Abstract Objective Onconeuronal antibodies are important diagnostic tool in patients with suspicion of paraneoplastic neurological syndromes (PNS. However, their role in PNS pathophysiology and specificity for particular neurological manifestation remains unclear. The aim of this study was to evaluate onconeuronal and antineuronal antibodies in patients with pulmonary pathologies and suspected for PNS. Materials and methods Twenty one patients with pulmonary pathologies were selected from the database of 525 consecutive patients with suspicion of PNS. Patients' sera were screened for the presence of onconeuronal and antineuronal antibodies by means of indirect immunofluorescence; the presence was confirmed by Western blotting. Clinical data were obtained from medical records, hospital data base, and questionnaire-based direct telephone contact with patients. Results Among 21 patients, aged 54 ± 11, with pulmonary pathologies, the most frequent neurological manifestations were neuropathies. Typical PNS included paraneoplastic cerebellar degeneration (PCD and limbic encephalitis (LE. We found cases with multiple onconeuronal antibodies (anti-Ri and anti-Yo and coexisting PNS (PCD/LE. Well-defined onconeuronal antibodies were identified in 23.8% of patients. Among antineuronal antibodies, the most frequent were anti-MAG (23.8%. ROC curves analysis revealed high sensitivity of onconeuronal and antineuronal antibodies for typical PNS and lower for pulmonary malignancies. Conclusions Tests for antibodies are highly sensitive for the diagnosis of typical paraneoplastic neurological syndromes. Anti-myelin and anti-MAG antibodies are associated with non-neoplastic pulmonary diseases. Patients with well-defined onconeuronal antibodies require careful screening and follow-up, because the PNS diagnosis indicates a high probability of an underlying malignancy.

  3. Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture.

    Science.gov (United States)

    Buddingh, Emilie P; Ruslan, S Eriaty N; Reijnders, Christianne M A; Szuhai, Karoly; Kuijjer, Marieke L; Roelofs, Helene; Hogendoorn, Pancras C W; Maarten Egeler, R; Cleton-Jansen, Anne-Marie; Lankester, Arjan C

    2015-01-01

    In vitro expanded mesenchymal stromal cells (MSCs) are increasingly used as experimental cellular therapy. However, there have been concerns regarding the safety of their use, particularly with regard to possible oncogenic transformation. MSCs are the hypothesized precursor cells of high-grade osteosarcoma, a tumor with often complex karyotypes occurring mainly in adolescents and young adults. To determine if MSCs from osteosarcoma patients could be predisposed to malignant transformation we cultured MSCs of nine osteosarcoma patients and five healthy donors for an average of 649 days (range 601-679 days). Also, we compared MSCs derived from osteosarcoma patients at diagnosis and from healthy donors using genome wide gene expression profiling. Upon increasing passage, increasing frequencies of binucleate cells were detected, but no increase in proliferation suggestive of malignant transformation occurred in MSCs from either patients or donors. Hematopoietic cell specific Lyn substrate 1 (HLCS1) was differentially expressed (fold change 0.25, P value 0.0005) between MSCs of osteosarcoma patients (n = 14) and healthy donors (n = 9). This study shows that although HCLS1 expression was downregulated in MSCs of osteosarcoma patients and binucleate cells were present in both patient and donor derived MSCs, there was no evidence of neoplastic changes to occur during long-term culture.

  4. Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples.

    Science.gov (United States)

    Alemany, L; Saunier, M; Tinoco, L; Quirós, B; Alvarado-Cabrero, I; Alejo, M; Joura, E A; Maldonado, P; Klaustermeier, J; Salmerón, J; Bergeron, C; Petry, K U; Guimerà, N; Clavero, O; Murillo, R; Clavel, C; Wain, V; Geraets, D T; Jach, R; Cross, P; Carrilho, C; Molina, C; Shin, H R; Mandys, V; Nowakowski, A M; Vidal, A; Lombardi, L; Kitchener, H; Sica, A R; Magaña-León, C; Pawlita, M; Quint, W; Bravo, I G; Muñoz, N; de Sanjosé, S; Bosch, F X

    2014-11-01

    This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases. HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

    International Nuclear Information System (INIS)

    Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng; Ping, Yu; Liu, Shasha; Shi, Xiaojuan; Li, Lifeng; Wang, Liping; Huang, Lan; Zhang, Bin; Sun, Yan

    2015-01-01

    Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells. - Highlights: • Esophageal cancer sphere-forming cells possess cancer stem cell properties. • Sphere-forming cells enhance TGF-β1 pathway activity. • TGF-β 1 inhibitor suppresses the migration and invasion of sphere-forming cells

  6. No Effect of the Transforming Growth Factor {beta}1 Promoter Polymorphism C-509T on TGFB1 Gene Expression, Protein Secretion, or Cellular Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Reuther, Sebastian; Metzke, Elisabeth [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Bonin, Michael [Department of Medical Genetics, University of Tuebingen (Germany); Petersen, Cordula [Clinic of Radiotherapy and Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Dikomey, Ekkehard, E-mail: dikomey@uke.de [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Raabe, Annette [Laboratory of Radiobiology and Experimental Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany)

    2013-02-01

    Purpose: To study whether the promoter polymorphism (C-509T) affects transforming growth factor {beta}1 gene (TGFB1) expression, protein secretion, and/or cellular radiosensitivity for both human lymphocytes and fibroblasts. Methods and Materials: Experiments were performed with lymphocytes taken either from 124 breast cancer patients or 59 pairs of normal monozygotic twins. We used 15 normal human primary fibroblast strains as controls. The C-509T genotype was determined by polymerase chain reaction-restriction fragment length polymorphism or TaqMan single nucleotide polymorphism (SNP) genotyping assay. The cellular radiosensitivity of lymphocytes was measured by G0/1 assay and that of fibroblasts by colony assay. The amount of extracellular TGFB1 protein was determined by enzyme-linked immunosorbent assay, and TGFB1 expression was assessed via microarray analysis or reverse transcription-polymerase chain reaction. Results: The C-509T genotype was found not to be associated with cellular radiosensitivity, neither for lymphocytes (breast cancer patients, P=.811; healthy donors, P=.181) nor for fibroblasts (P=.589). Both TGFB1 expression and TGFB1 protein secretion showed considerable variation, which, however, did not depend on the C-509T genotype (protein secretion: P=.879; gene expression: lymphocytes, P=.134, fibroblasts, P=.605). There was also no general correlation between TGFB1 expression and cellular radiosensitivity (lymphocytes, P=.632; fibroblasts, P=.573). Conclusion: Our data indicate that any association between the SNP C-509T of TGFB1 and risk of normal tissue toxicity cannot be ascribed to a functional consequence of this SNP, either on the level of gene expression, protein secretion, or cellular radiosensitivity.

  7. Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Ping, Yu; Liu, Shasha [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); School of Life Sciences, Zhengzhou University, Zhengzhou 450000 (China); Shi, Xiaojuan; Li, Lifeng [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Wang, Liping [Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Huang, Lan [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Zhang, Bin [Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, PR China (China); Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Sun, Yan [Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (China); and others

    2015-08-01

    Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells. - Highlights: • Esophageal cancer sphere-forming cells possess cancer stem cell properties. • Sphere-forming cells enhance TGF-β1 pathway activity. • TGF-β 1 inhibitor suppresses the migration and invasion of sphere-forming cells.

  8. Knowledge of nursing students about the care provided to people with neoplastic wounds

    Directory of Open Access Journals (Sweden)

    Roseane Ferreira Gomes

    2017-05-01

    Full Text Available Objective: To investigate the knowledge of nursing students about the care provided to patients with neoplastic wound. Method: This is an exploratory research of a qualitative nature, which was attended by 15 students of the Bachelor's Degree in Nursing from the Center of Education and Health of the Federal University of Campina Grande, campus Cuité - PB, in the period from October to November 2015. For data collection, we used a form for an interview. The data were analyzed through the Technique of Thematic Analysis of Minayo. Results: From the analysis of the empirical material emerged the following thematic categories: Category 1 - Defining neoplastic wounds; Category 2 - Knowledge incipient on ‘neoplastic wounds’ for academic and professional practice; Category 3 - Envisioning the theme "neoplastic wound" in the Academy; Category 4 - Knowledge about methods of evaluation of neoplastic wounds and Category 5 - Knowledge of therapeutic modalities of neoplastic wounds. Conclusions: The academics know the evaluative method of a patient with neoplastic wound as integralizadora unit of care process; recognize palliative care as the best therapeutic modality for these customers, especially when they are in completion and indicate the products contraindicated in the treatment of these lesions; however, do not mention the covers and recommended substances for the control of the signs and symptoms of these injuries. In this context, it is believed that the creation of academic projects of extension, with the aim of creating opportunities for integration between theory and practice, is one of the ways to improve the knowledge.   Keywords: Knowledge; Students of Nursing; Skin Neoplasms.

  9. Epigenetic silencing of miR-218 by the lncRNA CCAT1, acting via BMI1, promotes an altered cell cycle transition in the malignant transformation of HBE cells induced by cigarette smoke extract

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Lu; Xu, Hui; Luo, Fei; Liu, Xinlu; Lu, Xiaolin; Yang, Qianlei; Xue, Junchao; Chen, Chao; Shi, Le; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2016-08-01

    Cigarette smoking is the strongest risk factor for the development of lung cancer, the leading cause of cancer-related deaths. However, the molecular mechanisms leading to lung cancer are largely unknown. A long-noncoding RNA (lncRNA), CCAT1, regarded as cancer-associated, has been investigated extensively. Moreover, the molecular mechanisms of lncRNAs in regulation of microRNAs (miRNAs) induced by cigarette smoke remain unclear. In the present investigation, cigarette smoke extract (CSE) caused an altered cell cycle and increased CCAT1 levels and decreased miR-218 levels in human bronchial epithelial (HBE) cells. Depletion of CCAT1 attenuated the CSE-induced decreases of miR-218 levels, suggesting that miR-218 is negatively regulated by CCAT1 in HBE cells exposed to CSE. The CSE-induced increases of BMI1 levels and blocked by CCAT1 siRNA were attenuated by an miR-218 inhibitor. Moreover, in CSE-transformed HBE cells, the CSE-induced cell cycle changes and elevated neoplastic capacity were reversed by CCAT1 siRNA or BMI1 siRNA. This epigenetic silencing of miR-218 by CCAT1 induces an altered cell cycle transition through BMI1 and provides a new mechanism for CSE-induced lung carcinogenesis. - Highlights: • CSE exposure induces increases of CCAT1 levels and decreases of miR-218 levels. • CCAT1 negatively regulates miR-218 expression. • CCAT1, regulated by miR-218, via BMI1, is involved in the CSE-induced altered cell cycle transition.

  10. Epigenetic silencing of miR-218 by the lncRNA CCAT1, acting via BMI1, promotes an altered cell cycle transition in the malignant transformation of HBE cells induced by cigarette smoke extract

    International Nuclear Information System (INIS)

    Lu, Lu; Xu, Hui; Luo, Fei; Liu, Xinlu; Lu, Xiaolin; Yang, Qianlei; Xue, Junchao; Chen, Chao; Shi, Le; Liu, Qizhan

    2016-01-01

    Cigarette smoking is the strongest risk factor for the development of lung cancer, the leading cause of cancer-related deaths. However, the molecular mechanisms leading to lung cancer are largely unknown. A long-noncoding RNA (lncRNA), CCAT1, regarded as cancer-associated, has been investigated extensively. Moreover, the molecular mechanisms of lncRNAs in regulation of microRNAs (miRNAs) induced by cigarette smoke remain unclear. In the present investigation, cigarette smoke extract (CSE) caused an altered cell cycle and increased CCAT1 levels and decreased miR-218 levels in human bronchial epithelial (HBE) cells. Depletion of CCAT1 attenuated the CSE-induced decreases of miR-218 levels, suggesting that miR-218 is negatively regulated by CCAT1 in HBE cells exposed to CSE. The CSE-induced increases of BMI1 levels and blocked by CCAT1 siRNA were attenuated by an miR-218 inhibitor. Moreover, in CSE-transformed HBE cells, the CSE-induced cell cycle changes and elevated neoplastic capacity were reversed by CCAT1 siRNA or BMI1 siRNA. This epigenetic silencing of miR-218 by CCAT1 induces an altered cell cycle transition through BMI1 and provides a new mechanism for CSE-induced lung carcinogenesis. - Highlights: • CSE exposure induces increases of CCAT1 levels and decreases of miR-218 levels. • CCAT1 negatively regulates miR-218 expression. • CCAT1, regulated by miR-218, via BMI1, is involved in the CSE-induced altered cell cycle transition.

  11. Transformational Leadership, Integrity, and Power

    Science.gov (United States)

    Harrison, Laura M.

    2011-01-01

    Transformational leadership enjoys widespread appeal among student affairs professionals. National Association of Student Personnel Administrators (NASPA) and American College Personnel Association (ACPA) conferences frequently feature speakers who promote transformational leadership's two primary tenets: (1) change is the central purpose of…

  12. How Transformational Learning Promotes Caring, Consultation and Creativity, and Ultimately Contributes to Sustainable Development: Lessons from the Partnership for Education and Research about Responsible Living (PERL) Network

    Science.gov (United States)

    Thoresen, Victoria Wyszynski

    2017-01-01

    Oases of learning which are transformative and lead to significant behavioural change can be found around the globe. Transformational learning has helped learners not only to understand what they have been taught but also to re-conceptualise and re-apply this understanding to their daily lives. Unfortunately, as many global reports indicate,…

  13. DNA measurements on cell nuclei of normal, proliferating and neoplastic thyroid tissues in rats

    International Nuclear Information System (INIS)

    Christov, K.; Thomas, C.; Sandritter, W.

    1975-01-01

    Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. In stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated that most chromosomes were diploid; only a few cells were hyperdiploid. In thyroid adenomas and carcinomas scattering of the diploid region and an increased number of hyperdiploid cells were found. Among the various types of thyroid tumors neither a difference in the number of hyperdiploid cells, nor the typical pattern of the distribution of these cells in a histogram was found. The increased number of hyperdiploid cells in hyperplastic and neoplastic thyroids only suggested an increase in the proportion of cells entering the cell cycle and not an appearance of a neoplastic strain. (author)

  14. Neoplastic lesions of the temporomandibular joint (TMJ): diagnosis, differential diagnosis and intervention

    International Nuclear Information System (INIS)

    Vogl, T.J.; Abolmaali, N.; Schedel, H.; Bergh, B.

    2001-01-01

    Purpose. To evaluate the effectiveness of diagnostic and interventional radiological techniques for neoplastic lesions of the temporomandibular joint (TMJ). Material and methods. Modern diagnosis of the TMJ is based on the clinical use of conventional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI) and interventional techniques like biopsies, vascular occlusion and ablation. Results. Conventional X-ray still forms the basic diagnostic procedure applied in open and closed mouth position. CT improves the diagnostic information and serves as the standard diagnostical instrument for cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue infiltration in multiplanar techniques and high spatial resolution. Interventional vascular and ablative techniques improve the treatment of neoplastic disorders. (orig.) [de

  15. Treatment of non-neoplastic renal hemorrhage with segmental embolization of renal artery

    International Nuclear Information System (INIS)

    Zhu Bing

    2007-01-01

    Objective: To explore the value of segmental embolization of renal artery in dealing with non- neoplastic renal hemorrhage. Methods: Four cases of non-neoplastic hemorrhage, including 2 with bleeding after renal acupuncture biopsy, 2 with bleeding after nephrolithotomy and 1 with congenital renal arteriovenous malformation, were treated with superselective segmental embolization of renal artery. 2 were embolized with coil, 1 with alcohol plus coil and 1 with PVA parcels. Results: Hematuria disappeared in 1-3 days. There was no recurrence in 7-45 months follow up and no complications induced by embolization. Conclusion: It is a safe and reliable therapy to treat non-neoplastic renal hemorrhage with segmental embolization of renal artery. (authors)

  16. DNA measurements on cell nuclei of normal, proliferating and neoplastic thyroid tissues in rats

    Energy Technology Data Exchange (ETDEWEB)

    Christov, K [National Center of Oncology, Academy of Medicine, Sofia-56 (Bulgaria); Thomas, C; Sandritter, W [Freiburg Univ. (F.R. Germany). Pathologisches Inst.

    1975-01-01

    Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. In stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated that most chromosomes were diploid; only a few cells were hyperdiploid. In thyroid adenomas and carcinomas scattering of the diploid region and an increased number of hyperdiploid cells were found. Among the various types of thyroid tumors neither a difference in the number of hyperdiploid cells, nor the typical pattern of the distribution of these cells in a histogram was found. The increased number of hyperdiploid cells in hyperplastic and neoplastic thyroids only suggested an increase in the proportion of cells entering the cell cycle and not an appearance of a neoplastic strain.

  17. Value of the biological data in the sonographic diagnosis of neoplastic biliary obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, F; Fagioli Zucchi, A; Rappuoli, G; Guercia, M; Terrosi Vagnoli, P

    1988-01-01

    The authors' purpose is to demonstrate the possibility of improving US reliability in the diagnosis of neoplastic obstructions of the bile ducts, basing their study on the hematic alkaline phosphates level (AP), wich is an earlier sign of obstruction than bilirubine values. All 368 patients observed had AP levels above the threshold of 270 IU/l. The 34 patients with neoplastic obstruction (including 13 without jaundice) had more than twice the normal level of AP, and presented with at least one dilated bile duct in the biliary tree. Coronal scans of the main bile duct are fundamental in the diagnosis of the level of obstruction. It seems thus possible to affirm that US diagnosis of the biliary obstruction, together with high AP values (more than twice the normal), provides with reliable information as to the neoplastic nature of the biliary obstruction, even if jaundice is not present.

  18. Value of the biological data in the sonographic diagnosis of neoplastic biliary obstruction

    International Nuclear Information System (INIS)

    Ferrari, F.; Fagioli Zucchi, A.; Rappuoli, G.; Guercia, M.; Terrosi Vagnoli, P.

    1988-01-01

    The authors' purpose is to demonstrate the possibility of improving US reliability in the diagnosis of neoplastic obstructions of the bile ducts, basing their study on the hematic alkaline phosphates level (AP), wich is an earlier sign of obstruction than bilirubine values. All 368 patients observed had AP levels above the threshold of 270 IU/l. The 34 patients with neoplastic obstruction (including 13 without jaundice) had more than twice the normal level of AP, and presented with at least one dilated bile duct in the biliary tree. Coronal scans of the main bile duct are fundamental in the diagnosis of the level of obstruction. It seems thus possible to affirm that US diagnosis of the biliary obstruction, together with high AP values (more than twice the normal), provides with reliable information as to the neoplastic nature of the biliary obstruction, even if jaundice is not present

  19. Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

    2016-04-01

    The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

  20. A HISTOPATHOLOGICAL STUDY OF NEOPLASTIC LESIONS OF UTERINE CERVIX OF PERI AND POSTMENOPAUSAL WOMEN

    Directory of Open Access Journals (Sweden)

    Jogesh Kakati

    2017-03-01

    Full Text Available BACKGROUND Neoplastic lesions of uterine cervix is one of the most common malignant neoplasms in women. The tremendous success in giving a confirmed diagnosis of the disease by doing histopathological examination is of prime importance in giving the most appropriate treatment and to understand the prognosis. The aim of the study is to study the incidence and age-wise distribution of the neoplastic lesions of the uterine cervix in peri and postmenopausal women by doing histopathological examination of neoplastic lesions and by doing correlation of clinical findings with histopathological examination. MATERIALS AND METHODS The study included 803 cases of total cervical specimens, out of which 180 cases of neoplastic cervical lesions were found, out of which 150 cases were found in the peri and postmenopausal age groups, i.e. above 40 years of age. The study was done in Gauhati Medical College and Hospital, Guwahati, from the period 1 st June, 2013, to 1 st June, 2014. The specimens that were included in the study were punch biopsies, hysterectomies and polypectomies and cervical specimens were studied by doing histopathological examinations. RESULTS Out of the 150 cases of neoplastic lesions in the peri and postmenopausal women, the most common neoplastic lesion was cervical intraepithelial neoplasia, i.e. CIN (8.3% of the cervix, followed by malignant (5.6% and benign (4.7% lesions of the cervix in this study group of patients. CONCLUSION Histopathological examination of the cervix is an effective method of giving a confirmed diagnosis of all the noncancerous, precancerous and cancerous lesions of uterine cervix, which helps in giving the most appropriate treatment and also helps in understanding the prognosis.

  1. Imaging of limbic para-neoplastic encephalitis; Imagerie de l`encephalite limbique paraneoplastique

    Energy Technology Data Exchange (ETDEWEB)

    Rimmelin, A.; Sellat, F.; Morand, G.; Quoix, E.; Clouet, P.L.; Dietemann, J.L. [Centre Hospitalier Universitaire, 67 - Strasbourg (France)

    1997-09-01

    Para-neoplastic limbic encephalitis is a rare syndrome mostly associated with small cell lung cancer. We present the case of a 69-year-old man with selective amnesia suggesting limbic encephalitis. A neuroendocrine cell lung cancer was found, confirming the diagnostics of para-neoplastic limbic encephalitis. Contrast-enhanced cerebral CT was normal whether magnetic resonance imaging showed signal abnormalities of the medial part of temporal lobes and hippocampal regions. Because neurologic improvement may follow treatment of the primary tumor, early diagnosis is important. (authors). 10 refs.

  2. Atypical focal non-neoplastic brain changes in neurofibromatosis type 1: mass effect and contrast enhancement

    International Nuclear Information System (INIS)

    Raininko, R.; Thelin, L.; Eeg-Olofsson, O.

    2001-01-01

    Abstract Children and young adults with neurofibromatosis type 1 often have small high-signal foci on T2-weighted images of the brain. We describe follow-up of two patients in whom one of the foci had atypical features, commonly regarded as signs of a neoplasm. In the first, one lesion showed temporary contrast enhancement and decreasing mass effect. The second developed an expanding lesion that increased minimally in size over 4.5 year's follow-up. The borderline between neoplastic and non-neoplastic lesions seems to be indistinct. (orig.)

  3. The role of nutritional factors in cellular protection against DNA damage, altered gene expression and malignant transformation

    International Nuclear Information System (INIS)

    Borek, C.

    1986-01-01

    In recent years data from epidemiological studies and laboratory experiments have revealed numerous links between diet and cancer. The complex role of nutritional factors in modifying cancer incidence may be attributed in part to dietary agents acting as potentiators or promoters of cancer, serving as auxilliary agents to other environmental factors; as causes of cancer, or as cancer preventive agents. Studies can be carried on in vitro, in cell culture systems, where malignant transformation serves as an end point. These systems afford the opportunity to study the direct effect of nutrition in oncogenesis and the role of dietary factors in modulating the frequency and course of neoplastic development in its various stages. 20 refs., 1 fig., 3 tabs

  4. [HMGA proteins and their genes as a potential neoplastic biomarkers].

    Science.gov (United States)

    Balcerczak, Ewa; Balcerczak, Mariusz; Mirowski, Marek

    2005-01-01

    HMGA proteins and their genes are described in this article. HMGA proteins reveal ability to bind DNA in AT-rich regions, which are characteristic for gene promoter sequences. This interaction lead to gene silencing or their overexpression. In normal tissue HMGA proteins level is low or even undetectable. During embriogenesis their level is increasing. High HMGA proteins level is characteristic for tumor phenotype of spontaneous and experimental malignant neoplasms. High HMGA proteins expression correlate with bad prognostic factors and with metastases formation. HMGA genes expression can be used as a marker of tumor progression. Present studies connected with tumor gene therapy based on HMGA proteins sythesis inhibition by the use of viral vectors containing gene encoding these proteins in antisence orientation, as well as a new potential anticancer drugs acting as crosslinkers between DNA and HMGA proteins suggest their usefulness as a targets in cancer therapy.

  5. Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

    DEFF Research Database (Denmark)

    Münstermann, U; Fritz, G; Seitz, G

    1990-01-01

    Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

  6. Arising podosomal structures are associated with neoplastic cell morphological phenotype induced by the microenvironment

    Czech Academy of Sciences Publication Activity Database

    Veselý, Pavel; Blase, C.; Matoušková, Eva; Bereiter-Hahn, J.

    2006-01-01

    Roč. 26, - (2006), s. 967-972 ISSN 0250-7005 R&D Projects: GA MZd(CZ) NR8145 Institutional research plan: CEZ:AV0Z50520514 Keywords : podosomes * neoplastic cell morphotype * phenotypic plasticity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.479, year: 2006

  7. Superficial inflammatory and primary neoplastic lymphadenopathy: diagnostic accuracy of power-doppler sonography

    International Nuclear Information System (INIS)

    Magarelli, N.; Guglielmi, G.; Savastano, M.; Toro, V.; Sborgia, M.; Fioritoni, G.; Mattei, P.A.; Steinbach, L.; Bonomo, L.

    2004-01-01

    Objective: To evaluate the sensitivity, specificity and diagnostic accuracy of a cut-off of the resistive index of 0.5 for the differentiation between inflammatory and neoplastic primary lymphadenopathies. Subjects and methods: We measured the resistive index of superficial enlarged lymph nodes in a total of 50 patients (29 males and 21 females; age range 12-72 years, mean age 41.6 year) using an ATL 5000 HDI. A resistive index greater than or equal to 0.5 indicated an inflammatory lymph node and a resistive index <0.5 was consistent with neoplastic primary lymphadenopathies. The gold standard was either surgical biopsy or lymph-node reduction seen with ultrasound examination after antibiotic therapy. Results: The sensitivity of the resistive index for distinguishing inflammatory from neoplastic lymphadenopathy was 84.6%, the specificity 100% and the diagnostic accuracy 95.7% (P<0.001, statistically significant). Conclusion: The results of this study indicate that power-Doppler using a resistive index cut-off of 0.5 was a valid technique for distinguising between inflammatory and primary neoplastic lymph nodes in patients with superficial lymphadenopathies

  8. How transformational learning promotes caring, consultation and creativity, and ultimately contributes to sustainable development: Lessons from the Partnership for Education and Research about Responsible Living (PERL) network

    Science.gov (United States)

    Thoresen, Victoria Wyszynski

    2017-12-01

    Oases of learning which are transformative and lead to significant behavioural change can be found around the globe. Transformational learning has helped learners not only to understand what they have been taught but also to re-conceptualise and re-apply this understanding to their daily lives. Unfortunately, as many global reports indicate, inspirational transformational learning approaches for sustainable development are rare and have yet to become the norm - despite calls for such approaches by several outstanding educators and organisations. This article examines three learning approaches developed by the network of the Partnership for Education and Research about Responsible Living (PERL). These approaches are structured around core elements of transformative learning for sustainable development, yet focus particularly on the ability to care, consult with others and be creative. They seem to depend on the learners' ability to articulate their perceptions of sustainable development in relation to their own values and to identify how these are actualised in their daily life. Together with other core elements of transformative learning, an almost magical (not precisely measurable) synergy then emerges. The intensity of this synergy appears to be directly related to the individual learner's understanding of the contradictions, interlinkages and interdependencies of modern society. The impact of this synergy seems to be concurrent with the extent to which the learner engages in a continual learning process with those with whom he/she has contact. The findings of this study suggest that mainstreaming transformational learning for sustainable development in ways that release the "magic synergy of creative caring" can result in the emergence of individuals who are willing and able to move from "business as usual" towards more socially just, economically equitable, and environmentally sensitive behaviour.

  9. KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406).

    Science.gov (United States)

    Peter, Barbara; Hadzijusufovic, Emir; Blatt, Katharina; Gleixner, Karoline V; Pickl, Winfried F; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Willmann, Michael; Valent, Peter

    2010-09-01

    Advanced systemic mastocytosis (SM) is characterized by uncontrolled growth of neoplastic mast cells (MC) and drug resistance. The tyrosine kinase receptor KIT is often mutated and activated and thus contributes to malignant growth of MC. Therefore, KIT-targeting drugs are currently tested for their ability to block growth of malignant MC. We determined the effects of the multikinase inhibitor INNO-406 (bafetinib) on primary neoplastic MC, the canine mastocytoma cell line C2, the human MC leukemia cell line HMC-1.1 bearing the KIT mutant V560G, and HMC-1.2 cells harboring KIT V560G and KIT D816V. INNO-406 was found to inhibit proliferation in HMC-1.1 cells (IC(50): 30-40 nM), but not in HMC-1.2 cells or primary neoplastic cells in patients with KIT D816V-positive SM. In canines, growth-inhibitory effects of INNO-406 were seen in C2 cells (IC(50): 50-100 nM) exhibiting a KIT exon 11 internal tandem-duplication and in primary neoplastic MC harboring wild-type exon 11, whereas no effects were seen in MC exhibiting a polymorphism at amino acid 581 in exon 11. INNO-406 was found to block KIT phosphorylation and expression in HMC-1.1 cells and C2 cells, but not in HMC-1.2 cells, whereas Lyn-phosphorylation was blocked by INNO-406 in all types of MC. In neoplastic MC, the major target of INNO-406 appears to be KIT. Drug responses may depend on the presence and type of KIT mutation. In human MC, the KIT D816V mutant introduces resistance, and in canine mastocytomas, an exon 11 polymorphism may be indicative of resistance against INNO-406.

  10. DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

    Science.gov (United States)

    Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

    2018-06-08

    Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

  11. The Mediating Role of Principals' Transformational Leadership Behaviors in Promoting Teachers' Emotional Wellness at Work: A Study in Israeli Primary Schools

    Science.gov (United States)

    Berkovich, Izhak; Eyal, Ori

    2017-01-01

    The present study aims to examine whether principals' emotional intelligence (specifically, their ability to recognize emotions in others) makes them more effective transformational leaders, measured by the reframing of teachers' emotions. The study uses multisource data from principals and their teachers in 69 randomly sampled primary schools.…

  12. How Does Transformational Leadership Promote Innovation in Construction? The Mediating Role of Innovation Climate and the Multilevel Moderation Role of Project Requirements

    Directory of Open Access Journals (Sweden)

    Yanchun Zhang

    2018-05-01

    Full Text Available Innovation plays a critical role in the sustainable development of the construction industry. This research aims at examining transformational leadership’s role in shaping employees’ innovative behavior by analyzing the mediating effect of innovation climate and the cross-level moderating effect of innovativeness as a project requirement. To achieve this aim, a questionnaire survey was conducted with 300 construction industry professionals in China and 251 valid replies were received. Data collected by the questionnaire were analyzed using the method of hierarchical linear modeling (HLM. The results showed that transformational leaders could nurture a mutual climate for innovation to motivate employees’ innovative behaviors. In addition, innovativeness as a project requirement at the project level strengthens the indirect link amongst transformational leadership and innovative behavior via the innovation climate. Therefore, in the presence of higher innovativeness as a project requirement, transformational leadership is more prone to exert a positive influence upon an individual’s innovative behavior via the perceived innovation climate. The research findings improve understanding of the roles of leadership and innovation climate in affecting individual behavioral outcomes, and could help project managers and leaders encourage innovative ideas within project organizations.

  13. Quantification of transforming growth factor-beta in biological material using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct

    NARCIS (Netherlands)

    VanWaarde, MAWH; VanAssen, AJ; Kampinga, HH; Konings, AWT; Vujaskovic, Z

    1997-01-01

    Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, can be quantified by a variety of bioassays or immunoassays. One of the disadvantages of these techniques is that they require sample purification to remove components that interfere with the TGF-beta signal. In the current

  14. Transforming growth factor (type beta) promotes the addition of chondroitin sulfate chains to the cell surface proteoglycan (syndecan) of mouse mammary epithelia

    OpenAIRE

    1989-01-01

    Cultured monolayers of NMuMG mouse mammary epithelial cells have augmented amounts of cell surface chondroitin sulfate glycosaminoglycan (GAG) when cultured in transforming growth factor-beta (TGF-beta), presumably because of increased synthesis on their cell surface proteoglycan (named syndecan), previously shown to contain chondroitin sulfate and heparan sulfate GAG. This increase occurs throughout the monolayer as shown using soluble thrombospondin as a binding probe. However, comparison o...

  15. Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

    Directory of Open Access Journals (Sweden)

    Geni NL Camara

    2003-10-01

    Full Text Available As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061 were less frequent (= or < 2.5% each. The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

  16. Some growth factors in neoplastic tissues of brain tumors of different histological structure

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

  17. Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

    Directory of Open Access Journals (Sweden)

    Patrícia F. Castro

    2016-01-01

    Full Text Available Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates.

  18. Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

    Science.gov (United States)

    Castro, Patrícia F.; Fantoni, Denise T.; Miranda, Bruna C.; Matera, Julia M.

    2016-01-01

    Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates. PMID:26981315

  19. Early neuroimaging findings of glioblastoma mimicking non-neoplastic cerebral lesion.

    Science.gov (United States)

    Jung, Tae-Young; Jung, Shin

    2007-09-01

    A 54-year-old man and a 63-year-old woman presented with glioblastoma manifesting as seizure and headache, respectively. Magnetic resonance imaging of the two patients revealed hypointense area on T(1)-weighted imaging, and hyperintense area on T(2)-weighted and diffusion-weighted imaging, with no enhancement after gadolinium administration. Both patients underwent conservative therapy under diagnoses of non-neoplastic cerebral lesion. Six months later, they suffered aggravated symptoms and new neurological deficits. Follow-up magnetic resonance imaging revealed hypointense area on diffusion-weighted imaging and ring enhancement on T(1)-weighted imaging with gadolinium at the site of the previously detected lesions. The tumors showed growth pattern of superficial origin. The large enhanced masses were totally removed through craniotomy under neuronavigator guidance. The histological diagnoses were glioblastoma. Glioblastoma may mimic non-neoplastic conditions on neuroimaging in the early stages. Close follow up of such patients is essential.

  20. A Study of the Pathomorphology of Non-Neoplastic Changes in Canine Mammary Glands

    OpenAIRE

    Knauer, Steffen

    2010-01-01

    Whilst neoplasia in canine mammae has been the subject of a considerable number of studies, little is known about non-neoplastic changes of the mammae. The aim of the present study was therefore to conduct pathological anatomical and histopathological examinations of mammary glands in order to draw up a survey of the type and frequency of non-tumorous changes in the lactiferous tissues. The material under examination consis...

  1. Gallium SPECT detection of neoplastic intravascular obstruction of the superior vena cava

    International Nuclear Information System (INIS)

    Swayne, L.C.; Kaplan, I.L.

    1989-01-01

    A rare case of an intravascular neoplastic obstruction of the superior vena cava is discussed. The lesion was detected with gallium single photon emission computed tomography (SPECT) despite a normal appearance on a concurrent radiographic CT study. A computer-generated composite SPECT-CT image confirmed the intravascular localization of the radioisotope, and a subsequent CT-guided transthoracic needle biopsy revealed a poorly differentiated adenocarcinoma

  2. Temperature dependence of 1H NMR relaxation time, T2, for intact and neoplastic plant tissues

    Science.gov (United States)

    Lewa, Czesław J.; Lewa, Maria

    Temperature dependences of the spin-spin proton relaxation time, T2, have been shown for normal and tumorous tissues collected from kalus culture Nicotiana tabacum and from the plant Kalanchoe daigremontiana. For neoplastic plant tissues, time T2 was increased compared to that for intact plants, a finding similar to that for animal and human tissues. The temperature dependences obtained were compared to analogous relations observed with animal tissues.

  3. Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

    International Nuclear Information System (INIS)

    Boll, Daniel T.; Lewin, Jonathan S.; Young, Philip; Gilkeson, Robert C.; Siwik, Ernest S.

    2005-01-01

    The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, nonembolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel centerlines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries. (orig.)

  4. pH regulation of recombinant glucoamylase production in Fusarium venenatum JeRS 325, a transformant with a Fusarium oxysporum alkaline (trypsin-like) protease promoter.

    Science.gov (United States)

    Wiebe, M G; Robson, G D; Shuster, J R; Trinci, A P

    1999-08-05

    Fusarium venenatum (formerly Fusarium graminearum) JeRS 325 produces heterologous glucoamylase (GAM) under the regulation of a Fusarium oxysporum alkaline (trypsin-like) protease promoter. The glucoamylase gene was used as a reporter gene to study the effects of ammonium and pH on GAM production under the control of the alkaline protease promoter. Between pH 4.0 and 5.8, GAM production in glucose-limited chemostat cultures of JeRS 325 grown at a dilution rate of 0.10 h-1 (doubling time, 6.9 h) on (NH4)2SO4 medium increased in a linear manner with increase in pH. However, at pH 4.0 and below GAM production was almost completely repressed in glucose-limited chemostat cultures grown on (NH4)2SO4 or NaNO3 medium. Thus GAM production in JeRS 325 is regulated by culture pH, not by the nature of the nitrogen source in the medium. The difficulty of using unbuffered medium when investigating putative ammonium repression is also shown. The study demonstrates the potential for use of the alkaline protease promoter in F. graminearum for the production of recombinant proteins in a pH dependent man ner. Copyright 1999 John Wiley & Sons, Inc.

  5. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Marolla, Ana Paula Cleto [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Waisberg, Jaques [Hospital do Servidor Público Estadual, São Paulo, SP (Brazil); Faculdade de Medicina do ABC, Santo André, SP (Brazil); Saba, Gabriela Tognini [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Waisberg, Daniel Reis [Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva [Faculdade de Medicina do ABC, Santo André, SP (Brazil)

    2015-07-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

  6. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

    Science.gov (United States)

    Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

    2015-01-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

  7. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

    International Nuclear Information System (INIS)

    Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

    2015-01-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues

  8. Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Kanematsu, M. E-mail: masa-gif@umin.ac.jp; Kondo, H.; Semelka, R.C.; Matsuo, M.; Goshima, S.; Hoshi, H.; Moriyama, N.; Itai, Y

    2003-10-01

    AIM: To assess the frequency, cause, and significance of early-enhancing, non-neoplastic (EN) lesions on gadolinium-enhanced magnetic resonance imaging (MRI) of the liver performed for the detection of malignant hepatic tumours. MATERIALS AND METHODS: From September 1997 to September 2000, we reviewed the images of 125 patients, suspected of having hepatic tumours, in whom (1) gadolinium-enhanced triphasic dynamic gradient-recalled-echo (GRE) imaging in addition to unenhanced T1- and T2-weighted MRI was performed, (2) conventional angiography and combination computed tomography (CT) hepatic arteriography and CT during arterial portography were performed within 2 weeks of the MRI, and (3) definitive surgery within 2 weeks of the MRI or follow-up study by means of intravenously contrast-enhanced CT or MRI in 10 months or more was performed. Angiographic studies were correlated to determine the underlying causes of the EN lesions. RESULTS: We found 78 EN lesions in 36 patients (29%), ranging in size from 4 and 50 mm (mean, 12.2 mm). From the MR reports, our radiologists had prospectively diagnosed EN lesions as probable malignant tumours in eight (10%), possible malignant tumours in 36 (46%), and probable non-neoplastic lesion in 34 (44%). EN lesions were found in 27 of 81 (33%) cirrhotic patients and in nine of 44 (20%) non-cirrhotic patients. Fifty-one EN lesions (65%) were located along the liver edge. The shape was circular in 42 (54%), oval in 14 (18%), irregular in 12 (15%), wedge-shaped in seven (9%), and fan-shaped in three (4%). Twenty EN lesions (26%) appeared slightly hyperintense on T2-weighted images. The causes were non-neoplastic arterio-portal shunting in 48 (62%), cystic venous drainage in four (5%), rib compression in four (5%), aberrant right gastric venous drainage in two (3%), and unknown in 20 (26%). CONCLUSION: Over half the number of EN lesions were caused by non-neoplastic arterio-portal shunting, occasionally showing slight hyperintensity on

  9. Pitfalls of improperly procured adjacent non-neoplastic tissue for somatic mutation analysis using next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Lei Wei

    2016-10-01

    Full Text Available Abstract Background The rapid adoption of next-generation sequencing provides an efficient system for detecting somatic alterations in neoplasms. The detection of such alterations requires a matched non-neoplastic sample for adequate filtering of non-somatic events such as germline polymorphisms. Non-neoplastic tissue adjacent to the excised neoplasm is often used for this purpose as it is simultaneously collected and generally contains the same tissue type as the neoplasm. Following NGS analysis, we and others have frequently observed low-level somatic mutations in these non-neoplastic tissues, which may impose additional challenges to somatic mutation detection as it complicates germline variant filtering. Methods We hypothesized that the low-level somatic mutation observed in non-neoplastic tissues may be entirely or partially caused by inadvertent contamination by neoplastic cells during the surgical pathology gross assessment or tissue procurement process. To test this hypothesis, we applied a systematic protocol designed to collect multiple grossly non-neoplastic tissues using different methods surrounding each single neoplasm. The procedure was applied in two breast cancer lumpectomy specimens. In each case, all samples were first sequenced by whole-exome sequencing to identify somatic mutations in the neoplasm and determine their presence in the adjacent non-neoplastic tissues. We then generated ultra-deep coverage using targeted sequencing to assess the levels of contamination in non-neoplastic tissue samples collected under different conditions. Results Contamination levels in non-neoplastic tissues ranged up to 3.5 and 20.9 % respectively in the two cases tested, with consistent pattern correlated with the manner of grossing and procurement. By carefully controlling the conditions of various steps during this process, we were able to eliminate any detectable contamination in both patients. Conclusion The results demonstrated that the

  10. IDH1R132H Promotes Malignant Transformation of Benign Prostatic Epithelium by Dysregulating MicroRNAs: Involvement of IGF1R-AKT/STAT3 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Lili Zhang

    2018-02-01

    Full Text Available Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa. Mutations in isocitrate dehydrogenase (IDH acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa. However, the function of IDH1R132H in PCa development and progression is largely unknown. In this study, we showed that the prevalence of IDH1R132H in Chinese PCa patients is 0.6% (2/336. Of note, IDH1R132H-mutant PCa patients lacked other canonical genomic lesions (e.g., ERG rearrangement, PTEN deletion that are common in most other PCa patients. The in vitro experiment suggested that IDH1R132H can promote proliferation of benign prostate epithelial cell RWPE-1 when under the situation of low cytokine. It could also promote migration capacity of RWPE-1 cells. Mechanistically, IDH1R132H was an important regulator of insulin-like growth factor 1receptor (IGF1R by downregulating a set of microRNAs (miR-141-3p, miR-7-5p, miR-223-3p. These microRNAs were repressed by the alteration of epigenetic modification to decrease the enrichment of active marker H3K4me3 or to increase repressive marker H3K27me3 at their promoters. Collectively, we proposed a novel model for an IDH1R132H-microRNAs-IGF1R regulatory axis, which might provide insight into the function of IDH1R132H in PCa development.

  11. Mammalian cell transformation: Mechanisms of carcinogenesis and assays for carcinogens

    International Nuclear Information System (INIS)

    Barrett, J.C.; Tennant, R.W.

    1985-01-01

    This book contains nine sections, each consisting of several papers. The section titles are: Molecular Changes in Cell Transformation; Differentiation, Growth Control, and Cell Transformation; Mutagenesis and Cell Transformation; Tumor Promotion and Cell Transformation; Mechanisms of Transformation of Human Fibroblasts; Mechanisms of Transformation of Epithelial Cells; Mechanisms of C 3 H 10T12 Cell Transformation; Mechanisms of Radiation-Induced Cell Transformation; and Use of Cell Transformation Assays for Carcinogen Testing

  12. Radiogenic cell transformation and carcinogenesis

    Science.gov (United States)

    Yang, T. C.; Georgy, K. A.; Mei, M.; Durante, M.; Craise, L. M.

    1995-01-01

    Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic

  13. Increased radiation-induced transformation in C3H/10T1/2 cells after transfer of an exogenous c-myc gene

    International Nuclear Information System (INIS)

    Sorrentino, V.; Drozdoff, V.; Zeitz, L.; Fleissner, E.

    1987-01-01

    C3H/10T 1/2 cells were infected with a retroviral vector expressing a mouse c-myc oncogene and a drug-selection marker. The resulting cells, morphologically indistinguishable from C3H/10T l/1, displayed a greatly enhanced sensitivity to neoplastic transformation by ionizing radiation or by a chemical carcinogen. Constitutive expression of myc therefore appears to synergize with an initial carcinogenic event, providing a function analogous to a subsequent event that apparently is required for the neoplastic transformation of these cells. This cell system should prove useful in exploring early stages in radiation-induced transformation

  14. Arsenic-Redox Transformation and Plant Growth Promotion by Purple Nonsulfur Bacteria Rhodopseudomonas palustris CS2 and Rhodopseudomonas faecalis SS5.

    Science.gov (United States)

    Batool, Kanza; Tuz Zahra, Fatima; Rehman, Yasir

    2017-01-01

    Arsenic (As) is a well-known toxic metalloid found naturally and released by different industries, especially in developing countries. Purple nonsulfur bacteria (PNSB) are known for wastewater treatment and plant growth promoting abilities. As-resistant PNSB were isolated from a fish pond. Based on As-resistance and plant growth promoting attributes, 2 isolates CS2 and SS5 were selected and identified as Rhodopseudomonas palustris and Rhodopseudomonas faecalis , respectively, through 16S rRNA gene sequencing. Maximum As(V) resistance shown by R. faecalis SS5 and R. palustris CS2 was up to 150 and 100 mM, respectively. R . palustris CS2 showed highest As(V) reduction up to 62.9% (6.29 ± 0.24 mM), while R. faecalis SS5 showed maximum As(III) oxidation up to 96% (4.8 ± 0.32 mM), respectively. Highest auxin production was observed by R. palustris CS2 and R. faecalis SS, up to 77.18 ± 3.7 and 76.67 ± 2.8  μ g mL -1 , respectively. Effects of these PNSB were tested on the growth of Vigna mungo plants. A statistically significant increase in growth was observed in plants inoculated with isolates compared to uninoculated plants, both in presence and in absence of As. R. palustris CS2 treated plants showed 17% (28.1 ± 0.87 cm) increase in shoot length and 21.7% (7.07 ± 0.42 cm) increase in root length, whereas R. faecalis SS5 treated plants showed 12.8% (27.09 ± 0.81 cm) increase in shoot length and 18.8% (6.9 ± 0.34 cm) increase in root length as compared to the control plants. In presence of As, R. palustris CS2 increased shoot length up to 26.3% (21.0 ± 1.1 cm), while root length increased up to 31.3% (5.3 ± 0.4 cm), whereas R. faecalis SS5 inoculated plants showed 25% (20.7 ± 1.4 cm) increase in shoot length and 33.3% (5.4 ± 0.65 cm) increase in root length as compared to the control plants. Bacteria with such diverse abilities could be ideal for plant growth promotion in As-contaminated sites.

  15. Gender-transformative Bandebereho couples' intervention to promote male engagement in reproductive and maternal health and violence prevention in Rwanda: Findings from a randomized controlled trial.

    Science.gov (United States)

    Doyle, Kate; Levtov, Ruti G; Barker, Gary; Bastian, Gautam G; Bingenheimer, Jeffrey B; Kazimbaya, Shamsi; Nzabonimpa, Anicet; Pulerwitz, Julie; Sayinzoga, Felix; Sharma, Vandana; Shattuck, Dominick

    2018-01-01

    Rigorous evidence of the effectiveness of male engagement interventions, particularly on how these interventions impact relationship power dynamics and women's decision-making, remains limited. This study assessed the impact of the Bandebereho gender-transformative couples' intervention on impact on multiple behavioral and health-related outcomes influenced by gender norms and power relations. We conducted a multi-site randomised controlled trial in four Rwandan districts with expectant/current fathers and their partners, who were randomised to the intervention (n = 575 couples) or control group (n = 624 couples). Primary outcomes include women's experience of physical and sexual IPV, women's attendance and men's accompaniment at ANC, modern contraceptive use, and partner support during pregnancy. At 21-months post-baseline, 1123 men and 1162 partners were included in intention to treat analysis. Generalized estimating equations with robust standard errors were used to fit the models. The Bandebereho intervention led to substantial improvements in multiple reported outcomes. Compared to the control group, women in the intervention group reported: less past-year physical (OR 0.37, p<0.001) and sexual IPV (OR 0.34, p<0.001); and greater attendance (IRR 1.09, p<0.001) and male accompaniment at antenatal care (IRR 1.50, p<0.001); and women and men in the intervention group reported: less child physical punishment (women: OR 0.56, p = 0.001; men: OR 0.66, p = 0.005); greater modern contraceptive use (women: OR 1.53, p = 0.004; men: OR 1.65, p = 0.001); higher levels of men's participation in childcare and household tasks (women: beta 0.39, p<0.001; men: beta 0.33, p<0.001); and less dominance of men in decision-making. Our study strengthens the existing evidence on male engagement approaches; together with earlier studies our findings suggest that culturally adapted gender-transformative interventions with men and couples can be effective at changing deeply entrenched

  16. Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars.

    Science.gov (United States)

    Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

    2016-01-01

    Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape ( Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L -tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N -acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N -acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N -acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro . Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant-rhizobacterium interactions that affect

  17. Teriflunomide (Leflunomide Promotes Cytostatic, Antioxidant, and Apoptotic Effects in Transformed Prostate Epithelial Cells: Evidence Supporting a Role for Teriflunomide in Prostate Cancer Chemoprevention

    Directory of Open Access Journals (Sweden)

    Numsen Hail, Jr

    2010-06-01

    Full Text Available Teriflunomide (TFN is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN's apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention.

  18. Transforming growth factor β-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium.

    Science.gov (United States)

    Wang, Jun; Wang, Youliang; Wang, Yu; Ma, Ying; Lan, Yu; Yang, Xiao

    2013-04-12

    The TGF-β pathway plays an important role in physiological and pathological angiogenesis. MicroRNAs (miRNAs) are a class of 18- to 25-nucleotide, small, noncoding RNAs that function by regulating gene expression. A number of miRNAs have been found to be regulated by the TGF-β pathway. However, the role of endothelial miRNAs in the TGF-β-mediated control of angiogenesis is still largely unknown. Here we investigated the regulation of endothelial microRNA-29a (miR-29a) by TGF-β signaling and the potential role of miR-29a in angiogenesis. MiR-29a was directly up-regulated by TGF-β/Smad4 signaling in human and mice endothelial cells. In a chick chorioallantoic membrane assay, miR-29a overexpression promoted the formation of new blood vessels, and miR-29a suppression completely blocked TGF-β1-stimulated angiogenesis. Consistently, miR-29a overexpression increased tube formation and migration in endothelial cultures. Mechanistically, miR-29a directly targeted the phosphatase and tensin homolog (PTEN) in endothelial cells, leading to activation of the AKT pathway. PTEN knockdown recapitulated the role of miR-29a in endothelial migration, whereas AKT inhibition completely attenuated the stimulating role of miR-29a in angiogenesis. Taken together, these results reveal a crucial role of a TGF-β-regulated miRNA in promoting angiogenesis by targeting PTEN to stimulate AKT activity.

  19. BRIDGING THE COMPETING VIEWS OF EUROPEAN CULTURAL INTEGRATION: THE TRANSFORMATIVE VIEW OF CULTURE AS A MEANS TO PROMOTE GROWTH, EMPLOYMENT AND SOCIAL COHESION

    Directory of Open Access Journals (Sweden)

    María Luz SUÁREZ CASTIÑEIRA

    2018-05-01

    Full Text Available The concept of a European culture became very complex with the enlargement of 2004 towards the East, when the EU, as Delanty pointed out, moved “beyond postnationality to an encounter with multiple civilizational forms,” multiple histories and competing visions of European integration. The “unity-in-diversity” paradigm turned into a huge challenge for the European institutions. On the one hand, achieving a European image of cultural unity without excluding all the local, regional and national cultures is a very complex, if not impossible, task. On the othe hand, culture remains an ambiguous term in European institutions due to the lack of a full-fledged European cultural policy. This paper focuses first on how in the early 1970s the EC/EU started to be concerned with defining the role of culture, and second on how since the year 2000 culture has progressively acquired a new status with potentially transformative powers to bridge the competing views of cultural integration. Programmes, such as the “2014-2020 Creative Europe” programme, focus on culture as a creative accelerator and promotor of different forms of cultural participation and production. Culture generates “smart, sustainable and inclusive growth”, and contributes to “high employment, high productivity, and high social cohesion.”

  20. Achieving the sustainable development goals: transforming public ...

    African Journals Online (AJOL)

    Achieving the sustainable development goals: transforming public health ... PROMOTING ACCESS TO AFRICAN RESEARCH ... The conference focused on transforming public health education and practice in the context of South Africa.

  1. Dasatinib inhibits the growth and survival of neoplastic human eosinophils (EOL-1) through targeting of FIP1L1-PDGFRalpha.

    Science.gov (United States)

    Baumgartner, Christian; Gleixner, Karoline V; Peter, Barbara; Ferenc, Veronika; Gruze, Alexander; Remsing Rix, Lily L; Bennett, Keiryn L; Samorapoompichit, Puchit; Lee, Francis Y; Pickl, Winfried F; Esterbauer, Harald; Sillaber, Christian; Superti-Furga, Giulio; Valent, Peter

    2008-10-01

    Chronic eosinophilic leukemia (CEL) is a myeloproliferative disorder characterized by molecular and/or cytogenetic evidence of clonality of eosinophils, marked eosinophilia, and organ damage. In many patients, the transforming mutation FIP1L1-PDGFRalpha and the related CHIC2 deletion are found. The respective oncoprotein, FIP1L1-PDGFRalpha, is considered to play a major role in malignant cell growth in CEL. The tyrosine kinase (TK) inhibitor imatinib (STI571) has been described to counteract the TK activity of FIP1L1-PDGFRalpha in most patients. However, not all patients with CEL show a response to imatinib. Therefore, several attempts have been made to identify other TK inhibitors that counteract growth of neoplastic eosinophils. We provide evidence that dasatinib, a multi-targeted kinase inhibitor, blocks the growth and survival of EOL-1, an eosinophil leukemia cell line carrying FIP1L1-PDGFRalpha. The effects of dasatinib on proliferation of EOL-1 cells were dose-dependent, with an IC50 of 0.5 to 1 nM, which was found to be in the same range when compared to IC50 values produced with imatinib. Dasatinib was also found to induce apoptosis in EOL-1 cells in a dose-dependent manner (IC50: 1-10 nM). The apoptosis-inducing effects of dasatinib on EOL-1 cells were demonstrable by light microscopy, flow cytometry, and in a TUNEL assay. In Western blot experiments, dasatinib completely blocked the phosphorylation of FIP1L1-PDGFRalpha in EOL-1 cells. Dasatinib inhibits the growth of leukemic eosinophils through targeting of the disease-related oncoprotein FIP1L1-PDGFRalpha. Based on this observation, dasatinib may be considered as a new interesting treatment option for patients with CEL.

  2. CDNA Microarray Based Comparative Gene Expression Analysis of Primary Breast Tumors Versus In Vitro Transformed Neoplastic Breast Epithelium

    National Research Council Canada - National Science Library

    Szallasi, Zoltan

    2001-01-01

    .... The first group of clones is being sorted by their ability to form tumors. We are currently performing cDNA microarray analysis quantifying the expression level of about 15,000 genes in these cell lines...

  3. Inhibiting glycogen synthase kinase-3 and transforming growth factor-β signaling to promote epithelial transition of human adipose mesenchymal stem cells.

    Science.gov (United States)

    Setiawan, Melina; Tan, Xiao-Wei; Goh, Tze-Wei; Hin-Fai Yam, Gary; Mehta, Jodhbir S

    2017-09-02

    This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h. The mesenchymal-epithelial transition was shown by down-regulation of mesenchymal genes (Slug, Zinc Finger E-box Binding Homeobox 1 ZEB1, integrin α5 ITGA5 and vimentin VIM) and up-regulation of epithelial genes (E-cadherin, Epithelial Cell Adhesion Molecule EpCAM, Zonula Occludens-1 ZO-1, occludin, deltaN p63 δNp63, Transcription Factor 4 TCF4 and Twist Family bHLH Transcription Factor TWIST), compared to untreated ADSCs. Cell morphology and stress fiber pattern were examined and the treated cells became less migratory in scratch wound closure assay. The formation of cell junction complexes was observed under transmission electron microscopy. Global gene expression using GeneChip ® Human Genome U133 Array (Affymetrix) showed that the treatment up-regulated 540 genes (containing genes for cell cycle, cytoskeleton reorganization, chemotaxis, epithelium development and regulation of cell migration) and down-regulated 483 genes. Human ADSCs were transited to epithelial lineage by inhibiting GSK3 and TGFβ signaling. It can be an adult stem cell source for epithelial cell-based therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Neoplastic meningitis: a retrospective review of clinical presentations, radiological and cerebrospinal fluid findings.

    Science.gov (United States)

    Jearanaisilp, Sorrawit; Sangruji, Tumthip; Danchaivijitr, Chotipat; Danchaivijitr, Nasuda

    2014-08-01

    To review the clinical, radiological, and laboratory presentations of patients with neoplastic meningitis. Patients with neoplastic meningitis were recruited by a retrospective search of cerebrospinal fluid (CSF) cytopathological report database of Siriraj Hospital between 1997 and 2006. Clinical information and CSF result of these patients were extracted from their medical records. Neuroimagings were reviewed by a neuroradiologist. The present study revealed 40 cases of neoplastic meningitis, which comprised of 17 cases with carcinomatous meningitis (CM) and 23 lymphoma/leukemia meningitis (LM) cases. In patients with CM, the majority (70%) had adenocarcinoma of lung or breast. Three of 17 cases with unknown primary tumor had carcinomatous meningitis as an initial presentation. In LM most of the cases (70%) were diagnosed with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The most common symptom among patients with CM and LM was headache follow by cranial nerve palsy. In CM cases, CSF cytology was positive in the first specimen in 15 cases (82.35%) and in 22 from 23 cases (95.7%) in LM cases. Overall CSF showed pleocytosis in 36 cases (90%), most of which were lymphocyte predominant. The most common findings from brain imagings were leptomeningeal enhancement and hydrocephalus. The common primary sites were lung and breast cancer in the CM group and ALL and NHL in the LM group. The common symptoms were headache and cranial nerve palsy. Routine CSF examination was abnormal in virtually all cases. Positive CSF cytology was a gold standard for a diagnosis of leptomeningeal metastasis. High index of suspicious and awareness were required to avoid miss diagnosis.

  5. Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

    Science.gov (United States)

    Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

    1982-01-01

    Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

  6. Comparison of the circadian variation in cell proliferation in normal and neoplastic colonic epithelial cells.

    Science.gov (United States)

    Kennedy, M F; Tutton, P J; Barkla, D H

    1985-09-15

    Circadian variations in cell proliferation in normal tissues have been recognised for many years but comparable phenomena in neoplastic tissues appear not to have been reported. Adenomas and carcinomas were induced in mouse colon by injection of dimethylhydrazine (DMH) and cell proliferation in these tumors was measured stathmokinetically. In normal intestine cell proliferation is fastest at night whereas in both adenomas and carcinomas it was found to be slower at night than in the middle of the day. Chemical sympathectomy was found to abolish the circadian variation in tumor cell proliferation.

  7. Bombyx mori E26 transformation-specific 2 (BmEts2), an Ets family protein, represses Bombyx mori Rels (BmRels)-mediated promoter activation of antimicrobial peptide genes in the silkworm Bombyx mori.

    Science.gov (United States)

    Tanaka, H; Sagisaka, A; Suzuki, N; Yamakawa, M

    2016-10-01

    E26 transformation-specific (Ets) family transcription factors are known to play roles in various biological phenomena, including immunity, in vertebrates. However, the mechanisms by which Ets proteins contribute to immunity in invertebrates remain poorly understood. In this study, we identified a cDNA encoding BmEts2, which is a putative orthologue of Drosophila Yan and human translocation-ets-leukemia/Ets-variant gene 6, from the silkworm Bombyx mori. Expression of the BmEts2 gene was significantly increased in the fat bodies of silkworm larvae in response to injection with Escherichia coli and Staphylococcus aureus. BmEts2 overexpression dramatically repressed B. mori Rels (BmRels)-mediated promoter activation of antimicrobial peptide genes in silkworm cells. Conversely, gene knockdown of BmEts2 significantly enhanced BmRels activity. In addition, two κB sites located on the 5' upstream region of cecropin B1 were found to be involved in the repression of BmRels-mediated promoter activation. Protein-competition analysis further demonstrated that BmEts2 competitively inhibited binding of BmRels to κB sites. Overall, BmEts2 acts as a repressor of BmRels-mediated transactivation of antimicrobial protein genes by inhibiting the binding of BmRels to κB sites. © 2016 The Royal Entomological Society.

  8. Transforming growth factor-β-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells.

    Science.gov (United States)

    Liu, Xiujuan; Hong, Quan; Wang, Zhen; Yu, Yanyan; Zou, Xin; Xu, Lihong

    2016-02-01

    Renal fibrosis is a progressive pathological change characterized by tubular cell apoptosis, tubulointerstitial fibroblast proliferation, and excessive deposition of extracellular matrix (ECM). miR-21 has been implicated in transforming growth factor-β (TGF-β)-stimulated tissue fibrosis. Recent studies showed that sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) are also critical for TGF-β-stimulated tissue fibrosis; however, it is not clear whether SphK/S1P interacts with miR-21 or not. In this study, we hypothesized that SphK/S1P signaling is linked to upregulation of miR-21 by TGF-β. To verify this hypothesis, we first determined that miR-21 was highly expressed in renal tubular epithelial cells (TECs) stimulated with TGF-β by using qRT-PCR and Northern blotting. Simultaneously, inhibition of miR-21, mediated by the corresponding antimir, markedly decreased the expression and deposition of type I collagen, fibronectin (Fn), cysteine-rich protein 61 (CCN1), α-smooth muscle actin, and fibroblast-specific protein1 in TGF-β-treated TECs. ELISA and qRT-PCR were used to measure the S1P and SphK1 levels in TECs. S1P production was induced by TGF-β through activation of SphK1. Furthermore, it was observed that TGF-β-stimulated upregulation of miR-21 was abolished by SphK1 siRNA and was restored by the addition of exogenous S1P. Blocking S1PR2 also inhibited upregulation of miR-21. Additionally, miR-21 overexpression attenuated the repression of TGF-β-stimulated ECM deposition and epithelial-mesenchymal transition by SphK1 and S1PR2 siRNA. In summary, our study demonstrates a link between SphK1/S1P and TGF-β-induced miR-21 in renal TECs and may represent a novel therapeutic target in renal fibrosis. © 2015 by the Society for Experimental Biology and Medicine.

  9. Transformative Learning

    Science.gov (United States)

    Wang, Victor C. X.; Cranton, Patricia

    2011-01-01

    The theory of transformative learning has been explored by different theorists and scholars. However, few scholars have made an attempt to make a comparison between transformative learning and Confucianism or between transformative learning and andragogy. The authors of this article address these comparisons to develop new and different insights…

  10. Repair-dependent cell radiation survival and transformation: an integrated theory

    International Nuclear Information System (INIS)

    Sutherland, John C

    2014-01-01

    The repair-dependent model of cell radiation survival is extended to include radiation-induced transformations. The probability of transformation is presumed to scale with the number of potentially lethal damages that are repaired in a surviving cell or the interactions of such damages. The theory predicts that at doses corresponding to high survival, the transformation frequency is the sum of simple polynomial functions of dose; linear, quadratic, etc, essentially as described in widely used linear-quadratic expressions. At high doses, corresponding to low survival, the ratio of transformed to surviving cells asymptotically approaches an upper limit. The low dose fundamental- and high dose plateau domains are separated by a downwardly concave transition region. Published transformation data for mammalian cells show the high-dose plateaus predicted by the repair-dependent model for both ultraviolet and ionizing radiation. For the neoplastic transformation experiments that were analyzed, the data can be fit with only the repair-dependent quadratic function. At low doses, the transformation frequency is strictly quadratic, but becomes sigmodial over a wider range of doses. Inclusion of data from the transition region in a traditional linear-quadratic analysis of neoplastic transformation frequency data can exaggerate the magnitude of, or create the appearance of, a linear component. Quantitative analysis of survival and transformation data shows good agreement for ultraviolet radiation; the shapes of the transformation components can be predicted from survival data. For ionizing radiations, both neutrons and x-rays, survival data overestimate the transforming ability for low to moderate doses. The presumed cause of this difference is that, unlike UV photons, a single x-ray or neutron may generate more than one lethal damage in a cell, so the distribution of such damages in the population is not accurately described by Poisson statistics. However, the complete

  11. Backlund transformations as canonical transformations

    International Nuclear Information System (INIS)

    Villani, A.; Zimerman, A.H.

    1977-01-01

    Toda and Wadati as well as Kodama and Wadati have shown that the Backlund transformations, for the exponential lattice equation, sine-Gordon equation, K-dV (Korteweg de Vries) equation and modifies K-dV equation, are canonical transformation. It is shown that the Backlund transformation for the Boussinesq equation, for a generalized K-dV equation, for a model equation for shallow water waves and for the nonlinear Schroedinger equation are also canonical transformations [pt

  12. Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions.

    Science.gov (United States)

    Pinho, Andreia V; Mawson, Amanda; Gill, Anthony; Arshi, Mehreen; Warmerdam, Max; Giry-Laterriere, Marc; Eling, Nils; Lie, Triyana; Kuster, Evelyne; Camargo, Simone; Biankin, Andrew V; Wu, Jianmin; Rooman, Ilse

    2016-11-15

    Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered.To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH.The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival.These findings open perspectives for novel targeted therapies in pancreatic cancer.

  13. Immunogenetical study of the atomic-bombed patients of neoplastic diseases

    International Nuclear Information System (INIS)

    Hirota, Masaki; Miyazaki, Takashige; Tomonaga, Akimitsu; Hara, Kohei; Hirose, Takeshi

    1978-01-01

    The immunogenetical backgrounds of 30 patients with neoplastic diseases (group I) and 30 with non-neoplastic diseases (group II) who were exposed to the A-bomb within 30 km of the center of explosion were studied using human leucocyte antigen (HLA), whose gene combines with Ir-gene, as an index. Eighty-four healthy, non-exposed persons (group III) were selected as controls. Regarding phenotype and genotype frequency, type A9 showed Aw24 and type A10 showed A26 in all cases. Except for Bw40, there was no significant difference among the groups (frequency of A9, I>II; that of A10, II< III). Bw40 was frequently observed in group I although it had racial specificity. There were 16 cases of Bw40 in group I (53.3%), 10 cases in group II (33.3%), and 23 cases in group III (27.3%). Further analysis of Bw40 revealed that Bw40.1 and Bw40.2 were more frequent in group I than in the control group. Bw40.3 was not observed in any of the groups. (Tsunoda, M.)

  14. [Non-neoplastic enlargement of salivary glands: clinico-histologic analysis].

    Science.gov (United States)

    González Guevara, Martha Beatriz; Torres Tejero, Marco Antonio; Martínez Mata, Guillermo

    2005-01-01

    We carried out a retrospective study on non-neoplastic enlargement of the salivary glands at the Oral Histopathology Diagnostic Center of the Autonomous Metropolitan University at Xochimilco (UAM-Xochimilco) in Mexico during a period of 24 years (1979-2003). From 5,625 biopsies received and analyzed, a total of 461 (8.2%) were non-neoplastic enlargement of the salivary glands; for each case, we registered demographic data as well as clinic characteristics. These lesions were characterized as a heterogeneous group of pathologic entities among which we included local, obstructive, infectious, and immunopathologic lesions. The most frequent lesion was the extravasation cyst in 341 (74%) cases, followed by chronic sialoadenitis and Sjögren's syndrome with 54 (11.7%) and 41 (8.8%) cases, respectively, and at a lesser percentage mucous retention cyst, sialosis, benign lymphoepithelial lesions and those related with sialolytes. Females were affected more frequently; mean age was second to third life decades. These lesions were most frequently localized on inferior labial mucosa.

  15. Sensitivity to radiation of human normal, hyperthyroid, and neoplastic thyroid epithelial cells in primary culture

    International Nuclear Information System (INIS)

    Miller, R.C.; Hiraoka, Toshio; Kopecky, K.J.; Nakamura, Nori; Jones, M.P.; Ito, Toshio; Clifton, K.H.

    1986-09-01

    Samples of thyroid tissue removed surgically from 63 patients were cultured in vitro and X-irradiated to investigate the radiosensitivities of various types of thyroid epithelial cells. A total of 76 samples were obtained, including neoplastic cells from patients with papillary carcinoma (PC) or follicular adenoma (FA), cells from hyperthyroidism (HY) patients, and normal cells from the surgical margins of PC and FA patients. Culturing of the cells was performed in a manner which has been shown to yield a predominance of epithelial cells. Results of colony formation assays indicated that cells from HY and FA patients were the least radiosensitive: when adjusted to the overall geometric mean plating efficiency of 5.5 %, the average mean lethal dose D 0 was 97.6 cGy for HY cells, and 96.7 cGy and 94.3 cGy, respectively, for neoplastic and normal cells from FA patients. Cells from PC patients were more radiosensitive, normal cells having an adjusted average D 0 of 85.0 cGy and PC cells a significantly (p = .001) lower average D 0 of 74.4 cGy. After allowing for this variation by cell type, in vitro radiosensitivity was not significantly related to age at surgery (p = .82) or sex (p = .10). These results suggest that malignant thyroid cells may be especially radiosensitive. (author)

  16. Interobserver agreement for the spine instability neoplastic score varies according to the experience of the evaluator

    Directory of Open Access Journals (Sweden)

    William Gemio Jacobsen Teixeira

    2013-01-01

    Full Text Available OBJECTIVES: To evaluate the interobserver agreement for the Neoplastic Spine Instability Score (SINS among spine surgeons with or without experience in vertebral metastasis treatment and physicians in other specialties. METHODS: Case descriptions were produced based on the medical records of 40 patients with vertebral metastases. The descriptions were then published online. Physicians were invited to evaluate the descriptions by answering questions according to the Neoplastic Spine Instability Score (SINS. The agreement among physicians was calculated using the kappa coefficient. RESULTS: Seventeen physicians agreed to participate: three highly experienced spine surgeons, seven less-experienced spine surgeons, three surgeons of other specialties, and four general practitioners (n = 17. The agreement for the final SINS score among all participants was fair, and it varied according to the SINS component. The agreement was substantial for the spine location only. The agreement was higher among experienced surgeons. The agreement was nearly perfect for spinal location among the spine surgeons who were highly experienced in vertebral metastases. CONCLUSIONS: This study demonstrates that the experience of the evaluator has an impact on SINS scale classification. The interobserver agreement was only fair among physicians who were not spine surgeons and among spine surgeons who were not experienced in the treatment of vertebral metastases, which may limit the use of the SINS scale for the screening of unstable lesions by less-experienced evaluators.

  17. Alcohol consumption and the neoplastic progression in Barrett's esophagus: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhifeng Lou

    Full Text Available PURPOSE: In the developed countries, the incidence of esophageal adenocarcinoma (EAC is increasing over recent decades. The purpose of this meta-analysis was to arrive at quantitative conclusions about the contribution of alcohol intakes and the progression of Barrett's esophagus. METHODS: A comprehensive, systematic bibliographic search of medical literature published up to Oct 2013 was conducted to identify relevant studies. A meta-analysis was conducted for alcohol consumption on the Barrett's esophagus progression. RESULTS: A total of 882 cases in 6,867 individuals from 14 observational studies were indemnified in this meta-analysis. The result of this current meta-analysis, including 10 case-control and 4 cohort studies, indicated that alcohol consumption was not associated with the neoplastic progression in Barrett's esophagus (RR, 1.17; 95% CI, 0.93-1.48. When stratified by the study designs, no significant association was detected in either high vs low group or ever vs never group. CONCLUSIONS: Alcohol drinking is not associated with risk of neoplastic progression in Barrett's esophagus. Further well designed studies are needed in this area.

  18. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

    Science.gov (United States)

    Granger, D L; Lehninger, A L

    1982-11-01

    Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

  19. Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions

    Science.gov (United States)

    Pinho, Andreia V.; Mawson, Amanda; Gill, Anthony; Arshi, Mehreen; Warmerdam, Max; Giry-Laterriere, Marc; Eling, Nils; Lie, Triyana; Kuster, Evelyne; Camargo, Simone; Biankin, Andrew V.; Wu, Jianmin; Rooman, Ilse

    2016-01-01

    Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered. To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH. The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival. These findings open perspectives for novel targeted therapies in pancreatic cancer. PMID:27494892

  20. Immunohistochemistry expression of TCF4 protein on carcinoma, adenoma and non neoplastic colorectal mucosa

    Directory of Open Access Journals (Sweden)

    Leonardo Huber Tauil

    2014-01-01

    Full Text Available Purpose: To detect and quantify the immunoreactivity of TCF4 protein in colorectal carci- noma, colorectal adenoma and non-neoplasic colorectal epithelium. Methods: We studied 129 individuals: 40 with colorectal cancer, 52 with colorectal ad- enoma and 37 with non-neoplastic colorectal epithelium. The colorectal adenoma and carcinoma samples were obtained from patients who underwent surgical procedures, and colonoscopies and samples of non-neoplastic colorectal epithelium were taken from patients who died from cardiovascular diseases, without diseases of the large intestine. Samples of different tissues were included in paraffin blocks, and the immunohistochem- ical expression of protein TCF4 was analyzed using the technique of tissue microarray (TMA with polyclonal antibody TCF4. The immunoreactivity was analyzed and classified as positive and negative. Results: The immunohistochemical expression of TCF4 protein was significantly higher (p < 0.01 in colorectal carcinoma than in the non-neoplastic colorectal epithelium and adenoma. There was no difference (p = 0.76 between TCF4 protein immunohistochemical expression in colorectal adenoma and non-neoplastic colorectal tissue. Conclusions: TCF4 protein showed a more intense expression in colorectal carcinoma than in non-neoplastic colorectal epithelium and adenoma, indicating that this protein is in- volved in colorectal carcinogenesis. Resumo: Objetivos: Detectar e quantificar a imunoexpressão da proteína TCF4 no carcinoma e no adenoma colorretal e no epitélio colorretal não neoplásico. Método: Foram estudados 129 indivíduos: 40 com carcinoma colorretal, 52 com adenoma colorretal e 37 com epitélio colorretal não neoplásico. Os tecidos de adenoma e carcinoma colorretais foram representados por amostras da lesão retirada de doentes submetidos a procedimentos cirúrgicos e colonoscópicos, e as amostras de epitélio colorretal não neo- plásico foram retiradas de doentes falecidos por

  1. Telomerase promoter reprogramming and interaction with general transcription factors in the human mesenchymal stem cell

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Hoare, Stacey F.; Kassem, Moustapha

    2006-01-01

    The human adult mesenchymal stem cell (hMSC) does not express telomerase and has been shown to be the target for neoplastic transformation after transduction with hTERT. These findings lend support to the stem cell hypothesis of cancer development but by supplying hTERT, the molecular events requ...

  2. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111In-DTPA ventriculography

    International Nuclear Information System (INIS)

    Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

    1982-01-01

    Cerebrospinal fluid flow dynamics were evaluated by 111 In-diethylenetriamine pentaacetic acid ( 111 In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that 111 In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis

  3. Hadamard Transforms

    CERN Document Server

    Agaian, Sos; Egiazarian, Karen; Astola, Jaakko

    2011-01-01

    The Hadamard matrix and Hadamard transform are fundamental problem-solving tools in a wide spectrum of scientific disciplines and technologies, such as communication systems, signal and image processing (signal representation, coding, filtering, recognition, and watermarking), digital logic (Boolean function analysis and synthesis), and fault-tolerant system design. Hadamard Transforms intends to bring together different topics concerning current developments in Hadamard matrices, transforms, and their applications. Each chapter begins with the basics of the theory, progresses to more advanced

  4. Gastric diffuse large B cell lymphoma presenting as para neoplastic cerebellar degeneration: Case report and review of literature

    International Nuclear Information System (INIS)

    Lakshmaiah, K.C.; Viveka, B.K.; Kumar, N.A.; Saini, M.L.; Sinha, S.; Saini, K.S.

    2013-01-01

    Para neoplastic cerebellar degeneration (PCD) is a type of para neoplastic neurological disorder (PND) that is associated with many solid tumors, Hodgkins lymphoma (HL) and very rarely with non-Hodgkin lymphoma (NHL). We report a case of PCD associated with gastric diffuse large B-cell lymphoma (DLBCL) in a patient who presented with acute onset of giddiness and double vision and had complete remission of the gastric lesion and marked improvement of cerebellar syndrome with rituximab-based combination chemotherapy. A brief review of the literature is also presented.

  5. Hydrolytic Amino Acids Employed as a Novel Organic Nitrogen Source for the Preparation of PGPF-Containing Bio-Organic Fertilizer for Plant Growth Promotion and Characterization of Substance Transformation during BOF Production

    Science.gov (United States)

    Feng, Chenglong; Ran, Wei; Yu, Guanghui; Zhang, Yingjun; Shen, Qirong

    2016-01-01

    Opportunity costs seriously limit the large-scale production of bio-organic fertilizers (BOFs) both in China and internationally. This study addresses the utilization of amino acids resulting from the acidic hydrolysis of pig corpses as organic nitrogen sources to increase the density of TrichodermaharzianumT-E5 (a typical plant growth-promoting fungi, PGPF). This results in a novel, economical, highly efficient and environmentally friendly BOF product. Fluorescence excitation-emission matrix (EEM) spectroscopy combined with fluorescence regional integration (FRI) was employed to monitor compost maturity levels, while pot experiments were utilized to test the effects of this novel BOF on plant growth. An optimization experiment, based on response surface methodologies (RSMs), showed that a maximum T-E5 population (3.72 × 108 ITS copies g−1) was obtained from a mixture of 65.17% cattle manure compost (W/W), 19.33% maggot manure (W/W), 15.50% (V/W)hydrolytic amino acid solution and 4.69% (V/W) inoculum at 28.7°C after a 14 day secondary solid fermentation. Spectroscopy analysis revealed that the compost transformation process involved the degradation of protein-like substances and the formation of fulvic-like and humic-like substances. FRI parameters (PI, n, PII, n, PIII, n and PV, n) were used to characterize the degree of compost maturity. The BOF resulted in significantly higher increased chlorophyll content, shoot length, and shoot and root dry weights of three vegetables (cucumber, tomato and pepper) by 9.9%~22.4%, 22.9%~58.5%, 31.0%~84.9%, and 24.2%~34.1%, respectively. In summary, this study presents an operational means of increasing PGPF T-E5 populations in BOF to promote plant growth with a concomitant reduction in production cost. In addition, a BOF compost maturity assessment using fluorescence EEM spectroscopy and FRI ensured its safe field application. PMID:26974549

  6. CD147 overexpression promotes tumorigenicity in Chinese hamster ovary cells.

    Science.gov (United States)

    Yong, Yu-Le; Liao, Cheng-Gong; Wei, Ding; Chen, Zhi-Nan; Bian, Huijie

    2016-04-01

    CD147 overexpresses in many epithelium-originated tumors and plays an important role in tumor migration and invasion. Most studies aim at the role of CD147 in tumor progression using tumor cell models. However, the influence of abnormal overexpression of CD147 on neoplastic transformation of normal cells is unknown. Here, the role of CD147 in malignant phenotype transformation in CHO cells was investigated. Three CHO cell lines that stably overexpressed CD147 (CHO-CD147), EGFP-CD147 (CHO-EGFP-CD147), and EGFP (CHO-EGFP) were generated by transfection of plasmids containing human CD147, EGFP-human CD147, and EGFP genes into CHO cells. Cell migration and invasion were detected by wound healing and transwell matrix penetration assay. Trypan blue exclusion, MTT, cell cycle analysis, and BrdU cell proliferation assay were used to detect cell viability and cell proliferation. Annexin V-FITC analysis was performed to detect apoptosis. We found that CD147 overexpression promoted the migration and invasion of CHO cells. CD147 accelerated the G1 to S phase transition and enhanced the CHO cell proliferation. Overexpression of CD147 inhibited both early- and late-stages of apoptosis of CHO-CD147 cells, which is caused by serum deprivation. CHO-EGFP-CD147 cells showed an increased anchorage-independent growth compared with CHO-EGFP cells as detected by soft-agar colony formation assay. The tumors formed by CHO-CD147 cells in nude mice were larger and coupled with higher expression of proliferating cell nuclear antigen and Ki-67 than that of CHO cells. In conclusion, human CD147 overexpression induces malignant phenotype in CHO cells. © 2015 International Federation for Cell Biology.

  7. Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine.

    Science.gov (United States)

    Ogino, Shuji; Nishihara, Reiko; VanderWeele, Tyler J; Wang, Molin; Nishi, Akihiro; Lochhead, Paul; Qian, Zhi Rong; Zhang, Xuehong; Wu, Kana; Nan, Hongmei; Yoshida, Kazuki; Milner, Danny A; Chan, Andrew T; Field, Alison E; Camargo, Carlos A; Williams, Michelle A; Giovannucci, Edward L

    2016-07-01

    Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public

  8. Pancreatic endocrine tumor with neoplastic venous thrombus and bilobar liver metastasis. A case report.

    Science.gov (United States)

    Barbier, L; Turrini, O; Sarran, A; Delpero, J-R

    2010-02-01

    We report the case of an asymptomatic 56-year-old woman with a metastatic pancreatic endocrine tumor, fortuitously discovered by abdominal imaging. A CT-scan showed a large mass in the pancreatic tail invading the spleen and stomach; in addition, there was neoplastic thrombus within the spleno-mesentericoportal venous confluence and bilobar liver metastases. Surgical resection was performed in two stages. The first procedure was an extended left pancreatectomy with venous thrombectomy and "clearance" of the left hepatic lobe. During the interval, embolization of the right portal vein was carried out. Right hepatectomy and radiofrequency destruction of residual metastases was then performed. On the basis of completeness of the resection and the histopathological data, the patient did not undergo any adjuvant therapy, in accordance with French guidelines. At 1 year of follow-up, there was no evidence of recurrence. (c) 2010 Elsevier Masson SAS. All rights reserved.

  9. Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

    Science.gov (United States)

    Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

    2018-01-01

    Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

  10. Expression of the α2-macroglobulin receptor on human neoplastic fibroblastoid cells

    International Nuclear Information System (INIS)

    Grofova, M.; Matoska, J.; Bies, J.; Bizik, J.; Vaheri, A.

    1995-01-01

    The α 2 -macroglobulin membrane-associated receptor ( α 2 MR) has been previously detected on hepatocytes, fibroblast, macrophages, syncytiotrophoblasts and recently on human malignant blood cells of myelomonocytic leukemia. In cells growing in vitro from human germ cell tumors α 2 MR mRNA was detected by Northern blotting. Endocytosis of α 2 MR from culture medium was detected in these cells by indirect immunofluorescence. In cell extracts α 2 MR and its degradation products were detected by immunoblotting. The cells expressing α 2 MR and internalizing α 2 MR were identified as fibroblast both by their morphology and expression of vimentin intermediate filaments. The role and function of α 2 MR receptor in the analyzed neoplastic cells of teratomatous origin is discussed. (author)

  11. Compact energy dispersive X-ray microdiffractometer for diagnosis of neoplastic tissues

    Science.gov (United States)

    Sosa, C.; Malezan, A.; Poletti, M. E.; Perez, R. D.

    2017-08-01

    An energy dispersive X-ray microdiffractometer with capillary optics has been developed for characterizing breast cancer. The employment of low divergence capillary optics helps to reduce the setup size to a few centimeters, while providing a lateral spatial resolution of 100 μm. The system angular calibration and momentum transfer resolution were assessed by a detailed study of a polycrystalline reference material. The performance of the system was tested by means of the analysis of tissue-equivalent samples previously characterized by conventional X-ray diffraction. In addition, a simplified correction model for an appropriate comparison of the diffraction spectra was developed and validated. Finally, the system was employed to evaluate normal and neoplastic human breast samples, in order to determine their X-ray scatter signatures. The initial results indicate that the use of this compact energy dispersive X-ray microdiffractometer combined with a simplified correction procedure is able to provide additional information to breast cancer diagnosis.

  12. Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

    International Nuclear Information System (INIS)

    Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

    1986-01-01

    Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

  13. Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects.

    Science.gov (United States)

    Bini, E J; Green, B; Poles, M A

    2009-08-01

    Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects >or=50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas >or=10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, pscreening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study.

  14. Visualizing Transformation

    DEFF Research Database (Denmark)

    Pedersen, Pia

    2012-01-01

    Transformation, defined as the step of extracting, arranging and simplifying data into visual form (M. Neurath, 1974), was developed in connection with ISOTYPE (International System Of TYpographic Picture Education) and might well be the most important legacy of Isotype to the field of graphic...... design. Recently transformation has attracted renewed interest because of the book The Transformer written by Robin Kinross and Marie Neurath. My on-going research project, summarized in this paper, identifies and depicts the essential principles of data visualization underlying the process...... of transformation with reference to Marie Neurath’s sketches on the Bilston Project. The material has been collected at the Otto and Marie Neurath Collection housed at the University of Reading, UK. By using data visualization as a research method to look directly into the process of transformation, the project...

  15. Cerebellar hemangioblastomas: A study of the immunoprofile of neoplastic stromal component

    Directory of Open Access Journals (Sweden)

    Tasić Desanka

    2004-01-01

    Full Text Available Background. Central nervous system hemangioblastomas (HBs are uncommon highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. Methods. A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg, CD34, vimentin, factor XIIIa (FXIIIa, S-100 protein, glial fibrillary acidic protein (GFAP, neuron-specific enolase (NSE neurofilaments (NF, synaptophysin, chromogranin, and somatostatin. Results. Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34 GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". Conclusion. The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme in the HBs stromal cells might be related to the loss of the VHL protein function.

  16. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

    Science.gov (United States)

    Carvalho, Filomena M; Zaganelli, Fabricia L; Almeida, Bernardo G L; Goes, Joao Carlos Sampaio; Baracat, Edmund C; Carvalho, Jesus P

    2010-01-01

    OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas. PMID:21340215

  17. Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

    Directory of Open Access Journals (Sweden)

    Filomena M Carvalho

    2010-01-01

    Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

  18. In vitro transformation: interactions of chemical carcinogens and radiation

    International Nuclear Information System (INIS)

    DiPaolo, J.A.

    1976-01-01

    The development of reproducible quantitative in vitro procedures resulting in neoplastic transformation of mammalian cells has made possible the separation of events related to the process leading to transformation from secondary events that interfere with the early recognition of transformation. The use of chemical carcinogens on Syrian hamster cell strains results in a dose-response relation consistent with a Poisson distribution, indicating that the transformation phenomenon is inductive. In some circumstances, the joint action or interaction of chemical carcinogens with other agents results in an increased incidence of transformation. The pretreatment of Syrian hamster cells with ionizing radiation (250 R) or alkylating chemicals enhances the frequency of transformation on a cell or colony basis ordinarily obtained with known chemical carcinogens. Pretreatment with non-ionizing irradiation (uv, 254 nm) did not have a similar effect. The two types of irradiation and the alkylating agents reduced the cloning efficiency of the cells. X ray alone produced no transformation; the alkylating chemicals produced transformations infrequently, whereas uv produced a significant number of transformations. The number of transformations associated with uv is increased by pretreatment of the cells by x-irradiation. The enhancement of transformation by x-ray or x-ray-type agents appears to be independent of the type of second carcinogen used

  19. Does India's Economic Transformation Promote Women's Economic ...

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

    This has been accompanied by a narrowing of the gender gap in education. ... in which economic growth can affect women's access to, and control over, resources. ... In partnership with UNESCO's Organization for Women in Science for the ...

  20. Adult stem cell theory of the multi-stage, multi-mechanism theory of carcinogenesis: role of inflammation on the promotion of initiated stem cells.

    Science.gov (United States)

    Trosko, James E; Tai, Mei-Hui

    2006-01-01

    Inflammation, induced by microbial agents, radiation, endogenous or exogenous chemicals, has been associated with chronic diseases, including cancer. Since carcinogenesis has been characterized as consisting of the 'initiation', 'promotion' and 'progression' phases, the inflammatory process could affect any or all three phases. The stem cell theory of carcinogenesis has been given a revival, in that isolated human adult stem cells have been isolated and shown to be 'targets' for neoplastic transformation. Oct4, a transcription factor, has been associated with adult stem cells, as well as their immortalized and tumorigenic derivatives, but not with the normal differentiated daughters. These data are consistent with the stem cell theory of carcinogenesis. In addition, Gap Junctional Intercellular Communication (GJIC) seems to play a major role in cell growth. Inhibition of GJIC by non-genotoxic chemicals or various oncogenes seems to be the mechanism for the tumor promotion and progression phases of carcinogenesis. Many of the toxins, synthetic non-genotoxicants, and endogenous inflammatory factors have been shown to inhibit GJIC and act as tumor promoters. The inhibition of GJIC might be the mechanism by which the inflammatory process affects cancer and that to intervene during tumor promotion with anti-inflammatory factors might be the most efficacious anti-cancer strategy.

  1. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

    NARCIS (Netherlands)

    Haycock, P.C.; Burgess, S.; Nounu, A.; Zheng, J.; Okoli, G.N.; Bowden, J.; Wade, K.H.; Timpson, N.J.; Evans, D.M.; Willeit, P.; Aviv, A.; Gaunt, T.R.; Hemani, G.; Mangino, M.; Ellis, H.P.; Kurian, K.M.; Pooley, K.A.; Eeles, R.A.; Lee, J.E.; Fang, S.; Chen, W.V.; Law, M.H.; Bowdler, L.M.; Iles, M.M.; Yang, Q.; Worrall, B.B.; Markus, H.S.; Hung, R.J.; Amos, C.I.; Spurdle, A.B.; Thompson, D.J.; O'Mara, T.A.; Wolpin, B.; Amundadottir, L.; Stolzenberg-Solomon, R.; Trichopoulou, A.; Onland-Moret, N.C.; Lund, E.; Duell, E.J.; Canzian, F.; Severi, G.; Overvad, K.; Gunter, M.J.; Tumino, R.; Svenson, U.; Rij, A. van; Baas, A.F.; Bown, M.J.; Samani, N.J.; t'Hof, F.N.G. van; Tromp, G.; Jones, G.T.; Kuivaniemi, H.; Elmore, J.R.; Johansson, M.; McKay, J.; Scelo, G.; Carreras-Torres, R.; Gaborieau, V.; Brennan, P.; Bracci, P.M.; Neale, R.E.; Olson, S.H.; Gallinger, S.; Li, D.; Petersen, G.M.; Risch, H.A.; Klein, A.P.; Han, J.; Abnet, C.C.; Freedman, N.D.; Taylor, P.R.; Maris, J.M.; Aben, K.K.H.; Kiemeney, L.A.; Vermeulen, S.H.; Wiencke, J.K.; Walsh, K.M.; Wrensch, M.; Rice, T.; Turnbull, C.; Litchfield, K.; Paternoster, L.; Standl, M.; Abecasis, G.R.; SanGiovanni, J.P.; Li, Y.; Mijatovic, V.; Sapkota, Y.; Low, S.K.; Zondervan, K.T.; Montgomery, G.W.; Nyholt, D.R.; Heel, D.A. van; Hunt, K.; Arking, D.E.; Ashar, F.N.; Sotoodehnia, N.; Woo, D.; et al.,

    2017-01-01

    Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study,

  2. Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

    International Nuclear Information System (INIS)

    Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

    1979-01-01

    Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

  3. Adenocarcinoma of the rete testis with prominent papillary structure and clear neoplastic cells: Morphologic and immunohistochemical findings and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Pei-Wen Huang

    2015-01-01

    Full Text Available Adenocarcinoma of the rete testis is rare, and its etiology is unknown. The definite diagnosis merely depends on the exclusion of other tumors and histological features. We first describe a 38-year-old man with a carcinoma arising in the rete testis. The tumor was characterized by clear neoplastic cells and branching papillary growth. Focal stromal invasion and transition of normal rete epithelium to neoplastic cells were seen. The neoplastic cells were positive for epithelial membrane antigen, Ber-Ep4, vimentin, renal cell carcinoma marker, and CD10, while negative for Wilms′ tumor 1, thyroid transcription factor-1, estrogen receptor, prostate specific antigen, placental alkaline phosphate, CD117, and alpha-1-fetoprotein. According to the above features, we diagnosed this tumor as adenocarcinoma of the rete testis. To our best knowledge, this is the first reported case of adenocarcinoma of the rete testis with prominently papillary structure and clear neoplastic cells. The rarity of adenocarcinoma of the rete testis and the unique features in our case cause diagnostic pitfalls. A complete clinicopathological study and thorough differential diagnosis are crucial for the correct result.

  4. Case of a rare type of non-neoplastic mucinous pancreatic cyst – likely new pathological entity?

    International Nuclear Information System (INIS)

    Hilendarov, A.; Nedeva, M.; Belovejdov, V.; Aleksieva, D.; Sirakov, N.

    2013-01-01

    Full text:Introduction: The cystic lesions of the pancreas consists of a range of pathologies which may be broadly divided into neoplastic, non- neoplastic and cysts. Recently a new non-neoplastic cystic lesions, called mucinous non-neoplastic cysts, have been described. Materials and Methods: The imaging methods (ultrasound and CT ) were used as well as invasive imaging methods under image control with a view of the histological verification of the diagnosis. A case of pancreatic cystic lesion is described, accidentally detected by ultrasound and CT scan made for different purpose. Results : The finding was a 28/32 mm cyst in the body of the pancreas, apparently communicating with the pancreatic duct . The Endoscopic Retrograde Cholangiopancreatography and laboratory tests of liver function, serum CEA and carbohydrate antigen C19 -9 were within normal limits. After the distal pancreatectomy and splenectomy the lasting histological specimen showed a simple cyst, lined with mucinous epithelium. Conclusion: The presented case guides the imaging diagnosticians and surgeons towards seeking a thorough preoperative clarification of pancreatic cystic lesions. It is recommended that patients diagnosed with 'benign' mucinous neoplasm are closely monitored due to the inability to completely confirm the benign nature of the lesion

  5. Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma

    Directory of Open Access Journals (Sweden)

    Spyros Darmanis

    2017-10-01

    Full Text Available Summary: Glioblastoma (GBM is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor’s genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration. : Darmanis et al. perform single-cell transcriptomic analyses of neoplastic and stromal cells within and proximal to primary glioblastomas. The authors describe a population of neoplastic-infiltrating glioblastoma cells as well as a putative role of tumor-infiltrating immune cells in supporting tumor growth. Keywords: single cell, RNA-seq, glioma, glioblastoma, GBM, brain, heterogeneity, infiltrating, diffuse, checkpoint

  6. Security Transformation

    National Research Council Canada - National Science Library

    Metz, Steven

    2003-01-01

    ... adjustment. With American military forces engaged around the world in both combat and stabilization operations, the need for rigorous and critical analysis of security transformation has never been greater...

  7. Landskabets transformation

    DEFF Research Database (Denmark)

    Munck Petersen, Rikke

    2005-01-01

    Seminaroplæg fra forskere. Faglige seminarer på KA, forår 2005. Belyser transformation af det danske landskab fysisk som holdningsmæssigt, samt hvordan phd-arbejdets egen proces håndterer den.......Seminaroplæg fra forskere. Faglige seminarer på KA, forår 2005. Belyser transformation af det danske landskab fysisk som holdningsmæssigt, samt hvordan phd-arbejdets egen proces håndterer den....

  8. Covariant Transform

    OpenAIRE

    Kisil, Vladimir V.

    2010-01-01

    The paper develops theory of covariant transform, which is inspired by the wavelet construction. It was observed that many interesting types of wavelets (or coherent states) arise from group representations which are not square integrable or vacuum vectors which are not admissible. Covariant transform extends an applicability of the popular wavelets construction to classic examples like the Hardy space H_2, Banach spaces, covariant functional calculus and many others. Keywords: Wavelets, cohe...

  9. Transforming Anatomy

    OpenAIRE

    Hall, Anndee

    2017-01-01

    Abstract: Transforming Anatomy Studying historic books allows people to witness the transformation of the world right before their very eyes. The Bruxellensis Icones Anatomicae[1] by Andreas Vesalius is a vital piece of evidence in the movement from a more rudimentary understanding of the human body into the more complex and accurate development of modern anatomy. Vesalius’ research worked to both refute and confirm findings of his predecessor, the great historical Greek philosopher, Galen...

  10. Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

    Science.gov (United States)

    Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

    1998-12-01

    Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

  11. Membrane associated ion transport enzymes in normal and transformed fibroblasts and epithelial cells

    International Nuclear Information System (INIS)

    Borek, C.

    1982-01-01

    In an effort to evaluate membrane changes associated with neoplastic transformation of fibroblasts and epithelial cells by radiation and chemicals, alterations in membrane-associated (Na + + K + )-ATPase and 5'-nucleotidase activities were investigated. Cell cultures consisted of normal and radiation transformed hamster embryo fibroblasts (HE) and mouse C3H 10T 1/2 fibroblasts, normal and chemically transformed adult rat liver epithelial cells (ARL), as well as hepatocarcinoma cells induced by the liver transformants. Transformed fibroblasts demonstrated a 1-2 fold increase in (Na + + K + )-ATPase activity over the normal, while the transformed liver epithelial cells and carcinoma cells showed a 60% and 40% decrease in activity compared to the normal values, respectively. The 5'-nucleotidase activity was 2 to 3 times higher in the transformed fibroblasts

  12. Transgene Expression and Repression in Transgenic Rats Bearing the Phosphoenolpyruvate Carboxykinase-Simian Virus 40 T Antigen or the Phosphoenolpyruvate Carboxykinase-Transforming Growth Factor-α Constructs

    Science.gov (United States)

    Haas, Michael J.; Dragan, Yvonne P.; Hikita, Hiroshi; Shimel, Randee; Takimoto, Koichi; Heath, Susan; Vaughan, Jennifer; Pitot, Henry C.

    1999-01-01

    Transgenic Sprague-Dawley rats expressing either human transforming growth factor-α (TGFα) or simian virus 40 large and small T antigen (TAg), each under the control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter, were developed as an approach to the study of the promotion of hepatocarcinogenesis in the presence of a transgene regulatable by diet and/or hormones. Five lines of PEPCK-TGFα transgenic rats were established, each genetic line containing from one to several copies of the transgene per haploid genome. Two PEPCK-TAg transgenic founder rats were obtained, each with multiple copies of the transgene. Expression of the transgene was undetectable in the TGFα transgenic rats and could not be induced when the animals were placed on a high-protein, low-carbohydrate diet. The transgene was found to be highly methylated in all of these lines. No pathological alterations in the liver and intestine were observed at any time (up to 2 years) during the lives of these rats. One line of transgenic rats expressing the PEPCK-TAg transgene developed pancreatic islet cell hyperplasias and carcinomas, with few normal islets evident in the pancreas. This transgene is integrated as a hypomethylated tandem array of 10 to 12 copies on chromosome 8q11. Expression of large T antigen is highest in pancreatic neoplasms, but is also detectable in the normal brain, kidney, and liver. Mortality is most rapid in males, starting at 5 months of age and reaching 100% by 8 months. Morphologically, islet cell differentiation in the tumors ranges from poor to well differentiated, with regions of necrosis and fibrosis. Spontaneous metastasis of TAg-positive tumor cells to regional lymph nodes was observed. These studies indicate the importance of DNA methylation in the repression of specific transgenes in the rat. However, the expression of the PEPCK-TAg induces neoplastic transformation in islet cells, probably late in neuroendocrine cell differentiation. T antigen expression

  13. Induction of malignant transformation in CHL-1 cells by exposure to tritiated water

    International Nuclear Information System (INIS)

    Zou Shu'ai; Wang Hui

    1992-01-01

    The induction of neoplastic transformation in CHL-1 cells by low-dose-rate exposure to tritiated water was reported. CHL-1 cells were exposed to tritiated water (9.25 x 10 5 - 3.7 x 10 6 Bq/mL) for 24-96 hours and the accumulated doses were estimated to be 0.055-0.88 Gy, respectively. Neoplastic transformation was found in all exposed cell groups. The morphological study and transplantation test was carried out for demonstration malignancy of the transformed cells and the results show that they are with the morphology and behaviour for malignant tumour cells. For CHL-1 cells exposed to various doses of tritiated water, transformation rates were found to be from 3.28% to 13.0% at dose of 0.055-0.88 Gy. In order to estimate RBE of tritium for malignant transformation in CHL-1 cells, the induction of malignant transformation in CHL-1 cells by exposure to 137 Cs gamma-rays was carried out at dose rates of 0.359 Gy/24 hr and transformation rates for irradiated CHL-1 cells were found to be from 2.59% to 13.4%. Based on these data, RBE of tritium for malignant transformation in CHL-1 cells was estimated to be 1.6

  14. Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

    1990-11-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs.

  15. Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

    International Nuclear Information System (INIS)

    Yang, Tracy Chui-hsu; Craise, L.M; Prioleau, J.C.; Stampfer, M.R.; Rhim, J.S.

    1990-11-01

    For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude nice. Neoplastic transformation was achieved by irradiation cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level. 15 refs., 9 figs., 2 tabs

  16. Active vitamin D potentiates the anti-neoplastic effects of calcium in the colon: A cross talk through the calcium-sensing receptor.

    Science.gov (United States)

    Aggarwal, Abhishek; Höbaus, Julia; Tennakoon, Samawansha; Prinz-Wohlgenannt, Maximilian; Graça, João; Price, Sally A; Heffeter, Petra; Berger, Walter; Baumgartner-Parzer, Sabina; Kállay, Enikö

    2016-01-01

    Epidemiological studies suggest an inverse correlation between dietary calcium (Ca(2+)) and vitamin D intake and the risk of colorectal cancer (CRC). It has been shown in vitro that the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3) can upregulate expression of the calcium-sensing receptor (CaSR). In the colon, CaSR has been suggested to regulate proliferation of colonocytes. However, during tumorigenesis colonic CaSR expression is downregulated and we hypothesized that the loss of CaSR could influence the anti-tumorigenic effects of Ca(2+) and vitamin D. Our aim was to assess the impact of CaSR expression and function on the anti-neoplastic effects of 1,25-D3 in colon cancer cell lines. We demonstrated that in the healthy colon of mice, high vitamin D diet (2500 IU/kg diet) increased expression of differentiation and apoptosis markers, decreased expression of proliferation markers and significantly upregulated CaSR mRNA expression, compared with low vitamin D diet (100 IU/kg diet). To determine the role of CaSR in this process, we transfected Caco2-15 and HT29 CRC cells with wild type CaSR (CaSR-WT) or a dominant negative CaSR mutant (CaSR-DN) and treated them with 1,25-D3 alone, or in combination with CaSR activators (Ca(2+) and NPS R-568). 1,25-D3 enhanced the anti-proliferative effects of Ca(2+) and induced differentiation and apoptosis only in cells with a functional CaSR, which were further enhanced in the presence of NPS R-568, a positive allosteric modulator of CaSR. The mutant CaSR inhibited the anti-tumorigenic effects of 1,25-D3 suggesting that the anti-neoplastic effects of 1,25-D3 are, at least in part, mediated by the CaSR. Taken together, our data provides molecular evidence to support the epidemiological observation that both, vitamin D and calcium are needed for protection against malignant transformation of the colon and that their effect is modulated by the presence of a functional CaSR. This article is part of a Special Issue

  17. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt......, that it can be adapted to changing functional needs, and that it has an architectural and cultural value. A specific proposal for a transformation that enhances the architectural qualities and building heritage values of an existing building forms the empirical material, which is discussed using different...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  18. Identity transformation

    DEFF Research Database (Denmark)

    Neergaard, Helle; Robinson, Sarah; Jones, Sally

    , as well as the resources they have when they come to the classroom. It also incorporates perspectives from (ii) transformational learning and explores the concept of (iii) nudging from a pedagogical viewpoint, proposing it as an important tool in entrepreneurship education. The study incorporates......This paper develops the concept of ‘pedagogical nudging’ and examines four interventions in an entrepreneurship classroom and the potential it has for student identity transformation. Pedagogical nudging is positioned as a tool, which in the hands of a reflective, professional......) assists students in straddling the divide between identities, the emotions and tensions this elicits, and (iv) transform student understanding. We extend nudging theory into a new territory. Pedagogical nudging techniques may be able to unlock doors and bring our students beyond the unacknowledged...

  19. Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal

    Directory of Open Access Journals (Sweden)

    Peter Valent

    2017-12-01

    Full Text Available Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection.

  20. Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal.

    Science.gov (United States)

    Valent, Peter; Akin, Cem; Arock, Michel; Bock, Christoph; George, Tracy I; Galli, Stephen J; Gotlib, Jason; Haferlach, Torsten; Hoermann, Gregor; Hermine, Olivier; Jäger, Ulrich; Kenner, Lukas; Kreipe, Hans; Majeti, Ravindra; Metcalfe, Dean D; Orfao, Alberto; Reiter, Andreas; Sperr, Wolfgang R; Staber, Philipp B; Sotlar, Karl; Schiffer, Charles; Superti-Furga, Giulio; Horny, Hans-Peter

    2017-12-01

    Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent) and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Study on the measurement of serum thymidine kinase and its clinical significance in hematological neoplastic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Torizumi, Kazutami; Aibata, Hirofumi; Yamada, Ryusaku; Shimizu, Eiji; Okamoto, Yukiharu; Tsujimoto, Masato; Tsuda, Tadaaki; Ota, Kiichiro

    1988-06-01

    A 'Prolifigen TK-REA' kit for measuring serum thymidine kinase (TK) was fundamentally and clinically evaluated. Laboratory findings for recovery, dilution, and reproducibility were satisfactory. There was no correlation between serum TK activity and serum lactic dehydrogenase, carcinoembryonic antigen, or ..cap alpha..-fetoprotein. The serum concentration of TK in normal volunteers ranged from 1.6 to 6.5 U/L. It was extremely high for chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), as compared to the normal value. In the AML group, higher incidence of blasts in peripheral blood tended to be associated with higher serum concentration of TK. A similar tendency was seen in the case of acute lymphocytic leukemia (ALL) and myelodysplasia syndrome (MDS). A positive correlation between serum TK activity and the absolute counts of myeloblasts in peripheral blood existed in CML and AML patients. Since patients with hematological neoplastic disorders, who have abnormality in DNA metabolism, tended to have higher serum TK activity than did normal volunteers, serum TK activity may have a potential marker for abnormal DNA metabolism. (Namekawa, K.).

  2. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    International Nuclear Information System (INIS)

    Price, Paul S.; Keenan, Russell E.; Swartout, Jeffrey C.

    2008-01-01

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals

  3. Imaging the cranial nerves: part II: primary and secondary neoplastic conditions and neurovascular conflicts

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil- Centro de Lisboa, Radiology Department, Lisboa Codex (Portugal); Casselman, Jan [A. Z. St Jan Brugge and A. Z. St Augustinus Antwerpen Hospitals, Department of Radiology, Antwerp (Belgium)

    2007-09-15

    There have been unprecedented improvements in cross-sectional imaging in the last decades. The emergence of volumetric CT, higher field MR scanners and higher resolution MR sequences is largely responsible for the increasing diagnostic yield of imaging in patients presenting with cranial nerve deficits. The introduction of parallel MR imaging in combination with small surface coils allows the depiction of submillimetric nerves and nerve branches, and volumetric CT and MR imaging is able to provide high quality multiplanar and curved reconstructions that can follow the often complex course of cranial nerves. Seeking the cause of a cranial nerve deficit is a common indication for imaging, and it is not uncommon that radiologists are the first specialists to see a patient with a cranial neuropathy. To increase the diagnostic yield of imaging, high-resolution studies with smaller fields of view are required. To keep imaging studies within a reasonable time frame, it is mandatory to tailor the study according to neuro-topographic testing. This review article focuses on the contribution of current imaging techniques in the depiction of primary and secondary neoplastic conditions affecting the cranial nerves as well as on neurovascular conflicts, an increasingly recognized cause of cranial neuralgias. (orig.)

  4. Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease

    Directory of Open Access Journals (Sweden)

    Patrick S. Randolph-Quinney

    2016-07-01

    Full Text Available We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa, dated to 1.98 million years ago. The affected individual was male and developmentally equivalent to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from well-vascularised connective tissue within which there is active production of osteoid and woven bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in the hominin record, highlighting the importance of this discovery. The presence of this disease at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by perhaps 200 000 years.

  5. Diagnostic Accuracy of CT in Paediatric Intracranial Neoplastic Lesions - Radiologic and Pathologic Correlation

    International Nuclear Information System (INIS)

    Qureshi, A.

    2011-01-01

    The frequency of paediatric tumours in developing countries could be attributed to the increased percentage (39% of total population of children) in the overall population. Therefore, extensive researches should be under taken in the field of Paediatric Oncology in the third world. Objective: This study was conducted to determine the diagnostic accuracy of CT by comparing the pre-operative radiological findings of paediatric brain tumours with post-operative histopathological findings on the basis of characteristic radiological features of various tumours. Materials and Methods: This was a hospital based prospective, cross-sectional and descriptive study carried out in Radiology Dept, KEMU / Mayo Hospital, Lahore. Study was conducted over a period of 3 years from June 2005 till June 2008 and comprised of 100 cases of paediatric brain tumours up to 12 years of age. Cases were also collected from Mayo and Children Hospital, Lahore. Results: Topographically, supratentorial tumours were found more than infratentorial 55 : 45. Low grade were more common than high grade 73 : 27. The most common tumour was astrocytoma with 52 cases. Medulloblastoma ranked the second with 16 cases followed by craniopharyngioma with 12 cases. Conclusion: The diagnostic accuracy of CT scan was found to be 83% when correlated with histopathology. CT proved fairly accurate in detection of paediatric intracranial neoplastic lesions. As CT is relatively commonly available inexpensive modality than MRI so it can be used as non invasive imaging modality. (author)

  6. Imaging the cranial nerves: part II: primary and secondary neoplastic conditions and neurovascular conflicts

    International Nuclear Information System (INIS)

    Borges, Alexandra; Casselman, Jan

    2007-01-01

    There have been unprecedented improvements in cross-sectional imaging in the last decades. The emergence of volumetric CT, higher field MR scanners and higher resolution MR sequences is largely responsible for the increasing diagnostic yield of imaging in patients presenting with cranial nerve deficits. The introduction of parallel MR imaging in combination with small surface coils allows the depiction of submillimetric nerves and nerve branches, and volumetric CT and MR imaging is able to provide high quality multiplanar and curved reconstructions that can follow the often complex course of cranial nerves. Seeking the cause of a cranial nerve deficit is a common indication for imaging, and it is not uncommon that radiologists are the first specialists to see a patient with a cranial neuropathy. To increase the diagnostic yield of imaging, high-resolution studies with smaller fields of view are required. To keep imaging studies within a reasonable time frame, it is mandatory to tailor the study according to neuro-topographic testing. This review article focuses on the contribution of current imaging techniques in the depiction of primary and secondary neoplastic conditions affecting the cranial nerves as well as on neurovascular conflicts, an increasingly recognized cause of cranial neuralgias. (orig.)

  7. The effects of environmental deuterium on normal and neoplastic cultured cell development

    International Nuclear Information System (INIS)

    Bild, W.; Schuller, T.; Zhihai, Qin; Blankenstein, T.; Nastasa, V.; Haulica, I.

    2000-01-01

    The powdered culture media (RPMI - 1640) were reconstituted either with normal distilled water (150 ppm deuterium) either with deuterium - depleted water (DDW) in various concentrations (30, 60, 90 ppm) and sterilized by filtration with 0.2 μm filters. The cell lines used were NIH (normal mouse fibroblasts), RAG (mouse renal carcinoma) and TS/A (mouse mammary adenocarcinoma). In auxiliary tests, BAIBC mouse splenocytes in direct culture were used, stimulated for growth with concanavalin A or LPS (bacterial lipopolysaccharide). The estimation of the growth was made using the MTT assay or direct counting with trypan blue exclusion. The following results were obtained: Deuterium - depleted water had a stimulating effect on cell growth, the most important stimulating action being from the 90 ppm deuterium-water. The growth curves show, in a first phase, a stimulation of the rapid -growing neoplastic cells, followed by a slower growth of the normal cells. Amiloride 100 mM blocking of the Na + /K + membrane pump did not affect the cell growth curves, while the lansoprazole 100 mM blocking of the K + /H + ATP-ase brought the growth curves at the level of those with normal water. This might show an eventual involvement of the K + /H + antiport in the stimulating effects of the DDW. (authors)

  8. The difficulties of pseudo-Cushing's syndrome (or "non-neoplastic hypercortisolism").

    Science.gov (United States)

    Chabre, Olivier

    2018-06-01

    Pseudo-Cushing's syndrome covers different pathological conditions responsible for mild-to-moderate ACTH-dependent hypercortisolism, related not to an ACTH-secreting tumor but rather to CRH and/or AVP hypothalamic secretion through activation of various neural pathways, in patients generally displaying excess central adiposity. It is better termed "non-neoplastic hypercortisolism" (NNH). The main conditions implicated in NNH comprise: neuropsychiatric disorder, alcohol abuse, insulin-resistant obesity, polycystic ovary syndrome, and end-stage kidney disease. Glucocorticoid resistance is one differential diagnosis, as are some cases of primary adrenal disease with incompletely suppressed ACTH. Differentiating between NNH and mild-to-moderate Cushing's disease can be a real challenge. Clinical analysis, based on thorough history taking and screening for catabolic signs is essential; useful explorations include midnight serum or salivary cortisol and Dex/CRH and ddAVP stimulation response. Pituitary MRI suffers from limitations regarding both sensitivity and specificity, while bilateral inferior petrosal sinus sampling cannot distinguish between pituitary ACTH secretion by a tumor or by normal cells stimulated by endogenous CRH. Definitive diagnosis of functional etiology requires demonstrating that treatment of the underlying condition restores normal secretion of ACTH and cortisol, but this is not always possible. Lingering diagnostic uncertainty has to be accepted in certain patients, who will have to be followed up for some time before diagnosis can be considered more or less definitive. Copyright © 2018. Published by Elsevier Masson SAS.

  9. Complications after tracheal and cricotracheal resection and anastomosis for inflammatory and neoplastic stenoses.

    Science.gov (United States)

    Piazza, Cesare; Del Bon, Francesca; Paderno, Alberto; Grazioli, Paola; Mangili, Stefano; Lombardi, Davide; Nicolai, Piero; Peretti, Giorgio

    2014-11-01

    This study aimed to evaluate complications and success rates of tracheal resection and anastomosis (TRA) and cricotracheal resection and anastomosis (CTRA) in patients treated in 2 academic institutions. Retrospective charts review of 137 patients submitted to TRA/CTRA. Fifty (36.5%) had neoplastic (group A) and 87 (63.5%) benign (group B) stenoses. Using univariate analysis, age, medical comorbidities, previous radiotherapy, type of TRA/CTRA, association with neck dissection and thyroidectomy, length of resected airway, and preoperative tracheotomy were evaluated to identify factors predictive of complications and outcomes. The mean length of resected airway was 2.7 and 3 cm in groups A and B, respectively. Overall decannulation and complication rates for group A were 96% and 36%, and 99% and 46% for group B, respectively. Length of airway resected and presence of preoperative tracheotomy had a statistically significant effect on major surgical complications. Age older than 70 and cardiovascular and pulmonary comorbidities were significantly associated with the incidence of major medical complications. No statistically significant difference was found considering the complication rates of group A versus group B. Even though the overall success rate of TRA/CTRA is high, it should always be regarded as a major surgical procedure with a non-negligible incidence of complications. © The Author(s) 2014.

  10. Is there an association with constitutional structural chromosomal abnormalities and hematologic neoplastic process? A short review.

    Science.gov (United States)

    Panani, Anna D

    2009-04-01

    The occasional observation of constitutional chromosomal abnormalities in patients with a malignant disease has led to a number of studies on their potential role in cancer development. Investigations of families with hereditary cancers and constitutional chromosomal abnormalities have been key observations leading to the molecular identification of specific genes implicated in tumorigenesis. Large studies have been reported on the incidence of constitutional chromosomal aberrations in patients with hematologic malignancies, but they could not confirm an increased risk for hematologic malignancy among carriers of structural chromosomal changes. However, it is of particular interest that constitutional structural aberrations with breakpoints similar to leukemia-associated specific breakpoints have been reported in patients with hematologic malignancies. Because of insufficient data, it remains still unclear if these aberrations represent random events or are associated with malignancy. There has been a substantial discussion about mechanisms involved in constitutional structural chromosomal changes in the literature. The documentation of more patients with constitutional structural chromosomal changes could be of major importance. Most importantly, the molecular investigation of chromosomal regions involved in rearrangements could give useful information on the genetic events underlying constitutional anomalies, contributing to isolation of genes important in the development of the neoplastic process. Regarding constitutional anomalies in patients with hematologic disorders, a survey of the cytogenetic data of our cytogenetics unit is herein also presented.

  11. [Microsatellite instability and human papilloma virus genotypes in preneoplastic and neoplastic uterine cervix lesions].

    Science.gov (United States)

    Roa S, Juan Carlos; Martínez S, Ricardo; Montenegro, Sonia; Roa E, Iván; Capurro V, Italo; Ibacache S, Gilda; Melo A, Angélica

    2007-01-01

    The association between some specific human papilloma virus (HPV) types and cervix cancer is well known. However, the genetic conditions that favor the development of cervical cancer are less well known. To determine the presence of satellite instability (MSI) in preneoplastic and neoplastic lesions of the cervix and correlate these findings with HPV genotypes. Biopsy samples of cervical lesions were studied. Sixteen had low grade lesions, 22 had high grade lesions and 28 had an epidermoid cancer. Viral types were identified with polymerase chain reaction, dot-blot hybridization and restriction fragment length polymorphism. MSI was determined using a panel of eight highly informative microsatellites. Microsatellite instability in at least one locus was observed in 91, 56 and 69% of low grade lesions, high grade lesions and epidermoid carcinomas, respectively. MSI-High grade, MSI-Low grade instability and microsatellite stability were observed in 5, 60 and 46% of samples, respectively. Two of three samples with high grade instability had HPV 52 genotype. Other viral subtypes had frequencies that ranged from 78% to 100%, with the exception of HPV16 that was present in only 53% of samples with low grade instability. Two thirds of biopsy samples from cervical lesions had MSI, mechanism that can be involved in the first stages of cervical carcinogenesis. The low frequency of high grade instability, its association with HPV52 and the low frequency of HPV16 in samples with low grade instability, suggest different coadjutant mechanisms in cervical carcinogenesis.

  12. Biochemical aspects of the neoplastic cell in relation to positive indicators

    International Nuclear Information System (INIS)

    Strom, R.

    1975-01-01

    In scintigraphic diagnoses with positive indicators, the capacity of these indicators to fix themselves or to selectively concentrate in the neoplastic tissue is utilized. This selectivity could be due to several biochemical peculiarities of the tumor cells in relation to surrounding cells: the presence on the membrane of particular chemical groups which allow these cells to invade adjacent tissue without being subject to contact inhibition; the presence on these same membranes of antigenic determinants which are particular to these cells and which can be revealed with specific antibodies; a high concentration of nucleic acid in tumor cells, with the associated possibility of fixing substances having a particular tropism for nucleic acids or for their chemical constituents; an elevated rate of nucleic acid synthesis, with an associated increase in the incorporation of precursors and also of substances which specifically interfere with this biochemical pathway; in numerous cases, tumor cells produce high quantities of acidic metabolites which must be neutralized by equivalent quantities of anions, the latter entering the cells by active transport phenomena; in tumors which develop particularly rapidly, there is a development of degenerative processes with an accumulation of degradation products; in metastatic tumors, the cells have metabolic and biosynthetic activities which are a function of the original tissue, with the possiblity of a clear metabolic difference in relation to adjacent tissues [fr

  13. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuil...

  14. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2008-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  15. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2010-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  16. Transformation & Metamorphosis

    Science.gov (United States)

    Lott, Debra

    2009-01-01

    The sculptures of Canadian artist Brian Jungen are a great inspiration for a lesson on creating new forms. Jungen transforms found objects into unique creations without fully concealing their original form or purpose. Frank Stella's sculpture series, including "K.132,2007" made of stainless steel and spray paint, is another great example of…

  17. Transforming Society

    DEFF Research Database (Denmark)

    Enemark, Stig; Dahl Højgaard, Pia

    2017-01-01

    , was a result of transforming society from a feudal system to a capitalistic and market based economy. This story is interesting in itself - but it also provides a key to understanding the cadastral system of today. The system has evolved over time and now serves a whole range of functions in society. The paper...

  18. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    International Nuclear Information System (INIS)

    Antoniassi, M.; Conceição, A.L.C.; Poletti, M.E.

    2012-01-01

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: ► Electron density of normal and neoplastic breast tissues was measured using Compton scattering. ► Monochromatic synchrotron radiation was used to obtain the Compton scattering data. ► The area of Compton peaks was used to determine the electron densities of samples. ► Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. ► Comparison with previous results showed differences smaller than 4%.

  19. Age and Spatial Peculiarities of Non-neoplastic Diseases of the Skin and Subcutaneous Tissue in Kazakhstan, 2003–2015

    OpenAIRE

    IGISSINOV, Nurbek; KULMIRZAYEVA, Dariyana; BILYALOVA, Zarina; AKPOLATOVA, Gulnur; MAMYRBAYEVA, Marzya; ZHUMAGALIYEVA, Galina

    2017-01-01

    Background: Arrangement of effective management aimed at improving dermatological services and consistent care of patients with skin diseases depends on understanding the epidemiological situation. Methods: This retrospective study presents an epidemiological assessment of non-neoplastic skin and subcutaneous tissue diseases in Kazakhstan registered in 2003–2015. Results: The yearly incidence rate of the diseases among the whole population was in average 3,341.8±121.1 per 100000 population. T...

  20. Para neoplastic syndromes: Usefulness of 18F-fluoro-deoxy-glucose (F.D.G.) positron emission tomography (PET)

    International Nuclear Information System (INIS)

    Banayan, S.; Janier, M.; Guillerma-Zucchi, N.; Billotey, C.; Ninet, J.; Delmas, P.; Thivolet, C.; Pellet, O.

    2008-01-01

    Background We evaluated the performance of 18 F-fluorodeoxyglucose ( 18 F.D.G.) positron emission tomography (PET) in the diagnosis of underlying malignancy in cases of suspected para neoplastic syndrome (P.S.). Methods 18 F.D.G.-PET was performed in 31 patients, clinically suspected to have P.S.. The P.S. were 34, among which 12 neurological diseases, eight endocrine, seven rheumatological, one dermatological and six vascular. We compared computed tomography (CT), iodine-enhanced most of the time, and 18 F.D.G.-PET reports to clinicians definitive conclusion at the end of the work-up and a follow-up period of, at least, two months. Results We obtained a histological diagnosis of cancer for ten patients, but could only identify the primary site of malignancy for nine of them. 18 F.D.G.-PET showed six primary sites among which three were not seen on CT. CT disclosed four primary sites, among which one was not seen on 18 F.D.G.-PET. In one case, 18 F.D.G.-PET disclosed regional lymph node metastases whereas these were not identified by CT. Eleven non-neoplastic causes were evidenced, among which 18 F.D.G.-PET played a major role in three cases. Ten causes were still undetermined at the end of the study. Conclusion Whole-body 18 F.D.G.-PET study plays an important role in the identification of underlying malignancy in clinically suspected para neoplastic syndromes; either by identifying the primary tumor or by directing biopsy of metastases. Furthermore, it can identify non-neoplastic causes. (authors)

  1. Ribosomal protein S6 phosphorylation and morphological changes in response to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate in primary human tumour cells, established and transformed cell lines

    DEFF Research Database (Denmark)

    Rance, A J; Thönnes, M; Issinger, O G

    1985-01-01

    lifespan (fibroblasts, primary human tumour cells) can be mimicked by unknown steps also associated with immortalization (establishment function) and the transformed state of the tumour cells. Another interesting observation were morphological changes of the established and SV40-transformed cells which...

  2. Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    A. Silvani

    2013-01-01

    Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

  3. Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

    2012-07-15

    In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

  4. Differentiation of osteoporotic and neoplastic vertebral fractures by chemical shift {in-phase and out-of phase} MR imaging

    International Nuclear Information System (INIS)

    Ragab, Yasser; Emad, Yasser; Gheita, Tamer; Mansour, Maged; Abou-Zeid, A.; Ferrari, Serge; Rasker, Johannes J.

    2009-01-01

    Objective: The objective of this study was to establish the cut-off value of the signal intensity drop on chemical shift magnetic resonance imaging (MRI) with appropriate sensitivity and specificity to differentiate osteoporotic from neoplastic wedging of the spine. Patients and methods: All patients with wedging of vertebral bodies were included consecutively between February 2006 and January 2007. A chemical shift MRI was performed and signal intensity after (in-phase and out-phase) images were obtained. A DXA was performed in all. Results: A total of 40 patients were included, 20 with osteoporotic wedging (group 1) and 20 neoplastic (group 2). They were 21 males and 19 females. Acute vertebral collapse was observed in 15 patients in group 1 and subacute collapse in another 5 patients, while in group 2, 11 patients showed acute collapse and 9 patients (45%) showed subacute vertebral collapse. On the chemical shift MRI a substantial reduction in signal intensity was found in all lesions in both groups. The proportional changes observed in signal intensity of bone marrow lesions on in-phase compared with out-of-phase images showed significant differences in both groups (P < 0.05). At a cut-off value of 35%, the observed sensitivity of out-of-phase images was 95%, specificity was 100%, positive predictive value was 100% and negative predictive value was 95.2%. Conclusion: A chemical shift MRI is useful in order to differentiate patients with vertebral collapse due to underlying osteoporosis or neoplastic process.

  5. Neoplastic lesions of the temporomandibular joint (TMJ): diagnosis, differential diagnosis and intervention; Neoplasien des Temporomandibulargelenks (TMG). Diagnostik, Differenzialdiagnostik und Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J.; Abolmaali, N.; Schedel, H.; Bergh, B. [Frankfurt Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Maeurer, J. [Radiologische Praxis am Prinzregentenplatz, Muenchen (Germany)

    2001-09-01

    Purpose. To evaluate the effectiveness of diagnostic and interventional radiological techniques for neoplastic lesions of the temporomandibular joint (TMJ). Material and methods. Modern diagnosis of the TMJ is based on the clinical use of conventional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI) and interventional techniques like biopsies, vascular occlusion and ablation. Results. Conventional X-ray still forms the basic diagnostic procedure applied in open and closed mouth position. CT improves the diagnostic information and serves as the standard diagnostical instrument for cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue infiltration in multiplanar techniques and high spatial resolution. Interventional vascular and ablative techniques improve the treatment of neoplastic disorders. (orig.) [German] Zielsetzung. Vorstellung der Wertigkeit bildgebender Verfahren fuer die diagnostische und interventionelle Radiologie des Temporomandibulargelenks (TMG). Material und Methodik. Die moderne Radiologie des TMG basiert auf dem Einsatz der konventionellen Roentgendiagnostik, der Computertomographie (CT) und der Magnetresonanztomographie (MRT), sowie interventioneller Verfahren wie der Biopsie, vaskulaerer Embolisationsverfahren und tumorablativer Verfahren. Ergebnisse. Als Basisdiagnostik dient die konventionelle Diagnostik in offener und geschlossener Mundposition der Erfassung von Funktionsstoerungen sowie ossaerer Destruktionen. Die CT erweitert das diagnostische Spektrum und verbessert die Differenzialdiagnostik fuer ossifizierende Prozesse. Der Einsatz der MRT erlaubt die Erfassung der Weichteilinfiltration sowie der Gelenkstrukturen. Vaskulaere interventionelle Verfahren dienen der praetherapeutischen Okklusion bzw. der palliativen Tumortherapie in Form der okklusiven Embolisation, der Chemoembolisation, oder auch der Tumorablation. (orig.)

  6. Accelerating the Transformation of Economic Development Mode to Promote the Sable and Rapid Development of Industry%加快转变经济发展方式 推进行业平稳较快发展

    Institute of Scientific and Technical Information of China (English)

    张新民

    2012-01-01

    It is pointed out through the interpretation of the "Twelfth Five-Year Plan" of the woodworking machinery industry that the next five years is a very import period when the transformation development of woodworking machinery industry and the breakthrough development of industry transfer should be accelerated, structural adjustment and technical innovation should serve as important support for the development of woodworking machinery industry in the following five years , the change in the marked demand should be followed closely to realize the shift to new industries featuring structural optimization, advanced technology, cleanness and safety and high added value, enterprise famous brands should be expanded, strong alliance between enterprises should be promoted in order to be bigger and stronger and great importance should be attached to the soft strength construction of enterprises in terms of human resources, corporate culture and internal management to realize the long-term development of enterprises and enhance the intangible wealth for enterprise development.%对木工机械行业“十二五”规划进行解读,指出未来五年是加快木机行业转型发展、产业转移突破发展的关键五年,要坚持把结构调整和科技创新作为未来五年木机行业发展的重要支撑,要紧跟市场需求变化。向结构优化、技术先进、清洁安全、附加值高的新型产业转向,要扩大企业知名品牌,推进强强联合,做大做强,要重视企业的人力资源、企业文化、内部管理等软实力建设,增加企业发展的无形财富,实现企业长久发展。

  7. The Loss of TGF-β Signaling Promotes Prostate Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    William H. Tu

    2003-05-01

    Full Text Available In breast and colon cancers, transforming growth factor (TGIF-β signaling initially has an antineoplastic effect, inhibiting tumor growth, but eventually exerts a proneoplastic effect, increasing motility and cancer spread. In prostate cancer, studies using human samples have correlated the loss of the TGIF-β type II receptor (TβRll with higher tumor grade. To determine the effect of an inhibited TGIF-β pathway on prostate cancer, we bred transgenic mice expressing the tumorigenic SV40 large T antigen in the prostate with transgenic mice expressing a dominant negative TβRII mutant (DNIIR in the prostate. Transgene(s and TGIF-β expression were identified in the prostate and decreased protein levels of plasminogen activator inhibitor type I, as a marker for TGIF-β signaling, correlated with expression of the DNIIR. Although the sizes of the neoplastic prostates were not enlarged, increased amounts of metastasis were observed in mice expressing both transgenes compared to age-matched control mice expressing only the large T antigen transgene. Our study demonstrates for the first time that a disruption of TGIF-β signaling in prostate cancer plays a causal role in promoting tumor metastasis.

  8. Discrete transforms

    CERN Document Server

    Firth, Jean M

    1992-01-01

    The analysis of signals and systems using transform methods is a very important aspect of the examination of processes and problems in an increasingly wide range of applications. Whereas the initial impetus in the development of methods appropriate for handling discrete sets of data occurred mainly in an electrical engineering context (for example in the design of digital filters), the same techniques are in use in such disciplines as cardiology, optics, speech analysis and management, as well as in other branches of science and engineering. This text is aimed at a readership whose mathematical background includes some acquaintance with complex numbers, linear differen­ tial equations, matrix algebra, and series. Specifically, a familiarity with Fourier series (in trigonometric and exponential forms) is assumed, and an exposure to the concept of a continuous integral transform is desirable. Such a background can be expected, for example, on completion of the first year of a science or engineering degree cour...

  9. Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

    International Nuclear Information System (INIS)

    Grau, C.

    1994-01-01

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD 50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

  10. YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

    Science.gov (United States)

    Jaramillo-Rodríguez, Yolanda; Cerda-Flores, Ricardo M; Ruiz-Ramos, Ruben; López-Márquez, Francisco C; Calderón-Garcidueñas, Ana Laura

    2014-04-01

    Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  11. Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A Systematic Review.

    Science.gov (United States)

    Gérard, S; Bréchemier, D; Lefort, A; Lozano, S; Abellan Van Kan, G; Filleron, T; Mourey, L; Bernard-Marty, C; Rougé-Bugat, M E; Soler, V; Vellas, B; Cesari, M; Rolland, Y; Balardy, L

    2016-01-01

    The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.

  12. Chest wall – a structure underestimated in ultrasonography. Part III: Neoplastic lesions

    Directory of Open Access Journals (Sweden)

    Andrzej Smereczyński

    2017-12-01

    Full Text Available Chest wall neoplasms mainly include malignancies, metastatic in particular. Differential diagnosis should include clinical data; tumor location, extent, delineation; the degree of homogeneity; the presence of calcifications; the nature of bone destruction and the degree of vascularization. The aim of the paper is to present both the benefits and limitations of ultrasound for the diagnosis of chest wall neoplasms. The neoplastic process may be limited to the chest wall; it may spread from the chest wall into the intrathoracic structures or spread from the inside of the chest towards the chest wall. Benign tumors basically originate from vessels, nerves, bones, cartilage and soft tissues. In this paper, we briefly discuss malformations of blood and lymphatic vessels, glomus tumor as well as neurogenic tumors originating in the thoracic branches of the spinal nerves and the autonomic visceral system. Metastases, particularly lung, breast, kidney cancer, melanoma and prostate cancer, are predominant tumors of the osteocartilaginous structures of the chest wall. Plasma cell myeloma is also relatively common. The vast majority of these lesions are osteolytic, which is reflected in ultrasound as irregular cortical defects. Osteoblastic foci result only in irregular outline of the bone surface. Lipomas are the most common neoplasms of the chest wall soft tissue. Elastofibroma is another tumor with characteristic echostructure. Desmoid fibromatosis, which is considered to be a benign lesion with local aggressivity and recurrences after surgical resection, represents an interesting tumor form the clinical point of view. Ultrasonography represents an optimal tool for the monitoring of different biopsies of pathological lesions located in the chest wall. Based on our experiences and literature data, this method should be considered as a preliminary diagnosis of patients with chest wall tumors.

  13. Psidium guajava L. anti-neoplastic effects: induction of apoptosis and cell differentiation.

    Science.gov (United States)

    Bontempo, P; Doto, A; Miceli, M; Mita, L; Benedetti, R; Nebbioso, A; Veglione, M; Rigano, D; Cioffi, M; Sica, V; Molinari, A M; Altucci, L

    2012-02-01

    Curative properties of medicinal plants such as Psidium guajava L. (Myrtaceae) have often been indicated by epidemiological studies on populations in which these fruits are consumed daily. However, complete characterization of the active principles responsible for this ability has never been performed. Here, we have characterized P. guajava's anti-cancer potential and identified the parts of the fruit involved in its anti-neoplastic action. We studied morphology of our cells, cell cycle characteristics and apoptosis and performed immunostaining, differentiation and western blot analyses. We report that the P. guajava extract exerted anti-cancer control on both haematological and solid neoplasias. P. guajava extract's anti-tumour properties were found to be tightly bound to induction of apoptosis and differentiation. Use of ex vivo myeloid leukaemia blasts corroborated that P. guajava was able to induce cell death but did not exhibit anti-cancer effects on all malignant cells investigated, indicating selective activity against certain types of tumour. Analyses of P. guajava pulp, peel and seeds identified the pulp as being the most relevant component for causing cell cycle arrest and apoptosis, whereas peel was responsible for causing cell differentiation. P. guajava itself and its pulp-derived extract were found to induce apoptosis accompanied by caspase activation and p16, p21, Fas ligand (FASL TNF super-family, member 6), Bcl-2-associated agonist of cell death (BAD) and tumour necrosis factor receptor super-family, member 10b (DR5), overexpression. Our findings showed that P. guajava L. extract was able to exert anti-cancer activity on cultures in vitro and ex vivo, supporting the hypothesis of its anti malignant pro-apoptotic modulation. © 2011 Blackwell Publishing Ltd.

  14. Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa

    Directory of Open Access Journals (Sweden)

    Mäki Markku

    2008-04-01

    Full Text Available Abstract Background Human gastrointestinal mucosa regenerates vigorously throughout life, but the factors controlling cell fate in mature mucosa are poorly understood. GATA transcription factors direct cell proliferation and differentiation in many organs, and are implicated in tumorigenesis. GATA-4 and GATA-6 are considered crucial for the formation of murine gastrointestinal mucosa, but their role in human gastrointestinal tract remains unexplored. We studied in detail the expression patterns of these two GATA factors and a GATA-6 down-stream target, Indian hedgehog (Ihh, in normal human gastrointestinal mucosa. Since these factors are considered important for proliferation and differentiation, we also explored the possible alterations in their expression in gastrointestinal neoplasias. The expression of the carcinogenesis-related protein Indian hedgehog was also investigated in comparison to GATA factors. Methods Samples of normal and neoplastic gastrointestinal tract from children and adults were subjected to RNA in situ hybridization with 33P labelled probes and immunohistochemistry, using an avidin-biotin immunoperoxidase system. The pathological tissues examined included samples of chronic and atrophic gastritis as well as adenomas and adenocarcinomas of the colon and rectum. Results GATA-4 was abundant in the differentiated epithelial cells of the proximal parts of the gastrointestinal tract but was absent from the distal parts. In contrast, GATA-6 was expressed throughout the gastrointestinal epithelium, and in the distal gut its expression was most intense at the bottom of the crypts, i.e. cells with proliferative capacity. Both factors were also present in Barrett's esophagus and metaplasia of the stomach. GATA-6 expression was reduced in colon carcinoma. Ihh expression overlapped with that of GATA-6 especially in benign gastrointestinal neoplasias. Conclusion The results suggest differential but overlapping functions for GATA-4 and

  15. XML Transformations

    Directory of Open Access Journals (Sweden)

    Felician ALECU

    2012-04-01

    Full Text Available XSLT style sheets are designed to transform the XML documents into something else. The two most popular parsers of the moment are the Document Object Model (DOM and the Simple API for XML (SAX. DOM is an official recommendation of the W3C (available at http://www.w3.org/TR/REC-DOM-Level-1, while SAX is a de facto standard. A good parser should be fast, space efficient, rich in functionality and easy to use.

  16. RF transformer

    Science.gov (United States)

    Smith, James L.; Helenberg, Harold W.; Kilsdonk, Dennis J.

    1979-01-01

    There is provided an improved RF transformer having a single-turn secondary of cylindrical shape and a coiled encapsulated primary contained within the secondary. The coil is tapered so that the narrowest separation between the primary and the secondary is at one end of the coil. The encapsulated primary is removable from the secondary so that a variety of different capacity primaries can be utilized with one secondary.

  17. Transformative Agency

    DEFF Research Database (Denmark)

    Majgaard, Klaus

    The purpose of this paper is to enhance the conceptual understanding of the mediatory relationship between paradoxes on an organizational and an individual level. It presents a concept of agency that comprises and mediates between a structural and individual pole. The constitution of this agency ...... is achieved through narrative activity that oscillates between the poles and transforms paradoxes through the configuration of plots and metaphors. Empirical cases are introduced in order to illustrate the implications of this understanding....

  18. Composing a Tumor Specific Bacterial Promoter.

    Directory of Open Access Journals (Sweden)

    Igor V Deyneko

    Full Text Available Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.

  19. Non-neoplastic cystic and cystic-like lesions of the pancreas: may mimic pancreatic cystic neoplasms.

    Science.gov (United States)

    Goh, Brian K P; Tan, Yu-Meng; Chung, Yaw-Fui A; Chow, Pierce K H; Ong, Hock-Soo; Lim, Dennis T H; Wong, Wai-Keong; Ooi, London L P J

    2006-05-01

    Cystic lesions of the pancreas consist of a broad range of pathological entities. With the exception of the pancreatic pseudocyst, these are usually caused by pancreatic cystic neoplasms. Non-neoplastic pancreatic cystic and cystic-like lesions are extremely rare. In the present article, the surgical experience with these unusual entities over a 14-year period is reported. Between 1991 and 2004, all patients who underwent surgical exploration for a cystic lesion of the pancreas were retrospectively reviewed. Patients with a pancreatic pseudocyst were excluded. There were 106 patients of whom 8 (7.5%) had a final pathological diagnosis consistent with a non-neoplastic pancreatic cystic or cystic-like lesion, including 3 patients with a benign epithelial cyst, 2 with a pancreatic abscess (one tuberculous and one foreign body), 2 with mucous retention cysts and 1 with a mucinous non-neoplastic cyst. These eight patients are the focus of this study. There were six female and two male patients with a median age of 61.5 years (range, 41-71 years). All the patients were of Asian origin including seven Chinese and one Indian. Four of the patients were asymptomatic and their pancreatic cysts were discovered incidentally on radiological imaging for other indications. All the patients underwent preoperative radiological investigations, including ultrasonography, computed tomography or magnetic resonance imaging, which showed a cystic lesion of the pancreas. Three patients, all of whom were symptomatic, were diagnosed preoperatively with a malignant cystic neoplasm on the basis of radiological imaging. Two patients were eventually found to have a pancreatic abscess, one tuberculous and the other, secondary to foreign body perforation. The third patient was found on final histology to have chronic pancreatitis with retention cysts. The remaining five patients had a preoperative diagnosis of an indeterminate cyst; on pathological examination, they were found to have a benign

  20. HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

    Science.gov (United States)

    DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

    2016-01-01

    The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL  CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions

  1. M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

    Directory of Open Access Journals (Sweden)

    Yasushi Hara

    Full Text Available Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs, acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt pathway and the signal transducer and activator of transcription 5 (STAT5 but only on endolysosomes and on the endoplasmic reticulum (ER, respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide, an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM. Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is

  2. M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

    Science.gov (United States)

    Hara, Yasushi; Obata, Yuuki; Horikawa, Keita; Tasaki, Yasutaka; Suzuki, Kyohei; Murata, Takatsugu; Shiina, Isamu; Abe, Ryo

    2017-01-01

    Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM). Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is unable to

  3. Transformational Leadership in Research Universities

    Science.gov (United States)

    Gilmore, Ryann M.

    2011-01-01

    In order to preserve research integrity, leaders at postsecondary research institutions must utilize transformational leadership behaviors in order to promote a campus culture that is the most conducive to responsible research conduct. In support of this assertion, the issue of research misconduct and its potential consequences for both…

  4. Electrical transformer handbook

    Energy Technology Data Exchange (ETDEWEB)

    Hurst, R.W.; Horne, D. (eds.)

    2005-07-01

    This handbook is a valuable user guide intended for electrical engineering and maintenance personnel, electrical contractors and electrical engineering students. It provides current information on techniques and technologies that can help extend the life of transformers. It discusses transformer testing, monitoring, design, commissioning, retrofitting and other elements involved in keeping electrical transformers in safe and efficient operation. It demonstrates how a power transformer can be put to use and common problems faced by owners. In addition to covering control techniques, testing and maintenance procedures, this handbook covers the power transformer; control electrical power transformer; electrical power transformer; electrical theory transformer; used electrical transformer; down electrical step transformer; electrical manufacturer transformer; electrical picture transformer; electrical transformer work; electrical surplus transformer; current transformer; step down transformer; voltage transformer; step up transformer; isolation transformer; low voltage transformer; toroidal transformer; high voltage transformer; and control power transformer. The handbook includes articles from leading experts on overcurrent protection of transformers; ventilated dry-type transformers; metered load factors for low-voltage, and dry-type transformers in buildings. The maintenance of both dry-type or oil-filled transformers was discussed with reference to sealing, gaskets, oils, moisture and testing. The adoption of dynamic load practices was also discussed along with the reclamation or recycling of used lube oil, transformer dielectric fluids and aged solid insulation. A buyer's guide and directory of transformer manufacturers and suppliers was also included. refs., tabs., figs.

  5. Hamlet's Transformation.

    Science.gov (United States)

    Usher, P. D.

    1997-12-01

    William Shakespeare's Hamlet has much evidence to suggest that the Bard was aware of the cosmological models of his time, specifically the geocentric bounded Ptolemaic and Tychonic models, and the infinite Diggesian. Moreover, Shakespeare describes how the Ptolemaic model is to be transformed to the Diggesian. Hamlet's "transformation" is the reason that Claudius, who personifies the Ptolemaic model, summons Rosencrantz and Guildenstern, who personify the Tychonic. Pantometria, written by Leonard Digges and his son Thomas in 1571, contains the first technical use of the word "transformation." At age thirty, Thomas Digges went on to propose his Perfit Description, as alluded to in Act Five where Hamlet's age is given as thirty. In Act Five as well, the words "bore" and "arms" refer to Thomas' vocation as muster-master and his scientific interest in ballistics. England's leading astronomer was also the father of the poet whose encomium introduced the First Folio of 1623. His oldest child Dudley became a member of the Virginia Company and facilitated the writing of The Tempest. Taken as a whole, such manifold connections to Thomas Digges support Hotson's contention that Shakespeare knew the Digges family. Rosencrantz and Guildenstern in Hamlet bear Danish names because they personify the Danish model, while the king's name is latinized like that of Claudius Ptolemaeus. The reason Shakespeare anglicized "Amleth" to "Hamlet" was because he saw a parallel between Book Three of Saxo Grammaticus and the eventual triumph of the Diggesian model. But Shakespeare eschewed Book Four, creating this particular ending from an infinity of other possibilities because it "suited his purpose," viz. to celebrate the concept of a boundless universe of stars like the Sun.

  6. TRANSFORMER APPARATUS

    Science.gov (United States)

    Wolfgang, F.; Nicol, J.

    1962-11-01

    Transformer apparatus is designed for measuring the amount of a paramagnetic substance dissolved or suspended in a diamagnetic liquid. The apparatus consists of a cluster of tubes, some of which are closed and have sealed within the diamagnetic substance without any of the paramagnetic material. The remaining tubes are open to flow of the mix- ture. Primary and secondary conductors are wrapped around the tubes in such a way as to cancel noise components and also to produce a differential signal on the secondaries based upon variations of the content of the paramagnetic material. (AEC)

  7. Rotary Transformer

    Science.gov (United States)

    McLyman, Colonel Wm. T.

    1996-01-01

    None given. From first Par: Many spacecraft (S/C) and surface rovers require the transfer of signals and power across rotating interfaces. Science instruments, antennas and solar arrays are elements needing rotary power transfer for certain (S/C) configurations. Delivery of signal and power has mainly been done by using the simplest means, the slip ring approach. This approach, although simple, leaves debris generating noise over a period of time...The rotary transformer is a good alternative to slip rings for signal and power transfer.

  8. Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

    Directory of Open Access Journals (Sweden)

    Annika Mohr

    Full Text Available Immunohistochemistry (IHC is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1, progesterone receptor (PGR, prolactin receptor (PRLR and growth hormone receptor (GHR gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

  9. Optimization of Agrobacterium -mediated transformation parameters ...

    African Journals Online (AJOL)

    Agrobacterium-mediated transformation factors for sweet potato embryogenic calli were optimized using -glucuronidase (GUS) as a reporter. The binary vector pTCK303 harboring the modified GUS gene driven by the CaMV 35S promoter was used. Transformation parameters were optimized including bacterial ...

  10. Spine Instability Neoplastic Score: agreement across different medical and surgical specialties.

    Science.gov (United States)

    Arana, Estanislao; Kovacs, Francisco M; Royuela, Ana; Asenjo, Beatriz; Pérez-Ramírez, Úrsula; Zamora, Javier

    2016-05-01

    Spinal instability is an acknowledged complication of spinal metastases; in spite of recent suggested criteria, it is not clearly defined in the literature. This study aimed to assess intra and interobserver agreement when using the Spine Instability Neoplastic Score (SINS) by all physicians involved in its management. Independent multicenter reliability study for the recently created SINS, undertaken with a panel of medical oncologists, neurosurgeons, radiologists, orthopedic surgeons, and radiation oncologists, was carried out. Ninety patients with biopsy-proven spinal metastases and magnetic resonance imaging, reviewed at the multidisciplinary tumor board of our institution, were included. Intraclass correlation coefficient (ICC) was used for SINS score agreement. Fleiss kappa statistic was used to assess agreement on the location of the most affected vertebral level; agreement on the SINS category ("stable," "potentially stable," or "unstable"); and overall agreement with the classification established by tumor board. Clinical data and imaging were provided to 83 specialists in 44 hospitals across 14 Spanish regions. No assessment criteria were pre-established. Each clinician assessed the SINS score twice, with a minimum 6-week interval. Clinicians were blinded to assessments made by other specialists and to their own previous assessment. Subgroup analyses were performed by clinicians' specialty, experience (≤7, 8-13, ≥14 years), and hospital category (four levels according to size and complexity). This study was supported by Kovacs Foundation. Intra and interobserver agreement on the location of the most affected levels was "almost perfect" (κ>0.94). Intra-observer agreement on the SINS score was "excellent" (ICC=0.77), whereas interobserver agreement was "moderate" (ICC=0.55). Intra-observer agreement in SINS category was "substantial" (k=0.61), whereas interobserver agreement was "moderate" (k=0.42). Overall agreement with the tumor board classification

  11. Acute erythroid neoplastic proliferations. A biological study based on 62 patients.

    Science.gov (United States)

    Domingo-Claros, Alicia; Larriba, Itziar; Rozman, Maruja; Irriguible, Dolors; Vallespí, Teresa; Aventin, Anna; Ayats, Ramon; Millá, Fuensanta; Solé, Francesc; Florensa, Lourdes; Gallart, Miquel; Tuset, Esperanza; Lopez, Carmen; Woessner, Soledad

    2002-02-01

    The terms acute erythroleukemia and AML-M6 are defined in the FAB classification as proliferations of dysplastic erythroid elements mixed with blasts of myeloid origin, but pure erythroid leukemias are not included. The recent WHO classification has a category of acute myeloid leukemia not otherwise categorized, which includes acute erythroid leukemia (M6) of two subtypes: M6a-erythroleukemia (erythroid/myeloid) and M6b-pure erythroid leukemia. The aims of this co-operative study were to discover the incidences of these different subtypes, and pay special attention to the morphology of these entities. We reviewed a series of 62 patients with erythroid neoplastic proliferations. Previous medical history, age, sex, peripheral blood and bone marrow cell counts, cytochemical stains, immunophenotype, and cytogenetics were evaluated at presentation. We analyzed the incidence of erythrocyte, leukocyte and platelet abnormalities in the peripheral blood. In bone marrow we analyzed dysplastic features of erythroblasts, granulocytic elements and the megakaryocytic lineage. Fifty-three patients met the criteria of M6a subtype of the WHO classification, and 2 were classified as having pure erythremia (M6b); 7 cases could not be classified according to the WHO criteria. Fifty-five patients presented with de novo acute leukemia, and seven patients had secondary acute leukemia. The most frequent dysplastic features in blood smears were: schistocytes, tear-drop and pincered cells in erythrocytes; hypogranulation and hyposegmentation in leukocytes; gigantism and hypogranulation in platelets. In bone marrow, megaloblastic changes, multinuclearity, karyorrhexis and basophilic stippling in erythroblasts; hypogranulation and gigantism in granulocytic series, and micromegakaryocytes and unconnected nuclei in megakarocytes were the most dysplastic features. A positive PAS reaction and increase of bone marrow iron with ring sideroblasts were common features. Trilineage dysplasia was

  12. Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

    International Nuclear Information System (INIS)

    Staibano, Stefania; Fusco, Alfredo; Chieffi, Paolo; Celetti, Angela; Ilardi, Gennaro; Leone, Vincenza; Luise, Chiara; Merolla, Francesco; Esposito, Francesco; Morra, Francesco; Siano, Maria; Franco, Renato

    2013-01-01

    be part of a pro-survival pathway that helps to evade the toxic effects of endogenous oxidants and contributes to testicular neoplastic growth

  13. Cytological and oncogene alterations in radiation-transformed Syrian hamster embryo cells

    International Nuclear Information System (INIS)

    Trutschler, K.; Hieber, L.; Kellerer, A.M.

    1991-01-01

    Syrian hamster embryo (SHE) cells were neoplastically transformed by different types of ionizing radiation (γ-rays, α-particles or carbon ions). Transformed and tumor cell lines (derived from nude mice tumors) were analysed for alterations of the oncogenes c-Ha-ras and c-myc, i.e. RFLPs, gene amplifications, activation by point mutation, gene expression, and for cytological changes. In addition, the chromosome number and the numbers of micronuclei per cell have been determined in a series of cell lines. (author)

  14. Forestry transformation

    International Nuclear Information System (INIS)

    Beer, G.

    2003-01-01

    State forestry company Lesy, s.p., Banska Bystrica have chosen Austrian state forestry company to operate as their restructuring advisor. 20 million Sk (0.142 mn Euro) were assigned to transformation of Lesy SR from a state enterprise to a state-owned joint-stock company. The whole process should take two years. The joint-stock company should be established at the beginning of next year. 'What we have to do first is to define the objectives and perspectives of this restructuring,' claims new director, Karol Vins. The new boss recalled all directors of the 26 branches. They were given a lot of freedom to trade with wood. The new management wants to establish a profit-making company. At the moment the company has total claims of 600 million Sk (14.59 million Eur) it will have to provision for

  15. Transforming vulnerability.

    Science.gov (United States)

    Jones, Patricia S; Zhang, Xinwei Esther; Meleis, Afaf I

    2003-11-01

    Asian American immigrant women engaged in filial caregiving are at special risk for health problems due to complex contextual factors related to immigration, cultural traditions, and role transition. This study examines the experience of two groups of immigrant Asian American women who are caring for older parents. A total of 41 women (22 Chinese American and 19 Filipino American) were interviewed in a study based on Strauss and Corbin's grounded theory methodology. The women were determined to be loyal to their traditional culture, which included strong filial values, while adapting to a new culture. Through the struggle of meeting role expectations and coping with paradox, the women mobilized personal and family resources to transform vulnerability into strength and well-being.

  16. Radioactive transformations

    CERN Document Server

    Rutherford, Ernest

    2012-01-01

    Radioactive Transformations describes Ernest Rutherford's Nobel Prize-winning investigations into the mysteries of radioactive matter. In this historic work, Rutherford outlines the scientific investigations that led to and coincided with his own research--including the work of Wilhelm Rӧntgen, J. J. Thomson, and Marie Curie--and explains in detail the experiments that provided a glimpse at special relativity, quantum mechanics, and other concepts that would shape modern physics. This new edition features a comprehensive introduction by Nobel Laureate Frank Wilczek which engagingly explains how Rutherford's early research led to a better understanding of topics as diverse as the workings of the atom's nucleus, the age of our planet, and the fusion in stars.

  17. The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics

    Directory of Open Access Journals (Sweden)

    Huang Yung-Cheng

    2011-12-01

    Full Text Available Abstract Background Brown adipose tissue (BAT has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG positron emission tomography/computed tomography (PET/CT in people living in the tropics, where the influence of outdoor temperature was low. Methods 18F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and 18F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature. Results Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043 and a higher TMA (p = 0.028 than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016. Conclusions Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.

  18. Selenium, selenoenzymes, oxidative stress and risk of neoplastic progression from Barrett's esophagus: results from biomarkers and genetic variants.

    Directory of Open Access Journals (Sweden)

    Yumie Takata

    Full Text Available Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1 concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85. SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR = 3.95, 95% confidence intervals (CI = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58, but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69. Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1

  19. Determination and correlation of spatial distribution of trace elements in normal and neoplastic breast tissues evaluated by μ-XRF

    International Nuclear Information System (INIS)

    Silva, M.P.; Oliveira, M.A.; Poletti, M.E.

    2012-01-01

    Full text: Some trace elements, naturally present in breast tissues, participate in a large number of biological processes, which include among others, activation or inhibition of enzymatic reactions and changes on cell membranes permeability, suggesting that these elements may influence carcinogenic processes. Thus, knowledge of the amounts of these elements and their spatial distribution in normal and neoplastic tissues may help in understanding the role of these elements in the carcinogenic process and tumor progression of breast cancers. Concentrations of trace elements like Ca, Fe, Cu and Zn, previously studied at LNLS using TXRF and conventional XRF, were elevated in neoplastic breast tissues compared to normal tissues. In this study we determined the spatial distribution of these elements in normal and neoplastic breast tissues using μ-XRF technique. We analyzed 22 samples of normal and neoplastic breast tissues (malignant and benign) obtained from paraffin blocks available for study at the Department of Pathology HC-FMRP/USP. From the blocks, a small fraction of material was removed and subjected to histological sections of 60 μm thick made with a microtome. The slices where placed in holder samples and covered with ultralen film. Tissue samples were irradiated with a white beam of synchrotron radiation. The samples were positioned at 45 degrees with respect to the incident beam on a table with 3 freedom degrees (x, y and z), allowing independent positioning of the sample in these directions. The white beam was collimated by a 20 μm microcapillary and samples were fully scanned. At each step, a spectrum was detected for 10 s. The fluorescence emitted by elements present in the sample was detected by a Si (Li) detector with 165 eV at 5.9 keV energy resolution, placed at 90 deg with respect to the incident beam. Results reveal that trace elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman

  20. Analysis of plasma membrane Ca(2+)-ATPase expression in control and SV40-transformed human fibroblasts.

    Science.gov (United States)

    Reisner, P D; Brandt, P C; Vanaman, T C

    1997-01-01

    It has been long known that neoplastic transformation is accompanied by a lowered requirement for extracellular Ca2+ for growth. The studies presented here demonstrate that human fibroblastic cell lines produce the two commonly found 'housekeeping' isoforms of the plasma membrane Ca(2+)-ATPase (PMCA), PMCA1b and 4b, and at the expression of both is demonstrably lower in cell lines neoplastically transformed by SV40 than in the corresponding parental cell lines. Western blot analyses of lysates from control (GM00037) and SV40-transformed (GM00637) skin fibroblasts revealed a 138 kDa PMCA whose level was significantly lower in the SV40-transformed cells relative to either total cellular protein or alpha-tubulin. Similar analyses of plasma membrane preparations from control WI-38) and SV40-transformed (WI-38VA13) lung fibroblasts revealed 3-4-fold lower levels of PMCA in the SV40-transformed cells. Competitive ELISAs performed on detergent solubilized plasma membrane preparations indicated at least 3-4-fold lower levels of PMCA in the SV40-transformed cell lines compared to controls. Reverse transcriptase coupled-PCR analyses showed that PMCA1b and PMCA4b were the only isoforms expressed in all four cell lines. The PMCA4b mRNA level detected by Northern analysis also was substantially lower in SV40 transformed skin fibroblasts than in non-transformed fibroblasts. Quantitative RT-PCR analyses showed levels of PMCA1b and 4b mRNAs to be 5 and 10-fold lower, respectively, in GM00637 than in GM00037 when the levels of PCR products were normalized to glyceraldehyde-3-phosphate dehydrogenase (G3PDH) mRNA. These results demonstrate that the expression of these distinct PMCA genes is substantially lower in SV40 transformed human skin and lung fibroblasts and may be coordinately regulated in these cells.

  1. Thermochemical transformations of anthracite fractions

    Energy Technology Data Exchange (ETDEWEB)

    Belkina, T.V.; Privalov, V.E.; Stepanenko, atM.A.

    1979-08-01

    Research on the nature of thermochemical transformations of anthracite fractions and the possibility of increasing their activity and identifying conditions for their use in the electrode pitch process is described. From research done on different anthracite fractions processed at varying temperatures it was concluded that accumulations of condensates from heating anthracite fractions occur significantly slower in comparison with pitch. As a result the electrode pitch process is prolonged. Thermal treatment of an anthracite fraction causes the formation and accumulation of condensates and promotes thermochemical transformations. Lastly, the use of thermally treated anthracite fractions apparently intensifies the electrode pitch process and improves its quality. (16 refs.) (In Russian)

  2. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2012-07-15

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

  3. Fatal haemorrhage and neoplastic thrombosis in a captive African lion (Panthera leo) with metastatic testicular sex cord-stromal tumour.

    Science.gov (United States)

    Gonzales-Viera, Omar Antonio; Sánchez-Sarmiento, Angélica María; Fernandes, Natália Coelho Couto de Azevedo; Guerra, Juliana Mariotti; Ressio, Rodrigo Albergaria; Catão-Dias, José Luiz

    2017-10-13

    The study of neoplasia in wildlife species contributes to the understanding of cancer biology, management practices, and comparative pathology. Higher frequencies of neoplasms among captive non-domestic felids have been reported most commonly in aging individuals. However, testicular tumours have rarely been reported. This report describes a metastatic testicular sex cord-stromal tumour leading to fatal haemorrhage and thrombosis in a captive African lion (Panthera leo). During necropsy of a 16-year-old male African lion, the left testicle and spermatic cord were found to be intra-abdominal (cryptorchid), semi-hard and grossly enlarged with multiple pale-yellow masses. Encapsulated haemorrhage was present in the retroperitoneum around the kidneys. Neoplastic thrombosis was found at the renal veins opening into the caudal vena cava. Metastases were observed in the lungs and mediastinal lymph nodes. Histology revealed a poorly differentiated pleomorphic neoplasm comprised of round to polygonal cells and scattered spindle cells with eosinophilic cytoplasm. An immunohistochemistry panel of inhibin-α, Ki-67, human placental alkaline phosphatase, cytokeratin AE1/AE3, cKit, vimentin and S100 was conducted. Positive cytoplasmic immunolabeling was obtained for vimentin and S100. The gross, microscopic and immunohistochemical findings of the neoplasm were compatible with a poorly differentiated pleomorphic sex cord-stromal tumour. Cause of death was hypovolemic shock from extensive retroperitoneal haemorrhage and neoplastic thrombosis may have contributed to the fatal outcome. To our knowledge, this is the first report of sex cord-stromal tumour in non-domestic felids.

  4. Age and Spatial Peculiarities of Non-neoplastic Diseases of the Skin and Subcutaneous Tissue in Kazakhstan, 2003-2015.

    Science.gov (United States)

    Igissinov, Nurbek; Kulmirzayeva, Dariyana; Bilyalova, Zarina; Akpolatova, Gulnur; Mamyrbayeva, Marzya; Zhumagaliyeva, Galina

    2017-11-01

    Arrangement of effective management aimed at improving dermatological services and consistent care of patients with skin diseases depends on understanding the epidemiological situation. This retrospective study presents an epidemiological assessment of non-neoplastic skin and subcutaneous tissue diseases in Kazakhstan registered in 2003-2015. The yearly incidence rate of the diseases among the whole population was in average 3,341.8±121.1 per 100000 population. This represents 4835.0±156.1 for children, 5503.2±141.8 for adolescents and 2646.6±106.7 for adults per 100000 inhabitants. Space and time incidence rate was evaluated according to the administrative division. The overall trend decreased to 3.5% in children to 2.8% in adolescents to 1.9%, and in adults to 3.9%. Considerable variation in rates was seen across the country, with highest rates in East Kazakhstan, Mangystau and Aktobe regions, the lowest - in Atyrau and South-Kazakhstan regions. Non-neoplastic diseases of skin and subcutaneous tissue continue to be an urgent public health problem, especially among children in many regions of Kazakhstan.

  5. Imaging of demyelinating and neoplastic diseases of the spinal cord; Bildgebung bei demyelinisierenden und tumoroesen Erkrankungen des Rueckenmarks

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Mang, C. [Institut fuer CT und MRT Gaenserndorf, Gaenserndorf (Austria)

    2010-12-15

    The clinical symptoms of myelopathy are variable and non-specific. Demyelinating as well as neoplastic spinal cord diseases can cause paresthesia, progressive sensomotoric deficits and bowel and bladder dysfunction. Imaging of the spine, especially with magnetic resonance imaging (MRI), is an essential component in the diagnostic assessment of myelopathy and makes a substantial contribution to achieving the correct diagnosis. Although intramedullary neoplasms are far less common than demyelinating spinal cord diseases, radiologists should be familiar with the three most common entities, astrocytoma, ependymoma and hemangioblastoma, which represent over 70% of all spinal cord neoplasms. An early diagnosis and therapy is essential with neoplastic and demyelinating spinal cord diseases to hold residual neurological deficits as low as possible. (orig.) [German] Die klinische Symptomatik von Myelopathien ist aeusserst variabel und unspezifisch. Sowohl demyelinisierende als auch tumoroese Rueckenmarkerkrankungen koennen Paraesthesien, progrediente sensomotorische Ausfaelle und eine Sphinkterdysfunktion hervorrufen. Bildgebende Untersuchungen, und hier allen voran die MRT, sind ein unerlaesslicher Bestandteil zur Abklaerung von Myelopathien und tragen wesentlich zur korrekten Diagnose bei. Intramedullaere Tumoren sind zwar weitaus seltener als demyelinisierende Rueckenmarkerkrankungen, dennoch sollte der Radiologe mit den Bildmerkmalen der 3 haeufigsten Tumorarten, dem Astrozytom, Ependymom und Haemangioblastom vertraut sein, die ueber 70% aller Rueckenmarktumoren verursachen. Eine moeglichst fruehe Diagnostik und Therapie sind bei tumoroesen und demyelinisierenden Rueckenmarkerkrankungen essenziell, um bleibende neurologische Defizite moeglichst gering zu halten. (orig.)

  6. Neoplastic pleural effusion and intrathoracic metastasis of a scapular osteosarcoma in a dog: a multidisciplinary integrated diagnostic approach.

    Science.gov (United States)

    Mesquita, Luis; Mortier, Jeremy; Ressel, Lorenzo; Finotello, Riccardo; Silvestrini, Paolo; Piviani, Martina

    2017-06-01

    A 10-year-old, female spayed mixed-breed or cross-bred dog was referred to the Small Animal Teaching Hospital of the University of Liverpool due to tachypnea, dyspnea, and pleural effusion not responding to diuretics and antibiotics. The chest was drained and cytology of the pleural fluid was consistent with a modified transudate with presence of atypical cells initially attributed to mesothelial hyperplasia and dysplasia. Computed tomography detected, in addition to the bilateral pleural effusion, diffuse pleural thickening, multiple pleural and pulmonary nodules, and a mineralized and lytic mass in the left scapula. Imaging findings were suggestive of a primary bone tumor with intrathoracic metastasis. Cytology of the left scapular and pleural masses revealed a malignant neoplasm highly suggestive of osteosarcoma. The diagnosis was confirmed by demonstration of a positive cytochemical reaction for alkaline phosphatase on prestained cytology slides. This finding prompted review of the initial interpretation of the pleural effusion cytology. The presence of neoplastic osteoblasts in the thoracic fluid was identified by a combination of cytochemistry, cell pellet immunohistochemistry, and transmission electron microscopy findings. In this report, a multidisciplinary integrated diagnostic approach was used to diagnose and confirm a neoplastic pleural effusion due to osteosarcoma metastasis in a dog. © 2017 American Society for Veterinary Clinical Pathology.

  7. Regulation of protein kinase C-related kinase (PRK) signalling by the TPα and TPβ isoforms of the human thromboxane A2 receptor: Implications for thromboxane- and androgen- dependent neoplastic and epigenetic responses in prostate cancer.

    Science.gov (United States)

    O'Sullivan, Aine G; Mulvaney, Eamon P; Kinsella, B Therese

    2017-04-01

    The prostanoid thromboxane (TX) A 2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA 2 /TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA 2 -TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC. Hence the aim of the current study was to investigate whether TXA 2 /TP-induced PRK activation can mimic and/or enhance AR-mediated cellular responses in the model androgen-responsive prostate adenocarcinoma LNCaP cell line. We reveal that TXA 2 /TP signalling can act as a neoplastic- and epigenetic-regulator, promoting and enhancing both AR-associated chromatin remodelling (H3Thr11 phosphorylation, WDR5 recruitment and acetylation of histone H4 at lysine 16) and AR-mediated transcriptional activation (e.g of the KLK3/prostate-specific antigen and TMPRSS2 genes) through mechanisms involving TPα/TPβ mediated-PRK1 and PRK2, but not PRK3, signalling complexes. Overall, these data demonstrate that TPα/TPβ can act as neoplastic and epigenetic regulators by mimicking and/or enhancing the actions of androgens within the prostate and provides further mechanistic insights into the role of the TXA 2 /TP signalling axis in PCa, including potentially in CRPC. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Transforming giants.

    Science.gov (United States)

    Kanter, Rosabeth Moss

    2008-01-01

    Large corporations have long been seen as lumbering, inflexible, bureaucratic--and clueless about global developments. But recently some multinationals seem to be transforming themselves: They're engaging employees, moving quickly, and introducing innovations that show true connection with the world. Harvard Business School's Kanter ventured with a research team inside a dozen global giants--including IBM, Procter & Gamble, Omron, CEMEX, Cisco, and Banco Real--to discover what has been driving the change. After conducting more than 350 interviews on five continents, she and her colleagues came away with a strong sense that we are witnessing the dawn of a new model of corporate power: The coordination of actions and decisions on the front lines now appears to stem from widely shared values and a sturdy platform of common processes and technology, not from top-down decrees. In particular, the values that engage the passions of far-flung workforces stress openness, inclusion, and making the world a better place. Through this shift in what might be called their guidance systems, the companies have become as creative and nimble as much smaller ones, even while taking on social and environmental challenges of a scale that only large enterprises could attempt. IBM, for instance, has created a nonprofit partnership, World Community Grid, through which any organization or individual can donate unused computing power to research projects and see what is being done with the donation in real time. IBM has gained an inspiring showcase for its new technology, helped business partners connect with the company in a positive way, and offered individuals all over the globe the chance to contribute to something big.

  9. Isolation and characterization of a neoplastic epithelial cell line derived from irradiated human submaxillary gland

    International Nuclear Information System (INIS)

    Shirasuna, Kanemitsu; Sato, Mitsunobu; Yura, Yoshiaki; Yanagawa, Tetuo; Kubo, Kazuko

    1979-01-01

    Submaxillary tissues taken from a patient whose oral base was irradiated for squamous cell carcinoma were cultured in order to isolate transformed epithelial cells in vitro. The cells showed a fine structure similar to an intermediate duct cell. When they were transplanted in nude mice, salivary tumors developed. It is epidemiologically known that irradiation induces salivary tumors. In this study, the risk of inducement was revealed and a salivary epithelial cell line was used as a model for the analysis of salivary tumors. (Ichikawa, K.)

  10. Use of magnetic resonance imaging to detect neoplastic meningitis: Limited use in leukemia and lymphoma but convincing results in solid tumors

    International Nuclear Information System (INIS)

    Pauls, Sandra; Fischer, Ann-Cathrin; Brambs, Hans-Jürgen; Fetscher, Sebastian; Höche, Wolfram; Bommer, Martin

    2012-01-01

    Background: An early diagnosis of meningitis is important to improve patients’ survival. Data about a direct comparison of cerebrospinal fluid cytology (CSF-cytology) and MRI are very limited. Therefore, the aim of this study was to compare these two diagnostic modalities in diagnosing meningitis in patients with hematopoietic and solid malignancies. Methods: In 68 patients suspicious for neoplastic meningitis, cytology and MRI (1.5 T) was performed. The meningeal, pial or intraparenchymal hyperintense signal or contrast enhancement was correlated to the final CNS diagnosis and to cytology. Results: 44 patients (64.7%) had neoplastic meningitis, 21 patients (30.9%) had non-neoplastic meningitis. The sensitivity to diagnose meningeal disease was 49.2% for MRI and 95.4% for cytology (p < 0.001). In patients with neoplastic meningitis, sensitivity was 45.5% for MRI and 93.2% for cytology (p < 0.001). In patients with infectious meningitis, sensitivity was 57.1% for MRI and 100% for cytology (p = 0.0013). In patients with solid tumors, the sensitivity was 84.6% for both diagnostic methods. The sensitivity for MRI was low in patients with leukemia (20.0%) and lymphoma (37.5%). The positive predictive value (PPV) for MRI to differentiate infectious from neoplastic meningitis was high in patients with infectious meningitis (75.0%), in patients with lymphoma (83.3%), and in patients with solid tumors (72.7%). Ppv was low in patients with leukemia (33.3%). Conclusion: Diagnostic value of MRI for diagnosing meningitis is especially limited in patients with hematopoietic malignancies. MRI better detected leptomeningeal involvement caused by solid tumors than by leukemia or lymphoma. The ppv to specify neoplastic meningitis depends on tumor subtype.

  11. Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

    Science.gov (United States)

    Lee, Jeong Sub; Kim, Jung Hoon; Kim, Yong Jae; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Young; Han, Joon Koo

    2017-07-01

    To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.

  12. Recent Developments of the Local Effect Model (LEM) - Implications of clustered damage on cell transformation

    Science.gov (United States)

    Elsässer, Thilo

    Exposure to radiation of high-energy and highly charged ions (HZE) causes a major risk to human beings, since in long term space explorations about 10 protons per month and about one HZE particle per month hit each cell nucleus (1). Despite the larger number of light ions, the high ionisation power of HZE particles and its corresponding more complex damage represents a major hazard for astronauts. Therefore, in order to get a reasonable risk estimate, it is necessary to take into account the entire mixed radiation field. Frequently, neoplastic cell transformation serves as an indicator for the oncogenic potential of radiation exposure. It can be measured for a small number of ion and energy combinations. However, due to the complexity of the radiation field it is necessary to know the contribution to the radiation damage of each ion species for the entire range of energies. Therefore, a model is required which transfers the few experimental data to other particles with different LETs. We use the Local Effect Model (LEM) (2) with its cluster extension (3) to calculate the relative biological effectiveness (RBE) of neoplastic transformation. It was originally developed in the framework of hadrontherapy and is applicable for a large range of ions and energies. The input parameters for the model include the linear-quadratic parameters for the induction of lethal events as well as for the induction of transformation events per surviving cell. Both processes of cell inactivation and neoplastic transformation per viable cell are combined to eventually yield the RBE for cell transformation. We show that the Local Effect Model is capable of predicting the RBE of neoplastic cell transformation for a broad range of ions and energies. The comparison of experimental data (4) with model calculations shows a reasonable agreement. We find that the cluster extension results in a better representation of the measured RBE values. With this model it should be possible to better

  13. The analysis of health condition and the assessment of the risk of neoplastic diseases among residents of villages

    Directory of Open Access Journals (Sweden)

    Anna Lewandowska

    2017-06-01

    Full Text Available Introduction: Neoplastic diseases have been classified as civilization diseases and are a big problem for modern medicine. According to the data from the International Agency for Research of Cancer, about 10 million people suffer from cancer and a number of deaths due to this disease has exceeded 6 million; until 2020 those numbers may double. In Poland, cancer survivors of five years concern 22% of men and 35% of women suffering from tumours, while in northern and western Europe there is a cure rate of 40% for men and 50% for women. The main reason for the adverse situation in Poland is a low percentage of early diagnosis of cancer. On the one hand this results from insufficient preparation of both family doctors and physicians of other specialties, but on the other, from insufficient dissemination of early diagnosis methods. Objective: The objective of the study is to analyze the health condition and to assess the risk of a neoplastic disease among residents of villages. Material and methods: The research involved 1000 residents of villages in Podkarpackie Voivodeship. The age of the researched ranges from 18 to 30 years, with mean age 26.96±0.84 (range [18;30], median 25.95%CI [18,9;29,01]. The researched group is represented in 43,8% by women in 56,2% by men. In order to obtain the research material, a standardized questionnaire has been applied including interview and physical examination, enabling assessment of symptoms reported during the interview and analysis of symptoms indicating a disease, including cancer. Results: According to the data analysis, during last few months the respondents have suffered from such ailments as cough (8.22% W, 7.12% M, dyspnea (3.2% W, 1.78% M, abdominal pain (13.7% W, 4.27% M, pain (5.48% W, 2.14% M and weakness (14.61% W, 4.98% M. During observations, one female respondent was diagnosed with symptoms of melanoma (0.46%, which has been confirmed in later dermatological test. Conclusions: No changes in

  14. Transformer Protection Using the Wavelet Transform

    OpenAIRE

    ÖZGÖNENEL, Okan; ÖNBİLGİN, Güven; KOCAMAN, Çağrı

    2014-01-01

    This paper introduces a novel approach for power transformer protection algorithm. Power system signals such as current and voltage have traditionally been analysed by the Fast Fourier Transform. This paper aims to prove that the Wavelet Transform is a reliable and computationally efficient tool for distinguishing between the inrush currents and fault currents. The simulated results presented clearly show that the proposed technique for power transformer protection facilitates the a...

  15. Modulation of basal cell fate during productive and transforming HPV-16 infection is mediated by progressive E6-driven depletion of Notch.

    Science.gov (United States)

    Kranjec, Christian; Holleywood, Christina; Libert, Diane; Griffin, Heather; Mahmood, Radma; Isaacson, Erin; Doorbar, John

    2017-08-01

    In stratified epithelia such as the epidermis, homeostasis is maintained by the proliferation of cells in the lower epithelial layers and the concomitant loss of differentiated cells from the epithelial surface. These differentiating keratinocytes progressively stratify and form a self-regenerating multi-layered barrier that protects the underlying dermis. In such tissue, the continual loss and replacement of differentiated cells also limits the accumulation of oncogenic mutations within the tissue. Inactivating mutations in key driver genes, such as TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the long-term persistence of expanding mutant clones in the tissue. Here we show that through the expression of E6, HPV-16 prevents the early fate commitment of human keratinocytes towards differentiation and confers a strong growth advantage to human keratinocytes. When E6 is expressed either alone or with E7, it promotes keratinocyte proliferation at high cell densities, through the combined inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6 is restricted to the basal layer of the epithelium and is enhanced during the progression from productive to abortive or transforming HPV-16 infection. Consistent with this, the expression of p53 and cleaved Notch1 becomes progressively more disrupted, and is associated with increased basal cell density and reduced commitment to differentiation. The expression of cleaved Notch1 is similarly disrupted also in HPV-16-positive cervical lesions, depending on neoplastic grade. When taken together, these data depict an important role of high-risk E6 in promoting the persistence of infected keratinocytes in the basal and parabasal layers through the inactivation of gene products that are commonly mutated in non-HPV-associated neoplastic squamous epithelia. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great

  16. The Bargmann transform and canonical transformations

    International Nuclear Information System (INIS)

    Villegas-Blas, Carlos

    2002-01-01

    This paper concerns a relationship between the kernel of the Bargmann transform and the corresponding canonical transformation. We study this fact for a Bargmann transform introduced by Thomas and Wassell [J. Math. Phys. 36, 5480-5505 (1995)]--when the configuration space is the two-sphere S 2 and for a Bargmann transform that we introduce for the three-sphere S 3 . It is shown that the kernel of the Bargmann transform is a power series in a function which is a generating function of the corresponding canonical transformation (a classical analog of the Bargmann transform). We show in each case that our canonical transformation is a composition of two other canonical transformations involving the complex null quadric in C 3 or C 4 . We also describe quantizations of those two other canonical transformations by dealing with spaces of holomorphic functions on the aforementioned null quadrics. Some of these quantizations have been studied by Bargmann and Todorov [J. Math. Phys. 18, 1141-1148 (1977)] and the other quantizations are related to the work of Guillemin [Integ. Eq. Operator Theory 7, 145-205 (1984)]. Since suitable infinite linear combinations of powers of the generating functions are coherent states for L 2 (S 2 ) or L 2 (S 3 ), we show finally that the studied Bargmann transforms are actually coherent states transforms

  17. Health Promotion

    DEFF Research Database (Denmark)

    Povlsen, Lene; Borup, I.

    2015-01-01

    and Adolescent Health Promotion', Salutogenesis - from theory to practice' and Health, Stress and Coping'. More than half of all doctoral theses undertaken at NHV during these years had health promotion as their theme. As a derivative, the Nordic Health Promotion Research Network (NHPRN) was established in 2007......In 1953 when the Nordic School of Public Health was founded, the aim of public health programmes was disease prevention more than health promotion. This was not unusual, since at this time health usually was seen as the opposite of disease and illness. However, with the Ottawa Charter of 1986......, the World Health Organization made a crucial change to view health not as a goal in itself but as the means to a full life. In this way, health promotion became a first priority and fundamental action for the modern society. This insight eventually reached NHV and in 2002 - 50 years after the foundation...

  18. Computed tomography in neoplastic diseases of the skull base and adjacent areas using EMI scanner CT-1000

    International Nuclear Information System (INIS)

    Ono, Yoshimi; Ohtake, Eiji; Asakura, Koichi; Tanohata, Kazunori; Ito, Otomasa

    1980-01-01

    CT-findings of 145 patients with and without neoplastic diseases of the skull base were evaluated using EMI CT-1000. Analysis of 64 patients without any lesion at the skull base showed more artifacts compared with that of higher slices, so that good or fair images were obtained only in 64% of this groups of patients. The most important factor in producing artifacts are considered to be caused by patient's movement. We also evaluated the tumor extension to the skull base in 81 patients. They were 24 brain tumors, 21 pituitary adenomas, and 36 nasopharyngeal and paranasal cancers. Four out of 24 brain tumors showed extracranial extension, 12 pituitary adenomas infiltrating outside of the sella turcica, and 10 cases of nasopharyngeal cancers showed intracranial extension. It was concluded that CT presented an excellent information in evaluating the degree of extension of neoplasms which invading to the skull base. (author)

  19. Three-dimensional lithographically-defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Celeste M.; Inman, Jamie L.; Bissell, Mina J.

    2008-02-13

    Here we describe a simple micromolding method to construct three-dimensional arrays of organotypic epithelial tissue structures that approximate in vivo histology. An elastomeric stamp containing an array of posts of defined geometry and spacing is used to mold microscale cavities into the surface of type I collagen gels. Epithelial cells are seeded into the cavities and covered with a second layer of collagen. The cells reorganize into hollow tissues corresponding to the geometry of the cavities. Patterned tissue arrays can be produced in 3-4 h and will undergo morphogenesis over the following one to three days. The protocol can easily be adapted to study a variety of tissues and aspects of normal and neoplastic development.

  20. Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

    Science.gov (United States)

    Paggi, Silvia; Mogavero, Giuseppe; Amato, Arnaldo; Rondonotti, Emanuele; Andrealli, Alida; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Terreni, Natalia; Conforti, Francesco Simone; Conte, Dario; Spinzi, Giancarlo; Radaelli, Franco

    2018-04-01

     Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI).  Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate.  Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively ( P  one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group ( P  = 0.01).  LCI could reduce the miss rate of neoplastic lesions in the right colon. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Generalized Fourier transforms classes

    DEFF Research Database (Denmark)

    Berntsen, Svend; Møller, Steen

    2002-01-01

    The Fourier class of integral transforms with kernels $B(\\omega r)$ has by definition inverse transforms with kernel $B(-\\omega r)$. The space of such transforms is explicitly constructed. A slightly more general class of generalized Fourier transforms are introduced. From the general theory foll...... follows that integral transform with kernels which are products of a Bessel and a Hankel function or which is of a certain general hypergeometric type have inverse transforms of the same structure....

  2. Army Maintenance System Transformation

    National Research Council Canada - National Science Library

    Gilbertson, Frank V

    2006-01-01

    .... Used in conjunction with pertinent historical data and developed with Army transformation goals in mind, General Systems thinking can provide the framework for guiding maintenance transformation...

  3. Late biological effects of ionizing radiation as influenced by dose, dose rate, age at exposure, and genetic sensitivity to neoplastic transformation

    International Nuclear Information System (INIS)

    Spalding, J.F.; Prine, J.R.; Tietjen, G.L.

    1978-01-01

    A most comprehensive investigation is in progress at the Los Alamos Scientific Laboratory to study the late biological effects of whole-body exposure to gamma irradiation as they may be influenced by total dose, dose rate, age at exposure, and genetic background. Strain C57B1/6J mice of four age groups (newborn, 2, 6, and 15 months) were given five doses (20, 60, 180, 540, and 1620 rad) of gamma rays, with each dose being delivered at six dose rates (0.7, 2.1, 6.3, 18.9, 56.7 rad/day and 25 rad/min). Forty to sixty mice were used in each of the approximately 110 dose/dose-rate and age combinations. The study was done in two replications with an equal number of mice per replication. Strain RF/J mice were used in a companion study to investigate the influence of genetic background on the type and magnitude of effect. Results of the first and second replications of the 15-month-old age group and data on the influence of genetic background on biological response have been completed, and the results show no significant life shortening within the dose and dose-rate range used

  4. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  5. Characterization of the neoplastic disease in childhood in the province of Ciego de Avila

    International Nuclear Information System (INIS)

    Perez Calleja, Norma C

    2010-01-01

    We conducted a cross-sectional descriptive study to characterize from the standpoint of childhood cancer epidemiology in the province of Ciego de Avila from January to December 2008. The sample consisted of all the managers or guardians, with inclusion criteria and signed informed consent. We applied a structured interview criteria validated by experts. The data were divided into tables and comments. Acute leukemias were most prevalent. The northern area had a higher proportional mortality and crude with 10.7 x c/100 people died and 0.05 respectively x c/1000 plus higher incidence rate, with 0.8 x c/10000 inhabitants. The higher prevalence of cancer diseases in the municipality of the chamber. The specific rates were in the group of 1 to 4 years and only 16.3% underwent early diagnosis of the disease. We conclude that working in the promotion, teaching and research to reduce childhood cancer mortality in the province

  6. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

    NARCIS (Netherlands)

    Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

    2000-01-01

    Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

  7. Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP

    Czech Academy of Sciences Publication Activity Database

    Tolde, O.; Rosel, D.; Mierke, C.T.; Paňková, D.; Folk, P.; Veselý, Pavel; Brabek, J.

    2010-01-01

    Roč. 36, č. 4 (2010), s. 833-839 ISSN 1019-6439 R&D Projects: GA MŠk(CZ) LC06061 Institutional research plan: CEZ:AV0Z50520514 Keywords : invasiveness * neoplastic progression * cytoskeletal dynamics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.571, year: 2010

  8. Supervision as transformative leadership in the context of university ...

    African Journals Online (AJOL)

    This article discusses different models of supervision and promotion of Masters', Doctoral and PhD students. It argues that leadership is inherent in and underpins any model of supervision or promotion of students. The article advances a view that supervision and promotion of the said students should be transformative ...

  9. Steroid hormones as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1988-01-01

    Glucocorticoid and mineralocorticoid receptors are present in normal epithelial cells of both the small and large intestine and there have also been contentious reports of androgen, oestrogen and progesterone receptors in the epithelium of the normal large intestine. The majority of reports suggest that stimulation of the intestinal glucocorticoid receptors results in increased proliferation of epithelial cells in the small bowel, as does stimulation of androgen receptors and possibly mineralocorticoid receptors. The proliferative response of the normal intestine to oestrogens is difficult to evaluate and that to progestigens appears not to have been reported. Epidemiological studies reveal a higher incidence of bowel cancer in premenopausal women than in men of the same age and yet there is a lower incidence of these tumors in women of higher parity. These findings have been atributted to a variety of non-epithelial gender characteristic such as differences in bile metabolism, colonic bacterial and fecal transit times. In experimental animals, androgens have also been shown to influence carcinogenesis and this could well be attributed to changes in food intake etc. However, many studies have now revealed steroid hormone receptors on colorectal tumor cells and thus a direct effect of the steroid hormones on the epithelium during and after malignant transformation must now be considered.

  10. The Roles of Telomerase in the Generation of Polyploidy during Neoplastic Cell Growth

    Directory of Open Access Journals (Sweden)

    Agni Christodoulidou

    2013-02-01

    Full Text Available Polyploidy contributes to extensive intratumor genomic heterogeneity that characterizes advanced malignancies and is thought to limit the efficiency of current cancer therapies. It has been shown that telomere deprotection in p53-deficient mouse embryonic fibroblasts leads to high rates of polyploidization. We now show that tumor genome evolution through whole-genome duplication occurs in ∼15% of the karyotyped human neoplasms and correlates with disease progression. In a panel of human cancer and transformed cell lines representing the two known types of genomic instability (chromosomal and microsatellite, as well as the two known pathways of telomere maintenance in cancer (telomerase activity and alternative lengthening of telomeres, telomere dysfunction-driven polyploidization occurred independently of the mutational status of p53. Depending on the preexisting context of telomere maintenance, telomerase activity and its major components, human telomerase reverse transcriptase (hTERT and human telomerase RNA component (hTERC, exert both reverse transcriptase-related (canonical and noncanonical functions to affect tumor genome evolution through suppression or induction of polyploidization. These new findings provide a more complete mechanistic understanding of cancer progression that may, in the future, lead to novel therapeutic interventions.

  11. The construction of a library of synthetic promoters revealed some specific features of strong Streptomyces promoters

    DEFF Research Database (Denmark)

    Seghezzi, Nicolas; Amar, Patrick; Købmann, Brian

    2011-01-01

    Streptomyces are bacteria of industrial interest whose genome contains more than 73% of bases GC. In order to define, in these GC-rich bacteria, specific sequence features of strong promoters, a library of synthetic promoters of various sequence composition was constructed in Streptomyces. To do so...... cloned into the promoter-probe plasmid pIJ487 just upstream of the promoter-less aphII gene that confers resistance to neomycin. This synthetic promoter library was transformed into Streptomyces lividans, and the resulting transformants were screened for their ability to grow in the presence of different...... projects. Thirty-eight promoters were sequenced, and the sequences of the 14 weakest and 14 strongest promoters were compared using the WebLogo software with small sample correction. This comparison revealed that the −10 box, the −10 extended motif as well as the spacer of the strong Streptomyces promoters...

  12. Negotiated Grammar Transformation

    NARCIS (Netherlands)

    V. Zaytsev (Vadim)

    2012-01-01

    htmlabstractIn this paper, we study controlled adaptability of metamodel transformations. We consider one of the most rigid metamodel transformation formalisms — automated grammar transformation with operator suites, where a transformation script is built in such a way that it is essentially meant

  13. On Hurwitz transformations

    International Nuclear Information System (INIS)

    Kibler, M.; Hage Hassan, M.

    1991-04-01

    A bibliography on the Hurwitz transformations is given. We deal here, with some details, with two particular Hurwitz transformations, viz, the R 4 → R 3 Kustaanheimo-Stiefel transformation and its R 8 → R 5 compact extension. These transformations are derived in the context of Fock-Bargmann-Schwinger calculus with special emphasis on angular momentum theory

  14. Generalized Fourier transforms classes

    DEFF Research Database (Denmark)

    Berntsen, Svend; Møller, Steen

    2002-01-01

    The Fourier class of integral transforms with kernels $B(\\omega r)$ has by definition inverse transforms with kernel $B(-\\omega r)$. The space of such transforms is explicitly constructed. A slightly more general class of generalized Fourier transforms are introduced. From the general theory...

  15. Vasohibin 2 promotes epithelial-mesenchymal transition in human breast cancer via activation of transforming growth factor β 1 and hypoxia dependent repression of GATA-binding factor 3.

    Science.gov (United States)

    Tu, Min; Li, Zhanjun; Liu, Xian; Lv, Nan; Xi, Chunhua; Lu, Zipeng; Wei, Jishu; Song, Guoxin; Chen, Jianmin; Guo, Feng; Jiang, Kuirong; Wang, Shui; Gao, Wentao; Miao, Yi

    2017-03-01

    Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFβ1 expression, but negatively correlated with E-cadherin (a marker of EMT) expression. Under hypoxic conditions in vitro or in vivo, we found that down-regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive cells suppressed E-cadherin. Correlation coefficient analysis indicated that VASH2 and ESR1 expression were negatively correlated in clinical human breast cancer tissues. Further study revealed that a transcription factor of ESR1, GATA-binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo. These findings suggest that VASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. 4-Hydroxyestradiol induces mammary epithelial cell transformation through Nrf2-mediated heme oxygenase-1 overexpression

    OpenAIRE

    Park, Sin-Aye; Lee, Mee-Hyun; Na, Hye-Kyung; Surh, Young-Joon

    2016-01-01

    Estrogen (17?-estradiol, E2) undergoes oxidative metabolism by CYP1B1 to form 4-hydroxyestradiol (4-OHE2), a putative carcinogenic metabolite of estrogen. Our previous study showed that 4-OHE2-induced production of reactive oxygen species contributed to neoplastic transformation of human breast epithelial (MCF-10A) cells. In this study, 4-OHE2, but not E2, increased the expression of heme oxygenase-1 (HO-1), a sensor and regulator of oxidative stress, in MCF-10A cells. Silencing the HO-1 gene...

  17. Specification of fast neutron radiation quality from cell transformation data

    International Nuclear Information System (INIS)

    Coppola, M.

    1992-01-01

    Experimental data on the neoplastic transformation of C3H 10T1/2 cells measured at Casaccia after neutron and X-ray irradiation were used to determine neutron RBE values for the RSV-Tapiro fast reactor energy spectrum and for monoenergetic neutrons of 0.5, 1, and 6 MeV. In parallel, micro-dosimetric measurements provided the actual lineal energy distributions and related mean parameters for the reactor radiation. From these experiments, values of the neutron quality factor were derived for the reactor neutron energy spectrum and, in turn, for the other neutron energies tested. A mathematical expression giving a smooth dependence on neutron energy was also determined for the effective quality factor in the entire energy range examined. The results were compared with other proposals

  18. Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens.

    Science.gov (United States)

    Ohanian, S H; McCabe, R P; Evans, C H

    1981-12-01

    The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit antisera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other culture cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

  19. Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens

    International Nuclear Information System (INIS)

    Ohanian, S.H.; McCabe, R.P.; Evans, C.H.

    1981-01-01

    The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit anitsera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other cultured cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens

  20. Biomarkers for screening of lung cancer and pre-neoplastic lesions in a high risk Chilean population

    Directory of Open Access Journals (Sweden)

    Marta I Adonis

    2014-01-01

    Full Text Available BACKGROUND: The mortality of lung cancer (LC, increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 μg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70 and Auto Fluorescence Bronchoscopy (AFB might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL and neoplastic lesions (NL. RESULTS: Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8% and specificity (91.9% than AQC. However, for PNL AQC showed a higher sensitivity (91.9% than DR70 (27.3%, although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%. CONCLUSION: This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC

  1. An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

    Science.gov (United States)

    Klein, B; Schuppe, H-C; Bergmann, M; Hedger, M P; Loveland, B E; Loveland, K L

    2017-07-01

    Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6

  2. Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress.

    Directory of Open Access Journals (Sweden)

    Tiziana Triulzi

    Full Text Available We recently showed that differential expression of extracellular matrix (ECM genes delineates four subgroups of breast carcinomas (ECM1, -2, -3- and -4 with different clinical outcome. To further investigate the characteristics of ECM signature and its impact on tumor progression, we conducted unsupervised clustering analyses in 6 additional independent datasets of invasive breast tumors from different platforms for a total of 643 samples. Use of four different clustering algorithms identified ECM3 tumors as an independent group in all datasets tested. ECM3 showed a homogeneous gene pattern, consisting of 58 genes encoding 43 structural ECM proteins. From 26 to 41% of the cases were ECM3-enriched, and analysis of datasets relevant to gene expression in neoplastic or corresponding stromal cells showed that both stromal and breast carcinoma cells can coordinately express ECM3 genes. In in vitro experiments, β-estradiol induced ECM3 gene production in ER-positive breast carcinoma cell lines, whereas TGFβ induced upregulation of the genes leading to ECM3 gene classification, especially in ER-negative breast carcinoma cells and in fibroblasts. Multivariate analysis of distant metastasis-free survival in untreated breast tumor patients revealed a significant interaction between ECM3 and histological grade (p = 0.001. Cox models, estimated separately in grade I-II and grade III tumors, indicated a highly significant association between ECM3 and worse survival probability only in grade III tumors (HR = 3.0, 95% CI = 1.3-7.0, p = 0.0098. Gene Set Enrichment analysis of ECM3 compared to non-ECM3 tumors revealed significant enrichment of epithelial-mesenchymal transition (EMT genes in both grade I-II and grade III subsets of ECM3 tumors. Thus, ECM3 is a robust cluster that identifies breast carcinomas with EMT features but with accelerated metastatic potential only in the undifferentiated (grade III phenotype. These findings support the

  3. Confocal laser endomicroscopy and ultrasound endoscopy during the same endoscopic session for diagnosis and staging of gastric neoplastic lesions.

    Science.gov (United States)

    Gheorghe, C; Iacob, R; Dumbrava, Mona; Becheanu, G; Ionescu, M

    2009-01-01

    Confocal LASER endomicroscopy (CLE) is a newly developed endoscopic technique which allows subsurface in vivo histological assessment during ongoing endoscopy and targeted biopsies. Ultrasound endoscopy (EUS) is a useful tool in staging upper GI malignant lesions. We describe for the first time the use of both techniques during the same endoscopic session, in a pilot study, in order to increase the diagnostic yield of histological assessment and provide the staging of the gastric neoplastic lesions thus decreasing the time to therapeutic decision. CLE has been performed with the Pentax EG-3870CIK confocal endomicroscope after a 5 ml intravenous 10% fluorescein injection; EUS has been performed subsequently, during the same endoscopic Propofol sedation session, using a standard radial EUS-scope. Eleven patients have been investigated, 4 females, 7 males, mean age 59.7 +/- 12.3 years. The indication of CLE/EUS exploration was the presence of a gastric polypoid lesion in 37% of cases, atypical gastric ulcer in 27% of patients, gastric lymphoma 18%, suspicion of gastric cancer recurrence after resection 9% and infiltrating type gastric cancer 9%. Histological assessment after targeted biopsy has established the diagnosis of gastric adenocarcinoma in 55% of cases, gastric lymphoma in 18% of cases, gastric adenoma, gastric GIST and gastric foveolar hyperplasia in 9% of cases respectively. CLE has allowed targeted biopsies in 81.8% of cases. In 2 patients - one case with suspected recurrent gastric cancer after surgery and one case of gastric lymphoma, CLE has indicated normal gastric mucosa. The EUS evaluation has shown TO lesion in two cases, T1 in 3 cases, T2 in 3 cases, T3 in one case. The EUS evaluation showed in one gastric lymphoma patient a lesion interesting the mucosa and submucosa with regional adenopathy and a submucosal lesion with regional adenopathy in the other gastric lymphoma case. The therapeutic decision was surgery in 73% of cases, chemotherapy and

  4. Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies.

    Science.gov (United States)

    Lee, Won Sok; Singh, Gurmukh

    2018-07-01

    Quantitative evaluation of serum free light chains is recommended for the work up of monoclonal gammopathies. Immunoglobulin light chains are generally produced in excess of heavy chains. In patients with monoclonal gammopathy, κ/λ ratio is abnormal less frequently with lambda chain lesions. This study was undertaken to ascertain if the levels of overproduction of the two light chain types and their detection rates are different in patients with neoplastic monoclonal gammopathies. Results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein electrophoresis (UPEP), urine protein immunofixation electrophoresis (UIFE), and serum free light chain assay (SFLCA) in patients with monoclonal gammopathies were examined retrospectively. The κ/λ ratios were appropriately abnormal more often in kappa chain lesions. Ratios of κ/λ were normal in about 25% of patients with lambda chain lesions in whom free homogenous lambda light chains were detectable in urine. An illustrative case suggests underproduction of free lambda light chains, in some instances. The lower prevalence of lambda dominant κ/λ ratio in lesions with lambda light chains is estimated to be due to relative under-detection of lambda dominant κ/λ ratio in about 25% of the patients and because lambda chains are not produced in as much excess of heavy chains as are kappa chains, in about 5% of the patients. The results question the medical necessity and clinical usefulness of the serum free light chain assay. UPEP/UIFE is under-utilized.

  5. Transforming the Way We Teach Function Transformations

    Science.gov (United States)

    Faulkenberry, Eileen Durand; Faulkenberry, Thomas J.

    2010-01-01

    In this article, the authors discuss "function," a well-defined rule that relates inputs to outputs. They have found that by using the input-output definition of "function," they can examine transformations of functions simply by looking at changes to input or output and the respective changes to the graph. Applying transformations to the input…

  6. The role of dynamic susceptibility contrast-enhanced perfusion MR imaging in differentiating between infectious and neoplastic focal brain lesions: results from a cohort of 100 consecutive patients.

    Directory of Open Access Journals (Sweden)

    Valdeci Hélio Floriano

    Full Text Available BACKGROUND AND PURPOSE: Differentiating between infectious and neoplastic focal brain lesions that are detected by conventional structural magnetic resonance imaging (MRI may be a challenge in routine practice. Brain perfusion-weighted MRI (PWI may be employed as a complementary non-invasive tool, providing relevant data on hemodynamic parameters, such as the degree of angiogenesis of lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR imaging (DSC-MRI to differentiate between infectious and neoplastic brain lesions by investigating brain microcirculation changes. MATERIALS AND METHODS: DSC-MRI perfusion studies of one hundred consecutive patients with non-cortical neoplastic (n = 54 and infectious (n = 46 lesions were retrospectively assessed. MRI examinations were performed using a 1.5-T scanner. A preload of paramagnetic contrast agent (gadolinium was administered 30 seconds before acquisition of dynamic images, followed by a standard dose 10 seconds after starting imaging acquisitions. The relative cerebral blood volume (rCBV values were determined by calculating the regional cerebral blood volume in the solid areas of lesions, normalized to that of the contralateral normal-appearing white matter. Discriminant analyses were performed to determine the cutoff point of rCBV values that would allow the differentiation of neoplastic from infectious lesions and to assess the corresponding diagnostic performance of rCBV when using this cutoff value. RESULTS: Neoplastic lesions had higher rCBV values (4.28±2.11 than infectious lesions (0.63±0.49 (p<0.001. When using an rCBV value <1.3 as the parameter to define infectious lesions, the sensitivity of the method was 97.8% and the specificity was 92.6%, with a positive predictive value of 91.8%, a negative predictive value of 98.0%, and an accuracy of 95.0%. CONCLUSION: PWI is a useful complementary tool in distinguishing between infectious and neoplastic brain

  7. Effects of Training and Feedback on Accuracy of Predicting Rectosigmoid Neoplastic Lesions and Selection of Surveillance Intervals by Endoscopists Performing Optical Diagnosis of Diminutive Polyps.

    Science.gov (United States)

    Vleugels, Jasper L A; Dijkgraaf, Marcel G W; Hazewinkel, Yark; Wanders, Linda K; Fockens, Paul; Dekker, Evelien

    2018-05-01

    Real-time differentiation of diminutive polyps (1-5 mm) during endoscopy could replace histopathology analysis. According to guidelines, implementation of optical diagnosis into routine practice would require it to identify rectosigmoid neoplastic lesions with a negative predictive value (NPV) of more than 90%, using histologic findings as a reference, and agreement with histology-based surveillance intervals for more than 90% of cases. We performed a prospective study with 39 endoscopists accredited to perform colonoscopies on participants with positive results from fecal immunochemical tests in the Bowel Cancer Screening Program at 13 centers in the Netherlands. Endoscopists were trained in optical diagnosis using a validated module (Workgroup serrAted polypS and Polyposis). After meeting predefined performance thresholds in the training program, the endoscopists started a 1-year program (continuation phase) in which they performed narrow band imaging analyses during colonoscopies of participants in the screening program and predicted histological findings with confidence levels. The endoscopists were randomly assigned to groups that received feedback or no feedback on the accuracy of their predictions. Primary outcome measures were endoscopists' abilities to identify rectosigmoid neoplastic lesions (using histology as a reference) with NPVs of 90% or more, and selecting surveillance intervals that agreed with those determined by histology for at least 90% of cases. Of 39 endoscopists initially trained, 27 (69%) completed the training program. During the continuation phase, these 27 endoscopists performed 3144 colonoscopies in which 4504 diminutive polyps were removed. The endoscopists identified neoplastic lesions with a pooled NPV of 90.8% (95% confidence interval 88.6-92.6); their proposed surveillance intervals agreed with those determined by histologic analysis for 95.4% of cases (95% confidence interval 94.0-96.6). Findings did not differ between the group

  8. Three dimensional canonical transformations

    International Nuclear Information System (INIS)

    Tegmen, A.

    2010-01-01

    A generic construction of canonical transformations is given in three-dimensional phase spaces on which Nambu bracket is imposed. First, the canonical transformations are defined as based on cannonade transformations. Second, it is shown that determination of the generating functions and the transformation itself for given generating function is possible by solving correspondent Pfaffian differential equations. Generating functions of type are introduced and all of them are listed. Infinitesimal canonical transformations are also discussed as the complementary subject. Finally, it is shown that decomposition of canonical transformations is also possible in three-dimensional phase spaces as in the usual two-dimensional ones.

  9. Aberrant Transforming Growth Factor β1 Signaling and SMAD4 Nuclear Translocation Confer Epigenetic Repression of ADAM19 in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Michael W.Y. Chan

    2008-09-01

    Full Text Available Transforming growth factor-beta (TGF-β/SMAD signaling is a key growth regulatory pathway often dysregulated in ovarian cancer and other malignancies. Although loss of TGF-β–mediated growth inhibition has been shown to contribute to aberrant cell behavior, the epigenetic consequence(s of impaired TGF-β/SMAD signaling on target genes is not well established. In this study, we show that TGF-β1 causes growth inhibition of normal ovarian surface epithelial cells, induction of nuclear translocation SMAD4, and up-regulation of ADAM19 (a disintegrin and metalloprotease domain 19, a newly identified TGF-β1 target gene. Conversely, induction and nuclear translocation of SMAD4 were negligible in ovarian cancer cells refractory to TGF-β1 stimulation, and ADAM19 expression was greatly reduced. Furthermore, in the TGF-β1 refractory cells, an inactive chromatin environment, marked by repressive histone modifications (trimethyl-H3K27 and dimethyl-H3K9 and histone deacetylase, was associated with the ADAM19 promoter region. However, the CpG island found within the promoter and first exon of ADAM19 remained generally unmethylated. Although disrupted growth factor signaling has been linked to epigenetic gene silencing in cancer, this is the first evidence demonstrating that impaired TGF-β1 signaling can result in the formation of a repressive chromatin state and epigenetic suppression of ADAM19. Given the emerging role of ADAMs family proteins in growth factor regulation in normal cells, we suggest that epigenetic dysregulation of ADAM19 may contribute to the neoplastic process in ovarian cancer.

  10. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    International Nuclear Information System (INIS)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-01-01

    Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  11. Differentiation of benign osteoporotic and neoplastic vertebral compression fractures with a diffusion-weighted, steady-state free precession sequence

    International Nuclear Information System (INIS)

    Baur, A.; Huber, A.; Nikolaou, K.; Staebler, A.; Reiser, M.; Duerr, H.R.

    2002-01-01

    Purpose: To evaluate the diagnosic accuracy of a diffusion-weigthed, steady-state free precession (SSFP) sequence for the differentiation of acute benign osteoporotic and neoplastic vertebral compression fractures. Methods: 85 patients with 102 vertebral compression fractures were examined with MR imaging using a spine array surface coil (Siemens, Vision, 1.5 Tesla). The following sequences were performed in sagittal orientation: T 1 -weighted spin echo (SE), short-tau inversion recovery (STIR) and a diffusion-weighted SSFP sequence (TR=25 msec, diffusion pulse length δ=3 msec). The SSFP images were evaluated qualitatively on a 5-grade scale from strongly hypointense to strongly hyperintense. Quantitative analysis was performed with region of interest measurements (ROI) and calculation of a bone marrow ratio. Results: 60 fractures were due to osteoporosis and 42 fractures were caused by malignancy. 'Hyperintensity' in a vertebral fracture on a SSFP sequence provided a sensitivity of 100% and a specificity of 93%. The positive predictive value was 91%, the negative predictive value was 100%. Quantitative analysis of the bone marrow ratio showed a statistically significant difference between the osteoporosis and the tumor group (p [de

  12. Development of a method for the accurate measurement of protein turnover in neoplastic cells grown in culture

    International Nuclear Information System (INIS)

    Silverman, J.A.

    1984-01-01

    In this study, it was shown that standard techniques for cell recovery and sample preparation for liquid scintillation counting led to underestimation of the radioactivity present in cell proteins by 20-40%. These techniques involved labeling with 3 He leucine or 14 C leucine, scraping the cells from the dish in a buffer, TCA precipitation of the cell proteins, solubilization in NaOH and counting in a liquid scintillation counter. Hydrolysis of the proteins with HCl or Pronase significantly increased the recovery of the labeled proteins. Also, solubilization in situ with NaOH or hydrolysis in situ with Pronase recovered 5-10% additional labeled proteins. The techniques developed here allow the accurate measurement of radioactivity in cell proteins. In addition, these techniques were used to study protein turnover in rat hepatoma cells grown in culture. These cells regulated their growth rate through changes in the protein synthesis rate as opposed to changes in the protein degradation rate. These data support the hypothesis that neoplastic cells, unlike normal cells, do not regulate proteolysis in growth control; normal cells under similar conditions have been shown to activate lysosomal proteolysis as they reach confluence. The physiologic implications of this observation are discussed

  13. Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

    Science.gov (United States)

    Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

    2009-01-01

    Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

  14. Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

    Directory of Open Access Journals (Sweden)

    Kelly S Hayes

    2017-06-01

    Full Text Available Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+ mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

  15. LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

    Science.gov (United States)

    Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

    2017-01-02

    Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

  16. Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype

    Directory of Open Access Journals (Sweden)

    Shingo Sato

    2016-07-01

    Full Text Available The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype.

  17. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  18. Transformative Learning: Personal Empowerment in Learning Mathematics

    Science.gov (United States)

    Hassi, Marja-Liisa; Laursen, Sandra L.

    2015-01-01

    This article introduces the concept of personal empowerment as a form of transformative learning. It focuses on commonly ignored but enhancing elements of mathematics learning and argues that crucial personal resources can be essentially promoted by high engagement in mathematical problem solving, inquiry, and collaboration. This personal…

  19. Laplace Transforms without Integration

    Science.gov (United States)

    Robertson, Robert L.

    2017-01-01

    Calculating Laplace transforms from the definition often requires tedious integrations. This paper provides an integration-free technique for calculating Laplace transforms of many familiar functions. It also shows how the technique can be applied to probability theory.

  20. On Poisson Nonlinear Transformations

    Directory of Open Access Journals (Sweden)

    Nasir Ganikhodjaev

    2014-01-01

    Full Text Available We construct the family of Poisson nonlinear transformations defined on the countable sample space of nonnegative integers and investigate their trajectory behavior. We have proved that these nonlinear transformations are regular.

  1. Chemical Transformation Simulator

    Science.gov (United States)

    The Chemical Transformation Simulator (CTS) is a web-based, high-throughput screening tool that automates the calculation and collection of physicochemical properties for an organic chemical of interest and its predicted products resulting from transformations in environmental sy...

  2. Diffusionless phase transformations

    International Nuclear Information System (INIS)

    Vejman, K.M.

    1987-01-01

    Diffusionless phase transformations in metals and alloys in the process of which atomic displacements occur at the distances lower than interatomic ones and relative correspondence of neighbour atoms is preserved, are considered. Special attention is paid to the mechanism of martensitic transformations. Phenomenologic crystallographical theory of martensitic transformations are presented. Two types of martensitic transformations different from the energy viewpoint are pointed out - thermoelastic and non-thermoelastic ones - which are characterized by transformation hysteresis and ways of martensite - initial phase reverse transformation realization. Mechanical effect in the martensitic transformations have been analyzed. The problem of diffusionless formation of ω-phases and the effect of impurities and vacancies on the process are briefly discussed. The role of charge density waves in phase transformations of the second type (transition of initial phase into noncommensurate one) and of the first type (transition of noncommensurate phase into commensurate one) is considered

  3. Equations For Rotary Transformers

    Science.gov (United States)

    Salomon, Phil M.; Wiktor, Peter J.; Marchetto, Carl A.

    1988-01-01

    Equations derived for input impedance, input power, and ratio of secondary current to primary current of rotary transformer. Used for quick analysis of transformer designs. Circuit model commonly used in textbooks on theory of ac circuits.

  4. Wisdom and narcissism as predictors of transformational leadership

    NARCIS (Netherlands)

    Greaves, Claire E.; Zacher, Hannes; McKenna, Bernard; Rooney, David

    2014-01-01

    Purpose - Although leadership and organizational scholars have suggested that the virtue of wisdom may promote outstanding leadership behavior, this proposition has rarely been empirically tested. The purpose of this paper is to investigate the relationships between transformational leadership,

  5. Diagnostic capabilities of the virtual bronchoscopy at advanced neoplastic process of esophagus with formation of tracheobronchial fistula: Description of a case

    Directory of Open Access Journals (Sweden)

    M. A. Mitev

    2017-09-01

    Full Text Available The relevance of the problem is related to the continued increase in the neoplastic processes, and at the same time also to the development and improvement of the endoscopic and CT equipment, and thus expanding the diagnostic capabilities. Purpose: The presented research examines the results of the study of a rare case of ruptured trachea as a result of cancer of the esophagus. Methods: Fiberoptic esophagoscopy (FOE and CT of the chest followed by virtual bronchoscopy on a patient with a ruptured trachea, a 63 year-old man, were performed. Result: Performing MDCT with virtual bronchoscopy, according to this study, is crucial as the sole and complex methodology for the described case in connection with the finding of the trachea-oesophageal fistula and evaluation of the mediastinum and the pulmonary parenchyma. Conclusion: The VB is a successful method equally effective compared to the FB, to diagnose of advanced neoplastic processes.

  6. Detection of occult cancer with [18F]-FDG scintigraphy in case of limbic encephalitis, a rare neurologic para neoplastic syndrome

    International Nuclear Information System (INIS)

    Kerrou, K.; Aide, N.; Montravers, F.; Grahek, D.; Younsi-Pourtau, N.; Petegnief, Y.; Colombet-Lamau, C.; Beco, V. de; Talbot, J.N.

    2003-01-01

    Limbic encephalitis is a rare neurologic para-neoplastic syndrome due to the production of anti-neuronal antibodies induced by the presence of a malignant tumour, most frequently a small cell lung cancer: The discovery and the resection of the malignant tissue allows a stabilisation of the neurological syndrome, a complete recovery being impossible when irreversible lesions are present. ( 18 F)-FDG PET may play a determinant role when the cancer is still occult after conventional imaging work-up. We report here on a such patient with evolving limbic encephalitis and no detectable cancer with conventional imaging modalities. ( 18 F)-FDG CDET successfully localised neoplastic small cell lung cancer tissue in the lung. The malignant tumour was not even detectable at surgery and was only confirmed at post surgical histology exactly exactly where it has been spotted by CDET. After surgery, the neurologic syndrome is now steady. (authors)

  7. MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

    KAUST Repository

    Li, Yulin; Choi, Peter  S.; Casey, Stephanie  C.; Dill, David  L.; Felsher, Dean  W.

    2014-01-01

    The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

  8. MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

    KAUST Repository

    Li, Yulin

    2014-08-01

    The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

  9. Entropy of Baker's Transformation

    Institute of Scientific and Technical Information of China (English)

    栾长福

    2003-01-01

    Four theorems about four different kinds of entropies for Baker's transformation are presented. The Kolmogorov entropy of Baker's transformation is sensitive to the initial flips by the time. The topological entropy of Baker's transformation is found to be log k. The conditions for the state of Baker's transformation to be forbidden are also derived. The relations among the Shanonn, Kolmogorov, topological and Boltzmann entropies are discussed in details.

  10. Health promotion.

    Science.gov (United States)

    Miyake, S; Lucas-Miyake, M

    1989-01-01

    This article will describe a marketing model for the development of a role for occupational therapy in the industrial market. Health promotion activities are used as a means to diversify existing revenue bases by establishing new referral sources in industry. The technique of need satisfaction -selling or marketing one's services to a customer based on needs expressed by the customer - is reviewed, and implementation of this approach is described from two settings, one in psychiatry and the other in rehabilitation.

  11. Electrostatic shielding of transformers

    Energy Technology Data Exchange (ETDEWEB)

    De Leon, Francisco

    2017-11-28

    Toroidal transformers are currently used only in low-voltage applications. There is no published experience for toroidal transformer design at distribution-level voltages. Toroidal transformers are provided with electrostatic shielding to make possible high voltage applications and withstand the impulse test.

  12. Defense Business Transformation

    Science.gov (United States)

    2009-12-01

    Defense Business Transformation by Jacques S. Gansler and William Lucyshyn The Center for Technology and National...REPORT TYPE 3. DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Defense Business Transformation 5a. CONTRACT NUMBER 5b. GRANT NUMBER...vii Part One: DoD Business Transformation

  13. Three-Dimensional Printing as an Interdisciplinary Communication Tool: Preparing for Removal of a Giant Renal Tumor and Atrium Neoplastic Mass.

    Science.gov (United States)

    Golab, Adam; Slojewski, Marcin; Brykczynski, Miroslaw; Lukowiak, Magdalena; Boehlke, Marek; Matias, Daniel; Smektala, Tomasz

    2016-08-22

    Three-dimensional (3D) printing involves preparing 3D objects from a digital model. These models can be used to plan and practice surgery. We used 3D printing to plan for a rare complicated surgery involving the removal of a renal tumor and neoplastic mass, which reached the heart atrium. A printed kidney model was an essential element of communication for physicians with different specializations.

  14. Transforming the Force and Logistics Transformation

    National Research Council Canada - National Science Library

    Cook, Katherine M

    2006-01-01

    U.S. Army transformation strategy addresses the imperative to change the Army from a Cold War-oriented design to one that is more responsive, agile, and adaptable to present and emerging threats across...

  15. Effects of protease inhibitors on radiation transformation in vitro

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Little, J.B.

    1981-01-01

    We have investigated the effects of three protease inhibitors, antipain, leupeptin, and soybean trypsin inhibitor, on the induction of oncogenic transformation in mouse C3H10T 1/2 cells by X-rays. The patterns of inhibition by the three protease inhibitors were different. Antipain was the most effective, having the ability to suppress completely radiation transformation as well as radiation transformation enhanced by the phorbol ester promoting agent 12-O-tetradecanoylphorbol-13-acetate. The fact that antipain could suppress transformation when present for only 1 day following irradiation suggests that an effect on a DNA repair process might be important in its action. Leupeptin was less effective than antipain in its inhibition of radiation transformation. Soybean trypsin inhibitor suppressed only the promotional effects of 12-O-tetradecanoylphorbol-13-acetate on transformation. Our results suggest that there may be more than one protease involved in carcinogenesis

  16. Differentiation of osteoporotic and neoplastic vertebral fractures by chemical shift {l_brace}in-phase and out-of phase{r_brace} MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ragab, Yasser [Radiology Department, Faculty of Medicine, Cairo University (Egypt); Radiology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yragab61@hotmail.com; Emad, Yasser [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt); Rheumatology and Rehabilitation Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yasseremad68@yahoo.com; Gheita, Tamer [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt)], E-mail: gheitamer@yahoo.com; Mansour, Maged [Oncology Department, Faculty of Medicine, Cairo University (Egypt); Oncology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: magedmansour@yahoo.com; Abou-Zeid, A. [Public Health Department, Faculty of Medicine, Cairo University, Cairo (Egypt)], E-mail: alaabouzeid@yahoo.com; Ferrari, Serge [Division of Bone Diseases, Department of Rehabilitation and Geriatrics, and WHO, Collaborating Center for Osteoporosis Prevention, Geneva University Hospital (Switzerland)], E-mail: serge.ferrari@medecine.unige.ch; Rasker, Johannes J. [Rheumatologist University of Twente, Enschede (Netherlands)], E-mail: j.j.rasker@utwente.nl

    2009-10-15

    Objective: The objective of this study was to establish the cut-off value of the signal intensity drop on chemical shift magnetic resonance imaging (MRI) with appropriate sensitivity and specificity to differentiate osteoporotic from neoplastic wedging of the spine. Patients and methods: All patients with wedging of vertebral bodies were included consecutively between February 2006 and January 2007. A chemical shift MRI was performed and signal intensity after (in-phase and out-phase) images were obtained. A DXA was performed in all. Results: A total of 40 patients were included, 20 with osteoporotic wedging (group 1) and 20 neoplastic (group 2). They were 21 males and 19 females. Acute vertebral collapse was observed in 15 patients in group 1 and subacute collapse in another 5 patients, while in group 2, 11 patients showed acute collapse and 9 patients (45%) showed subacute vertebral collapse. On the chemical shift MRI a substantial reduction in signal intensity was found in all lesions in both groups. The proportional changes observed in signal intensity of bone marrow lesions on in-phase compared with out-of-phase images showed significant differences in both groups (P < 0.05). At a cut-off value of 35%, the observed sensitivity of out-of-phase images was 95%, specificity was 100%, positive predictive value was 100% and negative predictive value was 95.2%. Conclusion: A chemical shift MRI is useful in order to differentiate patients with vertebral collapse due to underlying osteoporosis or neoplastic process.

  17. Neutron-energy-dependent cell survival and oncogenic transformation.

    Science.gov (United States)

    Miller, R C; Marino, S A; Martin, S G; Komatsu, K; Geard, C R; Brenner, D J; Hall, E J

    1999-12-01

    Both cell lethality and neoplastic transformation were assessed for C3H10T1/2 cells exposed to neutrons with energies from 0.040 to 13.7 MeV. Monoenergetic neutrons with energies from 0.23 to 13.7 MeV and two neutron energy spectra with average energies of 0.040 and 0.070 MeV were produced with a Van de Graaff accelerator at the Radiological Research Accelerator Facility (RARAF) in the Center for Radiological Research of Columbia University. For determination of relative biological effectiveness (RBE), cells were exposed to 250 kVp X rays. With exposures to 250 kVp X rays, both cell survival and radiation-induced oncogenic transformation were curvilinear. Irradiation of cells with neutrons at all energies resulted in linear responses as a function of dose for both biological endpoints. Results indicate a complex relationship between RBEm and neutron energy. For both survival and transformation, RBEm was greatest for cells exposed to 0.35 MeV neutrons. RBEm was significantly less at energies above or below 0.35 MeV. These results are consistent with microdosimetric expectation. These results are also compatible with current assessments of neutron radiation weighting factors for radiation protection purposes. Based on calculations of dose-averaged LET, 0.35 MeV neutrons have the greatest LET and therefore would be expected to be more biologically effective than neutrons of greater or lesser energies.

  18. Fractional finite Fourier transform.

    Science.gov (United States)

    Khare, Kedar; George, Nicholas

    2004-07-01

    We show that a fractional version of the finite Fourier transform may be defined by using prolate spheroidal wave functions of order zero. The transform is linear and additive in its index and asymptotically goes over to Namias's definition of the fractional Fourier transform. As a special case of this definition, it is shown that the finite Fourier transform may be inverted by using information over a finite range of frequencies in Fourier space, the inversion being sensitive to noise. Numerical illustrations for both forward (fractional) and inverse finite transforms are provided.

  19. Transformational Leadership in Special Education: Leading the IEP Team

    Science.gov (United States)

    Lentz, Kirby

    2012-01-01

    Using the principles of transformational leadership, IEP teams become effective tools to ensure student success and achievements. There is a difference of teams that are simply chaired and those that are lead. Teams with transformational leaders promote the best efforts of all participants including parents and students to effectively deliver…

  20. Resident support for a landfill-to-park transformation

    Science.gov (United States)

    Christine A. Vogt; David B. Klenosky; Stephanie A. Snyder; Lindsay K. Campbell

    2015-01-01

    Globally, landfills are being transformed into other uses because land resources scarce, property values are increasing, and governments seek to reduce urban blight and adaptively reuse space. Park planners and city managers are likely to find that gauging public perceptions of a landfill-to-park project transformation and promoting such sites to potential visitors as...

  1. Data Transformations for Inference with Linear Regression: Clarifications and Recommendations

    Science.gov (United States)

    Pek, Jolynn; Wong, Octavia; Wong, C. M.

    2017-01-01

    Data transformations have been promoted as a popular and easy-to-implement remedy to address the assumption of normally distributed errors (in the population) in linear regression. However, the application of data transformations introduces non-ignorable complexities which should be fully appreciated before their implementation. This paper adds to…

  2. Engaging First Graders in Transformational Early Childhood Emergent Learning Themes

    Science.gov (United States)

    Pendergrass, Amanda Daniel

    2013-01-01

    The purpose of this qualitative case study was to encourage learners to care for others and make a difference in the world through Reggio Emilia-inspired teaching and learning practice that promoted transformational education. Students were anticipated to take an active role in helping to develop the transformational educational curriculum.…

  3. Nonsynchronous Noncommensurate Impedance Transformers

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy; Kim, K

    2012-01-01

    Nonsynchronous noncommensurate impedance transformers consist of a combination of two types of transmission lines: transmission lines with a characteristic impedance equal to the impedance of the source, and transmission lines with a characteristic impedance equal to the load. The practical...... advantage of such transformers is that they can be constructed using sections of transmission lines with a limited variety of characteristic impedances. These transformers also provide comparatively compact size in applications where a wide transformation ratio is required. This paper presents the data...... matrix approach and experimentally verified by synthesizing a 12-section nonsynchronous noncommensurate impedance transformer. The measured characteristics of the transformer are compared to the characteristics of a conventional tapered line transformer....

  4. Promoting industrialisation

    International Nuclear Information System (INIS)

    Hayfield, F.

    1986-04-01

    When the first nuclear power programme is decided upon, automatically the country has to initiate in parallel a programme to modify or add to its current industrial structure and resources. The extent of this new industrialisation depends upon many factors which both, the Government and the Industries have to consider. The Government has a vital role which includes the setting up of the background against which the industrial promotion should take place and in many cases may have also to play an active role all along this programme. Equally, the existing industries have an important role so as to achieve the most efficient participation in the nuclear programme. Invariably the industrial promotional programme will incur a certain degree of transfer of technology, the extent depending on the policies adopted. For this technology transfer to take place efficiently, both the donor and the receiver have to recognise each other's legitimate ambitions and fears. The transfer of technology is a process having a high human content and both donor and receiver have to take this into account. This can be further complicated when there is a difference in culture between them. Technology transfer is carried out within a contractual and organisational framework which will identify the donor (licensor) and the receiver (licensee). This framework may take various forms from a simple cooperative agreement, through a joint-venture organisation right to a standard contract between two separate entities. Each arrangement has its advantages and drawbacks and requires investment of different degrees. One of the keys to a successful industrial promotion is having it carried out in a timely fashion which will be parallel with the nuclear power programme. Experience in some countries has shown the problems when the industrialisation is out of phase with the programme whilst in other cases this industrialisation was at a level and scale unjustified. (author)

  5. Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

    Science.gov (United States)

    Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

    2006-06-01

    Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

  6. Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

    Science.gov (United States)

    Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

    2011-01-01

    Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

  7. Non-neoplastic parenchymal changes in kidney cancer and post-partial nephrectomy recovery of renal function.

    Science.gov (United States)

    Bazzi, Wassim M; Chen, Ling Y; Cordon, Billy H; Mashni, Joseph; Sjoberg, Daniel D; Bernstein, Melanie; Russo, Paul

    2015-09-01

    To explore the association of non-neoplastic parenchymal changes (nNPC) with patients' health and renal function recovery after partial nephrectomy (PN). This retrospective review identified 800 pT1a patients who underwent PN at Memorial Sloan Kettering Cancer Center from 2007 to 2012. Pathology reports were reviewed for nNPC graded as mild or severe: vascular sclerosis (VS), glomerulosclerosis (GS), and fibrosis/scarring. Correlations between nNPC and known preoperative predictors of renal function [age, sex, African-American race, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologists (ASA) score, body mass index, coronary artery disease, and hypertension (HTN)] were assessed using Spearman's rank correlation (ρ). Multivariable linear regression, adjusted for the described known preoperative risk predictors, was performed to evaluate whether the parenchymal features were able to predict 6-month postoperative eGFR. In this study, 46 % of tumors had benign surrounding parenchyma. We noted statistically significant yet weak associations of VS with age (ρ = 0.19; p < 0.001), ASA (ρ = 0.09; p < 0.001), preoperative eGFR (ρ = -0.14; p < 0.001), and HTN (ρ = 0.14; p < 0.001). GS also significantly correlated with HTN, but the correlation was again small (ρ = 0.12; p < 0.001). After adjusting for known risk predictors, only GS was a significant predictor of 6-month postoperative eGFR. When compared with no GS, mild and severe GS were negatively associated with a decrease of 4.9 and 10.8 mL/min/1.73 m(2) in 6-month postoperative eGFR, respectively. Presence of VS and GS correlated with patients' baseline health, and presence of GS predicted postoperative renal function recovery.

  8. β-carotene and canthaxanthin inhibit chemically- and physically-induced transformation in 10T1/2 cells

    International Nuclear Information System (INIS)

    Pung, A.; Rundhaug, J.E.; Yoshizawa, C.N.; Bertram, J.S.

    1988-01-01

    We have studied the effects of β-carotene (β-C), a vitamin A precursor of plant origin, and canthaxanthin (CTX), a non-provitamin A carotenoid, on the neoplastic transformation of C3H/10T1/2 murine fibroblast cells. We show that both β-C and CTX inhibit 3-methylcholanthrene (MCA)-induced transformation. Both carotenoids failed to inhibit X-ray-induced transformation when the cells were treated prior to and during irradiation. However, when the drugs were added 1 week after X-irradiation and maintained in the medium thereafter, both carotenoids inhibited subsequent development of transformed foci in a dose-dependent manner. Again, CTX was more effective than β-C. The inhibition of MCA-induced transformation was reversible; upon removal of the drug, transformed foci developed within 2 weeks, indicating that the carotenoids were not specifically toxic to initiated cells. Although both carotenoids caused a small dose-dependent decrease in the growth rate of both parental and initiated 10T1/2 cells, they did not markedly affect colony size or number when the cells were treated as in the transformation assays, nor did they influence the expression of neoplasia of two transformed cell lines. We suggest that the carotenoids' lipid anti-oxidant properties may be responsible for their inhibitory actions on transformation. (author)

  9. Transformative environmental governance

    Science.gov (United States)

    Chaffin, Brian C.; Garmestani, Ahjond S.; Gunderson, Lance H.; Harm Benson, Melinda; Angeler, David G.; Arnold, Craig Anthony (Tony); Cosens, Barbara; Kundis Craig, Robin; Ruhl, J.B.; Allen, Craig R.

    2016-01-01

    Transformative governance is an approach to environmental governance that has the capacity to respond to, manage, and trigger regime shifts in coupled social-ecological systems (SESs) at multiple scales. The goal of transformative governance is to actively shift degraded SESs to alternative, more desirable, or more functional regimes by altering the structures and processes that define the system. Transformative governance is rooted in ecological theories to explain cross-scale dynamics in complex systems, as well as social theories of change, innovation, and technological transformation. Similar to adaptive governance, transformative governance involves a broad set of governance components, but requires additional capacity to foster new social-ecological regimes including increased risk tolerance, significant systemic investment, and restructured economies and power relations. Transformative governance has the potential to actively respond to regime shifts triggered by climate change, and thus future research should focus on identifying system drivers and leading indicators associated with social-ecological thresholds.

  10. Quantized Bogoliubov transformations

    International Nuclear Information System (INIS)

    Geyer, H.B.

    1984-01-01

    The boson mapping of single fermion operators in a situation dominated by the pairing force gives rise to a transformation that can be considered a quantized version of the Bogoliubov transformation. This transformation can also be obtained as an exact special case of operators constructed from an approximate treatment of particle number projection, suggesting a method of obtaining the boson mapping in cases more complicated than that of pairing force domination

  11. Promoter Methylation and mRNA Expression of Response Gene to Complement 32 in Breast Carcinoma

    International Nuclear Information System (INIS)

    Nasab, E. E.; Nasab, E. E.; Hashemi, M.; Rafighdoost, F.

    2016-01-01

    Response gene to complement 32 (RGC32), induced by activation of complements, has been characterized as a cell cycle regulator; however, its role in carcinogenesis is still controversial. In the present study we compared RGC32 promoter methylation patterns and mRNA expression in breast cancerous tissues and adjacent normal tissues. Materials and Methods. Sixty-three breast cancer tissues and 63 adjacent non neoplastic tissues were included in our study. Design. Nested methylation-specific polymerase chain reaction (Nested-MSP) and quantitative PCR (qPCR) were used to determine RGC32 promoter methylation status and its mRNA expression levels, respectively. Results. RGC32 methylation pattern was not different between breast cancerous tissue and adjacent non neoplastic tissue (OR=2.30, 95% CI=0.95-5.54). However, qPCR analysis displayed higher levels of RGC32 mRNA in breast cancerous tissues than in noncancerous tissues (1.073 versus 0.959; P=0.001), irrespective of the promoter methylation status. The expression levels and promoter methylation of RGC32 were not correlated with any of patients’ clinical characteristics (P>0.05).

  12. Phase transformation and diffusion

    CERN Document Server

    Kale, G B; Dey, G K

    2008-01-01

    Given that the basic purpose of all research in materials science and technology is to tailor the properties of materials to suit specific applications, phase transformations are the natural key to the fine-tuning of the structural, mechanical and corrosion properties. A basic understanding of the kinetics and mechanisms of phase transformation is therefore of vital importance. Apart from a few cases involving crystallographic martensitic transformations, all phase transformations are mediated by diffusion. Thus, proper control and understanding of the process of diffusion during nucleation, g

  13. The convolution transform

    CERN Document Server

    Hirschman, Isidore Isaac

    2005-01-01

    In studies of general operators of the same nature, general convolution transforms are immediately encountered as the objects of inversion. The relation between differential operators and integral transforms is the basic theme of this work, which is geared toward upper-level undergraduates and graduate students. It may be read easily by anyone with a working knowledge of real and complex variable theory. Topics include the finite and non-finite kernels, variation diminishing transforms, asymptotic behavior of kernels, real inversion theory, representation theory, the Weierstrass transform, and

  14. Coaxial pulse matching transformer

    International Nuclear Information System (INIS)

    Ledenev, V.V.; Khimenko, L.T.

    1986-01-01

    This paper describes a coaxial pulse matching transformer with comparatively simple design, increased mechanical strength, and low stray inductance. The transformer design makes it easy to change the turns ratio. The circuit of the device and an expression for the current multiplication factor are presented; experiments confirm the efficiency of the transformer. Apparatus with a coaxial transformer for producing high-power pulsed magnetic fields is designed (current pulses of 1-10 MA into a load and a natural frequency of 100 kHz)

  15. Distributed photovoltaic grid transformers

    CERN Document Server

    Shertukde, Hemchandra Madhusudan

    2014-01-01

    The demand for alternative energy sources fuels the need for electric power and controls engineers to possess a practical understanding of transformers suitable for solar energy. Meeting that need, Distributed Photovoltaic Grid Transformers begins by explaining the basic theory behind transformers in the solar power arena, and then progresses to describe the development, manufacture, and sale of distributed photovoltaic (PV) grid transformers, which help boost the electric DC voltage (generally at 30 volts) harnessed by a PV panel to a higher level (generally at 115 volts or higher) once it is

  16. A relation connecting scale transformation, Galilean transformation and Baecklund transformation for the nonlinear Schroedinger equation

    International Nuclear Information System (INIS)

    Steudel, H.

    1980-01-01

    It is shown that the two-parameter manifold of Baecklund transformations known for the nonlinear Schroedinger equation can be generated from one Baecklund transformation with specified parameters by use of scale transformation and Galilean transformation. (orig.)

  17. Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

    Science.gov (United States)

    Abd El All, Howayda S; Refaat, Amany; Dandash, Khadiga

    2007-01-01

    Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Results EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH

  18. Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

    Directory of Open Access Journals (Sweden)

    Dandash Khadiga

    2007-07-01

    Full Text Available Abstract Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx, a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap smears were evaluated using the Bethesda system (TBS, followed by colposcopic guided biopsy (CGB for all epithelial abnormalities (EA. In a third step, HPV was tested on all EA by in-situ hybridization (ISH using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2, cytomegalovirus (CMV, and human immunodeficiency virus (HIV. Results EA representing 7.8% (424/5453, were categorized into atypical squamous cell of undetermined significance (ASCUS (34.4%, atypical glandular cell of undetermined significance (AGCUS (15.3%, combined ASCUS and AGCUS (3.1%, low grade squamous intraepithelial lesions (SIL (41.0%, high grade SIL (5.2% and invasive lesions (1%. CGB of EA (n = 281 showed non neoplastic lesions (12.8%, atypical squamous metaplasia (ASM (19.2%, cervical intraepithelial neoplasia I (CIN (44.4%, CIN II (4.4%, CINIII (2.8%, endocervical lesions (5.2%, combined squamous and endocervical lesions (10.0%, invasive squamous cell carcinoma (SCC (0.02% and extranodal marginal zone B cell lymphoma (MZBCL (0.02%. The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH revealed

  19. Malignant transformation in vitro: criteria, biological markers, and application in environmental screening of carcinogens

    International Nuclear Information System (INIS)

    Borek, C.

    1979-01-01

    Biological markers which distinguish malignantly transformed fibroblasts from their normal counterpart include pleomorphic morphology, lowered requirement for nutritional factors, loss of density inhibition of growth, complex topography as discernible by scanning electron microscopy, loss in surface proteins, incomplete glycosylation of membrane glycolylipids and glycoproteins, increased production of specific proteases, decreased organization of the cytoskeleton, and acquisition of neoantigens. Several of these markers are not consistently found in transformed epithelial cells and therefore cannot serve to distinguish unequivocally neoplastic epithelial cells from the normal counterparts. The only criteria associated with the transformed nature of both fibroblasts and epithelial cells are the ability of the cells to proliferate in semisolid medium and to induce tumors in appropriate hosts. In vitro systems represent a powerful tool for screening the mutagenic/oncogenic potential of physical, chemical, and environmental agents. Fibroblasts rather than epithelial cells are preferred for this purpose at the present time because of the clear-cut phenotypic differences between the normal and the transformed cells. These systems have been useful in establishing that malignant transformation can be induced by doses as low as 1 rad of X rays or 0.1 rad of neutrons, and that fractionation at low dose levelsleads to enhanced transformation. They have been useful in identifying a large number of hazardous chemicals and in evaluating the relationship between the mutagenic and carcinogenic potential of radiation and chemicals

  20. Discrete Gabor transform and discrete Zak transform

    NARCIS (Netherlands)

    Bastiaans, M.J.; Namazi, N.M.; Matthews, K.

    1996-01-01

    Gabor's expansion of a discrete-time signal into a set of shifted and modulated versions of an elementary signal or synthesis window is introduced, along with the inverse operation, i.e. the Gabor transform, which uses an analysis window that is related to the synthesis window and with the help of


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