Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

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Hirata, Naoya; Yamada, Shigeru [Division of Pharmacology, National Institute of Health Sciences (Japan); Asanagi, Miki [Division of Pharmacology, National Institute of Health Sciences (Japan); Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University (Japan); Sekino, Yuko [Division of Pharmacology, National Institute of Health Sciences (Japan); Kanda, Yasunari, E-mail: kanda@nihs.go.jp [Division of Pharmacology, National Institute of Health Sciences (Japan)

2016-02-05

Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

International Nuclear Information System (INIS)

Hirata, Naoya; Yamada, Shigeru; Asanagi, Miki; Sekino, Yuko; Kanda, Yasunari

2016-01-01

Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

Generation of a heterozygous knockout human embryonic stem cell line for the OCIAD1 locus using CRISPR/CAS9 mediated targeting: BJNhem20-OCIAD1-CRISPR-20

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Deeti K. Shetty

2016-03-01

Full Text Available Ovarian carcinoma immuno-reactive antigen domain containing 1(OCIAD1 single copy was knocked out generating an OCIAD1 heterozygous knockout human embryonic stem line named BJNhem20-OCIAD1-CRISPR-20. The line was generated using CRISPR-Cas9D10A double nickase knockout strategy (Mali et al., 2013.

Laminin binding protein, 34/67 laminin receptor, carries stage-specific embryonic antigen-4 epitope defined by monoclonal antibody Raft.2

International Nuclear Information System (INIS)

Katagiri, Yohko U.; Kiyokawa, Nobutaka; Nakamura, Kyoko; Takenouchi, Hisami; Taguchi, Tomoko; Okita, Hajime; Umezawa, Akihiro; Fujimoto, Junichiro

2005-01-01

We previously produced monoclonal antibodies against the detergent-insoluble microdomain, i.e., the raft microdomain, of the human renal cancer cell line ACHN. Raft.2, one of these monoclonal antibodies, recognizes sialosyl globopentaosylceramide, which has the stage-specific embryonic antigen (SSEA)-4 epitope. Although the mouse embryonal carcinoma (EC) cell line F9 does not express SSEA-4, some F9 cells stained with Raft.2. Western analysis and matrix-assisted laser desorption ionization-time of flight mass spectrometry identified the Raft.2 binding molecule as laminin binding protein (LBP), i.e., 34/67 laminin receptor. Weak acid treatment or digestion with Clostridium perfringens sialidase reduced Raft.2 binding to LBP on nitrocellulose sheets and [ 14 C]galactose was incorporated into LBP, indicating LBP to have a sialylated carbohydrate moiety. Subcellular localization analysis by sucrose density-gradient centrifugation and examination by confocal microscopy revealed LBP to be localized on the outer surface of the plasma membrane. An SSEA-4-positive human EC cell line, NCR-G3 cells, also expressed Raft.2-binding LBP

Metabolic fate of 18F-FDG in mice bearing either SCCVII squamous cell carcinoma or C3H mammary carcinoma

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Kaarstad, Katrin; Bender, Dirk; Bentzen, Lise

2002-01-01

in mice. METHODS: 18F-FDG was given intravenously to mice with either SCCVII squamous cell carcinoma or C3H mammary carcinoma grown on the back. 18F-Labeled metabolites were determined by radio-high-performance liquid chromatography in tumor tissue biopsies, in a time course of 180 min (12 mice of each...... tumor type), and in liver tissue biopsies 80 min after tracer injection (2 mice of each type). RESULTS: After the tracer injection, not only 18F-FDG and 18F-FDG-6-P but also 18F-FD-PG1 and 2-18F-fluoro-2-deoxy-1,6-biphosphate were detected in both tumors, relatively more in SCCVII carcinoma than in C3H...... carcinoma. Both tumors accumulated radioactivity throughout the 180-min measurement period, 4-fold more in SCCVII carcinoma than in C3H carcinoma. At 80 min, the radioactivity was approximately 6 and 1.2 times higher in the respective tumors than in liver tissue. CONCLUSION: Our results agree...

Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage

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Leloup, Corinne; Hopkins, Kevin M.; Wang, Xiangyuan; Zhu, Aiping; Wolgemuth, Debra J.; Lieberman, Howard B.

2010-01-01

RAD9 participates in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, apoptosis, embryogenesis, and regulation of transcription. A paralogue of RAD9 (named RAD9B) has been identified. To define the function of mouse Rad9b (Mrad9b), embryonic stem (ES) cells with a targeted gene deletion were constructed and used to generate Mrad9b mutant mice. Mrad9b−/− embryos are resorbed after E7.5 while some of the heterozygotes die between E12.5 and a few days after birth. Mrad9b is expressed in embryonic brain and Mrad9b+/− embryos exhibit abnormal neural tube closure. Mrad9b−/− mouse embryonic fibroblasts are not viable. Mrad9b−/− ES cells are more sensitive to gamma rays and mitomycin C than Mrad9b+/+ controls, but show normal gamma-ray-induced G2/M checkpoint control. There is no evidence of spontaneous genomic instability in Mrad9b−/− cells. Our findings thus indicate that Mrad9b is essential for embryonic development and mediates resistance to certain DNA damaging agents. PMID:20842695

Analysis list: E2f4 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available E2f4 Blood,Embryonic fibroblast,Liver,Muscle,Pluripotent stem cell + mm9 http://dba...rchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4....5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f4.10.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/colo/E2f4.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4....Embryonic_fibroblast.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f4.Liver.tsv,htt

Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis

DEFF Research Database (Denmark)

Giwercman, Alexander; Andrews, P W; Jørgensen, N

1993-01-01

Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell neoplasia would be strengthened by the finding of antigenic...

Bilobalide induces neuronal differentiation of P19 embryonic carcinoma cells via activating Wnt/β-catenin pathway.

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Liu, Mei; Guo, Jingjing; Wang, Juan; Zhang, Luyong; Pang, Tao; Liao, Hong

2014-08-01

Bilobalide, a natural product extracted from Ginkgo biloba leaf, is known to exhibit a number of pharmacological activities. So far, whether it could affect embryonic stem cell differentiation is still unknown. The main aim of this study was to investigate the effect of bilobalide on P19 embryonic carcinoma cells differentiation and the underlying mechanisms. Our results showed that bilobalide induced P19 cells differentiation into neurons in a concentration- and time-dependent manner. We also found that bilobalide promoted neuronal differentiation through activation of Wnt/β-catenin signaling pathway. Exposure to bilobalide increased inactive GSK-3β phosphorylation, further induced the nuclear accumulation of β-catenin, and also up-regulated the expression of Wnt ligands Wnt1 and Wnt7a. Neuronal differentiation induced by bilobalide was totally abolished by XAV939, an inhibitor of Wnt/β-catenin pathway. These results revealed a novel role of bilobalide in neuronal differentiation from P19 embryonic cells acting through Wnt/β-catenin signaling pathway, which would provide a better insight into the beneficial effects of bilobalide in brain diseases.

Melatonin antiproliferative effects require active mitochondrial function in embryonal carcinoma cells

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Loureiro, Rute; Magalhães-Novais, Silvia; Mesquita, Katia A.; Baldeiras, Ines; Sousa, Isabel S.; Tavares, Ludgero C.; Barbosa, Ines A.; Oliveira, Paulo J.; Vega-Naredo, Ignacio

2015-01-01

Although melatonin oncostatic and cytotoxic effects have been described in different types of cancer cells, the specific mechanisms leading to its antitumoral effects and their metabolic context specificity are still not completely understood. Here, we evaluated the effects of melatonin in P19 embryonal carcinoma stem cells (CSCs) and in their differentiated counterparts, cultured in either high glucose medium or in a galactose (glucose-free) medium which leads to glycolytic suppression and increased mitochondrial metabolism. We found that highly glycolytic P19 CSCs were less susceptible to melatonin antitumoral effects while cell populations relying on oxidative metabolism for ATP production were more affected. The observed antiproliferative action of melatonin was associated with an arrest at S-phase, decreased oxygen consumption, down-regulation of BCL-2 expression and an increase in oxidative stress culminating with caspase-3-independent cell death. Interestingly, the combined treatment of melatonin and dichloroacetate had a synergistic effect in cells grown in the galactose medium and resulted in an inhibitory effect in the highly resistant P19 CSCs. Melatonin appears to exert its antiproliferative activity in P19 carcinoma cells through a mitochondrially-mediated action which in turn allows the amplification of the effects of dichloroacetate, even in cells with a more glycolytic phenotype. PMID:26025920

18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scan Findings for Ductal Carcinomas of Breast: Association of Standardized Uptake Value and Histological Findings

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Bae, So Young; Lee, Eun Hye [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Park, Jung Mi [Dept. of Nuclear Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Kwak, Jeong Ja [Dept. of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

2012-02-15

To evaluate the factors associated with variations in 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) uptake in ductal carcinomas of the breast. We enrolled 216 ductal carcinoma cases that underwent 18F-FDG PET/CT. We evaluated the positivity and measured peak standardized uptake value (pSUV) of lesions that underwent 18F-FDG PET/CT. We analyzed the correlation between pSUV and invasiveness, lesion size, and the histologic factors of invasive ductal carcinoma (IDC). In the 18F-FDG PET/CT of ductal carcinomas, sensitivity was 90.2%, positive and negative predictive values were 99.5% and 25.0%, respectively. In ductal carcinoma in situ (DCIS) and IDC, the sensitivities were 68.8% and 92.0%, respectively. The mean pSUV of true positive (TP) DCIS and IDC were 2.6 and 5.1 (p < 0.05), respectively, whereas the false negative (FN) were 1.3 and 1.2 (p > 0.05), respectively, and that of false positive (FP) and true negative (TN) lesions were 2.2 and 0.9, respectively. The mean size of TP DCIS and IDC were 4.5 cm and 2.7 cm (p < 0.05), respectively, whereas the mean size of FN DCIS and IDC were 1.5 cm and 1.4 cm (p > 0.05), respectively, and that of FP and TN lesions were 1.8 cm and 1.2 cm respectively. Among the histological factors affecting IDC, mitosis showed the best correlation with pSUV (rho = 0.5). For 18F-FDG PET/CT of ductal carcinomas, the positive predictive value was 99.5% and the FN rate was 9.7%. False negative factors included DCIS and an IDC < 1.5 cm, whereas mitosis was the TP factor.

F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo.

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Thompson, Heather L; van Rooijen, Nico; McLelland, Bryce T; Manilay, Jennifer O

2016-01-01

Understanding how embryonic stem cells and their derivatives interact with the adult host immune system is critical to developing their therapeutic potential. Murine embryonic stem cell-derived hematopoietic progenitors (ESHPs) were generated via coculture with the bone marrow stromal cell line, OP9, and then transplanted into NOD.SCID.Common Gamma Chain (NSG) knockout mice, which lack B, T, and natural killer cells. Compared to control mice transplanted with adult lineage-negative bone marrow (Lin - BM) progenitors, ESHP-transplanted mice attained a low but significant level of donor hematopoietic chimerism. Based on our previous studies, we hypothesized that macrophages might contribute to the low engraftment of ESHPs in vivo . Enlarged spleens were observed in ESHP-transplanted mice and found to contain higher numbers of host F4/80 + macrophages compared to BM-transplanted controls. In vivo depletion of host macrophages using clodronate-loaded liposomes improved the ESHP-derived hematopoietic chimerism in the spleen but not in the BM. F4/80 + macrophages demonstrated a striking propensity to phagocytose ESHP targets in vitro . Taken together, these results suggest that macrophages are a barrier to both syngeneic and allogeneic ESHP engraftment in vivo .

CRISPR/Cas9-Mediated Genomic Deletion of the Beta-1, 4 N-acetylgalactosaminyltransferase 1 Gene in Murine P19 Embryonal Carcinoma Cells Results in Low Sensitivity to Botulinum Neurotoxin Type C.

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Kentaro Tsukamoto

Full Text Available Botulinum neurotoxins produced by Clostridium botulinum cause flaccid paralysis by inhibiting neurotransmitter release at peripheral nerve terminals. Previously, we found that neurons derived from the murine P19 embryonal carcinoma cell line exhibited high sensitivity to botulinum neurotoxin type C. In order to prove the utility of P19 cells for the study of the intracellular mechanism of botulinum neurotoxins, ganglioside-knockout neurons were generated by deletion of the gene encoding beta-1,4 N-acetylgalactosaminyltransferase 1 in P19 cells using the clustered regularly interspaced short palindromic repeats combined with Cas9 (CRISPR/Cas9 system. By using this system, knockout cells could be generated more easily than with previous methods. The sensitivity of the generated beta-1,4 N-acetylgalactosaminyltransferase 1-depleted P19 neurons to botulinum neurotoxin type C was decreased considerably, and the exogenous addition of the gangliosides GD1a, GD1b, and GT1b restored the susceptibility of P19 cells to botulinum neurotoxin type C. In particular, addition of a mixture of these three ganglioside more effectively recovered the sensitivity of knockout cells compared to independent addition of GD1a, GD1b, or GT1b. Consequently, the genome-edited P19 cells generated by the CRISPR/Cas9 system were useful for identifying and defining the intracellular molecules involved in the toxic action of botulinum neurotoxins.

Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

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Li, Yichun; Li, Yannan; Wang, Dan; Meng, Qingdong

2018-06-12

Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells.

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Yamada, Shigeru; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

2013-05-01

Organotin compounds such as tributyltin (TBT) are known to cause various forms of cytotoxicity, including developmental toxicity and neurotoxicity. However, the molecular target of the toxicity induced by nanomolar levels of TBT has not been identified. In the present study, we found that exposure to 100 nM TBT induced growth arrest in human pluripotent embryonic carcinoma cell line NT2/D1. Since glucose provides metabolic energy, we focused on the glycolytic system. We found that exposure to TBT reduced the levels of both glucose-6-phosphate and fructose-6-phosphate. To investigate the effect of TBT exposure on glycolysis, we examined glucose transporter (GLUT) activity. TBT exposure inhibited glucose uptake via a decrease in the level of cell surface-bound GLUT1. Furthermore, we examined the effect of AMP-activated protein kinase (AMPK), which is known to regulate glucose transport by facilitating GLUT translocation. Treatment with the potent AMPK activator, AICAR, restored the TBT-induced reduction in cell surface-bound GLUT1 and glucose uptake. In conclusion, these results suggest that exposure to nanomolar levels of TBT causes growth arrest by targeting glycolytic systems in human embryonic carcinoma cells. Thus, understanding the energy metabolism may provide new insights into the mechanisms of metal-induced cytotoxicity.

Evaluation of matrix metalloproteinase-9 expressions in nasopharyngeal carcinoma patients

Science.gov (United States)

Farhat; Asnir, R. A.; Yudhistira, A.; Daulay, E. R.; Puspitasari, D.; Yulius, S.

2018-03-01

Nasopharyngeal carcinoma (NPC) is one of head and neck cancer with a poor prognosis because of the position of the tumor adjacent to the skull base and vital structures. Degradation of extracellular matrix that will cause tumor cells to invade surrounding tissues, vascular or lymphatic vessels. One that plays a role in the extracellular matrix degradation process is matrix metalloproteinase-9 (MMP-9). MMP-9 plays a role in tumor invasion process, metastasis and induction of tumor tissue vascularization. To determine the expression of MMP-9 in patients with nasopharyngeal carcinoma, a descriptive study was conducted by examining immunohistochemistry MMP-9 in 30 NPC tissues that had never received radiotherapy, chemotherapy or combination. Frequency distribution of NPC patient mostly in the age group 41-50 years old and 51-60 years were nine people (30.0%); men (73.3%) and non-keratinizing squamous cell carcinoma (53.3%) histopathology type. The overexpression of MMP-9 in patients with nasopharyngeal carcinoma were mostly found in advance stage.

Regulation and patterns of endogenous and exogenous gene expression during differentiation of embryonal carcinoma cells

International Nuclear Information System (INIS)

Astigiano, S.; Sherman, M.I.; Abarzua, P.

1989-01-01

Embryonal carcinoma (EC) cells offer an interesting model system for evaluating differentiation because the cells are pluripotent, thus resembling germ cells and embryonic stem cells, and because a number of agents have been defined that are capable of promoting the differentiation of these cells. This chapter examines how EC cells might be triggered to differentiate, with emphasis on retinoic acid because this compound is a potent, naturally occurring inducer that has been studied extensively in this system. The nature of alterations in gene expression during EC cell differentiation is reviewed from the perspective of evaluating whether these changes are likely to be responsible for, or a result of, the differentiation event. Finally, the authors consider in molecular terms why EC cells, but not their differentiated derivatives, are refractory to the expression of many viral genomes following infection. Based upon these studies, they propose that fundamental changes in gene expression that are observed when differentiation is triggered in EC cells are likely to be due to the disappearance or neutralization of strong repressor elements

[Primary study on fluro [ 19F] berberine derivative for human hepatocellular carcinoma targetting in vitro].

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Zhang, Tong; Wu, Xiaoai; Cai, Huawei; Liang, Meng; Fan, Chengzhong

2017-04-01

[ 18 F]HX-01, a Fluorine-18 labeled berberine derivative, is a potential positron emission tomography (PET) tumor imaging agent, while [ 19 F]HX-01 is a nonradioactive reference substance with different energy state and has the same physical and chemical properties. In order to collect data for further study of [ 18 F]HX-01 PET imaging of hepatocellular carcinoma in vivo , this study compared the uptake of [ 19 F]HX-01 by human hepatocellular carcinoma and normal hepatocytes in vitro . The target compound, [ 19 F]HX-01, was synthesized in one step using berberrubine and 3-fluoropropyl 4-methylbenzenesulfonate. Cellular uptake and localization of [ 19 F]HX-01 were performed by a fluorescence microscope in human hepatocellular carcinoma HepG2, SMMC-7721 and human normal hepatocyte HL-7702. Cellular proliferation inhibition and cell cytotoxicity assay of the [ 19 F]HX-01 were conducted using cell counting kit-8 (CCK-8) on HepG2, SMMC-7721 and HL-7702 cells. Fluorescent microscopy showed that the combining ability of [ 19 F]HX-01 to the carcinoma SMMC-7721 and HepG2 was higher than that to the normal HL-7702. Cellular proliferation inhibition assay demonstrated that [ 19 F]HX-01 leaded to a dose-dependent inhibition on SMMC-7721, HepG2, and HL-7702 proliferation. Cell cytotoxicity assay presented that the cytotoxicity of [ 19 F]HX-01 to SMMC-7721 and HepG2 was obviously higher than that to HL-7702. This in vitro study showed that [ 19 F]HX-01 had a higher selectivity on human hepatocellular carcinoma cells (SMMC-7721, HepG2) but has less toxicity to normal hepatocytes (HL-7702). This could set up the idea that the radioactive reference substance [ 18 F]HX-01 may be worthy of further development as a potential molecular probe targeting human hepatocellular carcinoma using PET.

A practical guide for the identification of membrane and plasma membrane proteins in human embryonic stem cells and human embryonal carcinoma cells.

Science.gov (United States)

Dormeyer, Wilma; van Hoof, Dennis; Mummery, Christine L; Krijgsveld, Jeroen; Heck, Albert J R

2008-10-01

The identification of (plasma) membrane proteins in cells can provide valuable insights into the regulation of their biological processes. Pluripotent cells such as human embryonic stem cells and embryonal carcinoma cells are capable of unlimited self-renewal and share many of the biological mechanisms that regulate proliferation and differentiation. The comparison of their membrane proteomes will help unravel the biological principles of pluripotency, and the identification of biomarker proteins in their plasma membranes is considered a crucial step to fully exploit pluripotent cells for therapeutic purposes. For these tasks, membrane proteomics is the method of choice, but as indicated by the scarce identification of membrane and plasma membrane proteins in global proteomic surveys it is not an easy task. In this minireview, we first describe the general challenges of membrane proteomics. We then review current sample preparation steps and discuss protocols that we found particularly beneficial for the identification of large numbers of (plasma) membrane proteins in human tumour- and embryo-derived stem cells. Our optimized assembled protocol led to the identification of a large number of membrane proteins. However, as the composition of cells and membranes is highly variable we still recommend adapting the sample preparation protocol for each individual system.

The Use of a Liposomal Formulation Incorporating an Antimicrobial Peptide from Tilapia as a New Adjuvant to Epirubicin in Human Squamous Cell Carcinoma and Pluripotent Testicular Embryonic Carcinoma Cells

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Lo, Yu-Li; Lee, Hsin-Pin; Tu, Wei-Chen

2015-01-01

This study aims to explore the effects and mechanisms of hepcidin, a potential antimicrobial peptide from Tilapia, and epirubicin (Epi), an antineoplastic agent, on the generation of reactive oxygen species (ROS) and link the ROS levels to the reversal mechanisms of multidrug resistance (MDR) by epirubicin and hepcidin in human squamous cell carcinoma SCC15 and human embryonal carcinoma NT2D1 cells. The cells, pretreated with hepcidin, epirubicin, or a combination of these compounds in PEGylated liposomes, were used to validate the molecular mechanisms involved in inhibiting efflux transporters and inducing apoptosis as evaluated by cytotoxicity, intracellular accumulation, mRNA levels, cell cycle distribution, and caspase activity of this combination. We found that hepcidin significantly enhanced the cytotoxicity of epirubicin in liposomes. The co-incubation of epirubicin with hepcidin in liposomes intensified the ROS production, including hydrogen peroxide and superoxide free radicals. Hepcidin significantly increased epirubicin intracellular uptake into NT2D1 and SCC15 cells, as supported by the diminished mRNA expressions of MDR1, MDR-associated protein (MRP) 1, and MRP2. Hepcidin and/or epirubicin in liposomes triggered apoptosis, as verified by the reduced mitochondrial membrane potential, increased sub-G1 phase of cell cycle, incremental populations of apoptosis using annexin V/PI assay, and chromatin condensation. As far as we know, this is the first example showing that PEGylated liposomal TH1-5 and epirubicin gives rise to cell death in human squamous carcinoma and testicular embryonic carcinoma cells through the reduced epirubicin efflux via ROS-mediated suppression of P-gp and MRPs and concomitant initiation of mitochondrial apoptosis pathway. Hence, hepcidin in PEGylated liposomes may function as an adjuvant to anticancer drugs, thus demonstrating a novel strategy for reversing MDR. PMID:26393585

18F-FDG PET/CT in detection of gynecomastia in patients with hepatocellular carcinoma.

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Wang, Hsin-Yi; Jeng, Long-Bin; Lin, Ming-Chia; Chao, Chih-Hao; Lin, Wan-Yu; Kao, Chia-Hung

2013-01-01

We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC). Among the 127 male HCC patients who underwent 18F-FDG PET/CT scan, the 18FDG uptakes at the bilateral breasts in 9 patients with gynecomastia were recorded as standard uptake value (SUVmax) and the visual interpretation in both early and delayed images. The mean early SUVmax was 1.58/1.57 (right/left breast) in nine gynecomastia patients. The three patients with early visual score of 3 had higher early SUVmaxs. Gynecomastia is a possible cause of false-positive uptake on 18F-FDG PET/CT images. Copyright © 2013 Elsevier Inc. All rights reserved.

18F-FDG-PET/CT in Endometrial Carcinoma

International Nuclear Information System (INIS)

Jeon, Tae Joo

2008-01-01

Endometrial carcinoma is one of the most common gynecologic malignancies and which is predominant in postmenopausal women. Clinically many patients are hospitalized in early stage due to clinical sign and symptom such as vaginal bleeding and in this case, patient's prognosis is known to be good. However, considerable number of patients with advanced and relapsed disease reveal poor prognosis. Therefore, exact staging work up is essential for proper treatment as is primary lesion detection. 18 F-FDG-PET has been widely used for the evaluation of gynecologic malignancies such as cervical carcinoma and ovarian cancer. In contrast, FDG PET application to endometrial carcinoma is limited until now and there is no sufficient data to validate the usefulness of FDG PET for this disease yet. However, several studies showed promising results that FDG PET is sensitive and specific in detection of recurrent or metastatic lesions. Therefore further active investigation in this field can facilitate the use of FDG PET for endometrial carcinoma

In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET

International Nuclear Information System (INIS)

Wong, Peter K.; Lee, Sze Ting; Murone, Carmel; Eng, John; Lawrentschuk, Nathan; Berlangieri, Salvatore University; Pathmaraj, Kunthi; O’Keefe, Graeme J.; Sachinidis, John; Byrne, Amanda J.; Bolton, Damien M.; Davis, Ian D.; Scott, Andrew M.

2014-01-01

The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. The SUVmax (maximum standardized uptake value) mean±SD for FLT in tumour was 2.59±1.27, compared to normal kidney (2.47±0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60±1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean ± SD of 13.3%±9.2 (range 2.2% - 36.3%). There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology

Tributyltin induces mitochondrial fission through NAD-IDH dependent mitofusin degradation in human embryonic carcinoma cells.

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Yamada, Shigeru; Kotake, Yaichiro; Nakano, Mizuho; Sekino, Yuko; Kanda, Yasunari

2015-08-01

Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT acts at the nanomolar level through genomic pathways via the peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR). We recently reported that TBT inhibits cell growth and the ATP content in the human embryonic carcinoma cell line NT2/D1 via a non-genomic pathway involving NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which metabolizes isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we evaluated the effects of TBT on mitochondrial NAD-IDH and energy production. Staining with MitoTracker revealed that nanomolar TBT levels induced mitochondrial fragmentation. TBT also degraded the mitochondrial fusion proteins, mitofusins 1 and 2. Interestingly, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. Incubation with an α-ketoglutarate analogue partially recovered TBT-induced mitochondrial dysfunction, supporting the involvement of NAD-IDH. Our data suggest that nanomolar TBT levels impair mitochondrial quality control via NAD-IDH in NT2/D1 cells. Thus, mitochondrial function in embryonic cells could be used to assess cytotoxicity associated with metal exposure.

[Intracranial remote epidural haematoma as a complication after resection of an occipital lobe metastatic tumour from a testicular embryonal carcinoma – a case report].

Science.gov (United States)

Andrusewicz, Wojciech; Limanówka, Bartosz; Sagan, Leszek; Kojder, Ireneusz

We present the case of a patient who suffered from intracranial epidural haematoma in the left fronto -temporo -parietal region as a complication after left parieto -occipital craniotomy and a resection of a metastatic lesion from a testicular embryonal carcinoma to the left occipital lobe. We also discuss possible causes of this complication.

Negative regulation of retrovirus expression in embryonal carcinoma cells mediated by an intragenic domain.

Science.gov (United States)

Loh, T P; Sievert, L L; Scott, R W

1988-11-01

An intragenic region spanning the tRNA primer binding site of a Moloney murine leukemia virus recombinant retrovirus was found to restrict expression specifically in embryonal carcinoma (EC) cells. When the inhibitory domain was present, the levels of steady-state RNA synthesized from integrated recombinant templates in stable cotransformation assays were reduced 20-fold in EC cells but not in C2 myoblast cells. Transient-cotransfection assays showed that repression of a template containing the EC-specific inhibitory component was relieved by an excess of specific competitor DNA. In addition, repression mediated by the inhibitory component was orientation independent. This evidence demonstrates the presence of a saturable, trans-acting negative regulatory factor(s) in EC cells and suggests that the interaction of the factor(s) with the intragenic inhibitory component occurs at the DNA level.

In-vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine (FLT) PET

International Nuclear Information System (INIS)

Wong, P.; Lee, S. T.; Eng, J.; Berlangieri, S. U.; Pathmaraj, K.; O'Keefe, G. J.; Lawrentschuk, N.

2009-01-01

Full text:Background: The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) in renal cell carcinoma, and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). Methods: Twenty seven patients (16 men, 11 women; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. Results: The mean SUVmax (maximum standardized uptake value) ± SD for FLT in tumour was 2.53 ± 1.26, compared to normal kidney (2.47 ± 0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60 ± 1.08). Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.624, p=0.0008) in RCC. Ki-67 labelling index was mean ± SD of 13.3% ± 9.2 (range 2.2% to 36.3%). Conclusion: There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology.

Immunoscintigraphy of human pancreatic carcinoma in nude mice with I-131-F(ab')/sub 2/-fragments of monoclonal antibodies

International Nuclear Information System (INIS)

Senekowitsch, R.; Maul, F.D.; Wenisch, H.J.C.; Kriegel, H.; Hor, G.

1985-01-01

In the present study radioiodinated F(ab')/sub 2/-fragments of CA19-9 and antibody that reacts specifically with human gastrointestinal cancer were examined for their ability to detect human pancreatic carcinoma hosted in nude mice. Tumor-bearing mice received 80μCi of I-131-F(ab')/sub 2/ with a specific activity of 1.8μCi/μg. All mice were imaged after the injection and every 24hr up to 6 days. The retained radioactivity was also registered with a whole-body counter immediately after imaging. As a control F(ab's)/sub 2/ of a nonspecific antibody were administered in parallel to another group of animals bearing the same tumor. Three animals of each group were killed at 1,2,4 and 8 days for determination of the distribution of both labeled antibody-fragments. On scintigraphic images obtained with the CA19-9-F(ab')/sub 2/ the tumors could be visualized 24hr after injection, the best dilineation however was achieved 96hr p.i.. The biodistribution data exhibited a more rapid blood clearance for the specific fragments compared to that for the unspecific ones. Tumors showed an increase in uptake up to 48hr reaching 1.7% of the injected dose per gram, declining to values of 0.08%/g at day 6 p.i.. The highest tumor-to-blood ratios were found after 96h. They were 7 for the CA19-9-fragments compared to 1.5 for the unspecific fragments. The whole body counting revealed a more rapid excretion for the fragments of the specific monoclonal antibodies than for the unspecific ones. In summary the authors were able to show that CA19-9-F(ab')/sub 2/-fragments can be used for immunodetection of human pancreatic carcinoma hosted in nude mice

Induction of differentiation of murine embryonal carcinoma cells by ouabain

International Nuclear Information System (INIS)

Zimmerman, B.T.

1986-01-01

Embryonal carcinoma (EC) cells can be induced to differentiate by ouabain at concentrations which inhibit Na + , K + -ATPase activity as measured by inhibition of 86 Rb + uptake. Since the pharmacologic action of ouabain is thought to be specific, the authors investigated the role of Na + , K + -ATPase inhibition and specific metabolic consequences of this inhibition in the induction of EC differentiation, and explored whether this might be a common mode of action for a variety of structurally diverse inducers. The Na + , K + -ATPase maintains ionic gradients in cells. However, results of studies utilizing specific ionophores, channel blockers, and media deficient in specific components failed to demonstrate a consistent role for ion flux or concentration in the differentiation process. The Na + , K + -ATPase is a major consumer of ATP. They therefore examined the effect of Na + , K + -ATPase inhibition on the adenylate energy charge as measured by high performance liquid chromatography of adenylate nucleotides. Ouabain was found to significantly decrease the energy charge in sensitive cells suggesting a role for suppression of ATP turnover is triggering differentiation. However, direct inhibition of glycolysis also induced differentiation without decreasing the energy charge, suggesting that reduction of the energy charge is not a common mechanism for induction of differentiation of EC

Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.

Science.gov (United States)

Vercellino, Laetitia; Groheux, David; Thoury, Anne; Delord, Marc; Schlageter, Marie-Hélène; Delpech, Yann; Barré, Emmanuelle; Baruch-Hennequin, Valérie; Tylski, Perrine; Homyrda, Laurence; Walker, Francine; Barranger, Emmanuel; Hindié, Elif

2012-11-01

Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes. All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 μg/L (median, 102.5 μg/L). Patients with OPN greater than 144 μg/L had reduced progression-free survival compared with those with OPN less than 144 μg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels. Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

Phase resolved and coherence gated en face reflection imaging of multilayered embryonal carcinoma cells

Science.gov (United States)

Yamauchi, Toyohiko; Fukami, Tadashi; Iwai, Hidenao; Yamashita, Yutaka

2012-03-01

Embryonal carcinoma (EC) cells, which are cell lines derived from teratocarcinomas, have characteristics in common with stem cells and differentiate into many kinds of functional cells. Similar to embryonic stem (ES) cells, undifferentiated EC cells form multi-layered spheroids. In order to visualize the three-dimensional structure of multilayered EC cells without labeling, we employed full-field interference microscopy with the aid of a low-coherence quantitative phase microscope, which is a reflection-type interference microscope employing the digital holographic technique with a low-coherent light source. Owing to the low-coherency of the light-source (halogen lamp), only the light reflected from reflective surface at a specific sectioning height generates an interference image on the CCD camera. P19CL6 EC cells, derived from mouse teratocarcinomas, formed spheroids that are about 50 to 200 micrometers in diameter. Since the height of each cell is around 10 micrometers, it is assumed that each spheroid has 5 to 20 cell layers. The P19CL6 spheroids were imaged in an upright configuration and the horizontally sectioned reflection images of the sample were obtained by sequentially and vertically scanning the zero-path-length height. Our results show the threedimensional structure of the spheroids, in which plasma and nuclear membranes were distinguishably imaged. The results imply that our technique is further capable of imaging induced pluripotent stem (iPS) cells for the assessment of cell properties including their pluripotency.

Rat embryonic palatal shelves respond to TCDD in organ culture

International Nuclear Information System (INIS)

Abbott, B.D.; Birnbaum, L.S.

1990-01-01

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a highly toxic environmental contaminant, is teratogenic in mice, inducing cleft palate (CP) and hydronephrosis at doses which are not overtly maternally or embryo toxic. Palatal shelves of embryonic mice respond to TCDD, both in vivo and in organ culture, with altered differentiation of medial epithelial cells. By contrast, in the rat TCDD produces substantial maternal, embryonic, and fetal toxicity, including fetal lethality, with few malformations. In this study the possible effects of maternal toxicity on induction of cleft palate were eliminated by exposure of embryonic rat palatal shelves in organ culture. The shelves were examined for specific TCDD-induced alterations in differentiation of the medial cells. On Gestation Day (GD) 14 or 15 palatal shelves from embryonic F344 rats were placed in organ culture for 2 to 3 days (IMEM:F12 medium, 5% FBS, 0.1% DMSO) containing 0, 1 x 10(-8), 1 x 10(-9), 1 x 10(-10), or 5 x 10(-11) M TCDD. The medial epithelial peridermal cells degenerated on shelves exposed to control media or 5 x 10(-11) M TCDD. Exposure to 10(-10), 10(-9), and 10(-8) M TCDD inhibited this degeneration in 20, 36, and 60% of the shelves, respectively, and was statistically significant at the two highest doses. A normally occurring decrease in [3H]TdR incorporation was inhibited in some GD 15 shelves cultured with 10(-10) and 10(-9) M TCDD. The medial cells of TCDD-exposed shelves continued to express high levels of immunohistochemically detected EGF receptors. The altered differentiation of rat medial epithelium is similar to that reported for TCDD-exposed mouse medial cells in vivo and in vitro. However, in order to obtain these responses, the cultured rat shelves require much higher concentrations of TCDD than the mouse shelves

Value of 18F-FDG PET-CT in nasopharyngeal carcinoma target delineation and radiotherapy boost

International Nuclear Information System (INIS)

Wang Ying; Feng Yanlin

2011-01-01

18 F-FDG PET-CT has widely used in nasopharyngeal carcinoma diagnosis and staging in recent years, it's effecten target volume delineation has received great attention. The article lays stress on the clinical research progress of 18 F-FDG PET-CT in the radiotherapy of nasopharyngeal carcinoma improve the accuracy of target delineation, reduce the difference of target delineation, guide the dose painting and boost. (authors)

Forced diuresis 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced in detection of carcinoma of urinary bladder diverticulum

International Nuclear Information System (INIS)

Soundararajan, Ramya; Singh, Harmandeep; Arora, Saurabh; Nayak, Brusabhanu; Shamim, Shamim Ahmed; Bal, Chandrasekhar; Kumar, Rakesh

2015-01-01

Urinary bladder diverticular carcinomas are uncommon with a lesser incidence of 0.8–10% and its diagnosis still remains a challenge. Cystoscopy is the most reliable method, but evaluating diverticulum with narrow orifices is difficult. Before the initiation of appropriate treatment, proper detection of bladder diverticular carcinoma and its locoregional and distant sites of involvement is necessary. Here, we present a case of 48-year-old male with urinary bladder diverticular carcinoma detected by forced diuretic 18 F-fluorodeoxyglucose positron emission tomography/computerized tomography ( 18 F-FDG PET/CT). This case also highlights the significance of forced diuretic 18 F-FDG PET/CT in the detection, staging, and response evaluation of bladder diverticular carcinoma

CRISPR/Cas9-AAV Mediated Knock-in at NRL Locus in Human Embryonic Stem Cells

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Xianglian Ge

2016-01-01

Full Text Available Clustered interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9-mediated genome engineering technologies are sparking a new revolution in biological research. This technology efficiently induces DNA double strand breaks at the targeted genomic sequence and results in indel mutations by the error-prone process of nonhomologous end joining DNA repair or homologous recombination with a DNA repair template. The efficiency of genome editing with CRISPR/Cas9 alone in human embryonic stem cells is still low. Gene targeting with adeno-associated virus (AAV vectors has been demonstrated in multiple human cell types with maximal targeting frequencies without engineered nucleases. However, whether CRISPR/Cas9-mediated double strand breaks and AAV based donor DNA mediated homologous recombination approaches could be combined to create a novel CRISPR/Cas9-AAV genetic tool for highly specific gene editing is not clear. Here we demonstrate that using CRISPR/Cas9-AAV, we could successfully knock-in a DsRed reporter gene at the basic motifleucine zipper transcription factor (NRL locus in human embryonic stem cells. For the first time, this study provides the proof of principle that these two technologies can be used together. CRISPR/Cas9-AAV, a new genome editing tool, offers a platform for the manipulation of human genome.

Elevated 18F-NaF uptake in cricoid cartilage in a patient with laryngeal carcinoma

Science.gov (United States)

Xia, Yuxiao; Qi, Chi; Zhang, Shumao; Huang, Zhanwen; Chen, Yue

2017-01-01

Abstract Rationale: Laryngeal cancer is aggressive tumor that arises from the tissues of the larynx. Although any bone can be affected, involvement of cricoid cartilage was reported very rarely, and there has been no report of 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT) and 3D PET-CT for the evaluation of cricoid cartilage invasion. Patient concerns: A 54-year-old male discovered a protruding mass in the right anterior neck, which had rapidly increased in size over a period of 2 months. Subsequently, hoarseness, dysphagia, and dyspnea were gradually developed. Diagnoses: 18F-FDG PET-CT demonstrated that the abnormal activity was located in a soft tissue mass, which was about 4.2 cm × 3.8 cm × 3.6 cm in largest dimension in the laryngeal cavity of supraglottic portion (SUVmax: 23.6). A swollen lymph node was revealed in the right submandibular region, which had intense FDG activity with a SUVmax of 18.4. However, there is a high uptake of 18F-FDG in the region near the bone, which is uncertain whether there is any skeletal invasion. NaF PET-CT and 3D PET-CT demonstrated increased uptake in the right side of cricoid cartilage (SUVmax: 13.2). The histopathologic examination confirmed squamous cell carcinoma of larynx. Interventions: The patient underwent tracheotomy and received anti-infective treatment to relieve symptoms of dyspnea and prevent asphyxia. Outcomes: Clinical follow up of the patient revealed that dyspnea was significantly relieved. Lessons: The case report shows the imaging features of cricoid cartilage invasion, including 18F-FDG PET/CT, 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT), and 3D PET-CT. Precise understanding of the invasion scope, accurately staging of laryngeal carcinoma, and choosing of the most suitable surgical scheme are the factors that lead to the optimal treatment of laryngeal neoplasms. PMID:29245332

Toxoplasmic Lymphadenitis Mimicking a Metastatic Thyroid Carcinoma at 18F-FDG-PET/CT

International Nuclear Information System (INIS)

Treglia, Giorgio; Bongiovanni, Massimo; Ceriani, Luca; Paone, Gaetano; Giovanella, Luca

2013-01-01

A 28-year-old woman underwent total thyroidectomy for a papillary thyroid carcinoma in the right thyroid lobe (pTx, pN1b). Subsequently a 131 I-ablation (4.4 GBq) was performed. Four years later the patient presented increased thyroglobulin (Tg) serum levels (8.4 μg/l) during thyroxine treatment. Furthermore, enlarged hypoechoic and round-shaped bilateral cervical lymph nodes were detected at cervical ultrasonography (US). Based on laboratory and US findings suspicious for lymph nodal recurrence of thyroid carcinoma, the patient underwent an 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) to check for distant metastases (Fig. 1). The patient underwent a US-guided fine-needle aspiration cytology on an 18 F-FDG-avid cervical lymph-node. The smears were hypercellulated and consisted of numerous small- to medium-sized lymphocytes, macrophages, dendritic cells and tingible body macrophages. The cytological diagnosis was consistent with that of reactive lymphadenitis. Serological test revealed elevated IgM and IgG anti-Toxoplasma antibodies with a very low IgG-avidity, indicating an acute toxoplasmosis. Serum Tg was then measured by using heterophilic antibody blocking tubes, as previously reported, and serum value dropped to 18 F-FDG-PET/CT in oncological patients. Few reports have described toxoplasmic infection mimicking malignancy at 18 F-FDG-PET/CT; these findings were found mainly in immunodepressive patients or with history of lymphoma. Conversely, we described here a case of toxoplasmosis inducing false-positive Tg measurement, neck US and 18 F-FDG-PET/CT findings in a patient with papillary thyroid carcinoma

A complex RARE is required for the majority of Nedd9 embryonic expression.

Science.gov (United States)

Knutson, Danielle C; Clagett-Dame, Margaret

2015-02-01

Neural precursor cell expressed, developmentally down-regulated 9 (Nedd9, Casl, Hef1, p105cas, Ef1) is a scaffolding protein that assembles complexes involved in regulating cell adhesion, migration, division, and survival. Nedd9 is found very early in the developing embryonic nervous system. A highly conserved complex retinoic acid response element (RARE) is located 485 base pairs (bp) upstream of exon 2B in the promoter of the Nedd9 gene. Mice transgenic for a 5.2 kilobase (kb) region of the 2B Nedd9 promoter containing the RARE upstream of a lacZ reporter gene [Nedd9(RARE)-lacZ] show a large subset of the normal endogenous Nedd9 expression including that in the caudal hindbrain neuroepithelium, spinal cord, dorsal root ganglia (drg) and migrating neural crest (ncc). However, the transgenic mice do not recapitulate the native Nedd9 expression pattern in presumptive rhombomeres (pr) 3 and 5 of the early hindbrain, the base of the neuroepithelium in the midbrain, nor the forebrain telencephalon. Thus, the 5.2 kb region containing the intact RARE drives a large subset of Nedd9 expression, with additional sequences outside of this region needed to define the full complement of expression. When the 5.2 kb construct is modified (eight point mutations) to eliminate responsiveness of the RARE to all-trans retinoic acid (atRA) [Nedd9(mutRARE)-lacZ], virtually all β-galactosidase (β-gal, lacZ) expression is lost. Exposure of Nedd9(RARE)-lacZ transgenic embryos to excess atRA at embryonic day 8.0 (E8.0) leads to rostral ectopic transgene expression within 6 h whereas the Nedd9(mutRARE)-lacZ mutant does not show this effect. Thus the RARE upstream of the Nedd9 2B promoter is necessary for much of the endogenous gene expression during early development as well as ectopic expression in response to atRA.

File list: Oth.EmF.20.Smarca5.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.EmF.20.Smarca5.AllCell mm9 TFs and others Smarca5 Embryonic fibroblast SRX10220...84 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.EmF.20.Smarca5.AllCell.bed ...

Usefulness of (18)F-FDG PET/CT in recurrent basal cell carcinoma: Report of a case.

Science.gov (United States)

Ayala, S; Perlaza, P; Puig, S; Prats, E; Vidal-Sicart, S

2016-01-01

We analyze the case of a patient with left periorbital infiltrating basal cell carcinoma treated with surgical excision in October 2010. Surgery included orbital exenteration and reconstruction using skin graft and radiotherapy. In May 2013 a MR imaging showed a mass in the left orbital fossa, suggesting a recurrence in the graft. A basal cell carcinoma recurrence with perineural invasion was confirmed in the biopsy. On (18)F-FDG PET/CT performed, a hypermetabolic activity was observed in the left periorbital area with extension to surrounding sinus and bones. The use of (18)F-FDG PET/CT in patients with advanced basal cell carcinoma has not been fully explored due to the rarity of this entity. This case demonstrates the usefulness of this technique to determine the extent of non-melanocytic recurrent skin tumors, and its value in the staging and treatment control, supporting the incorporation of (18)F-FDG PET/CT in the management of advanced basal cell carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

File list: Oth.EmF.10.Ddit3.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Oth.EmF.50.Ddit3.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.EmF.50.Ddit3.AllCell mm9 TFs and others Ddit3 Embryonic fibroblast SRX119350,SR...X119351 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.EmF.50.Ddit3.AllCell.bed ...

Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

International Nuclear Information System (INIS)

Zou, Yang; Liu, Fa-Ying; Liu, Huai; Wang, Feng; Li, Wei; Huang, Mei-Zhen; Huang, Yan; Yuan, Xiao-Qun; Xu, Xiao-Yun; Huang, Ou-Ping; He, Ming

2014-01-01

The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Zou, Yang; Liu, Fa-Ying; Liu, Huai; Wang, Feng [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Li, Wei [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Huang, Mei-Zhen [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Yan; Yuan, Xiao-Qun [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Xu, Xiao-Yun [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Ou-Ping, E-mail: huangouping@gmail.com [Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); He, Ming, E-mail: jxhm56@hotmail.com [Department of Pharmacology and Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang 330006 (China)

2014-03-15

The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

File list: Pol.EmF.05.RNA_Polymerase_II.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.EmF.05.RNA_Polymerase_II.AllCell mm9 RNA polymerase RNA Polymerase II Embryonic...RX143288 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.EmF.05.RNA_Polymerase_II.AllCell.bed ...

Clinical value of 18F-FDG coincidence imaging for diagnosis of nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Ning Yanli; Lou Cen; Huang Zhongke; Shi Guohua; Chen Dongfang; Mu Da

2012-01-01

Objective: To investigate the value of 18 F-FDG coincidence imaging for diagnosis of nasopharyngeal carcinoma. Methods: A total of 45 patients with nasopharyngeal carcinoma (33 males and 12 females, average age (55.56 ± 13.50) years), who underwent 18 F-FDG coincidence imaging before treatment, were studied retrospectively. The images of 18 F-FDG coincidence imaging (GE Millennium VG SPECT) and MRI were analyzed. The radioactivity ratio of the accumulated regions to cerebellum (T/NT)was calculated by ROI technique. The volume of nasopharyngeal carcinoma was recorded by MRI. The positive rates of 18 F-FDG coincidence imaging and EB virus-related antibody measurements were compared by paired χ 2 test. The correlation between T/NT ratios and tumor volumes were tested by Pearson correlation, and then ROC curves were established. The T/NT ratios and tumor volumes of different groups (different first symptoms, clinical stages, T stages, pathological classification and outcomes, with or without lymph node enlargement) were compared by t-test and rank sum test. Results: The positive rate of 18 F-FDG coincidence imaging was 97.78% (44/45), and the positive rate of EB virus-related antibody measurement was 95.56% (43/45, χ 2 =1.33, P>0.05). The T/NT ratio (2.439 ±1.119) and tumor volume ((7.311 ± 8.280) cm 3 ) of primary lesions had a positive correlation (r=0.463, P<0.05). The cut-off values of T/NT ratio and the tumor volume were 2.396 and 7.348 cm 3 , respectively, by ROC curves. T/NT ratios in groups with or without first symptom of epistaxis (2.847 ± 1.254 vs 2.082 ± 0.863, t=-2.409) and groups with or without facial numbness (2.855 ± 1.261 vs 2.134 ± 0.913, t=-2.225) were both significantly different (both P<0.05). T/NT ratios of differentiated and undifferentiated cancer were 2.266 ± 0.997 and 2.971 ± 1.351, respectively (t=-2.018, P<0.05). There was a significant difference of tumor volumes between groups with or without facial numbness (t=-2.684, P<0

File list: InP.EmF.50.Input_control.AllCell [Chip-atlas[Archive

Lifescience Database Archive (English)

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Zinc oxide nanoparticle-enhanced ultrasensitive chemiluminescence immunoassay for the carcinoma embryonic antigen

International Nuclear Information System (INIS)

Pal, Souvik; Bhand, Sunil

2015-01-01

An ultrasensitive enzyme-linked immunosorbent assay (ELISA) is reported for the determination of carcinoma embryonic antigen (CEA) in human serum. It was realized using a microplate reader using a 384-well plate. Monoclonal antibody (Ab) against CEA (1° Ab) acting as the capture probe was immobilized on zinc oxide nanoparticles (ZnO-NPs) in the form of self-assembled monolayers (SAMs). CEA captured by 1° Ab was quantified using a sandwich ELISA wherein a polyclonal second antibody against CEA (2° Ab) was used for detection and quantified using an HRP-labeled secondary antibody (3° Ab). The ZnO-NPs-CEA capture probe was deposited on the bottom of the wells in order to enhance capture of CEA. A 3-fold enhancement in the chemiluminescence (CL) signal of luminol is found (compared to a conventional ELISA). CEA can be quantified by this method in concentrations as low as 1 pg · mL −1 . The upper limit of detection is 20 ng · mL −1 . The use of ZnO-NPs also imparts improved thermal stability. When stored at 4 °C in phosphate-buffered saline of pH 7.4, the probe displays stability of up to 30 days. (author)

Requirement of mitoses for the reversal of X-inactivation in cell hybrids between murine embryonal carcinoma cells and normal female thymocytes

International Nuclear Information System (INIS)

Takagi, N.

1988-01-01

By means of a 5-bromodeoxyuridine (BrdU) incorporation and acridine orange fluorescence staining method the authors studied reactivation of the inactivated X chromosome (X i ) in newly formed cell hybrids between the near-diploid HPRT-deficient OTF9-63 murine embryonal carcinoma cell (ECC) with an XO sex chromosome constitution and the normal female mouse thymocyte. Synchronization of the late replicating S chromosome in such hybrid cells, indicative of reactivation, was found for the first time on Day 3, and the frequency of reactivation was attained 90% on Day 5. Inhibition of cell cycle progression either by methylglyoxal bis(guanylhydrazone) dihydrochloride, an inhibitor of polyamine metabolism, or by isoleucine-deficient medium after cell fusion delayed reactivation of the X i , which implied that the number of cell division cycles traversed by individual cells rather than the length of time after cell fusion is critical for the reactivation. Double-labeling experiments using [ 3 H]thymidine and BrdU indicated that hybrid cells had undergone three or four mitoses before reactivation of the X i . Most probably reactivation of the X i is consequent to reversion of the thymocyte genome to an undifferentiated state under the influence of OTF9 genome. DNA demethylation or dilution of X i -specific factors by mitoses may be involved in this process

Requirement of mitoses for the reversal of X-inactivation in cell hybrids between murine embryonal carcinoma cells and normal female thymocytes

Energy Technology Data Exchange (ETDEWEB)

Takagi, N. (Hokkaido Univ., Sapporo (Japan))

1988-04-01

By means of a 5-bromodeoxyuridine (BrdU) incorporation and acridine orange fluorescence staining method the authors studied reactivation of the inactivated X chromosome (X{sub i}) in newly formed cell hybrids between the near-diploid HPRT-deficient OTF9-63 murine embryonal carcinoma cell (ECC) with an XO sex chromosome constitution and the normal female mouse thymocyte. Synchronization of the late replicating S chromosome in such hybrid cells, indicative of reactivation, was found for the first time on Day 3, and the frequency of reactivation was attained 90% on Day 5. Inhibition of cell cycle progression either by methylglyoxal bis(guanylhydrazone) dihydrochloride, an inhibitor of polyamine metabolism, or by isoleucine-deficient medium after cell fusion delayed reactivation of the X{sub i}, which implied that the number of cell division cycles traversed by individual cells rather than the length of time after cell fusion is critical for the reactivation. Double-labeling experiments using ({sup 3}H)thymidine and BrdU indicated that hybrid cells had undergone three or four mitoses before reactivation of the X{sub i}. Most probably reactivation of the X{sub i} is consequent to reversion of the thymocyte genome to an undifferentiated state under the influence of OTF9 genome. DNA demethylation or dilution of X{sub i}-specific factors by mitoses may be involved in this process.

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Combined early dynamic (18)F-FDG PET/CT and conventional whole-body (18)F-FDG PET/CT provide one-stop imaging for detecting hepatocellular carcinoma.

Science.gov (United States)

Wang, Shao-Bo; Wu, Hu-Bing; Wang, Quan-Shi; Zhou, Wen-Lan; Tian, Ying; Li, Hong-Sheng; Ji, Yun-Hai; Lv, Liang

2015-06-01

It is widely accepted that conventional (18)F-FDG PET/CT (whole-body static (18)F-FDG PET/CT, WB (18)F-FDG PET/CT) has a low detection rate for hepatocellular carcinoma (HCC). We prospectively assessed the role of early dynamic (18)F-FDG PET/CT (ED (18)F-FDG PET/CT) and WB (18)F-FDG PET/CT in detecting HCC, and we quantified the added value of ED (18)F-FDG PET/CT to WB (18)F-FDG PET/CT. Twenty-two patients with 37 HCC tumors (HCCs) who underwent both a liver ED (18)F-FDG PET/CT (performed simultaneously with a 5.5 MBq/kg (18)F-FDG bolus injection and continued for 240 s) and a WB (18)F-FDG PET/CT were enrolled in the study. The WB (18)F-FDG PET/CT and ED (18)F-FDG PET/CT scans were positive in 56.7% (21/37) and 78.4% (29/37) HCCs, respectively (PPET/CT in conjunction with WB (18)F-FDG PET/CT (one-stop (18)F-FDG PET/CT) improved the positive detection rates of WB and ED (18)F-FDG PET/CT alone from 56.7% and 78.4% to 91.9% (34/37) (P0.05, respectively). One-stop (18)F-FDG PET/CT appears to be useful to improve WB (18)F-FDG PET/CT for HCC detection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Diagnostic accuracy of 18F-FDG PET/CT for detection of suspected recurrence in patients with oesophageal carcinoma

International Nuclear Information System (INIS)

Sharma, Punit; Jain, Sachin; Karunanithi, Sellam; Malhotra, Arun; Bal, Chandrasekhar; Kumar, Rakesh; Pal, Sujoy; Julka, Pramod Kumar; Thulkar, Sanjay

2014-01-01

To evaluate the role of 18 F-FDG PET/CT in the detection of recurrence in patients with oesophageal carcinoma, suspected clinically or following conventional investigations. This was a retrospective study. Data from 180 patients (age 56.3 ± 10.4 years; 126 men, 54 women) with histopathologically proven oesophageal carcinoma (squamous cell 115, adenocarcinoma 59, neuroendocrine carcinoma 4, small cell 1, poorly differentiated 1) who had undergone 227 18 F-FDG PET/CT studies for suspected recurrence were analysed. Recurrence was suspected clinically or following conventional investigations. PET/CT images were revaluated by two nuclear medicine physicians in consensus. Findings were grouped into local, nodal and distant recurrence. Results were compared to those from contrast-enhanced (CE) CT when available (109 patients). Clinical/imaging follow-up (minimum 6 months) with histopathology (when available) was taken as the reference standard. Of the 227 18 F-FDG PET/CT studies,166 were positive and 61 were negative for recurrent disease. PET/CT showed local recurrence in 134, nodal recurrence in 115 and distant recurrence in 47, with more than one site of recurrence in 34. The PET/CT findings were true-positive in 153 studies, true-negative in 54, false-positive in 13 and false-negative in 7. The sensitivity of 18 F-FDG PET/CT was 96 %, the specificity was 81 %, the positive and negative predictive values were 92 % and 89 %, respectively, and the accuracy was 91 %. PET/CT showed similar accuracy in patients with squamous cell carcinoma and in those with adenocarcinoma (P = 0.181). 18 F-FDG PET/CT was more specific than CECT (67 % vs. 21 %; P 18 F-FDG PET/CT shows high accuracy in the detection of suspected recurrence in patients with oesophageal carcinoma. It is more specific than and is superior to CECT in the detection of nodal recurrence. (orig.)

Simple Meets Single: The Application of CRISPR/Cas9 in Haploid Embryonic Stem Cells

Directory of Open Access Journals (Sweden)

Zixi Yin

2017-01-01

Full Text Available The CRISPR/Cas9 system provides a powerful method for the genetic manipulation of the mammalian genome, allowing knockout of individual genes as well as the generation of genome-wide knockout cell libraries for genetic screening. However, the diploid status of most mammalian cells restricts the application of CRISPR/Cas9 in genetic screening. Mammalian haploid embryonic stem cells (haESCs have only one set of chromosomes per cell, avoiding the issue of heterozygous recessive mutations in diploid cells. Thus, the combination of haESCs and CRISPR/Cas9 facilitates the generation of genome-wide knockout cell libraries for genetic screening. Here, we review recent progress in CRISPR/Cas9 and haPSCs and discuss their applications in genetic screening.

Carcinoma fusocelular de cavidad oral: Revisión de 9 casos Spindle cell carcinoma of the oral cavity: A review of 9 cases

Directory of Open Access Journals (Sweden)

G. Gómez Oliveira

2006-02-01

Full Text Available El carcinoma fusocelular es una variedad maligna y poco frecuente del carcinoma de células escamosas. Es una tumoración constituida por una doble proliferación celular: una sarcomatosa de células fusocelulares y otra carcinomatosa de células epiteliales. Aunque puede afectar a cualquier parte del organismo, es más frecuente encontrarla en vías aerodigestivas superiores. Afecta con mayor frecuencia a varones entre la 6ª y 7ª décadas de la vida. Tiene un comportamiento agresivo con tendencia a la recurrencia. El alcohol y tabaco han sido identificados como los factores de riesgo más importantes. Su diagnóstico histológico es complicado y muchas veces es necesario recurrir a técnicas de inmunohistoquímica y al uso del microscopio electrónico. En la actualidad, se le atribuye un origen epitelial. El objetivo de este trabajo es presentar una revisión de 9 casos de carcinoma fusocelular localizados en cavidad oral recogidos en nuestro servicio entre los años 1985 a 2004, describiendo su comportamiento clínico y tratando de comprender la patogenia de esta controvertida estirpe tumoral.Spindle cell carcinoma is a malignant and rare variant of squamous cell carcinoma. The histological pattern is composed of a double cell proliferation: a sarcomatous component made up of spindle-shaped cells and a carcinomatous component made up of epithelial cells. Nearly all the anatomy of the body can be affected by these tumors although the most common location is the upper aerodigestive tract. With regard to sex distribution, it is more frequent in males than in females in their sixth and seventh decades of life. Its behavior is aggressive and it tends to recur after treatment. The most important risk factors are alcohol and tobacco. The histological diagnosis is complicated, so immunohistochemical techniques and the use of electron microscopy are usually necessary. Nowadays, its epithelial origin is accepted. The aim of this article is to report a

Tributyltin induces G2/M cell cycle arrest via NAD(+)-dependent isocitrate dehydrogenase in human embryonic carcinoma cells.

Science.gov (United States)

Asanagi, Miki; Yamada, Shigeru; Hirata, Naoya; Itagaki, Hiroshi; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

2016-04-01

Organotin compounds, such as tributyltin (TBT), are well-known endocrine-disrupting chemicals (EDCs). We have recently reported that TBT induces growth arrest in the human embryonic carcinoma cell line NT2/D1 at nanomolar levels by inhibiting NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the irreversible conversion of isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we examined whether TBT at nanomolar levels affects cell cycle progression in NT2/D1 cells. Propidium iodide staining revealed that TBT reduced the ratio of cells in the G1 phase and increased the ratio of cells in the G2/M phase. TBT also reduced cell division cycle 25C (cdc25C) and cyclin B1, which are key regulators of G2/M progression. Furthermore, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. The G2/M arrest induced by TBT was abolished by NAD-IDHα knockdown. Treatment with a cell-permeable α-ketoglutarate analogue recovered the effect of TBT, suggesting the involvement of NAD-IDH. Taken together, our data suggest that TBT at nanomolar levels induced G2/M cell cycle arrest via NAD-IDH in NT2/D1 cells. Thus, cell cycle analysis in embryonic cells could be used to assess cytotoxicity associated with nanomolar level exposure of EDCs.

Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells.

Directory of Open Access Journals (Sweden)

Wenjing Zhao

Full Text Available The effective treatment for pancreatic carcinoma remains critically needed. Herein, this current study showed that spiclomazine treatment caused a reduction in viability in pancreatic carcinoma cell lines CFPAC-1 and MIA PaCa-2 in vitro. It was notable in this regard that, compared with pancreatic carcinoma cells, normal human embryonic kidney (HEK-293 and liver (HL-7702 cells were more resistant to the antigrowth effect of spiclomazine. Biochemically, spiclomazine treatment regulated the expression of protein levels in the apoptosis related pathways. Consistent with this effect, spiclomazine reduced the mitochondria membrane potential, elevated reactive oxygen species, and activated caspase-3/9. In addition, a key finding from this study was that spiclomazine suppressed migration and invasion of cancer cells through down-regulation of MMP-2/9. Collectively, the proposed studies did shed light on the antiproliferation effect of spiclomazine on pancreatic carcinoma cell lines, and further clarified the mechanisms that spiclomazine induced apoptosis associated with the suppression of migration and invasion.

HDAC1 and HDAC3 underlie dynamic H3K9 acetylation during embryonic neurogenesis and in schizophrenia-like animals.

Science.gov (United States)

Večeřa, Josef; Bártová, Eva; Krejčí, Jana; Legartová, Soňa; Komůrková, Denisa; Rudá-Kučerová, Jana; Štark, Tibor; Dražanová, Eva; Kašpárek, Tomáš; Šulcová, Alexandra; Dekker, Frank J; Szymanski, Wiktor; Seiser, Christian; Weitzer, Georg; Mechoulam, Raphael; Micale, Vincenzo; Kozubek, Stanislav

2018-01-01

Although histone acetylation is one of the most widely studied epigenetic modifications, there is still a lack of information regarding how the acetylome is regulated during brain development and pathophysiological processes. We demonstrate that the embryonic brain (E15) is characterized by an increase in H3K9 acetylation as well as decreases in the levels of HDAC1 and HDAC3. Moreover, experimental induction of H3K9 hyperacetylation led to the overexpression of NCAM in the embryonic cortex and depletion of Sox2 in the subventricular ependyma, which mimicked the differentiation processes. Inducing differentiation in HDAC1-deficient mouse ESCs resulted in early H3K9 deacetylation, Sox2 downregulation, and enhanced astrogliogenesis, whereas neuro-differentiation was almost suppressed. Neuro-differentiation of (wt) ESCs was characterized by H3K9 hyperacetylation that was associated with HDAC1 and HDAC3 depletion. Conversely, the hippocampi of schizophrenia-like animals showed H3K9 deacetylation that was regulated by an increase in both HDAC1 and HDAC3. The hippocampi of schizophrenia-like brains that were treated with the cannabinoid receptor-1 inverse antagonist AM251 expressed H3K9ac at the level observed in normal brains. Together, the results indicate that co-regulation of H3K9ac by HDAC1 and HDAC3 is important to both embryonic brain development and neuro-differentiation as well as the pathophysiology of a schizophrenia-like phenotype. © 2017 Wiley Periodicals, Inc.

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

Science.gov (United States)

Yamada, Shigeru; Kotake, Yaichiro; Demizu, Yosuke; Kurihara, Masaaki; Sekino, Yuko; Kanda, Yasunari

2014-08-01

Tributyltin (TBT) is known to cause developmental defects as endocrine disruptive chemicals (EDCs). At nanomoler concentrations, TBT actions were mediated by genomic pathways via PPAR/RXR. However, non-genomic target of TBT has not been elucidated. To investigate non-genomic TBT targets, we performed comprehensive metabolomic analyses using human embryonic carcinoma NT2/D1 cells. We found that 100 nM TBT reduced the amounts of α-ketoglutarate, succinate and malate. We further found that TBT decreased the activity of NAD-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the conversion of isocitrate to α-ketoglutarate in the TCA cycle. In addition, TBT inhibited cell growth and enhanced neuronal differentiation through NAD-IDH inhibition. Furthermore, studies using bacterially expressed human NAD-IDH and in silico simulations suggest that TBT inhibits NAD-IDH due to a possible interaction. These results suggest that NAD-IDH is a novel non-genomic target of TBT at nanomolar levels. Thus, a metabolomic approach may provide new insights into the mechanism of EDC action.

Generation of a Nrf2 homozygous knockout human embryonic stem cell line using CRISPR/Cas9

Directory of Open Access Journals (Sweden)

So-Jung Kim

2017-03-01

Full Text Available Nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2 is a well-known transcription factor that regulates the expression of a large number of anti-oxidant genes in mammalian cells (J.H. Kim et al., 2014. Here, we generated a homozygous Nrf2 knockout human embryonic stem cell (hESC line, H9Nrf2KO-A13, using the CRISPR/Cas9 genome editing method. The Nrf2 homozygous knockout H9 cell line maintains pluripotency, differentiation potential into three germ layers, and a normal karyotype.

Caspase-9 has a nonapoptotic function in Xenopus embryonic primitive blood formation.

Science.gov (United States)

Tran, Hong Thi; Fransen, Mathias; Dimitrakopoulou, Dionysia; Van Imschoot, Griet; Willemarck, Nicolas; Vleminckx, Kris

2017-07-15

Caspases constitute a family of cysteine proteases centrally involved in programmed cell death, which is an integral part of normal embryonic and fetal development. However, it has become clear that specific caspases also have functions independent of cell death. In order to identify novel apoptotic and nonapoptotic developmental caspase functions, we designed and transgenically integrated novel fluorescent caspase reporter constructs in developing Xenopus embryos and tadpoles. This model organism has an external development, allowing direct and continuous monitoring. These studies uncovered a nonapoptotic role for the initiator caspase-9 in primitive blood formation. Functional experiments further corroborated that caspase-9, but possibly not the executioners caspase-3 and caspase-7, are required for primitive erythropoiesis in the early embryo. These data reveal a novel nonapoptotic function for the initiator caspase-9 and, for the first time, implicate nonapoptotic caspase activity in primitive blood formation. © 2017. Published by The Company of Biologists Ltd.

{sup 18}F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment

Energy Technology Data Exchange (ETDEWEB)

Sung, Pil Soo; Yang, Keungmo; Hwang, Seawon; Song, Myeong Jun; Jang, Jeong Won; Choi, Jong Young; Yoon, Seung Kew; Bae, Si Hyun [The Catholic University of Korea, Division of Hepatology, Department of Internal Medicine, The Catholic University Liver Research Center, College of Medicine, Seoul (Korea, Republic of); Park, Hye Lim; Yoo, Ie Ryung [The Catholic University of Korea, Division of Nuclear Medicine, Department of Radiology, College of Medicine, Seoul (Korea, Republic of)

2018-03-15

Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) for predicting tumour progression during sorafenib treatment. We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergoing {sup 18}F-FDG PET/CT within 1 month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured. Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR ≥ 2.9 (n = 17) had a median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with a TLR < 2.9 (n = 18) had median OS of 12.2 months (P < 0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR ≥ 2.9 (hazard ratio [HR] = 6.318, P = 0.002) and Child-Pugh class B (HR = 4.316, P = 0.044) were poor prognostic factors for OS, and a TLR ≥ 2.9 (HR = 2.911, P = 0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis. Pretreatment tumour metabolic activity assessed by {sup 18}F-FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment. (orig.)

Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial.

Science.gov (United States)

Schuster, David M; Nieh, Peter T; Jani, Ashesh B; Amzat, Rianot; Bowman, F Dubois; Halkar, Raghuveer K; Master, Viraj A; Nye, Jonathon A; Odewole, Oluwaseun A; Osunkoya, Adeboye O; Savir-Baruch, Bital; Alaei-Taleghani, Pooneh; Goodman, Mark M

2014-05-01

We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[(18)F]FACBC compared to ProstaScint® ((111)In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. A total of 93 patients met study inclusion criteria who underwent anti-3-[(18)F]FACBC positron emission tomography-computerized tomography plus (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[(18)F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to (111)In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[(18)F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to (111)In-capromab pendetide with 10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[(18)F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. Better diagnostic performance was noted for anti-3-[(18)F]FACBC positron emission tomography-computerized tomography than for (111)In-capromab pendetide single

Carcinoma in situ testis, the progenitor of testicular germ cell tumours

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Rajpert-De Meyts, E; Daugaard, G

2005-01-01

Testicular germ cell tumours (TGCT), including seminomas, embryonal carcinomas, teratomas and yolk sac tumours, have a common precursor, the carcinoma in situ (CIS) cell. Recent gene expression studies displaying close similarity of CIS cells to embryonic stem cells support the longstanding theory...... should be made to obtain diagnosis at the CIS stage, as intervention is possible before an invasive tumour develops, thus reducing the necessity for intensive therapy. CIS may be suspected in patients with an assumed extragonadal GCT or cryptorchidism, and in intersex patients and selected cases...

File list: Pol.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Emb.20.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.20.AllAg.Embryonic_heart.bed ...

File list: Pol.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Emb.10.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.10.AllAg.Embryonic_heart.bed ...

File list: Pol.Emb.05.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Emb.05.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.05.AllAg.Embryonic_heart.bed ...

File list: Pol.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Emb.50.AllAg.Embryonic_heart mm9 RNA polymerase Embryo Embryonic heart SRX11293...9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.50.AllAg.Embryonic_heart.bed ...

Toxoplasmic Lymphadenitis Mimicking a Metastatic Thyroid Carcinoma at {sup 18}F-FDG-PET/CT

Energy Technology Data Exchange (ETDEWEB)

Treglia, Giorgio; Bongiovanni, Massimo; Ceriani, Luca; Paone, Gaetano; Giovanella, Luca [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

2013-12-15

A 28-year-old woman underwent total thyroidectomy for a papillary thyroid carcinoma in the right thyroid lobe (pTx, pN1b). Subsequently a {sup 131}I-ablation (4.4 GBq) was performed. Four years later the patient presented increased thyroglobulin (Tg) serum levels (8.4 μg/l) during thyroxine treatment. Furthermore, enlarged hypoechoic and round-shaped bilateral cervical lymph nodes were detected at cervical ultrasonography (US). Based on laboratory and US findings suspicious for lymph nodal recurrence of thyroid carcinoma, the patient underwent an {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) to check for distant metastases (Fig. 1). The patient underwent a US-guided fine-needle aspiration cytology on an {sup 18}F-FDG-avid cervical lymph-node. The smears were hypercellulated and consisted of numerous small- to medium-sized lymphocytes, macrophages, dendritic cells and tingible body macrophages. The cytological diagnosis was consistent with that of reactive lymphadenitis. Serological test revealed elevated IgM and IgG anti-Toxoplasma antibodies with a very low IgG-avidity, indicating an acute toxoplasmosis. Serum Tg was then measured by using heterophilic antibody blocking tubes, as previously reported, and serum value dropped to <0.2 μg/l. It is well known that antibody interference may falsely increase serum Tg; in particular, increased anti-Toxoplasma antibodies likely interfered to the Tg measurement in our case. Additionally, activated granulocytes and macrophages may display significantly increased glucose consumption, giving false-positive results at {sup 18}F-FDG-PET/CT in oncological patients. Few reports have described toxoplasmic infection mimicking malignancy at {sup 18}F-FDG-PET/CT; these findings were found mainly in immunodepressive patients or with history of lymphoma. Conversely, we described here a case of toxoplasmosis inducing false-positive Tg measurement, neck US and {sup 18}F

Cannabinoids as modulators of cancer cell viability, neuronal differentiation, and embryonal development

OpenAIRE

Gustafsson, Sofia

2012-01-01

Cannabinoids (CBs) are compounds that activate the CB1 and CB2 receptors. CB receptors mediate many different physiological functions, and cannabinoids have been reported to decrease tumor cell viability, proliferation, migration, as well as to modulate metastasis. In this thesis, the effects of cannabinoids on human colorectal carcinoma Caco-2 cells (Paper I) and mouse P19 embryonal carcinoma (EC) cells (Paper III) were studied.  In both cell lines, the compounds examined produced a concentr...

Basement membrane components secreted by mouse yolk sac carcinoma cell lines

DEFF Research Database (Denmark)

Damjanov, A; Wewer, U M; Tuma, B

1990-01-01

Three new cell lines (NE, ME, LRD) were cloned from mouse-embryo-derived teratocarcinomas and characterized on the basis of developmental, ultrastructural, and cytochemical criteria as nullipotent embryonal carcinoma (EC), pure parietal yolk sac (PYS) carcinoma and mixed parieto-visceral yolk sac...

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) blocks differentiation and maintains the expression of pluripotency markers in human embryonic stem cells.

Science.gov (United States)

Burton, Peter; Adams, David R; Abraham, Achamma; Allcock, Robert W; Jiang, Zhong; McCahill, Angela; Gilmour, Jane; McAbney, John; Kaupisch, Alexandra; Kane, Nicole M; Baillie, George S; Baker, Andrew H; Milligan, Graeme; Houslay, Miles D; Mountford, Joanne C

2010-12-15

hESCs (human embryonic stem cells) have enormous potential for use in pharmaceutical development and therapeutics; however, to realize this potential, there is a requirement for simple and reproducible cell culture methods that provide adequate numbers of cells of suitable quality. We have discovered a novel way of blocking the spontaneous differentiation of hESCs in the absence of exogenous cytokines by supplementing feeder-free conditions with EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine], an established inhibitor of ADA (adenosine deaminase) and cyclic nucleotide PDE2 (phosphodiesterase 2). hESCs maintained in feeder-free conditions with EHNA for more than ten passages showed no reduction in hESC-associated markers including NANOG, POU5F1 (POU domain class 5 transcription factor 1, also known as Oct-4) and SSEA4 (stage-specific embryonic antigen 4) compared with cells maintained in feeder-free conditions containing bFGF (basic fibroblast growth factor). Spontaneous differentiation was reversibly suppressed by the addition of EHNA, but, upon removing EHNA, hESC populations underwent efficient spontaneous, multi-lineage and directed differentiation. EHNA also acts as a strong blocker of directed neuronal differentiation. Chemically distinct inhibitors of ADA and PDE2 lacked the capacity of EHNA to suppress hESC differentiation, suggesting that the effect is not driven by inhibition of either ADA or PDE2. Preliminary structure-activity relationship analysis found the differentiation-blocking properties of EHNA to reside in a pharmacophore comprising a close adenine mimetic with an extended hydrophobic substituent in the 8- or 9-position. We conclude that EHNA and simple 9-alkyladenines can block directed neuronal and spontaneous differentiation in the absence of exogenous cytokine addition, and may provide a useful replacement for bFGF in large-scale or cGMP-compliant processes.

Generation of genetically modified mice using CRISPR/Cas9 and haploid embryonic stem cell systems

Directory of Open Access Journals (Sweden)

Li-Fang JIN

2016-07-01

Full Text Available With the development of high-throughput sequencing technology in the post-genomic era, researchers have concentrated their efforts on elucidating the relationships between genes and their corresponding functions. Recently, important progress has been achieved in the generation of genetically modified mice based on CRISPR/Cas9 and haploid embryonic stem cell (haESC approaches, which provide new platforms for gene function analysis, human disease modeling, and gene therapy. Here, we review the CRISPR/Cas9 and haESC technology for the generation of genetically modified mice and discuss the key challenges in the application of these approaches.

Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

Science.gov (United States)

Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

2017-03-01

Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

File list: Unc.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Unc.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Emb.20.AllAg.Embryonic_pancreas mm9 Unclassified Embryo Embryonic pancreas http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.20.AllAg.Embryonic_pancreas.bed ...

File list: Unc.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Emb.10.AllAg.Embryonic_pancreas mm9 Unclassified Embryo Embryonic pancreas http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.10.AllAg.Embryonic_pancreas.bed ...

File list: Unc.Emb.50.AllAg.Embryonic_pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Emb.50.AllAg.Embryonic_pancreas mm9 Unclassified Embryo Embryonic pancreas http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Emb.50.AllAg.Embryonic_pancreas.bed ...

Difference in prognostic significance of maximum standardized uptake value on [18F]-fluoro-2-deoxyglucose positron emission tomography between adenocarcinoma and squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Tsutani, Yasuhiro; Miyata, Yoshihiro; Misumi, Keizo; Ikeda, Takuhiro; Mimura, Takeshi; Hihara, Jun; Okada, Morihito

2011-01-01

This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n=132) or squamous cell carcinoma (n=44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P 6.95 (P=0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P<0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P<0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P=0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P=0.001). Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung. (author)

File list: Pol.Emb.05.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Pol.Emb.20.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

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Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines.

Science.gov (United States)

Wang, Shihang; Liu, Chao; Liu, Xinjiang; He, Yanxin; Shen, Dongfang; Luo, Qiankun; Dong, Yuxi; Dong, Haifeng; Pang, Zhigang

2017-10-01

Gallbladder carcinoma is the most common and aggressive malignancy of the biliary tree and highly expresses CD147, which is closely related to disease prognosis in a variety of human cancers. Doxycycline exhibited anti-tumor properties in many cancer cells. CD147 antagonist peptide-9 is a polypeptide and can specifically bind to CD147. The effect of these two drugs on gallbladder cancer cells has not been studied. The aim of this study is to investigate the effect of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells and the possible mechanism of inhibition on cancer cell of doxycycline. To investigate the effects of doxycycline and antagonist peptide-9 on gallbladder carcinoma cells (GBC-SD and SGC-996), cell proliferation, CD147 expression, and early-stage apoptosis rate were measured after treated with doxycycline. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were measured after treated with different concentrations of doxycycline, antagonist peptide-9, and their combination. The results demonstrated that doxycycline inhibited cell proliferation, reduced CD147 expression level, and induced an early-stage apoptosis response in GBC-SD and SGC-996 cells. The matrix metalloproteinase-2 and matrix metalloproteinase-9 activities were inhibited by antagonist peptide-9 and doxycycline, and the inhibitory effects were enhanced by combined drugs in gallbladder carcinoma cell lines. Taken together, doxycycline showed inhibitory effects on gallbladder carcinoma cell lines and reduced the expression of CD147, and this may be the mechanism by which doxycycline inhibits cancer cells. This study provides new information and tries to implement the design of adjuvant therapy method for gallbladder carcinoma.

Enterocin F4-9, a Novel O-Linked Glycosylated Bacteriocin.

Science.gov (United States)

Maky, Mohamed Abdelfattah; Ishibashi, Naoki; Zendo, Takeshi; Perez, Rodney Honrada; Doud, Jehan Ragab; Karmi, Mohamed; Sonomoto, Kenji

2015-07-01

Enterococcus faecalis F4-9 isolated from Egyptian salted-fermented fish produces a novel bacteriocin, termed enterocin F4-9. Enterocin F4-9 was purified from the culture supernatant by three steps, and its molecular mass was determined to be 5,516.6 Da by mass spectrometry. Amino acid and DNA sequencing showed that the propeptide consists of 67 amino acid residues, with a leader peptide containing a double glycine cleavage site to produce a 47-amino-acid mature peptide. Enterocin F4-9 is modified by two molecules of N-acetylglucosamine β-O-linked to Ser37 and Thr46. The O-linked N-acetylglucosamine moieties are essential for the antimicrobial activity of enterocin F4-9. Further analysis of the enterocin F4-9 gene cluster identified enfC, which has high sequence similarity to a glycosyltransferase. The antimicrobial activity of enterocin F4-9 covered a limited range of bacteria, including, interestingly, a Gram-negative strain, Escherichia coli JM109. Enterocin F4-9 is sensitive to protease, active at a wide pH range, and moderately resistant to heat. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Diagnostic accuracy of {sup 18}F-FDG PET/CT for detection of suspected recurrence in patients with oesophageal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Sharma, Punit; Jain, Sachin; Karunanithi, Sellam; Malhotra, Arun; Bal, Chandrasekhar; Kumar, Rakesh [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Pal, Sujoy [All India Institute of Medical Sciences, Department of Surgical Gastroenterology, New Delhi (India); Julka, Pramod Kumar [All India Institute of Medical Sciences, Department of Radiation Oncology, New Delhi (India); Thulkar, Sanjay [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India)

2014-06-15

To evaluate the role of {sup 18}F-FDG PET/CT in the detection of recurrence in patients with oesophageal carcinoma, suspected clinically or following conventional investigations. This was a retrospective study. Data from 180 patients (age 56.3 ± 10.4 years; 126 men, 54 women) with histopathologically proven oesophageal carcinoma (squamous cell 115, adenocarcinoma 59, neuroendocrine carcinoma 4, small cell 1, poorly differentiated 1) who had undergone 227 {sup 18}F-FDG PET/CT studies for suspected recurrence were analysed. Recurrence was suspected clinically or following conventional investigations. PET/CT images were revaluated by two nuclear medicine physicians in consensus. Findings were grouped into local, nodal and distant recurrence. Results were compared to those from contrast-enhanced (CE) CT when available (109 patients). Clinical/imaging follow-up (minimum 6 months) with histopathology (when available) was taken as the reference standard. Of the 227 {sup 18}F-FDG PET/CT studies,166 were positive and 61 were negative for recurrent disease. PET/CT showed local recurrence in 134, nodal recurrence in 115 and distant recurrence in 47, with more than one site of recurrence in 34. The PET/CT findings were true-positive in 153 studies, true-negative in 54, false-positive in 13 and false-negative in 7. The sensitivity of {sup 18}F-FDG PET/CT was 96 %, the specificity was 81 %, the positive and negative predictive values were 92 % and 89 %, respectively, and the accuracy was 91 %. PET/CT showed similar accuracy in patients with squamous cell carcinoma and in those with adenocarcinoma (P = 0.181).{sup 18}F-FDG PET/CT was more specific than CECT (67 % vs. 21 %; P < 0.0001). PET/CT was superior to CECT for the detection of nodal recurrence (P < 0.0001), but not local recurrence (P = 0.093) or distant metastases (P = 0.441). {sup 18}F-FDG PET/CT shows high accuracy in the detection of suspected recurrence in patients with oesophageal carcinoma. It is more specific than

File list: Oth.Emb.10.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Emb.10.AllAg.Embryonic_palates mm9 TFs and others Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.10.AllAg.Embryonic_palates.bed ...

File list: Oth.Emb.20.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Emb.20.AllAg.Embryonic_palates mm9 TFs and others Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.20.AllAg.Embryonic_palates.bed ...

File list: Oth.Emb.50.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Oth.Emb.05.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Emb.05.AllAg.Embryonic_palates mm9 TFs and others Embryo Embryonic palates http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Emb.05.AllAg.Embryonic_palates.bed ...

File list: Pol.Emb.20.AllAg.Embryonic_pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Emb.20.AllAg.Embryonic_pancreas mm9 RNA polymerase Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.20.AllAg.Embryonic_pancreas.bed ...

File list: Pol.Emb.10.AllAg.Embryonic_pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Emb.10.AllAg.Embryonic_pancreas mm9 RNA polymerase Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.10.AllAg.Embryonic_pancreas.bed ...

File list: Pol.Emb.05.AllAg.Embryonic_pancreas [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Emb.05.AllAg.Embryonic_pancreas mm9 RNA polymerase Embryo Embryonic pancreas ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Emb.05.AllAg.Embryonic_pancreas.bed ...

Immunohistochemical demonstration of a hitherto undescribed localization of hemoglobin A and F in endodermal cells of normal human yolk sac and endodermal sinus tumor

DEFF Research Database (Denmark)

Albrechtsen, R; Wewer, U; Wimberley, P D

1980-01-01

In this study of 4 human yolk sacs, the presence of hemoglobin A and F (HbA and HbF) is demonstrated for the first time in epithelial cells (type 1) and erythroid-like cells (type 2) in the endodermal layer by immunoperoxidase technique. Our findings strongly support the hypothesis previously...... proposed that the red blood cells formed in the yolk sac are of endodermal origin. Tumor with yolk sac differentiation (8 endodermal sinus tumors and 1 embryonal carcinoma with vitelline areas) similarly showed HbA and HbF localisation in endodermal cells. None of 59 germ cell tumors of other types...

File list: DNS.Emb.20.AllAg.Embryonic_testis [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Emb.20.AllAg.Embryonic_testis mm9 DNase-seq Embryo Embryonic testis SRX1156635 ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Emb.20.AllAg.Embryonic_testis.bed ...

Ultrasound Backscatter Microscopy Image-Guided Intraventricular Gene Delivery at Murine Embryonic Age 9.5 and 10.5 Produces Distinct Transgene Expression Patterns at the Adult Stage

Directory of Open Access Journals (Sweden)

Jiwon Jang

2013-11-01

Full Text Available In utero injection of a retroviral vector into the embryonic telencephalon aided by ultrasound backscatter microscopy permits introduction of a gene of interest at an early stage of development. In this study, we compared the tissue distribution of gene expression in adult mice injected with retroviral vectors at different embryonic ages in utero. Following ultrasound image-guided gene delivery (UIGD into the embryonic telencephalon, adult mice were subjected to whole-body luciferase imaging and immunohistochemical analysis at 6 weeks and 1 year postinjection. Luciferase activity was observed in a wide range of tissues in animals injected at embryonic age 9.5 (E9.5, whereas animals injected at E10.5 showed brain-localized reporter gene expression. These results suggest that mouse embryonic brain creates a closed and impermeable structure around E10. Therefore, by injecting a transgene before or after E10, transgene expression can be manipulated to be local or systemic. Our results also provide information that widens the applicability of UIGD beyond neuroscience studies.

Oct3/4 directly regulates expression of E2F3a in mouse embryonic stem cells

International Nuclear Information System (INIS)

Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki; Yokota, Takashi; Koide, Hiroshi

2015-01-01

Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activity by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction

Oct3/4 directly regulates expression of E2F3a in mouse embryonic stem cells

Energy Technology Data Exchange (ETDEWEB)

Kanai, Dai; Ueda, Atsushi; Akagi, Tadayuki; Yokota, Takashi; Koide, Hiroshi, E-mail: hkoide@med.kanazawa-u.ac.jp

2015-04-10

Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activity by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth. - Highlights: • Oct3/4 positively regulates E2F3a expression in ES cells. • Oct3/4 binds to the promoter region of the E2F3a gene. • Overexpression of E2F6, an inhibitor of E2F3a, reduces ES cell growth. • E2F3a recovers growth retardation of ES cells caused by Oct3/4 reduction.

File list: ALL.Emb.05.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Emb.20.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Emb.50.AllAg.Embryonic_palates [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: His.Emb.10.AllAg.Embryonic_trunk [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: His.Emb.50.AllAg.Embryonic_trunk [Chip-atlas[Archive

Lifescience Database Archive (English)

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Immunoscintigraphy of recurrences of gynecologic carcinomas

International Nuclear Information System (INIS)

Chatal, J.F.; Fumoleau, P.; Saccavini, J.C.

1987-01-01

In a first, retrospective study, 15 patients with known ovarian carcinoma were injected with 131 I-OC 125 F(ab')2 monoclonal antibody (MAb). The sensitivity of immunoscintigraphy based on the number of the tumor sites was 67% (12/18). In a second, prospective study, 29 patients with gynecologic carcinoma were injected with 131 I-OC 125 F(ab')2 (24) or 131 I-19-9 F(ab')2 (5) MAbs according to the histologic type. Based on the number of tested anatomic sites, sensitivity was 72% and specificity 86%. In two patients injected with both 131 I-OC-125 F(ab')2 and 125 I-NS F(ab')2 (nonspecific immunoglobulin) 1 and 4 days before tumor resection, tumor uptake of the specific antibody was 2.2 and 4.5 times greater than that of NS. Immunoscintigraphic results were complementary with those of ultrasonography and computed tomography. Finally, in one patient injected successively with 131 I-OC 125 F(ab')2 and 111 In-DTPA-OC 125 F(ab')2, the recurrent tumor was visualized with both radionuclides, with 111 In providing better abdominal tumor contrast but causing much greater liver radioactivity than 131 I

File list: Oth.Emb.50.AllAg.embryonic_skin [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: Oth.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: Oth.Emb.05.AllAg.embryonic_skin [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Peculiarities of Embryonic and Post-Embryonic Development of Оesophagostomum dentatum (Nematoda, Strongylidae Larvae Cultured in Vitro

Directory of Open Access Journals (Sweden)

Yevstafieva V. А.

2017-02-01

Full Text Available Morphometric peculiarities of the development of Оesophagostomum dentatum Rudolphi, 1803 from egg to infective larva were studied under laboratory conditions at various temperatures. The determined optimum temperature for embryonic and post-embryonic development of О. dentatum larvae from domestic pig (Sus scrofa domesticus Linnaeus, 1758 is 22 °С. At this temperature, 81 % of larvae develop to the third stage (L3 on the 10th day. Temperatures of 24 °С and 20 °С are less favorable for the development of the nematode, at those temperatures only 67 and 63 % of larvae, respectively, reached infective stage by the 10th day of cultivation. Embryonic development of О. dentatum eggs is characterized by their lengthening (by 8.87-9.50 %, р < 0.01 and widening (by 6.77-9.35 %, р < 0.05-0.01, and post-embryonic larval development is associated with lengthening (by 4.59-17.33 %, р < 0.01-0.001.

File list: Unc.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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PET/CT in patients with hepatocellular carcinoma using [{sup 18}F]fluorocholine: preliminary comparison with [{sup 18}F]FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Talbot, Jean-Noel; Gutman, Fabrice; Kerrou, Khaldoun; Grahek, Dany; Montravers, Francoise [Hopital Tenon, AP-HP, et Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Fartoux, Laetitia; Poupon, Raoul; Rosmorduc, Olivier [Hopital Saint-Antoine, AP-HP, et Universite Pierre et Marie Curie, Department of Hepatology, Paris (France); Grange, Jean-Didier [Hopital Tenon, AP-HP, et Universite Pierre et Marie Curie, Department of Hepatology, Paris (France); Ganne, Nathalie [Hopital Jean Verdier, AP-HP, Department of Hepatology, Bondy (France)

2006-11-15

The diagnostic accuracy of [{sup 18}F]fluorodeoxyglucose (FDG) PET is insufficient to characterise hepatocellular carcinoma (HCC) in liver masses and to diagnose all cases of recurrent HCC. HCC has been reported to take up [{sup 11}C]acetate, but routine use of this tracer is difficult. Choline is another tracer of lipid metabolism, present in large amounts in HCC. In a proof-of-concept study, we evaluated [{sup 18}F]fluorocholine (FCH) uptake by HCC and compared FCH PET/CT with FDG PET/CT. Twelve patients with newly diagnosed (n=8) or recurrent HCC (n=4) were prospectively enrolled. HCC was assessed by histology in eight cases and by American Association for the Study of Liver Diseases (AASLD) criteria in four cases. All patients underwent whole-body PET/CT 10 min after injection of 4 MBq/kg FCH. Within 1 week, 9 of the 12 patients also underwent whole-body FDG PET/CT 1 h after injection of 5 MBq/kg FDG. The per-patient analysis showed a detection rate of 12/12 using FCH PET/CT for both newly diagnosed and recurrent HCC. The median signal to noise ratio was 1.5{+-}0.38. There was a trend towards a higher FCH SUV{sub max} in well-differentiated HCC (15.6{+-}7.9 vs 11.9{+-}0.9, NS). Of the nine patients who underwent FCH and FDG PET/CT, all nine were positive with FCH whereas only five were positive with FDG. FCH provides a high detection rate for HCC, making it potentially useful in the initial evaluation of HCC or in the detection of recurrent disease. The favourable result of this proof-of-concept study opens the way to a phase III prospective study. (orig.)

Clinical values for abnormal 18F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Lee, Hwan Seo; Kim, Jae Seung; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2014-01-01

Highlights: • Abnormal 18 F-FDG uptakes in the head and neck (HN) region can be carefully interpreted as being index primary, second primary cancer (SP) or benign. • 18 F-FDG PET/CT identified 91.9% primary HN squamous cell carcinomas (HNSCC). • The specificity and negative predictive value of 18 F-FDG PET/CT for identification of SP were as high as 98.7% and 99.3%, respectively. • Proper detection of primary tumors and SP in the HN region may promote appropriate therapeutic planning of HNSCC patients. - Abstract: Purpose: Fluorine 18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in 18 F-FDG uptake. However, both physiologic and abnormal lesions increase 18 F-FDG uptake. Therefore, we evaluated 18 F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake. Methods: A prospective study approved by the institutional review board was conducted in 314 patients with newly diagnosed HN squamous cell carcinoma (HNSCC) and informed consent was obtained from all enrolled patients. The patients received initial staging workups including 18 F-FDG PET/CT and biopsies. All lesions with abnormal HN 18 F-FDG uptake were recorded and most of those were confirmed by biopsies. Diagnostic values for abnormal 18 F-FDG uptake were calculated. Results: Abnormal 18 F-FDG uptake was identified in primary tumors from 285 (91.9%) patients. False-negative results were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P < 0.001). Thirty-eight regions of abnormal 18 F-FDG uptake were identified in 36 (11.5%) patients: the thyroid (n = 13), maxillary sinus (n = 7), palatine tonsil (n = 6), nasopharynx (n = 5), parotid gland (n = 2) and others (n = 5). Synchronous SP of the HN was identified in eight (2.5%) patients: the thyroid (n = 5), palatine tonsil (n = 2), and epiglottis (n = 1). The sensitivity and

File list: His.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Elevated 18F-NaF uptake in cricoid cartilage in a patient with laryngeal carcinoma: A case report and literature review.

Science.gov (United States)

Xia, Yuxiao; Qi, Chi; Zhang, Shumao; Huang, Zhanwen; Chen, Yue

2017-12-01

Laryngeal cancer is aggressive tumor that arises from the tissues of the larynx. Although any bone can be affected, involvement of cricoid cartilage was reported very rarely, and there has been no report of 18F-sodium fluoride positron emission tomography-computed tomography (F-NaF PET-CT) and 3D PET-CT for the evaluation of cricoid cartilage invasion. A 54-year-old male discovered a protruding mass in the right anterior neck, which had rapidly increased in size over a period of 2 months. Subsequently, hoarseness, dysphagia, and dyspnea were gradually developed. F-FDG PET-CT demonstrated that the abnormal activity was located in a soft tissue mass, which was about 4.2 cm × 3.8 cm × 3.6 cm in largest dimension in the laryngeal cavity of supraglottic portion (SUVmax: 23.6). A swollen lymph node was revealed in the right submandibular region, which had intense FDG activity with a SUVmax of 18.4. However, there is a high uptake of F-FDG in the region near the bone, which is uncertain whether there is any skeletal invasion. NaF PET-CT and 3D PET-CT demonstrated increased uptake in the right side of cricoid cartilage (SUVmax: 13.2). The histopathologic examination confirmed squamous cell carcinoma of larynx. The patient underwent tracheotomy and received anti-infective treatment to relieve symptoms of dyspnea and prevent asphyxia. Clinical follow up of the patient revealed that dyspnea was significantly relieved. The case report shows the imaging features of cricoid cartilage invasion, including F-FDG PET/CT, 18F-sodium fluoride positron emission tomography-computed tomography (F-NaF PET-CT), and 3D PET-CT. Precise understanding of the invasion scope, accurately staging of laryngeal carcinoma, and choosing of the most suitable surgical scheme are the factors that lead to the optimal treatment of laryngeal neoplasms.

Enterocin F4-9, a Novel O-Linked Glycosylated Bacteriocin

OpenAIRE

Maky, Mohamed Abdelfattah; Ishibashi, Naoki; Zendo, Takeshi; Perez, Rodney Honrada; Doud, Jehan Ragab; Karmi, Mohamed; Sonomoto, Kenji

2015-01-01

Enterococcus faecalis F4-9 isolated from Egyptian salted-fermented fish produces a novel bacteriocin, termed enterocin F4-9. Enterocin F4-9 was purified from the culture supernatant by three steps, and its molecular mass was determined to be 5,516.6 Da by mass spectrometry. Amino acid and DNA sequencing showed that the propeptide consists of 67 amino acid residues, with a leader peptide containing a double glycine cleavage site to produce a 47-amino-acid mature peptide. Enterocin F4-9 is modi...

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Diagnostic value of tissue polypeptide specific antigen in serum for patients with pancreatic carcinoma

International Nuclear Information System (INIS)

Lu Yun; Liu Xingdang; Li Ding; Dei Shouzhen

2009-01-01

Objective: To compare the diagnostic value of tissue polypeptide specific antigen (TPS) in serum, with the carbohydrate antigens (CA) 19-9, CA50, CA125 and CA242 in pancreatic carcinoma. Methods: Serum TPS was measured with enzyme linked immunosorbent assay (ELISA). CA19-9 and CA125 were measured with chemiluminescent immunoassay. CAS0 and CA242 were measured with immunoradiometric assay in 33 patients with pancreatitis, 34 patients with pathologically proven pancreatic carcinoma, and 35 patients with non-pancreatic malignancies. Statistic analysis was carried out with SPSS 9.0 software. Results: Patients with pancreatic carcinoma had relatively higher levels of TPS [(386.5 ± 315. 1) U/L] and CA19-9 [(10 820.9 ± 389.7) kU/L] when compared with patients with pancreatitis [(86. 2 ± 28.1) U/L and (61.5 ± 24.7) kU/L, respectively; F = 936. 42, P < 0. 001 ; F = 2217. 09, P < 0. 001], with a sensitivity and a specificity of 70.6% (48/68) and 57.4% (39/68), respectively, for TPS, and 82.4% (28/34) and 77.9% (53/68), respectively, for CA19-9. Diagnostic performance was further improved when TPS was assayed in combination with CA19-9, CA50, CA125 and CA242. Conclusion: Serum TPS has an incremental value in complementing CA19-9 in the diagnosis of pancreatic carcinoma. (authors)

File list: InP.Emb.20.AllAg.embryonic_skin [Chip-atlas[Archive

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Has F.D.G. PET/CT an impact on the management of patients with anal carcinoma?

International Nuclear Information System (INIS)

Vercellino, L.; Nataf, V.; Kerrou, K.; Huchet, V.; Pascal, O.; Montravers, F.; Talbot, J.N.; De Parades, V.; Bauer, P.; Touboul, E.

2010-01-01

Purpose: To evaluate the impact of F.D.G. PET/C Ton the management of patients referred for the staging and/or the follow-up of anal carcinoma, and PET/CT on patient management. Patients and methods: We included patients referred to our department for anal carcinoma whose therapeutic management was evaluable thanks to follow-up data during at least 6 months. Results: Data of 44 patients were analysed: 22 had PET/CT for initial staging and 36 during follow-up. PET/CT had impact in nine patients out of 44 (20%) and it was relevant in eight of them. Conclusion: F.D.G. PET/CT is an accurate imaging modality in anal cancer, its impact on patient management is more obvious when persistence or recurrence of disease is suspected. (authors)

Clinical values for abnormal {sup 18}F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Lee, Hwan Seo [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jae Seung [Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Jong-Lyel, E-mail: rohjl@amc.seoul.kr [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Seung-Ho; Nam, Soon Yuhl [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sang Yoon [Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Biomedical Research Institute, Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2014-08-15

Highlights: • Abnormal {sup 18}F-FDG uptakes in the head and neck (HN) region can be carefully interpreted as being index primary, second primary cancer (SP) or benign. • {sup 18}F-FDG PET/CT identified 91.9% primary HN squamous cell carcinomas (HNSCC). • The specificity and negative predictive value of {sup 18}F-FDG PET/CT for identification of SP were as high as 98.7% and 99.3%, respectively. • Proper detection of primary tumors and SP in the HN region may promote appropriate therapeutic planning of HNSCC patients. - Abstract: Purpose: Fluorine 18-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in {sup 18}F-FDG uptake. However, both physiologic and abnormal lesions increase {sup 18}F-FDG uptake. Therefore, we evaluated {sup 18}F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake. Methods: A prospective study approved by the institutional review board was conducted in 314 patients with newly diagnosed HN squamous cell carcinoma (HNSCC) and informed consent was obtained from all enrolled patients. The patients received initial staging workups including {sup 18}F-FDG PET/CT and biopsies. All lesions with abnormal HN {sup 18}F-FDG uptake were recorded and most of those were confirmed by biopsies. Diagnostic values for abnormal {sup 18}F-FDG uptake were calculated. Results: Abnormal {sup 18}F-FDG uptake was identified in primary tumors from 285 (91.9%) patients. False-negative results were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P < 0.001). Thirty-eight regions of abnormal {sup 18}F-FDG uptake were identified in 36 (11.5%) patients: the thyroid (n = 13), maxillary sinus (n = 7), palatine tonsil (n = 6), nasopharynx (n = 5), parotid gland (n = 2) and others (n = 5). Synchronous SP of the HN was identified in eight (2.5%) patients: the thyroid (n = 5), palatine

File list: ALL.Emb.20.AllAg.Embryonic_testis [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: ALL.Emb.10.AllAg.embryonic_skin [Chip-atlas[Archive

Lifescience Database Archive (English)

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Prognostic value of 18F-FDG-PET/CT in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis.

Science.gov (United States)

Lin, Jie; Xie, Guozhu; Liao, Guixiang; Wang, Baiyao; Yan, Miaohong; Li, Hui; Yuan, Yawei

2017-05-16

The prognostic role of 18F-fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT) parameters is still controversial in nasopharyngeal carcinoma patients. We sought to perform a systematic review and meta-analysis to explore the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on event-free survival (EFS) and overall survival (OS) in nasopharyngeal carcinoma patients. Fifteen studies comprising 1,938 patients were included in this study. The combined hazard ratios (HRs) for EFS were 2.63 (95%CI 1.71-4.05) for SUVmax, 2.55 (95%CI 1.49-4.35) for MTV, and 3.32 (95%CI 1.23-8.95) for TLG. The pooled HRs for OS were 2.07 (95%CI 1.54-2.79) for SUVmax, 3.86 (95%CI 1.85-8.06) for MTV, and 2.60 (95%CI 1.55-4.34) for TLG. The prognostic role of SUVmax, MTV and TLG remained similar in the sub-group analyses. A systematic literature search was performed to identify studies which associated 18F-FDG PET/CT to clinical survival outcomes of nasopharyngeal carcinoma patients. The summarized HRs for EFS and OS were estimated by using fixed- or random-effect models according to heterogeneity between trials. The present meta-analysis confirms that high values of SUVmax, MTV and TLG predicted a higher risk of adverse events or death in patients with nasopharyngeal carcinoma, despite clinically heterogeneous nasopharyngeal carcinoma patients and the various methods adopted between these studies.

The role of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in the management of patients with carcinoma of unknown primary.

Science.gov (United States)

Deonarine, P; Han, S; Poon, F W; de Wet, C

2013-08-01

Carcinoma of unknown primary is one of the ten most frequent cancers worldwide. Its median survival time is less than 10 months. Detecting primary tumour locations and/or occult metastatic lesions may inform definitive treatment and improve patients' prognosis. We aimed to determine: (1) the sensitivity, specificity and accuracy of (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography; (2) its detection rate of primary tumour locations and occult metastases and (3) factors associated with improved survival times. We retrospectively reviewed all cases in the West of Scotland for the period 1 December 2007 to 31 May 2011 that met all our selection criteria: (1) diagnosis of carcinoma of unknown primary; (2) a thorough but negative 'work-up' and (3) (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography report. Statistical methods included frequencies, Kaplan-Meier graphs and log-rank tests to compare survival times. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected primary tumour sites in 19/51 (37.3%) and occult metastases in 28/51 (54.9%) of eligible patients. Its sensitivity, specificity and accuracy were 79.2%, 70.4% and 74.5%, respectively; 20/51 (39.2%) patients died during the study period with a median survival of 8.4 months (range 21.4, SD ± 6.2). The number of metastatic locations was strongly associated with survival (p = 0.002), but detection of a primary tumour site (p = 0.174) or histopathology (p = 0.301) was not. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected occult metastatic sites in the majority and a primary cancer location in a substantial minority of patients. Our results were comparable with international literature and may indicate that (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography have an early role to improve the accuracy of cancer staging and to optimise carcinoma of unknown

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File list: NoD.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

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File list: NoD.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

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File list: ALL.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

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File list: ALL.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: ALL.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

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Clinical study of 18F-FDG PET/CT whole-body imaging in disseminated carcinoma of unknown primary site

International Nuclear Information System (INIS)

Wang Guohui; Liang Peiyan; Cai Yanjun; Zhang Weiguang; Xie Chuanmiao; Wu Peihong

2008-01-01

Objective: Carcinoma of unknown primary (CUP) is not uncommon in usual clinical settings. They are, by definition, those cases with clinically suspected primary malignancy but not revealed by conventional investigation. The aim of this study was to investigate the efficacy of whole-body 18 F-fluoro- deoxyglucose (FDG) PET/CT in detecting a primary neoplasm for these patients. Methods: A totle of 150 patients with retrievable records from 169 CUP patients were selected within a group of consecutive 2589 patients from Jan. 2006 to Jun. 2007. All cases underwent whole-body FDG PET/CT scan. The final diagnoses were confirmed by pathologic results, other imaging modalities or clinical follow-up. Results: Among 150 patients, primary tumor sites were successfully detected by whole-body 18 F-FDG PET/CT scan in 70 cases (46.7%), of which 52 were pathologically confirmed and 18 by clinical follow-up. And 38 cases (54.3%) were lung cancer, 8 (11.4%) were nasopharyngeal carcinoma, 13 (18.6%) in digestive sys- tem, and 11 (15.7%) in other systems. Three clinically suspected CUP cases with negative 18 F-FDG PET/ CT were subsequently confirmed of benign processes by clinical follow-up. Six patients were wrongly diagnosed by 18 F-FDG PET/CT, and 15 patients did not have a confirmed diagnosis by the end of research. The primary cause of malignancy after 18 F-FDG PET/CT remained obscure in 56 patients, only 3 of whom be- came known during the course of clinical follow-up (nasopharyngeal bladder and esophageal carcinoma). Conclusion: 18 F-FDG PET/CT whole-body imaging plays an important role in patients with metastatic CUP. (authors)

File list: InP.Emb.50.AllAg.Embryonic_limb [Chip-atlas[Archive

Lifescience Database Archive (English)

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Comparison of 68Ga-DOTA-Siglec-9 and 18F-Fluorodeoxyribose-Siglec-9: Inflammation Imaging and Radiation Dosimetry.

Science.gov (United States)

Virtanen, Helena; Silvola, Johanna M U; Autio, Anu; Li, Xiang-Guo; Liljenbäck, Heidi; Hellberg, Sanna; Siitonen, Riikka; Ståhle, Mia; Käkelä, Meeri; Airaksinen, Anu J; Helariutta, Kerttuli; Tolvanen, Tuula; Veres, Tibor Z; Saraste, Antti; Knuuti, Juhani; Jalkanen, Sirpa; Roivainen, Anne

2017-01-01

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68 Ga-DOTA- and 18 F-fluorodeoxyribose- (FDR-) labeled Siglec-9 motif peptides for PET imaging of inflammation. Methods . Firstly, we examined 68 Ga-DOTA-Siglec-9 and 18 F-FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18 F-FDR-Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and compared it with previous 68 Ga-DOTA-Siglec-9 results. Lastly, we estimated human radiation dosimetry from the rat data. Results . In rats, 68 Ga-DOTA-Siglec-9 (SUV, 0.88 ± 0.087) and 18 F-FDR-Siglec-9 (SUV, 0.77 ± 0.22) showed comparable ( P = 0.29) imaging of inflammation. In atherosclerotic mice, 18 F-FDR-Siglec-9 detected inflamed plaques with a target-to-background ratio (1.6 ± 0.078) similar to previously tested 68 Ga-DOTA-Siglec-9 ( P = 0.35). Human effective dose estimates for 68 Ga-DOTA-Siglec-9 and 18 F-FDR-Siglec-9 were 0.024 and 0.022 mSv/MBq, respectively. Conclusion . Both tracers are suitable for PET imaging of inflammation. The easier production and lower cost of 68 Ga-DOTA-Siglec-9 present advantages over 18 F-FDR-Siglec-9, indicating it as a primary choice for clinical studies.

Clinicopathologic assessment of pancreatic ductal carcinoma located at the head of the pancreas, in relation to embryonic development.

Science.gov (United States)

Okamura, Yukiyasu; Fujii, Tsutomu; Kanzaki, Akiyuki; Yamada, Suguru; Sugimoto, Hiroyuki; Nomoto, Shuji; Takeda, Shin; Nakao, Akimasa

2012-05-01

Pancreaticoduodenectomy is performed for pancreatic head cancer that originated from the dorsal or ventral primordium. Although the extent of lymph node (LN) dissection is the same irrespective of the origin, the lymphatic continuities may differ between the 2 primordia. Between March 2003 and September 2010, 152 patients underwent pancreaticoduodenectomy for pancreatic cancer. One hundred six patients were assigned into 2 groups according to tumor location on preoperative computed tomography, and their clinical and pathological features were retrospectively analyzed in view of the embryonic development of the pancreas. Sixty of 106 patients were classified with tumors that were derived from the dorsal pancreas (D group) and 46 from the ventral pancreas (V group). The frequency of LN involvement around the middle colic artery (LN 15) in the D group was higher than in the V group (P = 0.008). The rate of additional resection of the pancreas tended to be higher in the D group (P = 0.067). The present study showed the detailed pattern of spread of pancreatic ductal carcinoma to the LNs and provided important information for determining the optimal surgical strategy.

File list: InP.Emb.10.AllAg.Embryonic_testis [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: InP.Emb.50.AllAg.Embryonic_testis [Chip-atlas[Archive

Lifescience Database Archive (English)

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Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression.

Science.gov (United States)

Dong, Jianfeng; Cheng, Lijun; Zhao, Minchao; Pan, Xiangfeng; Feng, Zhiqiang; Wang, Dawei

2017-05-01

Oropharyngeal head and neck squamous cell carcinoma is a common malignant tumor in the oral cavity. High-risk human papillomavirus 16 infection is a major cause of oropharyngeal head and neck squamous cell carcinoma development. Strong antitumor immune responses, especially CD8 + T cell responses, are thought to be essential to effective cancer treatment and are associated with better prognosis in oropharyngeal head and neck squamous cell carcinoma. In this study, we examined the role of the Tim-3/Gal-9 pathway in oropharyngeal head and neck squamous cell carcinoma patients. We found that Gal-9 expression by CD4 + T cells was increased in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients, but not in human papillomavirus-negative oropharyngeal head and neck squamous cell carcinoma patients. Increased Gal-9 secretion by CD4 + T cells presented multiple immunosuppressive effects. Coculturing monocytes with high Gal-9-expressing CD4 + T cells resulted in the expansion of Tim-3 + monocytes, which suppressed interferon gamma production by activated CD8 + T cells. Subsequently, total monocytes incubated with exogenous Gal-9, or high Gal-9-expressing CD4 + T cells, suppressed the expression of interferon gamma by CD8 + T cells. Exogenous Gal-9 and high Gal-9-expressing CD4 + T cells also suppressed the secretion of both interleukin 10 and interleukin 12 by monocytes. These effects are Tim-3/Gal-9-dependent because blocking Tim-3 and/or Gal-9 could enhance the support of CD8 + T cell interferon gamma production and the interleukin 10 and interleukin 12 secretion by monocytes. Together, these data suggest that the high Tim-3 expression in monocytes could be utilized by tumor-promoting Gal-9 expression on CD4 + T cells. Immunotherapy in human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma patients therefore faces an additional challenge posed by Tim-3 and Gal-9 and likely requires the blockade of these

File list: InP.Emb.50.AllAg.Embryonic_heart [Chip-atlas[Archive

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File list: InP.Emb.20.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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File list: InP.Emb.10.AllAg.Embryonic_heart [Chip-atlas[Archive

Lifescience Database Archive (English)

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Monoclonal antibodies to carcino-embryonic antigen

International Nuclear Information System (INIS)

Teh, Jinghee; McKenzie, I.F.C.

1990-01-01

With the aim of producing new MoAb to colorectal carcinoma, immunization with cell suspensions of a fresh colonic tumour was performed and MoAb 17C4 was obtained. To produce other MoAb to colon cancer, an immunization protocol using fresh tumour, colonic cell lines and sera from patients with colonic tumours was employed and resulted in MoAb JGT-13, LK-4 and XPX-13. MoAb I-1 and O-1 were raised against sera from patients with colon cancer to produce MoAb directed against circulating tumour associated antigens. The six antibodies gave a range of reactions with normal and malignant tissues, indicating that they most likely reacted with different epitopes. Thus, apart from the reactions of 17C4, LK-4 and XPX-13 with fresh and formalin-fixed granulocytes, none of the antibodies reacted with formalin-fixed normal tissues. Despite the apparent specificity of these MoAb for colon cancer, serum testing using MoAb gave similar results to carcino-embryonic antigen polyclonal antibodies, that is the MoAb gave no obvious advantage. 9 refs., 1 tab., 3 figs

Radiative electron capture for F8+ and F9+ ions in collisions with a He gas target

International Nuclear Information System (INIS)

Kawatsura, K.; Richard, P.; Tawara, H.

1981-01-01

The x rays from the radiative electron capture (REC) to the projectile K-shell were investigated for F 8+ and F 9+ ions incident on the He target atoms in the projectile energy range from 15 to 40 MeV. The peak energies of the K-REC x-ray spectra were found to decrease linearly with a decrease of the projectile energies as expected and extrapolated to the correct ls binding energies at zero velocity. According to theory the distribution width of the REC energies should be independent of the binding energy of electrons in the projectile ions. However, it is found that this width for F 8+ ions is systematically smaller by 20% than that for F 9+ ions. The measured REC cross sections for F 9+ ions are slightly larger than twice those for F 8+ ions and the total REC cross sections for F 8+ and F 9+ ions were found to be more than three orders of magnitude smaller than the total electron capture cross sections and the capture cross sections into excited states

Diagnostic utility of PET/CT with {sup 18}F-DOPA and {sup 18}F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff

Energy Technology Data Exchange (ETDEWEB)

Romero-Lluch, Ana Reyes; Guerrero-Vazquez, Raquel; Martinez-Ortega, Antonio Jesus; Navarro-Gonzalez, Elena [Hospital Universitario Virgen del Rocio, Unidad de Gestion Clinica de Endocrinologia y Nutricion, Seville (Spain); Cuenca-Cuenca, Juan Ignacio; Tirado-Hospital, Juan Luis; Borrego-Dorado, Isabel [Hospital Universitario Virgen del Rocio, Unidad de Medicina Nuclear, Seville (Spain)

2017-11-15

This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) and 18-F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including {sup 18}F-DOPA PET/CT). We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a {sup 18}F-FDG PET/CT and a {sup 18}F-DOPA PET/CT. Abnormal uptakes were detected with {sup 18}F-DOPA (n=12) and {sup 18}F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with {sup 18}F-DOPA vs. 16 lesions with {sup 18}F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with {sup 18}F-FDG in comparison to {sup 18}F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both {sup 18}F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and {sup 18}F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of {sup 18}F-DOPA and {sup 18}F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients. {sup 18}F-DOPA PET/CT appears to be superior to {sup 18}F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL. (orig.)

Early restaging whole-body 18F-FDG PET during induction chemotherapy predicts clinical outcome in patients with locoregionally advanced nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Yen, Ruoh-Fang; Chen, Tony Hsiu-Hsi; Ting, Lai-Lei; Tzen, Kai-Yuan; Pan, Mei-Hsiu; Hong, Ruey-Long

2005-01-01

This study was undertaken to evaluate the utility of whole-body 18 F-FDG PET in monitoring therapeutic effect during induction chemotherapy (IC) and in predicting prognosis in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Fifty patients who had histologically proven, locoregionally advanced NPC without distant metastasis and had received IC were recruited in this study. The study cohort consisted of 19 females and 31 males (age 17-72 years, mean 45.9±11.9). Whole-body 18 F-FDG PET was performed in each patient after completion of one (33 patients) or two (17 patients) courses of IC. Each patient was restaged on the basis of the 18 F-FDG PET results. Patients who were downstaged to stage I or II were classified as major responders; the rest were classified as non-major responders. Only 1 of the 23 major responders subsequently developed local recurrence. At the time of data analysis, all major responders were alive; by contrast, of the 27 non-major responders, 15 had locoregional recurrence or distant metastasis and nine had died (seven of NPC and two of treatment-related complications). Kaplan-Meier survival analysis showed significantly longer recurrence-free survival and overall survival in major responders (56.4±9.2 and 58.1±2.2 months) as compared with non-major responders (33.7±23.2 and 44.7±20.0 months), with p 18 F-FDG PET scan after the first or second course of IC is useful for predicting therapeutic response and outcome in patients with locoregionally advanced NPC. (orig.)

Simple and rapid radiosynthesis of N-18F-labeled glutamic acid as a hepatocellular carcinoma PET tracer

International Nuclear Information System (INIS)

Sun, Aixia; Liu, Shaoyu; Tang, Xiaolan; Nie, Dahong; Tang, Ganghua; Zhang, Zhanwen; Wen, Fuhua; Wang, Xiaoyan

2017-01-01

Introduction: We have reported that N-(2- 18 F-fluoropropionyl)-L-glutamate ( 18 F-FPGLU) showed good tumor-to-background contrast and 18 F-FPGLU was prepared via complex multi-step reaction sequence; here, it is synthesized by a facile two-step reaction sequence. The objectives of this study are to synthesize 18 F-FPGLU via a two-step reaction sequence and to evaluate the value of 18 F-FPGLU in nude mice bearing human hepatocellular carcinoma SMCC-7721 (HCC SMCC-7721). Methods: 18 F-FPGLU was synthetized from the precursor (2S)-dimethyl 2-(2-bromopropanamido)pentanedioate via the two-step on-column hydrolysis using a modified commercial FDG synthesizer. To investigate the transport mechanism of 18 F-FPGLU, we conducted a series of competitive inhibition experiments on HCC SMCC-7721 cells in the absence or presence of Na + and various types of inhibitors. Small-animal PET–CT imaging was performed on tumor-bearing nude mice using 18 F-FPGLU and 2- 18 F-2-deoxy-D-glucose ( 18 F-FDG). Results: The radiochemical yield of 18 F-FPGLU was up to 15 ± 5% (EOS, n = 10) in 35 min with the two-step procedure and the radiochemical purity was higher than 95% with a specific activity of 30–40 GBq/μmol. In vitro cell experiments show that 18 F-FPGLU is primarily transported through the Na + -dependent system X AG − and Na + -independent system X C −. PET imaging in a tumor model indicates that 18 F-FPGLU may be superior to 18 F-FDG for hepatocellular carcinoma (HCC) imaging. Conclusion: An optimized route to prepare 18 F-FPGLU was developed and 18 F-FPGLU was synthetized from the precursor ((2S)-dimethyl 2-(2-bromopropanamido)pentanedioate) via the two-step on-column hydrolysis. 18 F-FPGLU was a potential novel PET tracer for HCC imaging.

Radiosynthesis and pharmacokinetics of [18F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

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Yang Z

2017-01-01

Full Text Available Zhaoshuo Yang,1 Jianhua Liu,2 Qingqing Huang,3 Zhouji Zhang,1 Jiawei Zhang,1 Yanjia Pan,1 Yunke Yang,1 Dengfeng Cheng4 1Department of Chinese Traditional Medicine, Zhongshan Hospital, Fudan University, 2School of Medicine, Shanghai Jiao Tong University, 3Department of Nuclear Medicine, Shanghai 10th People’s Hospital, Tongji University School of Medicine, 4Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Purpose: Bufalin, the main component of a Chinese traditional medicine chansu, shows convincing anticancer effects in a lot of tumor cell lines. However, its in vivo behavior is still unclear. This research aimed to evaluate how bufalin was dynamically absorbed after intravenous injection in animal models. We developed a radiosynthesis method of [18F]fluoroethyl bufalin to noninvasively evaluate the tissue biodistribution and pharmacokinetics in hepatocellular carcinoma-bearing mice. Methods: [18F]fluoroethyl bufalin was synthesized with conjugation of 18F-CH2CH2OTs and bufalin. The radiochemical purity was proved by the radio-high-performance liquid chromatography (HPLC. The pharmacokinetic studies of [18F]fluoroethyl bufalin were then performed in Institute of Cancer Research (ICR mice. Furthermore, the biodistribution and metabolism of [18F]fluoroethyl bufalin in HepG2 and SMMC-7721 tumor-bearing nude mice were studied in vivo by micro-positron emission tomography (micro-PET. Results: The radiochemical purity (RCP of [18F]fluoroethyl bufalin confirmed by radio-HPLC was 99%±0.18%, and [18F]fluoroethyl bufalin showed good in vitro and in vivo stabilities. Blood dynamics of [18F]fluoroethyl bufalin conformed to the two compartments in the ICR mice model. The pharmacokinetic parameters of [18F]fluoroethyl bufalin were calculated by DAS 2.0 software. The area under concentration–time curve (AUC0–t and the values of clearance (CL were 540.137 µg/L·min and 0.001�

MMP-9, uPA and uPAR proteins expression and its prognostic significance in esophageal squamous cell carcinoma treated by radiotherapy

International Nuclear Information System (INIS)

Zhu Shuchai; Wang Yafei; Su Jingwei; Wang Yuxiang; Shen Wenbin; Li Juan

2008-01-01

Objective: To explore the the prognostic significance of MMP-9, uPA and uPAR protein expression and its relationship with clinical-pathologic factors in esophageal squamous cell carcinoma treated by radiotherapy. Methods: MMP-9, uPA and uPAR protein expression was measured in 59 esophageal carcinomas and 41 peri-carcinoma tissues with immunohistochemistry. The relationship between the protein expression and the clinical-pathological parameters was analyzed, and the prognostic factors in esophageal squamous cell carcinoma treated by radiotherapy alone was evaluated. Results: The rates of positive expression of MMP-9, uPA and uPAR were 85%, 76% and 78% in esophageal carcinoma and 39%, 49% and 44% in peri-carcinoma tissues (χ 2 =22.54, 8.04 and 12.18; P=0.000,0.005 and 0.000). The rates of positive expression of MMP-9 was 79% and 100% when the depth of tumor invasion was ≤2 cm and >2 cm(P= 0.048), respectively. The expression of uPA was significantly correlated with the status of fat interspace between the esophageal lesion and the vertebra in CT scanning image. When the fat interspace existed and disappeared, the rates of strong positive expression was 44% and 70%, respectively (χ 2 =4.21, P=0.040). The positive expression rate of uPA was significantly correlated with distant metastasis, which was 100% in patients with distant metastasis and 68.89% in those without distant metastasis(χ 2 =4.12, P=0.042). The positive expression rate of MMP-9, uPA and uPAR did not affect the prognosis and the short-term result of esophageal carcinoma treated by radiotherapy alone. Conclusions: The protein expression of MMP-9, uPA and uPAR may correlate with local infiltration and distant metastasis in esophageal squamous cell carcinoma. Protein expression may not influence the prognosis of esophageal carcinoma treated by radio therapy, though long time followed-up is still needed. (authors)

Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of COX7A1 in embryonic and cancer cells.

Science.gov (United States)

West, Michael D; Labat, Ivan; Sternberg, Hal; Larocca, Dana; Nasonkin, Igor; Chapman, Karen B; Singh, Ratnesh; Makarev, Eugene; Aliper, Alex; Kazennov, Andrey; Alekseenko, Andrey; Shuvalov, Nikolai; Cheskidova, Evgenia; Alekseev, Aleksandr; Artemov, Artem; Putin, Evgeny; Mamoshina, Polina; Pryanichnikov, Nikita; Larocca, Jacob; Copeland, Karen; Izumchenko, Evgeny; Korzinkin, Mikhail; Zhavoronkov, Alex

2018-01-30

Here we present the application of deep neural network (DNN) ensembles trained on transcriptomic data to identify the novel markers associated with the mammalian embryonic-fetal transition (EFT). Molecular markers of this process could provide important insights into regulatory mechanisms of normal development, epimorphic tissue regeneration and cancer. Subsequent analysis of the most significant genes behind the DNNs classifier on an independent dataset of adult-derived and human embryonic stem cell (hESC)-derived progenitor cell lines led to the identification of COX7A1 gene as a potential EFT marker. COX7A1 , encoding a cytochrome C oxidase subunit, was up-regulated in post-EFT murine and human cells including adult stem cells, but was not expressed in pre-EFT pluripotent embryonic stem cells or their in vitro -derived progeny. COX7A1 expression level was observed to be undetectable or low in multiple sarcoma and carcinoma cell lines as compared to normal controls. The knockout of the gene in mice led to a marked glycolytic shift reminiscent of the Warburg effect that occurs in cancer cells. The DNN approach facilitated the elucidation of a potentially new biomarker of cancer and pre-EFT cells, the embryo-onco phenotype, which may potentially be used as a target for controlling the embryonic-fetal transition.

ALTERATIONS IN THE DEVELOPING TESTIS TRANSCRIPTOME FOLLOWING EMBRYONIC VINCLOZOLIN EXPOSURE

OpenAIRE

Clement, Tracy M.; Savenkova, Marina I.; Settles, Matthew; Anway, Matthew D.; Skinner, Michael K.

2010-01-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 di...

A homozygous Keap1-knockout human embryonic stem cell line generated using CRISPR/Cas9 mediates gene targeting

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So-Jung Kim

2017-03-01

Full Text Available Kelch-like ECH-associated protein 1 (keap1 is a cysteine-rich protein that interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to the degradation of Nrf2 (Kim et al., 2014a. Disruption of Keap1 results in the induction of Nrf2-related signaling pathways involving the expression of a set of anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic stem cell (hESC. The Keap1 homozygous-knockout H9 cell line retained normal morphology, gene expression, and in vivo differentiation potential.

Genetic Tools for Self-Organizing Culture of Mouse Embryonic Stem Cells via Small Regulatory RNA-Mediated Technologies, CRISPR/Cas9, and Inducible RNAi.

Science.gov (United States)

Takata, Nozomu; Sakakura, Eriko; Sakuma, Tetsushi; Yamamoto, Takashi

2017-01-01

Approaches to investigate gene functions in experimental biology are becoming more diverse and reliable. Furthermore, several kinds of tissues and organs that possess their original identities can be generated in petri dishes from stem cells including embryonic, adult and induced pluripotent stem cells. Researchers now have several choices of experimental methods and their combinations to analyze gene functions in various biological systems. Here, as an example we describe one of the better protocols, which combines three-dimensional embryonic stem cell culture with small regulatory RNA-mediated technologies, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), and inducible RNA interference (RNAi). This protocol allows investigation of genes of interest to better understand gene functions in target tissues (or organs) during in vitro development.

Embryonal carcinoma cell induction of miRNA and mRNA changes in co-cultured prostate stromal fibromuscular cells

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VÊNCIO, ENEIDA F.; PASCAL, LAURA E.; PAGE, LAURA S.; DENYER, GARETH; WANG, AMY J.; RUOHOLA-BAKER, HANNELE; ZHANG, SHILE; WANG, KAI; GALAS, DAVID J.; LIU, ALVIN Y.

2014-01-01

The prostate stromal mesenchyme controls organ-specific development. In cancer, the stromal compartment shows altered gene expression compared to non-cancer. The lineage relationship between cancer-associated stromal cells and normal tissue stromal cells is not known. Nor is the cause underlying the expression difference. Previously, the embryonal carcinoma (EC) cell line, NCCIT, was used by us to study the stromal induction property. In the current study, stromal cells from non-cancer (NP) and cancer (CP) were isolated from tissue specimens and co-cultured with NCCIT cells in a trans-well format to preclude heterotypic cell contact. After 3 days, the stromal cells were analyzed by gene arrays for microRNA (miRNA) and mRNA expression. In co-culture, NCCIT cells were found to alter the miRNA and mRNA expression of NP stromal cells to one like that of CP stromal cells. In contrast, NCCIT had no significant effect on the gene expression of CP stromal cells. We conclude that the gene expression changes in stromal cells can be induced by diffusible factors synthesized by EC cells, and suggest that cancer-associated stromal cells represent a more primitive or less differentiated stromal cell type. PMID:20945389

Induction of murine embryonic stem cell differentiation by medicinal plant extracts

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Reynertson, Kurt A. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Charlson, Mary E. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States)

2011-01-01

Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells.

The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma

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Behnke, Martha, E-mail: mbehnke@mcvh-vcu.edu [Transplant Program Administration, Virginia Commonwealth University Health System, 1200 E. Broad St., Richmond, VA 23298 (United States); Reimers, Mark [Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, 800 E Leigh St., Richmond, VA 23298 (United States); Fisher, Robert [Department of Surgery, Virginia Commonwealth University, 1200 E. Broad St., Richmond, VA 23298 (United States)

2012-09-18

Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Patient and disease heterogeneity, differences in statistical methods and multiple testing issues have resulted in a fragmented understanding of the molecular basis of tumor biology. Some researchers have suggested that HCC appears to share pathways with embryonic development. Therefore we generated targeted hypotheses regarding changes in developmental genes specific to the liver in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared to 12 normal livers. Genes specific to non-liver development have known associations with other cancer types but none were expressed in either adult liver or tumor tissue, while 98 of 179 (55%) genes specific to liver development had differential expression between normal and cirrhotic or HCC samples. We found genes from each developmental stage dysregulated in tumors compared to normal and cirrhotic samples. Although there was no single tumor marker, we identified a set of genes (Bone Morphogenetic Protein inhibitors GPC3, GREM1, FSTL3, and FST) in which at least one gene was over-expressed in 100% of the tumor samples. Only five genes were differentially expressed exclusively in late-stage tumors, indicating that while developmental genes appear to play a profound role in cirrhosis and malignant transformation, they play a limited role in late-stage HCC.

Comparison of CT and 18F-FDG PET for Detecting Peritoneal Metastasis on the Preoperative Evaluation for Gastric Carcinoma

International Nuclear Information System (INIS)

Lim, Joon Seok; Kim, Myeong Jin; Yun, Mi jin

2006-01-01

The aim of our study was to compare the accuracy of CT and 18 F-FDG PET for detecting peritoneal metastasis in patients with gastric carcinoma. One-hundred-twelve patients who underwent a histologic confirmative exam or treatment (laparotomy, n = 107; diagnostic laparoscopy, n = 4; peritoneal washing cytology, n = 1) were retrospectively enrolled. All the patients underwent CT and 18 F-FDG PET scanning for their preoperative evaluation. The sensitivities, specificities and accuracies of CT and 18 FFDG PET imaging for the detection of peritoneal metastasis were calculated and then compared using Fisher's exact probability test (p 18 F-FDG PET imaging for detecting peritoneal metastasis. Based on the original preoperative reports, CT and 18 F-FDG PET showed sensitivities of 76.5% and 35.3% (p = 0.037), specificities of 91.6% and 98.9% (p = 0.035), respectively, and equal accuracies of 89.3% (p = 1.0). The receptor operating characteristics curve analysis showed a significantly higher diagnostic performance for CT (Az 0.878) than for PET (Az = 0.686) (p 0.004). The interobserver agreement for detecting peritoneal metastasis was good (κ value = 0.684) for CT and moderate ((κ value = 0.460) for PET. For the detection of peritoneal metastasis, CT was more sensitive and showed a higher diagnostic performance than PET, although CT had a relatively lower specificity than did PET

[Fluorodeoxiglucose F18 positron emission tomography imaging (F18FDG) for the assessment of rising levels of serum CA 19-9 in pancreatic mucinous cystadenocarcinoma. Report of one case].

Science.gov (United States)

Canessa, José A; Larach, Jorge A; Massardo, Teresa; Parra, Juan; Jofré, Josefina; González, Patricio; Morales, Bernardo; Humeres, Pamela; Sierralta, Paulina; Galaz, Rodrigo

2004-03-01

We report a 38 year old female patient with a pancreatic mucinous cystadenocarcinoma. She presented at the onset with a peritoneal rupture that required emergency surgery. Five months later, the patient was subjected to a segmental pancreatectomy and splenectomy. One year later, the patient had a serious gastric bleeding secondary to a gastric ulcer. Due to a persistent increase in her CA 19-9 levels, a Positron Emission Tomography (PET) functional imaging with fluorine 18-deoxyglucose (F18FDG) was done. It showed an intense focal hypermetabolism in the gastric wall reported as a secondary tumour location. The patient was subjected to a total gastrectomy and Roux en Y anastomosis, with a good outcome. The pathological study confirmed the presence of a metastasis of an adenocarcinoma in the gastric wall. The relative value of CA 19-9 markers and FDG PET in pancreatic and gastric carcinomas is discussed.

Evaluation of uterine cervix cancer hypoxia by PET with {sup 18}F-F.E.T.N.I.M.. Relation with squamous cell carcinoma (S.C.C.) and osteopontin tumoral markers; Evaluation de l'hypoxie du cancer du col uterin par la TEP au {sup 18}F-FETNIM. Relation avec les marqueurs tumoraux SCC et osteopontine

Energy Technology Data Exchange (ETDEWEB)

Barre, E.; Schlageter, M.H.; Groheux, D.; Vercellino, L.; Lussato, D.; Thoury, A.; Hennequin, V.; Hindie, E.; Barranger, E.; Moretti, J.L. [CHU Saint-Louis-Lariboisiere, universite Paris-7, IMDCT, 75 - Paris (France)

2010-07-01

Purpose: to evaluate the imaging feasibility of hypoxia of cervical squamous cell carcinoma by PET with {sup 18}F-F.E.T.N.I.M. (Iason). to compare the {sup 18}F-F.E.T.N.I.M. uptake to the metabolic uptake in {sup 18}F-F.D.G. and to study their relationship with the squamous cell carcinoma, tumoral marker and osteoponin, circulating tracer of hypoxia. Conclusions: the F.E.T.N.I.M. uptake by the tumor is always of lower level than the {sup 18}F-F.D.G. uptake. By using the ratio Tumor/Muscle, these preliminary results do not enlighten any correlation between the circulating hypoxia tracer and the tumor uptake of {sup 18}F-F.E.T.N.I.M.. (N.C.)

Induction of murine embryonic stem cell differentiation by medicinal plant extracts.

Science.gov (United States)

Reynertson, Kurt A; Charlson, Mary E; Gudas, Lorraine J

2011-01-01

Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells. Copyright © 2010 Elsevier Inc. All rights reserved.

Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

Science.gov (United States)

Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

2016-01-19

Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

CA 19-9 in the diagnosis and differential diagnosis of exocrine pancreatic carcinoma

International Nuclear Information System (INIS)

Klapdor, R.; Lehmann, U.; Bahlo, M.; Greten, H.; Ackeren, H. v.; Dallek, M.; Schreiber, W.H.

1983-01-01

CA 19-9 serum concentrations were determined in 56 controls and 66 patients with various pancreatic diseases using a commercially available radioimmunoassay. 56 controls showed mean serum concentrations of 7.3 +- 9.6 U/ml (anti x +- 2 SD) range 0-24, median 6), n = 21 patients suffering from chronic pancreatitis mean values of 16 +- 24 U/ml (anti x +- 2 SD) (range 4.9-42, median 13). The majority of the patients with exocrine pancreatic carcinoma demonstrated significantly elevated values: in 91% and 82% respectively, CA 19-9 levels were elevated above the upper limit of 95% of the controls (> 15 U/ml) and of the patients with chronic pancreatitis (> 37 U/ml) (P [de

Glypican-3–Targeting F(ab′)2 for 89Zr PET of Hepatocellular Carcinoma

OpenAIRE

Sham, Jonathan G.; Kievit, Forrest M.; Grierson, John R.; Chiarelli, Peter A.; Miyaoka, Robert S.; Zhang, Miqin; Yeung, Raymond S.; Minoshima, Satoshi; Park, James O.

2014-01-01

Hepatocellular carcinoma (HCC) is an increasingly lethal malignancy for which management is critically dependent on accurate imaging. Glypican-3 (GPC3) is a cell surface receptor overexpressed in most HCCs and provides a unique target for molecular diagnostics. The use of monoclonal antibodies (mAbs) that target GPC3 (αGPC3) in PET imaging has shown promise but comes with inherent limitations associated with mAbs such as long circulation times. This study used 89Zr-conjugated F(ab′)2 fragment...

Resistance Switching Memory Characteristics of Si/CaF2/CdF2 Quantum-Well Structures Grown on Metal (CoSi2) Layer

Science.gov (United States)

Denda, Junya; Uryu, Kazuya; Watanabe, Masahiro

2013-04-01

A novel scheme of resistance switching random access memory (ReRAM) devices fabricated using Si/CaF2/CdF2/CaF2/Si quantum-well structures grown on metal CoSi2 layer formed on a Si substrate has been proposed, and embryonic write/erase memory operation has been demonstrated at room temperature. It has been found that the oxide-mediated epitaxy (OME) technique for forming the CoSi2 layer on Si dramatically improves the stability and reproducibility of the current-voltage (I-V) curve. This technology involves 10-nm-thick Co layer deposition on a protective oxide prepared by boiling in a peroxide-based solution followed by annealing at 550 °C for 30 min for silicidation in ultrahigh vacuum. A switching voltage of lower than 1 V, a peak current density of 32 kA/cm2, and an ON/OFF ratio of 10 have been observed for the sample with the thickness sequence of 0.9/0.9/2.5/0.9/5.0 nm for the respective layers in the Si/CaF2/CdF2/CaF2/Si structure. Results of surface morphology analysis suggest that the grain size of crystal islands with flat surfaces strongly affects the quality of device characteristics.

Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments

International Nuclear Information System (INIS)

Buchegger, F.; Pfister, C.; Fournier, K.; Prevel, F.; Schreyer, M.; Carrel, S.; Mach, J.P.

1989-01-01

Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of 131 I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi 131 I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi 131 I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation

A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

Institute of Scientific and Technical Information of China (English)

Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

2011-01-01

AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

CA19-9: A promising tumor marker for pancreatic carcinoma

International Nuclear Information System (INIS)

Sakahara, H.; Endo, K.; Nakajima, K.; Hidaka, A.; Nakashima, T.; Ohta, H.; Torizuka, K.; Naito, A.; Suzuki, T.

1984-01-01

In order to evaluate CA19-9 as a tumor marker for pancreatic carcinoma (PC), serum levels of CA19-9 were compared with those of CEA and elastase-1 in 56 patients, consisted of 43 cases with histologically proven adenocarcinomas and 13 cases with chronic pancreatitis. Serum levels were determined by using RIA kit obtained from CIS, France (CA19-9 and CEA) and Abbot (elastase-1). CA19-9 gave the highest accuracy among tumor markers the authors have studied and serum levels were markedly elevated over 100U/ml in 30 (70%) cases with PC, whereas none in chronic pancreatitis. CA19-9 values were closely related to the tumor size and the presence or absence of metastsis on CT findings. Small tumors of less than 3cm in diameter, although the site of tumor was limited to the head of the pancreas, showed positive results in 2 out of 5 cases. Furthermore, CA19-9 was at a level of less than 22U/ml in 98 normal controls and was found to be elevated in only 4 (3%) out of 124 patients with benign diseases, including liver diseases, gastric ulcer, cholelithiasis, and so on. These results indicate that CA19-9 is much better in diagnosis and management of PC than is CEA

Carcinoma triquilemal: relato de caso Trichilemmal carcinoma: case report

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Miguel Roismann

2011-10-01

Full Text Available O carcinoma triquilemal é um tumor raro, que ocorre, geralmente, na pele exposta ao sol, principalmente face, couro cabeludo, pescoço e dorso das mãos, em indivíduos idosos, entre a 4ª e 9ª décadas de vida, sem predilação por sexo. O presente estudo mostra um caso de carcinoma triquilemal, recidivado, de difícil tratamento, em mesma topografia de um carcinoma basocelular tratado previamente com cirurgia e radioterapia.The trichilemmal carcinoma is a rare tumor that usually occurs on sun-exposed skin, especially on the face, scalp, neck and back of hands, mainly in elderly subjects but commonly between the 4th and 9th decades of life. It is not a gender-based illness. This study shows a difficult to treat case of recurrent trichilemmal carcinoma on the same location of a basal-cell carcinoma previously treated with surgery and radiotherapy.

Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression

Energy Technology Data Exchange (ETDEWEB)

Xiao, Can [Department of Occupational Medicine and Environmental Health, School of Public Health, Soochow University, Suzhou 215123 (China); Department of Stomatology, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Wang, Lili; Zhu, Lifang [Department of Stomatology, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Zhang, Chenping, E-mail: zhang_cping@163.com [Department of Head and Neck Tumors, Shanghai Ninth People’s Hospital Affiliated Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhou, Jianhua [Department of Occupational Medicine and Environmental Health, School of Public Health, Soochow University, Suzhou 215123 (China)

2014-11-28

Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCC inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.

Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression

International Nuclear Information System (INIS)

Xiao, Can; Wang, Lili; Zhu, Lifang; Zhang, Chenping; Zhou, Jianhua

2014-01-01

Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCC inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future

Generation of Two Noradrenergic-Specific Dopamine-Beta-Hydroxylase-FLPo Knock-In Mice Using CRISPR/Cas9-Mediated Targeting in Embryonic Stem Cells.

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Jenny J Sun

Full Text Available CRISPR/Cas9 mediated DNA double strand cutting is emerging as a powerful approach to increase rates of homologous recombination of large targeting vectors, but the optimization of parameters, equipment and expertise required remain barriers to successful mouse generation by single-step zygote injection. Here, we sought to apply CRISPR/Cas9 methods to traditional embryonic stem (ES cell targeting followed by blastocyst injection to overcome the common issues of difficult vector construction and low targeting efficiency. To facilitate the study of noradrenergic function, which is implicated in myriad behavioral and physiological processes, we generated two different mouse lines that express FLPo recombinase under control of the noradrenergic-specific Dopamine-Beta-Hydroxylase (DBH gene. We found that by co-electroporating a circular vector expressing Cas9 and a locus-specific sgRNA, we could target FLPo to the DBH locus in ES cells with shortened 1 kb homology arms. Two different sites in the DBH gene were targeted; the translational start codon with 6-8% targeting efficiency, and the translational stop codon with 75% targeting efficiency. Using this approach, we established two mouse lines with DBH-specific expression of FLPo in brainstem catecholaminergic populations that are publically available on MMRRC (MMRRC_041575-UCD and MMRRC_041577-UCD. Altogether, this study supports simplified, high-efficiency Cas9/CRISPR-mediated targeting in embryonic stem cells for production of knock-in mouse lines in a wider variety of contexts than zygote injection alone.

Complexes of γ-tubulin with nonreceptor protein tyrosine kinases Src and Fyn in differentiating P19 embryonal carcinoma cells

International Nuclear Information System (INIS)

Kukharskyy, Vitaliy; Sulimenko, Vadym; Macurek, Libor; Sulimenko, Tetyana; Draberova, Eduarda; Draber, Pavel

2004-01-01

Nonreceptor protein tyrosine kinases of the Src family have been shown to play an important role in signal transduction as well as in regulation of microtubule protein interactions. Here we show that γ-tubulin (γ-Tb) in P19 embryonal carcinoma cells undergoing neuronal differentiation is phosphorylated and forms complexes with protein tyrosine kinases of the Src family, Src and Fyn. Elevated expression of both kinases during differentiation corresponded with increased level of proteins phosphorylated on tyrosine. Immunoprecipitation experiments with antibodies against Src, Fyn, γ-tubulin, and with anti-phosphotyrosine antibody revealed that γ-tubulin appeared in complexes with these kinases. In vitro kinase assays showed tyrosine phosphorylation of proteins in γ-tubulin complexes isolated from differentiated cells. Pretreatment of cells with Src family selective tyrosine kinase inhibitor PP2 reduced the amount of phosphorylated γ-tubulin in the complexes. Binding experiments with recombinant SH2 and SH3 domains of Src and Fyn kinases revealed that protein complexes containing γ-tubulin bound to SH2 domains and that these interactions were of SH2-phosphotyrosine type. The combined data suggest that Src family kinases might have an important role in the regulation of γ-tubulin interaction with tubulin dimers or other proteins during neurogenesis

[Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

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Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

2016-12-01

Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

Carcinoma of the cervical stump: comparison of radiation therapy factors, survival and patterns of failure with carcinoma of the intact uterus

International Nuclear Information System (INIS)

Igboeli, P.; Kapp, D.S.; Lawrence, R.; Schwartz, P.E.

1983-01-01

Eighty-nine patients with previously untreated invasive carcinoma of the cervical stump were seen at Yale-New Haven Hospital from 1953 through 1977. This represented 9.4% of the carcinomas of the cervix seen during this time period. Eighty-five of the 89 patients (95.5%) had ''true'' cancers of the cervical stump diagnosed 2 years or more after subtotal hysterectomy, while 4 of the 89 patients (4.5%) had ''coincident'' cancers diagnosed within 2 years of the subtotal hysterectomy. All cervical cancers were staged by the F.I.G.O. classification. Patient characteristics, methods of management, failure sites and survival of patients with carcinoma of the cervical stump were compared to those patients with carcinoma in the intact uterus. Patients with cervical stump cancers were treated in a similar manner to those with carcinomas of the intact uterus, using a combination of external beam irradiation and intracavitary radium. The stump cancer patients had a similar stage distribution to the patients with cancers of the intact uterus but, on the average, they were older and received less irradiation. The patterns of failure were similar on a stage for stage basis, but the survival and disease-free survival for stump cancer patients were superior to those of the patients with carcinoma of the intact uterus

Exploring Alternative Radiolabeling Strategies for Sialic Acid-Binding Immunoglobulin-Like Lectin 9 Peptide: [68Ga]Ga- and [18F]AlF-NOTA-Siglec-9

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Olli Moisio

2018-01-01

Full Text Available Amino acid residues 283–297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9 form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1. VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates for visualizing inflammation non-invasively using positron emission tomography (PET. Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA-conjugated Siglec-9 has been evaluated extensively for this purpose. Here, we explored two alternative strategies for radiolabeling Siglec-9 peptide using a 1,4,7-triazacyclononane-triacetic acid (NOTA-chelator to bind [68Ga]Ga or [18F]AlF. The radioligands were evaluated by in vivo PET imaging and ex vivo γ-counting of turpentine-induced sterile skin/muscle inflammation in Sprague-Dawley rats. Both tracers showed clear accumulation in the inflamed tissues. The whole-body biodistribution patterns of the tracers were similar.

Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma

NARCIS (Netherlands)

Sier, C.F.M.; Kubben, F.J.G.M.; Ganesh, S.; Heerding, M.M.; Griffioen, G.; Hanemaaijer, R.; Krieken, J.H.J.M. van; Lamers, C.B.H.W.; Verspaget, H.W.

1996-01-01

Proteinases are involved in tumour invasion and metastasis. Several matrix metalloproteinases (MMPs) have been shown to be increased in various human carcinomas. We assessed the levels of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in 50 gastric carcinomas and corresponding mucosa using

From embryonic stem cells to testicular germ cell cancer-- should we be concerned?

DEFF Research Database (Denmark)

Almstrup, Kristian; Sonne, Si Brask; Hoei-Hansen, Christina E

2006-01-01

that initial hypothesis but also indicating that CIS cells have a striking phenotypic similarity to embryonic stem cells (ESC). Many cancers have been proposed to originate from tissue-specific stem cells [so-called 'cancer stem cells' (CSC)] and we argue that CIS may be a very good example of a CSC......, but with exceptional features due to the retention of embryonic pluripotency. In addition, considering the fact that pre-invasive CIS cells are transformed from early fetal cells, possibly due to environmentally induced alterations of the niche, we discuss potential risks linked to the uncontrolled therapeutic use......Since the discovery of testicular carcinoma in situ (CIS) -- the precursor cell for the vast majority of germ cell tumours -- it has been proposed that CIS cells could be derived from transformed primordial germ cells or gonocytes. Here, we review recent discoveries not only substantiating...

Pretreatment evaluation of carcinomas of the hypopharynx and larynx with 18F-fluorodeoxyglucose, 123I-α-methyl-L-tyrosine and 99mTc-hexakis-2-methoxyisobutylisonitrile

International Nuclear Information System (INIS)

Henze, Marcus; Eisenhut, Michael; Haberkorn, Uwe; Mohammed, Ashour; Mier, Walter; Rudat, Volker; Dietz, Andreas; Nollert, Joerg

2002-01-01

While fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is helpful in the pretherapeutic evaluation of head and neck cancer, it is only available in selected centres. Therefore, single-photon emission tomography (SPET) tracers would be desirable if they were to demonstrate tumour uptake reliably. This multitracer study was performed to evaluate the pretherapeutic uptake of the SPET tracers iodine-123 α-methyl-L-tyrosine (IMT) and technetium-99m hexakis-2-methoxyisobutylisonitrile ( 99m Tc-MIBI) in primary carcinomas of the hypopharynx and larynx and to compare the results with those of FDG PET. We examined 22 fasted patients (20 male, 2 female, mean age 60.5±10.2 years) with histologically confirmed carcinoma of the hypopharynx (n=9) or larynx (n=13), within 1 week before therapy. In 20 patients a cervical PET scan was acquired after intravenous injection of 232±43 MBq 18 F-FDG. Data analysis was semiquantitative, being based on standardised uptake values (SUVs) obtained at 60-90 min after injection. After injection of 570±44 MBq 99m Tc-MIBI, cervical SPET scans (high-resolution collimator, 64 x 64 matrix, 64 steps, 40 s each) were obtained in 19 patients, 15 and 60 min after tracer injection. Finally, 15 min after injection of 327±93 MBq 123 I-IMT (medium-energy collimator, 64 x 64 matrix, 64 steps, 40 s each) SPET scans were acquired in 15 patients. All images were analysed visually and by calculating the tumour to nuchal muscle ratio. Eighteen of 20 (90%) carcinomas showed an increased glucose metabolism, with a mean SUV of 8.7 and a mean carcinoma to muscle ratio of 7.3. The IMT uptake was increased in 13 of 15 (87%) patients, who had a mean carcinoma to muscle ratio of 2.9. Only 13 of 19 (68%) carcinomas revealed pathological MIBI uptake, with a mean tumour to muscle ratio of 2.2 and no significant difference between early and late MIBI SPET images (P=0.23). In conclusion, in the diagnosis of primary carcinomas of the

Pretreatment evaluation of carcinomas of the hypopharynx and larynx with 18F-fluorodeoxyglucose, 123I-alpha-methyl-L-tyrosine and 99mTc-hexakis-2-methoxyisobutylisonitrile.

Science.gov (United States)

Henze, Marcus; Mohammed, Ashour; Mier, Walter; Rudat, Volker; Dietz, Andreas; Nollert, Jörg; Eisenhut, Michael; Haberkorn, Uwe

2002-03-01

While fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is helpful in the pretherapeutic evaluation of head and neck cancer, it is only available in selected centres. Therefore, single-photon emission tomography (SPET) tracers would be desirable if they were to demonstrate tumour uptake reliably. This multitracer study was performed to evaluate the pretherapeutic uptake of the SPET tracers iodine-123 alpha-methyl-L-tyrosine (IMT) and technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) in primary carcinomas of the hypopharynx and larynx and to compare the results with those of FDG PET. We examined 22 fasted patients (20 male, 2 female, mean age 60.5+/-10.2 years) with histologically confirmed carcinoma of the hypopharynx (n=9) or larynx (n=13), within 1 week before therapy. In 20 patients a cervical PET scan was acquired after intravenous injection of 232+/-43 MBq 18F-FDG. Data analysis was semiquantitative, being based on standardised uptake values (SUVs) obtained at 60-90 min after injection. After injection of 570+/-44 MBq 99mTc-MIBI, cervical SPET scans (high-resolution collimator, 64x64 matrix, 64 steps, 40 s each) were obtained in 19 patients, 15 and 60 min after tracer injection. Finally, 15 min after injection of 327+/-93 MBq 123I-IMT (medium-energy collimator, 64x64 matrix, 64 steps, 40 s each) SPET scans were acquired in 15 patients. All images were analysed visually and by calculating the tumour to nuchal muscle ratio. Eighteen of 20 (90%) carcinomas showed an increased glucose metabolism, with a mean SUV of 8.7 and a mean carcinoma to muscle ratio of 7.3. The IMT uptake was increased in 13 of 15 (87%) patients, who had a mean carcinoma to muscle ratio of 2.9. Only 13 of 19 (68%) carcinomas revealed pathological MIBI uptake, with a mean tumour to muscle ratio of 2.2 and no significant difference between early and late MIBI SPET images (P=0.23). In conclusion, in the diagnosis of primary carcinomas of the

A simplified one-pot synthesis of 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy

International Nuclear Information System (INIS)

Shiue, Grace G.; Shiue, Chyng-Yann; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A.

2001-01-01

9-[(3-[ 18 F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG, 2) has been synthesized by nucleophilic substitution of N 2 -(p-anisyldiphenylmethyl)-9-{[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl}guanine (1) with potassium [ 18 F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine ([ 18 F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126±0.022, n=5 and 0.165±0.023, n=5, respectively). Although it contains non-radioactive ganciclovir (∼5-30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains ∼10-25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is

Impacts of CA9 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

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Shian-Shiang Wang

Full Text Available Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC and the clinicopathological status.A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05 than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638 had a 4.75-fold (95% CI = 1.204-18.746 increased risk of invasive cancer.The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.

Erythrocytosis caused by giant chromophobe renal cell carcinoma: a case report indicating a 9-year misdiagnosis of polycythemia vera.

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Guo, Renbo; Liang, Yiran; Yan, Lei; Xu, Zhonghua; Ren, Juchao

2017-09-06

Erythrocytosis, a rare paraneoplastic syndrome, generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma. We report a case of a young man suffering from a giant (22-cm) mass on his left kidney. Because of a history of polycythemia vera, the patient had been treated for the condition for 9 years. Radical nephrectomy was successfully performed, and the postoperative pathologic examination confirmed a diagnosis of chromophobe renal cell carcinoma. Unexpectedly, the symptom of erythrocytosis disappeared after the surgery. Further examination and analysis were performed, and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma. Chromophobe renal cell carcinoma could cause erythrocytosis, but the clear-cut mechanism needs further research. Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

Preserving and using germplasm and dissociated embryonic cells for conserving Caribbean and Pacific coral.

Science.gov (United States)

Hagedorn, Mary; Carter, Virginia; Martorana, Kelly; Paresa, Malia K; Acker, Jason; Baums, Iliana B; Borneman, Eric; Brittsan, Michael; Byers, Michael; Henley, Michael; Laterveer, Michael; Leong, Jo-Ann; McCarthy, Megan; Meyers, Stuart; Nelson, Brian D; Petersen, Dirk; Tiersch, Terrence; Uribe, Rafael Cuevas; Woods, Erik; Wildt, David

2012-01-01

Coral reefs are experiencing unprecedented degradation due to human activities, and protecting specific reef habitats may not stop this decline, because the most serious threats are global (i.e., climate change), not local. However, ex situ preservation practices can provide safeguards for coral reef conservation. Specifically, modern advances in cryobiology and genome banking could secure existing species and genetic diversity until genotypes can be introduced into rehabilitated habitats. We assessed the feasibility of recovering viable sperm and embryonic cells post-thaw from two coral species, Acropora palmata and Fungia scutaria that have diffferent evolutionary histories, ecological niches and reproductive strategies. In vitro fertilization (IVF) of conspecific eggs using fresh (control) spermatozoa revealed high levels of fertilization (>90% in A. palmata; >84% in F. scutaria; P>0.05) that were unaffected by tested sperm concentrations. A solution of 10% dimethyl sulfoxide (DMSO) at cooling rates of 20 to 30°C/min most successfully cryopreserved both A. palmata and F. scutaria spermatozoa and allowed producing developing larvae in vitro. IVF success under these conditions was 65% in A. palmata and 53% in F. scutaria on particular nights; however, on subsequent nights, the same process resulted in little or no IVF success. Thus, the window for optimal freezing of high quality spermatozoa was short (∼5 h for one night each spawning cycle). Additionally, cryopreserved F. scutaria embryonic cells had∼50% post-thaw viability as measured by intact membranes. Thus, despite some differences between species, coral spermatozoa and embryonic cells are viable after low temperature (-196°C) storage, preservation and thawing. Based on these results, we have begun systematically banking coral spermatozoa and embryonic cells on a large-scale as a support approach for preserving existing bio- and genetic diversity found in reef systems.

Preserving and using germplasm and dissociated embryonic cells for conserving Caribbean and Pacific coral.

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Mary Hagedorn

Full Text Available Coral reefs are experiencing unprecedented degradation due to human activities, and protecting specific reef habitats may not stop this decline, because the most serious threats are global (i.e., climate change, not local. However, ex situ preservation practices can provide safeguards for coral reef conservation. Specifically, modern advances in cryobiology and genome banking could secure existing species and genetic diversity until genotypes can be introduced into rehabilitated habitats. We assessed the feasibility of recovering viable sperm and embryonic cells post-thaw from two coral species, Acropora palmata and Fungia scutaria that have diffferent evolutionary histories, ecological niches and reproductive strategies. In vitro fertilization (IVF of conspecific eggs using fresh (control spermatozoa revealed high levels of fertilization (>90% in A. palmata; >84% in F. scutaria; P>0.05 that were unaffected by tested sperm concentrations. A solution of 10% dimethyl sulfoxide (DMSO at cooling rates of 20 to 30°C/min most successfully cryopreserved both A. palmata and F. scutaria spermatozoa and allowed producing developing larvae in vitro. IVF success under these conditions was 65% in A. palmata and 53% in F. scutaria on particular nights; however, on subsequent nights, the same process resulted in little or no IVF success. Thus, the window for optimal freezing of high quality spermatozoa was short (∼5 h for one night each spawning cycle. Additionally, cryopreserved F. scutaria embryonic cells had∼50% post-thaw viability as measured by intact membranes. Thus, despite some differences between species, coral spermatozoa and embryonic cells are viable after low temperature (-196°C storage, preservation and thawing. Based on these results, we have begun systematically banking coral spermatozoa and embryonic cells on a large-scale as a support approach for preserving existing bio- and genetic diversity found in reef systems.

Alterations in the developing testis transcriptome following embryonic vinclozolin exposure.

Science.gov (United States)

Clement, Tracy M; Savenkova, Marina I; Settles, Matthew; Anway, Matthew D; Skinner, Michael K

2010-11-01

The current study investigates the direct effects of in utero vinclozolin exposure on the developing F1 generation rat testis transcriptome. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic days 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Categorization by major known functions of altered genes was performed. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. Copyright © 2010 Elsevier Inc. All rights reserved.

Usefulness of F-18 FDG PET/CT in the Evaluation of Early Treatment Response After Inverventional Therapy for Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Kim Sung Hoon; Won Kyoung Sook; Choi Byung Wook; Jo Il; Zeon Seok Kil; Chung Woo Jin; Kwon Jung Hyeok

2012-01-01

This retrospective study investigated the usefulness of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) after inter-ventional therapy for hepatocellular carcinoma (HCC). Between March 2007 and November 2010, 31 Patients (24 men, 7 women; mean age, 61.8±11.0 -5-

Stepwise development of hematopoietic stem cells from embryonic stem cells.

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Kenji Matsumoto

Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

Clinical value of 18F-FDG PET/CT in detecting viable tumor, recurrence and metastases of hepato-cellular carcinoma after transcatheter arterial chemoembolization

International Nuclear Information System (INIS)

Hu Silong; Zhang Yingjian; Zhu Beiling; Shi Wei; Men Zhiqiang; Li Peilen; Jiang Guoliang

2009-01-01

Objective: Accurate evaluation of treatment result of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) by conventional imaging is difficult. The objective of this study was to investigate the clinical value of 18 F-fluorodeoxyglucose (FDG) PET/CT for detecting residual viable tumor, recurrence and metastases in patients with HCC after TACE. Methods: Twenty-two patients with HCC after TACE were investigated with 18 F-FDG PET/CT. The accuracy of FDG PET/CT was determined by the histopathological results or evidences of clinical follow-up. Results: Of all 22 HCC patients after TACE, 18 had intra- and (or) extrahepatic lesions, detected by FDG PET/CT. Six-teen patients had intrahepatic FDG-avid lesion(s). Of the 16 patients, five had intrahepatic FDG-avid lesions located at both lipiodol-rich and -deprive regions, 13 had associated extrahepatic metastases. Of the two HCC patients who had no intrahepatic FDG-avid lesion, there were extrahepatic FDG-avid lesions at the retroperitoneal lymph nodes. In all, 15 HCC had extrahepatic lesions identified by FDG PET/CT. There were lung and lymph nodes (n = 9), bone (n = 2), tumor thrombus at portal vein (n - 1) and diaphragm crus (n = 1). Two patients were false negative. The sensitivity, specificity, accuracy of FDG PET/CT in detecting intra- and (or) extrahepatic lesions after TACE were 88.9% (16/18) vs 94.7 % (18/19), 4/4 vs 3/3, and 90.9% (20/22) vs 95.5% (21/22), respectively. Conclusion: 18 F-FDG PET/CT is potential useful for detection both intra- and (or) extrahepatic lesions in HCC patients after TACE. (authors)

Metachronous presentation of small-cell rectal carcinoma on an 18F-FDG PET/CT follow-up for follicular lymphoma.

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Qaseem, Yousuf; Fair, Joanna; Behnia, Sanaz; Elojeimy, Saeed

2017-09-01

We present a case of a 60-year-old woman with history of follicular lymphoma in remission presenting for an 18F-fluorodeoxyglucose positron emission tomography/computed tomography for suspected recurrence. Imaging showed widespread hypermetabolic lymphadenopathy consistent with lymphoma recurrence. A 3-month 18F-fluorodeoxyglucose positron emission tomography/computed tomography follow-up after chemotherapy showed resolution of hypermetabolic lymphadenopathy but multiple new hepatic lesions and a new subtle rectal lesion. Biopsies of both hepatic and rectal lesions revealed new diagnosis of metachronous high-grade small-cell carcinoma.

Metachronous presentation of small-cell rectal carcinoma on an 18F-FDG PET/CT follow-up for follicular lymphoma

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Yousuf Qaseem, BS

2017-09-01

Full Text Available We present a case of a 60-year-old woman with history of follicular lymphoma in remission presenting for an 18F-fluorodeoxyglucose positron emission tomography/computed tomography for suspected recurrence. Imaging showed widespread hypermetabolic lymphadenopathy consistent with lymphoma recurrence. A 3-month 18F-fluorodeoxyglucose positron emission tomography/computed tomography follow-up after chemotherapy showed resolution of hypermetabolic lymphadenopathy but multiple new hepatic lesions and a new subtle rectal lesion. Biopsies of both hepatic and rectal lesions revealed new diagnosis of metachronous high-grade small-cell carcinoma.

Non-Serotonergic Neurotoxicity by MDMA (Ecstasy in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells.

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Dina Popova

Full Text Available 3,4-methylenedioxymethamphetamine (MDMA; ecstasy is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays. The P19-derived neurons express both the serotonin reuptake transporter (SERT, that is functionally active, and the serotonin metabolizing enzyme monoamine oxidase A (MAO-A. The involvement of these proteins in the MDMA-induced toxicity was investigated by a pharmacological approach. The MAO inhibitors clorgyline and deprenyl, and the SERT inhibitor fluoxetine, per se or in combination, were not able to mimic the toxic effects of MDMA in the P19-derived neurons or block the MDMA-induced cell toxicity. Oxidative stress has been implicated in MDMA-induced neurotoxicity, but pre-treatment with the antioxidants α-tocopherol or N-acetylcysteine did not reveal any protective effects in the P19 neurons. Involvement of mitochondria in the MDMA-induced cytotoxicity was also examined, but MDMA did not alter the mitochondrial membrane potential (ΔΨm in the P19 neurons. We conclude that MDMA produce a concentration-, time- and temperature-dependent neurotoxicity and our results suggest that the mechanism behind MDMA-induced toxicity in mouse-derived neurons do not involve the serotonergic system, oxidative stress or mitochondrial dysfunction.

Non-Serotonergic Neurotoxicity by MDMA (Ecstasy) in Neurons Derived from Mouse P19 Embryonal Carcinoma Cells.

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Popova, Dina; Forsblad, Andréas; Hashemian, Sanaz; Jacobsson, Stig O P

2016-01-01

3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays. The P19-derived neurons express both the serotonin reuptake transporter (SERT), that is functionally active, and the serotonin metabolizing enzyme monoamine oxidase A (MAO-A). The involvement of these proteins in the MDMA-induced toxicity was investigated by a pharmacological approach. The MAO inhibitors clorgyline and deprenyl, and the SERT inhibitor fluoxetine, per se or in combination, were not able to mimic the toxic effects of MDMA in the P19-derived neurons or block the MDMA-induced cell toxicity. Oxidative stress has been implicated in MDMA-induced neurotoxicity, but pre-treatment with the antioxidants α-tocopherol or N-acetylcysteine did not reveal any protective effects in the P19 neurons. Involvement of mitochondria in the MDMA-induced cytotoxicity was also examined, but MDMA did not alter the mitochondrial membrane potential (ΔΨm) in the P19 neurons. We conclude that MDMA produce a concentration-, time- and temperature-dependent neurotoxicity and our results suggest that the mechanism behind MDMA-induced toxicity in mouse-derived neurons do not involve the serotonergic system, oxidative stress or mitochondrial dysfunction.

Expressão imuno-histoquímica das metaloproteinases 2 e 9 não está associada à progressão do carcinoma de células escamosas de esôfago Metalloproteinases 2 and 9 immunohistochemistry expression is not associated to esophageal squamous cell carcinoma progression

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Izabella Paz Danezi Felin

2009-08-01

Full Text Available INTRODUÇÃO: O carcinoma de células escamosas do esôfago está entre os tipos mais agressivos de câncer e de pior prognóstico. As metaloproteinases de matriz (MMPs, especialmente as MMP-2 e MMP-9, vêm sendo utilizadas para avaliação prognóstica do câncer, associadas a invasão, tamanho e crescimento tumoral. OBJETIVO: O presente estudo visa investigar as expressões imuno-histoquímicas de MMP-2 e MMP-9, avaliando se existe correlação entre sua expressão e o estadiamento tumoral, invasão vascular, invasão local (pT e diferenciação tumoral no carcinoma de células escamosas de esôfago. MATERIAL E MÉTODO: Foi realizado um estudo retrospectivo utilizando 31 blocos de parafina contendo tumores de carcinoma escamoso esofágico, obtidas por esofagectomias realizadas entre 1998 e 2003, no Hospital Universitário de Santa Maria (HUSM. Os cortes histológicos foram submetidos à reação imuno-histoquímica, com sistema de amplificação por polímero não-biotinilado Novolink para detecção de MMP-2 e MMP-9. RESULTADOS: A avaliação da MMP-2 apresentou positividade fraca em apenas cinco casos, não demonstrando correlação com as variáveis estudadas. Também não foram observadas associações significativas entre as variáveis do estudo e o grau de expressão imuno-histoquímica da MMP-9. CONCLUSÃO: A expressão imuno-histoquímica das MMP-2 e MMP-9 não parece ser influenciada pelos parâmetros investigados. Nesse sentido, estudos adicionais são necessários para melhor compreensão de sua associação aos fatores prognósticos do carcinoma de células escamosas de esôfago.INTRODUCTION: Esophageal squamous cell carcinoma is an aggressive malignant neoplasia with poor prognosis. The expression of matrix metalloproteinases (MMPs, mainly 2 and 9, has been used for the prognostic evaluation of cancer in association with tumor invasion, size and tumoral growth analysis. OBJECTIVE: The aim of the present study was to investigate

The zinc-finger transcription factor SALL4 is frequently expressed in human cancers: association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus.

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Kilic, Ergin; Tennstedt, Pierre; Högner, Anica; Lebok, Patrick; Sauter, Guido; Bokemeyer, Carsten; Izbicki, Jakob R; Wilczak, Waldemar

2016-04-01

SALL4 is a transcription factor originally identified as a homeotic gene essential for organ development. Early studies suggested that SALL4 is a useful marker to identify testicular and ovarian germ cell tumors. The aim of the study was to evaluate the diagnostic potential of SALL4 immunohistochemistry. Immunohistochemical staining was performed on a tissue microarray (TMA) with 3966 samples from 94 different tumor types and on a further TMA with 492 esophagus carcinomas. SALL4 immunostaining was by far most prevalent and most intensive in testicular tumors with a positivity rate of 93.1% in seminomas, 80% in mixed germ cell tumors (embryonic carcinomas/yolk sac tumors), and 18.5% in teratomas, respectively. However, SALL4 expression is not specific to germ cell tumors. We observed SALL4 positivity in non-germ cell tumors as carcinomas of the kidney (28.9% of chromophobe, 34.4% of clear cell carcinoma), in intestinal type adenocarcinoma of the stomach (10.9%), in adenocarcinoma (10.5%) and squamous cell carcinoma (7.2%) of the esophagus, and in malignant melanoma (8.1%) and invasive urothelial bladder carcinoma (20%). SALL4 expression was not found in lymphomas, in soft tissue tumors or breast tumors. At analysis of esophagus carcinoma TMA, no significant association was seen between SALL4 expression and overall survival in adenocarcinoma. However, SALL4 expression was strongly associated with worse overall survival in squamous cell carcinoma. SALL4 expression can be found at relevant frequencies in various tumors of different primary sites. SALL4 expression in squamous cell carcinoma of the esophagus may constitute a sign of dedifferentiation leading to poor patient prognosis.

Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

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Teik Hin Tan

2016-07-01

Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

The Usefulness of 18F-FDG PET as a Cancer Screening Test

International Nuclear Information System (INIS)

Ko, Doo Heun; Choi, Joon Young; Song, Yun Mi; Lee, Su Jin; Kim, Young Hwan; Lee, Kyung Han; Kim, Byung Tae; Lee, Moon Kyu

2008-01-01

The aim of this study was to evaluate the usefulness of whole body positron emission tomography (PET) using 18 F-fluorodeoxyglucose ( 18 F-FDG) for cancer screening in asymptomatic subjects. The subjects were 1,762 men and 259 women who voluntarily underwent 18 F-FDG PET for cancer screening as a part of a routine health examination. Final diagnosis was decided by other diagnostic studies, pathological results or clinical follow-up for 1 year. Of 2,021 subjects, 40 (2.0%) were finally proved to have cancer. Abnormal focal 18 F-FDG uptake suggesting malignancy was found in 102 subjects (5.0%). Among them, 21 subjects (1.0%) were proved to have cancer. Other tests in the routine health examination could not find 9 of 21 cancers (42.9%) detected by PET. The sensitivity, specificity, positive predictive value, and negative predictive value of PET for cancer screening were 52.5%, 95.9%, 20.6%, and 99.0%, respectively. Pathologies of cancers missed on PET were adenocarcinoma (n=9; 3 colon cancers, 3 prostate cancers, 2 stomach cancers, and 1 rectal cancer), differentiated thyroid carcinoma (n=6), bronchioalveolar cell carcinoma (n=2), urinary bladder cancer (n=1), and melanoma (n=1). More than half of cancers which were not detected by PET were smaller than 1 cm in diameter. 18 F-FDG PET might be useful for cancer screening in asymptomatic subjects due to its high specificity and negative predictive value and play a supplementary role to the conventional health check-up, but it could not replace due to limited sensitivity for urological cancers, small-sized tumors and some hypometaboic cancers

Generation of an ASS1 heterozygous knockout human embryonic stem cell line, WAe001-A-13, using CRISPR/Cas9

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Fang Yuan

2018-01-01

Full Text Available The ASS1 gene encodes argininosuccinate synthetase-1, a cytosolic enzyme with a critical role in the urea cycle. Mutations are found in all ASS1 exons and cause the autosomal recessive disorder citrullinemia. Using CRISPR/Cas9-editing, we established the WAe001-A-13 cell line, which was heterozygous for an ASS1 mutation, from the human embryonic stem cell line H1. The WAe001-A-13 cell line maintained the pluripotent phenotype, the ability to differentiate into all three germ layers and a normal karyotype.

Assessment of a serum tumour marker for carcinoma of the pancreas: the carbohydrate antigen C.A. 19-9

International Nuclear Information System (INIS)

Vincent, D.; Venot, J.; Catanzano, G.; Clement, M.N.; Piquet, M.F.; Veyriras, E.; Beck, C.

1985-01-01

A radio-immunological assay with monoclonal antibodies was used to measure the C 19-9 antigen in 51 patients to determine its diagnostic value in cancer of the pancreas. The results show that the C 19-9 antigen is a good marker for carcinoma of the pancreas and that it can be commonly used [fr

Pre-radiotherapy and post-radiotherapy serial serum Squamous Cell Carcinoma antigen (SCC) and CarcinoEmbryonic Antigen (CEA) in the monitoring of squamous cell carcinoma of uterine cervix

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Yun, Hyong Geun; Park, Choong Hak [College of Medicine, Dankook Univ., Chunan (Korea, Republic of)

1999-03-01

To evaluate the significance of squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) as tumor markers in uterine cervix carcinoma. In 22 patients with histologically proven primary squamous cell carcinoma of uterine cervix, tumor volume was checked either by using MRI (in 20 patients) or ultrasound (in 2 patients). Pre-treatment serum SCC levels were checked in 22 patients and CEA levels in 21 patients. After curative radiotherapy, post-treatment SCC and CEA were checked regularly. SCC was raised in 68.2% and CEA was raised in 19.0% before treatment. The coefficient of correlation between tumor volume and pre-reatment SCC was 0.59382 when one extremely deviated case was excluded. And there was no correlation between tumor volume and CEA. After the treatment, SCC was raised in 9.1% and CEA was raised in 4.8%. In further follow up measurement, raise of SCC was associated with clinical relapse or persistence of disease. The specificity of raised SCC level in association with recurrent or persistent disease was 93.8%. The sensitivity in association with recurrent or persistent disease was 100%. The positive predictive values was 85.7%. The median lead time for recurrence was 1.2 months. Both SCC and CEA were good tumor markers for monitoring treatment effect in patients with raised pre-treatment levels. But the sensitivity of pretreatment CEA was low, while that of pretreatment SCC was high. And there was no additional gain by adding CEA measurements to SCC measurements.

Pre-radiotherapy and post-radiotherapy serial serum Squamous Cell Carcinoma antigen (SCC) and CarcinoEmbryonic Antigen (CEA) in the monitoring of squamous cell carcinoma of uterine cervix

International Nuclear Information System (INIS)

Yun, Hyong Geun; Park, Choong Hak

1999-01-01

To evaluate the significance of squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) as tumor markers in uterine cervix carcinoma. In 22 patients with histologically proven primary squamous cell carcinoma of uterine cervix, tumor volume was checked either by using MRI (in 20 patients) or ultrasound (in 2 patients). Pre-treatment serum SCC levels were checked in 22 patients and CEA levels in 21 patients. After curative radiotherapy, post-treatment SCC and CEA were checked regularly. SCC was raised in 68.2% and CEA was raised in 19.0% before treatment. The coefficient of correlation between tumor volume and pre-reatment SCC was 0.59382 when one extremely deviated case was excluded. And there was no correlation between tumor volume and CEA. After the treatment, SCC was raised in 9.1% and CEA was raised in 4.8%. In further follow up measurement, raise of SCC was associated with clinical relapse or persistence of disease. The specificity of raised SCC level in association with recurrent or persistent disease was 93.8%. The sensitivity in association with recurrent or persistent disease was 100%. The positive predictive values was 85.7%. The median lead time for recurrence was 1.2 months. Both SCC and CEA were good tumor markers for monitoring treatment effect in patients with raised pre-treatment levels. But the sensitivity of pretreatment CEA was low, while that of pretreatment SCC was high. And there was no additional gain by adding CEA measurements to SCC measurements

IgG4-Related Disease Simulating Carcinoma Colon With Diffuse Peritoneal Carcinomatosis on 18F-FDG PET/CT.

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Vadi, Shelvin Kumar; Parihar, Ashwin Singh; Kumar, Rajender; Singh, Harmandeep; Mittal, Bhagwant Rai; Bal, Amanjit; Sinha, Saroj Kumar

2018-05-14

IgG4-related disease (IgG4-RD) continues to be a diagnostic challenge and a great mimicker of malignancies. We report here a case of young man who presented with subacute intestinal obstruction with initial imaging and clinical features suggestive of carcinoma colon. 18F-FDG PET/CT showed diffuse peritoneal carcinomatosis pattern typically seen with abdominal malignancies. However, the histopathology and the raised IgG4 levels diagnosed it to be IgG4-RD. Although 18F-FDG PET/CT has typical patterns corresponding to the multisystemic involvement of IgG4-RD, the index case did not show any such findings.

Functional image-guided stereotactic body radiation therapy planning for patients with hepatocellular carcinoma

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Tsegmed, Uranchimeg [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nakashima, Takeo [Division of Radiation Therapy, Hiroshima University Hospital, Hiroshima (Japan); Nakamura, Yuko; Higaki, Toru [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Imano, Nobuki; Doi, Yoshiko; Kenjo, Masahiro; Ozawa, Shuichi; Murakami, Yuji [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Awai, Kazuo [Department of Diagnostic Radiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan); Nagata, Yasushi [Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima (Japan)

2017-07-01

The aim of the current planning study is to evaluate the ability of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI)–guided stereotactic body radiation therapy (SBRT) planning by using intensity-modulated radiation therapy (IMRT) techniques in sparing the functional liver tissues during SBRT for hepatocellular carcinoma. In this study, 20 patients with hepatocellular carcinoma were enrolled. Functional liver tissues were defined according to quantitative liver-spleen contrast ratios ≥ 1.5 on a hepatobiliary phase scan. Functional images were fused with the planning computed tomography (CT) images; the following 2 SBRT plans were designed using a “step-and-shoot” static IMRT technique for each patient: (1) an anatomical SBRT plan optimization based on the total liver; and (2) a functional SBRT plan based on the functional liver. The total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters, including dose to 95% of the planning target volume (PTV D{sub 95%}), percentages of total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD, respectively) of the 2 plans were compared. Compared with anatomical plans, functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F, 5.1 Gy; p < 0.0001) and fMLD (mean: plan A, 5.4 Gy; and plan F, 4.9 Gy; p < 0.0001), as well as V5 to V30 and fV5 to fV30. No differences were noted in PTV coverage and nonhepatic organs at risk (OARs) doses. In conclusion, EOB-MRI–guided SBRT planning using the IMRT technique may preserve functional liver tissues in patients with hepatocellular carcinoma (HCC).

Three-dimensional positron emission tomography image texture analysis of esophageal squamous cell carcinoma: relationship between tumor 18F-fluorodeoxyglucose uptake heterogeneity, maximum standardized uptake value, and tumor stage.

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Dong, Xinzhe; Xing, Ligang; Wu, Peipei; Fu, Zheng; Wan, Honglin; Li, Dengwang; Yin, Yong; Sun, Xiaorong; Yu, Jinming

2013-01-01

To explore the relationship of a new PET image parameter, (18)F-fluorodeoxyglucose ((18)F-FDG) uptake heterogeneity assessed by texture analysis, with maximum standardized uptake value (SUV(max)) and tumor TNM staging. Forty consecutive patients with esophageal squamous cell carcinoma were enrolled. All patients underwent whole-body preoperative (18)F-FDG PET/CT. Heterogeneity of intratumoral (18)F-FDG uptake was assessed on the basis of the textural features (entropy and energy) of the three-dimensional images using MATLAB software. The correlations between the textural parameters and SUV(max), histological grade, tumor location, and TNM stage were analyzed. Tumors with higher SUV(max) were seen to be more heterogenous on (18)F-FDG uptake. Significant correlations were observed between T stage and SUV(max) (r(s)=0.390, P=0.013), entropy (rs=0.693, Pheterogeneity and the commonly used simplistic parameter of SUV and tumor stage. Our findings suggest a complementary role of these parameters in the staging and prognosis of esophageal squamous cell carcinoma.

Radioimmunoimaging of human colon carcinoma grafted into nudemice using 131I-labeled monoclonal anticea antibody and its F(ab')2 fragments

International Nuclear Information System (INIS)

Liu Guangda

1988-01-01

131 I-labeled monoclonal anti-CEA antibody and its F(ab') 2 fragments were injected into nude mice bearing human colon carcinoma xenografts for tumor localization and radioimmunoimaging studies. Transplanted tumors were visualized in 12 hours after injection of the labeled anti-CEA or its F(ab') 2 by gamma camera. Biodistribution data indicated that F(ab') 2 fragments were cleared more rapidly from blood (T 1/2 = 13.3 h for F(ab') 2 , T 1/2 = 21.1 h for intact antibody) over 6-24 h and had higher tumor blood ratios. The intact antibody was concentrated in the tumor better than F(ab') 2 . In double-label experiments, a nonspecific localization of the control ( 125 I-labeled anti-HCG) in the tumor was also observed

The Usefulness of {sup 18}F-FDG PET as a Cancer Screening Test

Energy Technology Data Exchange (ETDEWEB)

Ko, Doo Heun; Choi, Joon Young; Song, Yun Mi; Lee, Su Jin; Kim, Young Hwan; Lee, Kyung Han; Kim, Byung Tae; Lee, Moon Kyu [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2008-12-15

The aim of this study was to evaluate the usefulness of whole body positron emission tomography (PET) using {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) for cancer screening in asymptomatic subjects. The subjects were 1,762 men and 259 women who voluntarily underwent {sup 18}F-FDG PET for cancer screening as a part of a routine health examination. Final diagnosis was decided by other diagnostic studies, pathological results or clinical follow-up for 1 year. Of 2,021 subjects, 40 (2.0%) were finally proved to have cancer. Abnormal focal {sup 18}F-FDG uptake suggesting malignancy was found in 102 subjects (5.0%). Among them, 21 subjects (1.0%) were proved to have cancer. Other tests in the routine health examination could not find 9 of 21 cancers (42.9%) detected by PET. The sensitivity, specificity, positive predictive value, and negative predictive value of PET for cancer screening were 52.5%, 95.9%, 20.6%, and 99.0%, respectively. Pathologies of cancers missed on PET were adenocarcinoma (n=9; 3 colon cancers, 3 prostate cancers, 2 stomach cancers, and 1 rectal cancer), differentiated thyroid carcinoma (n=6), bronchioalveolar cell carcinoma (n=2), urinary bladder cancer (n=1), and melanoma (n=1). More than half of cancers which were not detected by PET were smaller than 1 cm in diameter. {sup 18}F-FDG PET might be useful for cancer screening in asymptomatic subjects due to its high specificity and negative predictive value and play a supplementary role to the conventional health check-up, but it could not replace due to limited sensitivity for urological cancers, small-sized tumors and some hypometaboic cancers.

Novel functions for atypical E2Fs, E2F7 and E2F8, in polyploidization and liver cancer

NARCIS (Netherlands)

Pandit, Shusil Kumar

2014-01-01

Atypical E2F transcription factors, E2F7 and E2F8, function as transcriptional repressors of E2F target genes and are crucial for controlling the cell proliferation. In this thesis, we reveal that these two factors are crucial for liver cell polyploidization, embryonic development and prevention of

Endolymphatic potassium of the chicken vestibule during embryonic development.

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Masetto, Sergio; Zucca, Giampiero; Bottà, Luisa; Valli, Paolo

2005-08-01

The endolymph fills the lumen of the inner ear membranous labyrinth. Its ionic composition is unique in vertebrates as an extracellular fluid for its high-K(+)/low-Na(+) concentration. The endolymph is actively secreted by specialized cells located in the vestibular and cochlear epithelia. We have investigated the early phases of endolymph secretion by measuring the endolymphatic K(+) concentration in the chicken vestibular system during pre-hatching development. Measurements were done by inserting K(+)-selective microelectrodes in chicken embryo ampullae dissected at different developmental stages from embryonic day 9 up to embryonic day 21 (day of hatching). We found that the K(+) concentration is low (<10mM/L) up to embryonic day 11, afterward it increases steeply to reach a plateau level of about 140 mM/L at embryonic day 19--21. We have developed a short-term in vitro model of endolymph secretion by culturing vestibular ampullae dissected from embryonic day 11 chicken embryos for a few days. The preparation reproduced a double compartment system where the luminal K(+) concentration increased along with the days of culturing. This model could be important for (1) investigating the development of cellular mechanisms contributing to endolymph homeostasis and (2) testing compounds that influence those mechanisms.

Linking incomplete reprogramming to the improved pluripotency of murine embryonal carcinoma cell-derived pluripotent stem cells.

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Gang Chang

Full Text Available Somatic cell nuclear transfer (SCNT has been proved capable of reprogramming various differentiated somatic cells into pluripotent stem cells. Recently, induced pluripotent stem cells (iPS have been successfully derived from mouse and human somatic cells by the over-expression of a combination of transcription factors. However, the molecular mechanisms underlying the reprogramming mediated by either the SCNT or iPS approach are poorly understood. Increasing evidence indicates that many tumor pathways play roles in the derivation of iPS cells. Embryonal carcinoma (EC cells have the characteristics of both stem cells and cancer cells and thus they might be the better candidates for elucidating the details of the reprogramming process. Although previous studies indicate that EC cells cannot be reprogrammed into real pluripotent stem cells, the reasons for this remain unclear. Here, nuclei from mouse EC cells (P19 were transplanted into enucleated oocytes and pluripotent stem cells (P19 NTES cells were subsequently established. Interestingly, P19 NTES cells prolonged the development of tetraploid aggregated embryos compared to EC cells alone. More importantly, we found that the expression recovery of the imprinted H19 gene was dependent on the methylation state in the differential methylation region (DMR. The induction of Nanog expression, however, was independent of the promoter region DNA methylation state in P19 NTES cells. A whole-genome transcriptome analysis further demonstrated that P19 NTES cells were indeed the intermediates between P19 cells and ES cells and many interesting genes were uncovered that may be responsible for the failed reprogramming of P19 cells. To our knowledge, for the first time, we linked incomplete reprogramming to the improved pluripotency of EC cell-derived pluripotent stem cells. The candidate genes we discovered may be useful not only for understanding the mechanisms of reprogramming, but also for deciphering the

An Efficient Method for Generation of Knockout Human Embryonic Stem Cells Using CRISPR/Cas9 System.

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Bohaciakova, Dasa; Renzova, Tereza; Fedorova, Veronika; Barak, Martin; Kunova Bosakova, Michaela; Hampl, Ales; Cajanek, Lukas

2017-11-01

Human embryonic stem cells (hESCs) represent a promising tool to study functions of genes during development, to model diseases, and to even develop therapies when combined with gene editing techniques such as CRISPR/CRISPR-associated protein-9 nuclease (Cas9) system. However, the process of disruption of gene expression by generation of null alleles is often inefficient and tedious. To circumvent these limitations, we developed a simple and efficient protocol to permanently downregulate expression of a gene of interest in hESCs using CRISPR/Cas9. We selected p53 for our proof of concept experiments. The methodology is based on series of hESC transfection, which leads to efficient downregulation of p53 expression even in polyclonal population (p53 Low cells), here proven by a loss of regulation of the expression of p53 target gene, microRNA miR-34a. We demonstrate that our approach achieves over 80% efficiency in generating hESC clonal sublines that do not express p53 protein. Importantly, we document by a set of functional experiments that such genetically modified hESCs do retain typical stem cells characteristics. In summary, we provide a simple and robust protocol to efficiently target expression of gene of interest in hESCs that can be useful for laboratories aiming to employ gene editing in their hESC applications/protocols.

Pretreatment evaluation of carcinomas of the hypopharynx and larynx with {sup 18}F-fluorodeoxyglucose, {sup 123}I-{alpha}-methyl-L-tyrosine and {sup 99m}Tc-hexakis-2-methoxyisobutylisonitrile

Energy Technology Data Exchange (ETDEWEB)

Henze, Marcus; Eisenhut, Michael; Haberkorn, Uwe [Department of Nuclear Medicine, University of Heidelberg (Germany); German Cancer Research Center, Heidelberg (Germany); Mohammed, Ashour; Mier, Walter [Department of Nuclear Medicine, University of Heidelberg (Germany); Rudat, Volker [Department of Radiotherapy, University of Heidelberg (Germany); Dietz, Andreas; Nollert, Joerg [Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg (Germany)

2002-03-01

While fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is helpful in the pretherapeutic evaluation of head and neck cancer, it is only available in selected centres. Therefore, single-photon emission tomography (SPET) tracers would be desirable if they were to demonstrate tumour uptake reliably. This multitracer study was performed to evaluate the pretherapeutic uptake of the SPET tracers iodine-123 {alpha}-methyl-L-tyrosine (IMT) and technetium-99m hexakis-2-methoxyisobutylisonitrile ({sup 99m}Tc-MIBI) in primary carcinomas of the hypopharynx and larynx and to compare the results with those of FDG PET. We examined 22 fasted patients (20 male, 2 female, mean age 60.5{+-}10.2 years) with histologically confirmed carcinoma of the hypopharynx (n=9) or larynx (n=13), within 1 week before therapy. In 20 patients a cervical PET scan was acquired after intravenous injection of 232{+-}43 MBq {sup 18}F-FDG. Data analysis was semiquantitative, being based on standardised uptake values (SUVs) obtained at 60-90 min after injection. After injection of 570{+-}44 MBq {sup 99m}Tc-MIBI, cervical SPET scans (high-resolution collimator, 64 x 64 matrix, 64 steps, 40 s each) were obtained in 19 patients, 15 and 60 min after tracer injection. Finally, 15 min after injection of 327{+-}93 MBq {sup 123}I-IMT (medium-energy collimator, 64 x 64 matrix, 64 steps, 40 s each) SPET scans were acquired in 15 patients. All images were analysed visually and by calculating the tumour to nuchal muscle ratio. Eighteen of 20 (90%) carcinomas showed an increased glucose metabolism, with a mean SUV of 8.7 and a mean carcinoma to muscle ratio of 7.3. The IMT uptake was increased in 13 of 15 (87%) patients, who had a mean carcinoma to muscle ratio of 2.9. Only 13 of 19 (68%) carcinomas revealed pathological MIBI uptake, with a mean tumour to muscle ratio of 2.2 and no significant difference between early and late MIBI SPET images (P=0.23). In conclusion, in the diagnosis of

Brown Tumors Due to Primary Hyperparathyroidism in a Patient with Parathyroid Carcinoma Mimicking Skeletal Metastases on (18)F-FDG PET/CT

DEFF Research Database (Denmark)

Andersen, Kim Francis; Albrecht-Beste, Elisabeth

2015-01-01

-so-called brown tumors. These benign, osteolytic lesions may demonstrate FDG-avidity on (18)F-FDG PET/CT, and as such are misinterpreted as skeletal metastases. Regression of the lesions may occur following successful treatment. We present a case demonstrating the diagnostic work-up and follow-up of a patient...... with PHPT due to parathyroid carcinoma and with presence of brown tumors on (18)F-FDG PET/CT, visualizing the possible role of this imaging modality in the evaluation of treatment response in these patients....

Oncological applications of 18F-FDG PET imaging

International Nuclear Information System (INIS)

Li Lin

2000-01-01

Considering normal distribution of 18 F-FDG in human body, 18 F-FDG imaging using PET can be applied to brain tumors, colorectal cancer, lymphoma, melanoma, lung cancer and head and neck cancer. The author briefly focuses on application of 18 F-FDG PET imaging to breast cancer, pancreatic cancer, hepatocellular carcinoma, musculoskeletal neoplasms, endocrine neoplasms, genitourinary neoplasms, esophageal and gastric carcinomas

Inhibition of proliferation and differentiation and promotion of apoptosis by cyclin L2 in mouse embryonic carcinoma P19 cells

International Nuclear Information System (INIS)

Zhuo, Lili; Gong, Jie; Yang, Rong; Sheng, Yanhui; Zhou, Lei; Kong, Xiangqing; Cao, Kejiang

2009-01-01

Cyclin L2 (CCNL2) is a novel member of the cyclin gene family. In a previous study, we demonstrated that CCNL2 expression was upregulated in ventricular septum tissues from patients with ventricular septal defect compared to healthy controls. In the present study, we established a stable CCNL2-overexpressing P19 cell line that can differentiate to myocardial cells when treated with 1% dimethyl sulfoxide (DMSO). Our data showed that stable CCNL2-overexpressing P19 cells were less differentiated after treatment with 1% DMSO and that expression of myocardial cell differentiation-related genes (such as cardiac actin, GATA4, Mef2C, Nkx2.5, and BNP) were reduced compared to vector-only transfected P19. Moreover, P19 cells overexpressing the CCNL2 gene had a reduced growth rate and a remarkably decreased S phase. We also found that these cells underwent apoptosis, as detected by two different apoptosis assays. The anti-apoptotic Bcl-2 protein was also downregulated in these cells. In addition, real-time PCR analysis revealed that expression of Wnt and β-catenin was suppressed and GSK3β was induced in the CCNL2-overexpressing P19 cells. These data suggest that overexpression of CCNL2 inhibited proliferation and differentiation of mouse embryonic carcinoma P19 cells and induced them to undergo apoptosis, possibly through the Wnt signal transduction pathway.

Evaluation of tumor targeting with radiolabeled F(ab2 fragment of a humanized monoclonal antibody

Directory of Open Access Journals (Sweden)

"Babaei MH

2002-08-01

Full Text Available Humanized monoclonal antibody U36 and its F(ab'2 fragment, radio labeled with 125I, were tested for tumor localization in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma. Monoclonal antibody IgG or F(ab'2 fragment were injected in parallel and at days 1, 2 and 3, mice were dissected for determination of isotope biodistribution. IgG as well as F(ab'2 showed highly specific localization in tumor tissue. The mean tumor uptake (n=3 is expressed as the percentage of the injected dose per gram of tumor tissue (%ID/g. %ID/g of IgG was 11.7% at day 1 and decreased to 10.9% at day 3 whereas %ID/g of F(ab'2 was 2.9% at day 1 and decreased on following days. Tumor to blood ratios (T/B at day 1 were 0.86 for IgG and 1.32 for F(ab'2 and reached a maximum at day 3 with values of 4.41 and 1.84 respectively. These findings suggest that the superior tumor to non-tumor ratios in the day of 1 render the F(ab'2 fragment more qualified for specific targeting radioisotopes to tumor xenografts in this exprimental setting.

Variability of Gross Tumor Volume in Nasopharyngeal Carcinoma Using 11C-Choline and 18F-FDG PET/CT.

Directory of Open Access Journals (Sweden)

Jun Jiang

Full Text Available This study was conducted to evaluate the variability of gross tumor volume (GTV using 11C-Choline and 18F-FDG PET/CT images for nasopharyngeal carcinomas boundary definition. Assessment consisted of inter-observer and inter-modality variation analysis. Four radiation oncologists were invited to manually contour GTV by using PET/CT fusion obtained from a cohort of 12 patients with nasopharyngeal carcinoma (NPC and who underwent both 11C-Choline and 18F-FDG scans. Student's paired-sample t-test was performed for analyzing inter-observer and inter-modality variability. Semi-automatic segmentation methods, including thresholding and region growing, were also validated against the manual contouring of the two types of PET images. We observed no significant variation in the results obtained by different oncologists in terms of the same type of PET/CT volumes. Choline fusion volumes were significantly larger than the FDG volumes (p < 0.0001, mean ± SD = 18.21 ± 8.19. While significantly consistent results were obtained between the oncologists and the standard references in Choline volumes compared with those in FDG volumes (p = 0.0025. Simple semi-automatic delineation methods indicated that 11C-Choline PET images could provide better results than FDG volumes (p = 0.076, CI = [-0.29, 0.025]. 11C-Choline PET/CT may be more advantageous in GTV delineation for the radiotherapy of NPC than 18F-FDG. Phantom simulations and clinical trials should be conducted to prove the possible improvement of the treatment outcome.

A simplified one-pot synthesis of 9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([{sup 18}F]FHPG) and 9-(4-[{sup 18}F]Fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG) for gene therapy

Energy Technology Data Exchange (ETDEWEB)

Shiue, Grace G.; Shiue, Chyng-Yann E-mail: Shiue@rad.upenn.edu; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A

2001-10-01

9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG, 2) has been synthesized by nucleophilic substitution of N{sup 2}-(p-anisyldiphenylmethyl)-9-{l_brace}[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl{r_brace}guanine (1) with potassium [{sup 18}F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126{+-}0.022, n=5 and 0.165{+-}0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ({approx}5-30 {mu}g) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains {approx}10-25 {mu}g of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in

Clinical significance of 18F-fluorodeoxyglucose PET/CT whole body imaging in detecting thyroid incidentaloma

International Nuclear Information System (INIS)

Zhai Ge; Li Biao; Zhang Miao; Xu Haoping; Jiang Xufeng; Wang Chao; Ge Guizhi; Shun Chengwei; Zhu Chengmo

2009-01-01

Objective: 18 F-fluorodeoxyglucose (FDG) PET/CT is a noninvasive whole-body imaging technique used to evaluate various types of malignancies. Recent advances have rapidly developed it into a diagnostic imaging modality in ontology. The aims of this study were two. One was to estimate the detection rate of thyroid indoleacetamide and the risk of thyroid malignancy by 18 F-FDG PET/CT scan and the other Was to further understand whether the maximum standardized uptake value (SUV max ) would be helpful in differentiating benign from malignant thyroid tumor. Methods: From June 2007 to January 2008, a total of 1190 subjects who had no previous history of thyroid cancer and had 18 F-FDG PET/CT scan were included. All had visual interpretation and semiquantitative analyses by SUV max at thyroid incidentalomas detected by FDG PET/CT. Kruskal-Wallis test and Spearman relation analysis were used. Results: The prevalence of thyroid incidentaloma on 18 F-FDG PET/CT wag 2.1% (25/1190). Of these 25 tumors, 20 had histologically proven. Of these 20 tumors, 9 were benign and 11 were malignant (papillary carcinoma of thyroid gland in 9, follicular carcinoma of thyroid gland in 1, metastatic squamous cell carcinoma from lung cancer in 1). Therefore,the cancer risk of thyroid incidentaloma was 55% (11/20). Significantly higher SUV max in malignant than in benign nodules were observed (Kruskal-Wallis test,χ 2 =8.8, P max (3.0-46.0) and maximal diameter (1.0-4.2 cm) of nodule findings was insignificant (r=0.25, P>0.01). Conclusion: Thyroid incidentaloma detected by 18 F-FDG PET/CT has higher risk rate for thyroid malignancy.(authors)

Levels of carcinoembryonic antigen and CA 19-9 in the sera and peritoneal washing of patients undergoing surgical treatment for gastric carcinoma Níveis do antígeno carcinoembriônico e do CA 19-9 no soro e no lavado peritonial em doentes submetidos ao tratamento cirúrgico do carcinoma gástrico

Directory of Open Access Journals (Sweden)

René Crepaldi-Filho

2008-09-01

Full Text Available BACKGROUND: Early peritoneal recurrence of gastric carcinoma following curative resection remains a great challenge in the treatment and prevention of this disease. AIM: To analyze the relationship between levels of tumor markers, carcinoembryonic antigen (CEA and CA 19-9 in the sera and peritoneal washing, and anatomopathological aspects of the gastric carcinoma. METHODS: Of the 46 patients in the study, 29 (63.0% were males and 17 (37.0% females. Mean age was 63.6 ± 11.7 years (31 to 91 years. Peripheral venous blood samples were collected from the upper limb vein from both patient groups after anesthetic induction, in order to determine serum levels of CEA and CA 19-9. After the end of the procedure, 50 mL of physiologic solution was introduced into the bottom of the Douglas sack and a portion aspirated to determine CEA and CA 19-9 levels in the peritoneal washing. Levels of CEA and CA 19-9 in the sera and peritoneal washing were compared to the following variables: lesion diameter ≤4 cm or >4 cm, lymph node involvement, angiolymphatic invasion, depth of invasion into gastric wall, and initial or late stage. RESULTS: Sera CEA levels were significantly higher in patients with lesions >5 cm. CEA levels in the sera and peritoneal washing were significantly greater in patients with signet ring cell gastric carcinoma. In addition, levels of CEA in peripheral blood and peritoneal washing showed significant association with the degree of carcinoma penetration into the gastric wall, while sera CEA was significantly higher in patients at more advanced stages. There was no significant difference between sera and peritoneal CEA values regarding grade of differentiation. Patients with gastric lesions measuring > 5cm and more differentiated lesions had significantly higher sera CA 19-9 values. In patients with lymph nodes invasion by gastric carcinoma, CA 19-9 levels in peritoneal washing were significantly higher than in peripheral blood. Levels of CA

Renal cell carcinoma: incidental detection and pathological staging.

Science.gov (United States)

Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

2000-10-01

In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

Metachronous colorectal carcinoma

DEFF Research Database (Denmark)

Bülow, Steffen; Svendsen, L B; Mellemgaard, A

1990-01-01

During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

Radioimmunoimaging of human breast carcinoma xenografts in nude mouse model with 111In-labeled new monoclonal antibody EBA-1 and F(ab')2 fragments

International Nuclear Information System (INIS)

Yemul, Shrishailam; Leon, J.A.; Pozniakoff, Ted; Esser, P.D.; Estabrook, Alison; Met-Path Inc., Teterboro, NJ

1993-01-01

Radioimmunoimaging characteristics of a new monoclonal antibody EBA-1 and its F(ab') 2 fragments utilizing nu/nu mice bearing human breast carcinoma xenografts are described. 111 In-DPTA conjugates of EBA-1 localized with tumor/blood ratios of 0.99 ± 0.10 (P 2 radioconjugates at 48 h. These results suggest that EBA-1 and its F(ab') 2 might be useful reagents in radioimmunoimaging and radioimmunotherapy. (author)

Inhibitory effects of kaempferol on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9.

Science.gov (United States)

Li, Chenglin; Zhao, Yuanwei; Yang, Dan; Yu, Yanyan; Guo, Hao; Zhao, Ziming; Zhang, Bei; Yin, Xiaoxing

2015-02-01

Matrix metalloproteinases (MMPs) have been regarded as major critical molecules assisting tumor cells during metastasis, for excessive ECM (ECM) degradation, and cancer cell invasion. In the present study, in vitro and in vivo assays were employed to examine the inhibitory effects of kaempferol, a natural polyphenol of flavonoid family, on tumor metastasis. Data showed that kaempferol could inhibit adhesion, migration, and invasion of MDA-MB-231 human breast carcinoma cells. Moreover, kaempferol led to the reduced activity and expression of MMP-2 and MMP-9, which were detected by gelatin zymography, real-time PCR, and western blot analysis, respectively. Further elucidation of the mechanism revealed that kaempferol treatment inhibited the activation of transcription factor activator protein-1 (AP-1) and MAPK signaling pathway. Moreover, kaempferol repressed phorbol-12-myristate-13-acetate (PMA)-induced MMP-9 expression and activity through suppressing the translocation of protein kinase Cδ (PKCδ) and MAPK signaling pathway. Our results also indicated that kaempferol could block the lung metastasis of B16F10 murine melanoma cells as well as the expression of MMP-9 in vivo. Taken together, these results demonstrated that kaempferol could inhibit cancer cell invasion through blocking the PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma

Energy Technology Data Exchange (ETDEWEB)

Alongi, Pierpaolo [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Evangelista, Laura [Veneto Institute of Oncology IOV - IRCCS, Nuclear Medicine and Molecular Imaging Unit, Padua (Italy); Caobelli, Federico [Basel University Hospital, Department of Nuclear Medicine, Basel (Switzerland); Spallino, Marianna [University of Milano-Bicocca, Milan (Italy); Gianolli, Luigi; Picchio, Maria [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Midiri, Massimo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); University of Palermo, Department of Radiology, DIBIMED, Palermo (Italy)

2018-01-15

The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of {sup 18}F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT). From the databases of two centers including 31,500 {sup 18}F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent {sup 18}F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted {sup 18}F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables. Recurrent GCT was confirmed in 47 of 52 patients with pathological {sup 18}F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of {sup 18}FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively.{sup 18}F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from ''wait and watch'' to new chemotherapy in six patients and the ''wait-and-watch'' approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological {sup 18}F-FDG PET/CT scan (98% and 95% vs 48% and

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma.

Science.gov (United States)

Alongi, Pierpaolo; Evangelista, Laura; Caobelli, Federico; Spallino, Marianna; Gianolli, Luigi; Midiri, Massimo; Picchio, Maria

2018-01-01

The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of 18 F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT). From the databases of two centers including 31,500 18 F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent 18 F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted 18 F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables. Recurrent GCT was confirmed in 47 of 52 patients with pathological 18 F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of 18 FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively. 18 F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from "wait and watch" to new chemotherapy in six patients and the "wait-and-watch" approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological 18 F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An unremarkable scan was associated also with a

Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma

International Nuclear Information System (INIS)

Alongi, Pierpaolo; Evangelista, Laura; Caobelli, Federico; Spallino, Marianna; Gianolli, Luigi; Picchio, Maria; Midiri, Massimo

2018-01-01

The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of 18 F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT). From the databases of two centers including 31,500 18 F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent 18 F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted 18 F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables. Recurrent GCT was confirmed in 47 of 52 patients with pathological 18 F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of 18 FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively. 18 F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from ''wait and watch'' to new chemotherapy in six patients and the ''wait-and-watch'' approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological 18 F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An

Usefulness of {sup 18}F-FDG PET, combined FDG-PET/CT and EUS in diagnosing primary pancreatic carcinoma: A meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Tang Shuang [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Huang Gang, E-mail: huang2802@163.com [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Liu Jianjun [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Liu Tao [Department of Orthopedics, Soochow University, Suzhou (China); Treven, Lyndal [Faculty of Public Health, University of Sydney, Sydney (Australia); Song Saoli; Zhang Chenpeng; Pan Lingling [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Zhang Ting [Department of Anesthesiology, Renji Hospital, Shanghai (China)

2011-04-15

The aim was to evaluate the diagnostic value of {sup 18}F-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG PET), combined {sup 18}F-fluorodeoxyglucose-positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and endoscopic ultrasonography (EUS) in diagnosing patients with pancreatic carcinoma. MEDLINE, EMBASE, Cochrane library and some other databases, from January 1966 to April 2009, were searched for initial studies. All the studies published in English or Chinese relating to the diagnostic value of {sup 18}F-FDG PET, PET/CT and EUS for patients with pancreatic cancer were collected. Methodological quality was assessed. The statistic software called 'Meta-Disc 1.4' was used for data analysis. Results: 51 studies were included in this meta-analysis. The pooled sensitivity estimate for combined PET/CT (90.1%) was significantly higher than PET (88.4%) and EUS (81.2%). The pooled specificity estimate for EUS (93.2%) was significantly higher than PET (83.1%) and PET/CT (80.1%). The pooled DOR estimate for EUS (49.774) was significantly higher than PET (32.778) and PET/CT (27.105). SROC curves for PET/CT and EUS showed a little better diagnostic accuracy than PET alone. For PET alone, when interpreted the results with knowledge of other imaging tests, its sensitivity (89.4%) and specificity (80.1%) were closer to PET/CT. For EUS, its diagnostic value decreased in differentiating pancreatic cancer for patients with chronic pancreatitis. In conclusion, PET/CT was a high sensitive and EUS was a high specific modality in diagnosing patients with pancreatic cancer. PET/CT and EUS could play different roles during different conditions in diagnosing pancreatic carcinoma.

Gene expression profiling distinguishes between spontaneous and radiation-induced rat mammary carcinomas

International Nuclear Information System (INIS)

Imaoka, Tatsuhiko; Nishimura, Mayumi; Kakinuma, Shizuko; Shimada, Yoshiya; Yamashita, Satoshi; Ushijima, Toshikazu

2008-01-01

The ability to distinguish between spontaneous and radiation-induced cancers in humans is expected to improve the resolution of estimated risk from low dose radiation. Mammary carcinomas were obtained from Sprague-Dawley rats that were either untreated (n=45) or acutely γ-irradiated (1 Gy; n=20) at seven weeks of age. Gene expression profiles of three spontaneous and four radiation-induced carcinomas, as well as those of normal mammary glands, were analyzed by microarrays. Differential expression of identified genes of interest was then verified by quantitative polymerase chain reaction (qPCR). Cluster analysis of global gene expression suggested that spontaneous carcinomas were distinguished from a heterogeneous population of radiation-induced carcinomas, though most gene expressions were common. We identified 50 genes that had different expression levels between spontaneous and radiogenic carcinomas. We then selected 18 genes for confirmation of the microarray data by qPCR analysis and obtained the following results: high expression of Plg, Pgr and Wnt4 was characteristic to all spontaneous carcinomas; Tnfsf11, Fgf10, Agtr1a, S100A9 and Pou3f3 showed high expression in a subset of radiation-induced carcinomas; and increased Gp2, Areg and Igf2 expression, as well as decreased expression of Ca3 and noncoding RNA Mg1, were common to all carcinomas. Thus, gene expression analysis distinguished between spontaneous and radiogenic carcinomas, suggesting possible differences in their carcinogenic mechanism. (author)

{sup 18}F-FDG PET/CT predicts survival after {sup 90}Y transarterial radioembolization in unresectable hepatocellular carcinoma

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Jreige, Mario; Mitsakis, Periklis; Gucht, Axel van der; Pomoni, Anastasia; Silva-Monteiro, Marina; Boubaker, Ariane; Nicod-Lalonde, Marie; Prior, John O.; Schaefer, Niklaus [Lausanne University Hospital, Department of Nuclear Medicine and Molecular Imaging, Lausanne (Switzerland); Gnesin, Silvano [Lausanne University Hospital, Institute of Radiation Physics, Lausanne (Switzerland); Duran, Rafael; Denys, Alban [Lausanne University Hospital, Department of Radiodiagnostic and Interventional Radiology, Lausanne (Switzerland)

2017-07-15

To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 ({sup 90}Y-TARE) for unresectable hepatocellular carcinoma (uHCC). We analysed data from 48 patients in our prospective database undergoing {sup 90}Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent {sup 18}F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and {sup 90}Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of {sup 18}F-FDG PET/CT metabolic parameters, including SUV{sub max}, tumour-to-liver (T/L) uptake ratio and SUV{sub mean} of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses. The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after {sup 90}Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUV{sub max} (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUV{sub max} and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUV{sub max} and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean

Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.

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Annunziato, Stefano; Kas, Sjors M; Nethe, Micha; Yücel, Hatice; Del Bravo, Jessica; Pritchard, Colin; Bin Ali, Rahmen; van Gerwen, Bas; Siteur, Bjørn; Drenth, Anne Paulien; Schut, Eva; van de Ven, Marieke; Boelens, Mirjam C; Klarenbeek, Sjoerd; Huijbers, Ivo J; van Miltenburg, Martine H; Jonkers, Jos

2016-06-15

Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice. © 2016 Annunziato et al.; Published by Cold Spring Harbor Laboratory Press.

Embryonic kidney function in a chronic renal failure model in rodents.

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Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

NTP Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

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1986-04-01

increased in dosed mice of each sex (male: 0/49; 5/46; 11/49; 7/48; female: 6/48; 10/44; 11/50; 10/47). The incidences of harderian gland adenomas (0/49; 9/46; 13/49; 11/48) in dosed male mice were greater than that in the vehicle controls. A marginal increase in the incidence of adenomas or carcinomas (combined) of the harderian gland was seen in high dose female mice (5/48; 6/44; 10/50; 10/47). The administration of benzene to male mice was associated with increased incidences of hyperplasia (1/21; 18/28; 9/29; 1/35) and squamous cell carcinomas (0/21; 3/28; 18/29; 28/35) of the preputial gland. Increased incidences of mammary gland carcinomas were found in mid dose and high dose female mice (0/49; 2/45; 5/50; 10/49) and carcinosarcomas in high dose female mice (0/49; 0/45; 1/50; 4/49). Increased incidences of various uncommon neoplastic and nonneoplastic lesions of the ovary (papillary cystadenoma, luteoma, granulosa cell tumor, tubular adenoma, benign mixed tumor, epithelial hyperplasia, and senile atrophy) were associated with the administration of benzene to female mice. In mid and high dose female mice, the incidences of granulosa cell tumors (1/47; 1/44; 6/49; 7/48) and benign mixed tumors (0/47; 1/44; 12/49; 7/48) were greater than those in the vehicle controls. Increased incidences of hepatocellular adenomas were observed in low dose female mice (1/49; 8/44; 5/50; 4/49) and hepatocellular adenomas or carcinomas (combined) in low dose and mid dose female mice (4/49; 12/44; 13/50; 7/49). An audit of the experimental data was conducted for these 2-year carcinogenesis studies on benzene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene for male F344/N rats, for female F344/N rats, for male B6C3F1 mice, and for female B6C3F1 mice. For male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and

18F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

International Nuclear Information System (INIS)

Archier, Aurelien; Mundler, Olivier; Heimburger, Celine; Guerin, Carole; Palazzo, Fausto F.; Henry, Jean-Francois; Sebag, Frederic; Morange, Isabelle; Schneegans, Olivier; Abdullah, Ahmad Esmaeel; Imperiale, Alessio; Taieb, David

2016-01-01

To evaluate the performance of 18 F-l-dihydroxyphenylalanine ( 18 F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone 18 F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. 18 F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of 18 F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. 18 F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by 18 F-DOPA PET/CT. (orig.)

Low morbidity following 9,000-rad intracavitary endocurietherapy (ECT) using the Kumar cervical applicator and external-beam radiotherapy (EXRT) in the management of carcinoma of the uterine cervix

International Nuclear Information System (INIS)

Kumar, P.P.; Good, R.R.; Scott, J.C.; Jones, E.O.; Lynch, G.; McCaul, G.F.

1988-01-01

The Kumar Cervical Applicator minimizes patient discomfort and improves patient mobility while reducing the tendency of the applicator to rotate during the 40 to 50 hours of uterine intracavitary endocurietherapy. Patients with previously untreated invasive carcinoma of the uterine cervix, F.I.G.O. stages IB-IVA, were treated with two Kumar intracavitary endocurietherapy (ECT) applications of 2,500 rad each to point ''A,'' and 4,000 rad external-beam radiotherapy (EXRT) to midplane, for a total dose of 9,000 rad. The major complication rate was 2.7 %, and the local control rate was 85 % (22/26 patients) for stage I and II, and 91 % (10/11 patients) for stage III and IVA. (author)

MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma

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Wang, Xinsheng; Jiang, Fuquan; Song, Haitao; Li, Xu; Xian, Jiantao; Gu, Xinquan, E-mail: guxqprofessor@163.com

2016-02-12

Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renal cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC. - Highlights: • MiR-200a-3p is downregulated in renal cell carcinoma. • MiR-200a-3p regulates cell proliferation through inducing apoptosis. • MiR-200a-3p is involved in cell cycle regulation. • SPAG9 is a potential target of miR-200a-3p.

Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice.

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Nakagawa, Kimie; Sawada, Natsumi; Hirota, Yoshihisa; Uchino, Yuri; Suhara, Yoshitomo; Hasegawa, Tomoka; Amizuka, Norio; Okamoto, Tadashi; Tsugawa, Naoko; Kamao, Maya; Funahashi, Nobuaki; Okano, Toshio

2014-01-01

UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme screened and identified from the human genome database. UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10 (CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by gene targeting. Ubiad1-deficient (Ubiad1(-/-)) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest. Ubiad1(-/-) embryonic stem (ES) cells failed to synthesize vitamin K2 but were able to synthesize CoQ9, similar to wild-type ES cells. Ubiad1(+/-) mice developed normally, exhibiting normal growth and fertility. Vitamin K2 tissue levels and synthesis activity were approximately half of those in the wild-type, whereas CoQ9 tissue levels and synthesis activity were similar to those in the wild-type. Similarly, UBIAD1 expression and vitamin K2 synthesis activity of mouse embryonic fibroblasts prepared from Ubiad1(+/-) E15.5 embryos were approximately half of those in the wild-type, whereas CoQ9 levels and synthesis activity were similar to those in the wild-type. Ubiad1(-/-) mouse embryos failed to be rescued, but their embryonic lifespans were extended to term by oral administration of MK-4 or CoQ10 to pregnant Ubiad1(+/-) mice. These results suggest that UBIAD1 is responsible for vitamin K2 synthesis but may not be responsible for CoQ9 synthesis in mice. We propose that UBIAD1 plays a pivotal role in embryonic development by synthesizing vitamin K2, but may have additional functions beyond the biosynthesis of vitamin K2.

Marked change in microRNA expression during neuronal differentiation of human teratocarcinoma NTera2D1 and mouse embryonal carcinoma P19 cells

International Nuclear Information System (INIS)

Hohjoh, Hirohiko; Fukushima, Tatsunobu

2007-01-01

MicroRNAs (miRNAs) are small noncoding RNAs, with a length of 19-23 nucleotides, which appear to be involved in the regulation of gene expression by inhibiting the translation of messenger RNAs carrying partially or nearly complementary sequences to the miRNAs in their 3' untranslated regions. Expression analysis of miRNAs is necessary to understand their complex role in the regulation of gene expression during the development, differentiation and proliferation of cells. Here we report on the expression profile analysis of miRNAs in human teratocarcinoma NTere2D1, mouse embryonic carcinoma P19, mouse neuroblastoma Neuro2a and rat pheochromocytoma PC12D cells, which can be induced into differentiated cells with long neuritic processes, i.e., after cell differentiation, such that the resultant cells look similar to neuronal cells. The data presented here indicate marked changes in the expression of miRNAs, as well as genes related to neuronal development, occurred in the differentiation of NTera2D1 and P19 cells. Significant changes in miRNA expression were not observed in Neuro2a and PC12D cells, although they showed apparent morphologic change between undifferentiated and differentiated cells. Of the miRNAs investigated, the expression of miRNAs belonging to the miR-302 cluster, which is known to be specifically expressed in embryonic stem cells, and of miR-124a specific to the brain, appeared to be markedly changed. The miR-302 cluster was potently expressed in undifferentiated NTera2D1 and P19 cells, but hardly in differentiated cells, such that miR-124a showed an opposite expression pattern to the miR-302 cluster. Based on these observations, it is suggested that the miR-302 cluster and miR-124a may be useful molecular indicators in the assessment of degree of undifferentiation and/or differentiation in the course of neuronal differentiation

Rhabdomyosarcoma of the urinary bladder in adults: predilection for alveolar morphology with anaplasia and significant morphologic overlap with small cell carcinoma.

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Paner, Gladell P; McKenney, Jesse K; Epstein, Jonathan I; Amin, Mahul B

2008-07-01

Rhabdomyosarcoma (RMS) represents the most common malignant soft tissue tumor in children and adolescents with the urinary bladder representing a frequent site. Most of these urinary bladder tumors are embryonal RMS, predominantly the botryoid subtype. RMSs of the urinary bladder in adults are distinctively rare and the subject of only case reports. We report the clinicopathologic features of 5 bladder neoplasms with rhabdomyosarcomatous differentiation in adults and emphasize the differential diagnosis in the adult setting. The patients, 4 men and 1 woman, ranged in age from 23 to 85 years (mean 65.4 y). Gross hematuria was the most common initial symptom, although 2 patients had metastatic disease at presentation. Four cases were pure primary RMSs of the bladder and 1 case was a sarcomatoid urothelial carcinoma with RMS representing the extensive heterologous component. All 5 cases demonstrated a diffuse growth pattern (ie, non-nested), of which 4 cases had nuclear anaplasia (Wilms criteria without the atypical mitotic figure requirement); only 1 case (the sarcomatoid carcinoma) showed obvious rhabdomyoblastic differentiation (ie, strap cells). Three cases were of the alveolar subtype (1 admixed with embryonal histology) and 2 were RMS, not further classified. Microscopically, all tumors had a primitive undifferentiated morphology with cells containing scant cytoplasm, varying round to fusiform nuclei with even chromatin distribution, and frequent mitoses. The degree of morphologic overlap with small cell carcinoma of the bladder, a relatively more common round cell tumor in adults, was striking. The epithelial component of the sarcomatoid carcinoma was high-grade invasive urothelial carcinoma with glandular differentiation. No other case had previous history of bladder cancer or concurrent carcinoma in situ or invasive urothelial carcinoma. All tumors showed immunohistochemical expression for desmin, myogenin, and/or MyoD1. Synaptophysin was performed in 4 cases

Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

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Garcia-Lavandeira, Montserrat; Saez, Carmen; Diaz-Rodriguez, Esther; Perez-Romero, Sihara; Senra, Ana; Dieguez, Carlos; Japon, Miguel A; Alvarez, Clara V

2012-01-01

Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells). Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells. We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary). Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously. Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated

Embryonic hypoxia programmes postprandial cardiovascular function in adult common snapping turtles (Chelydra serpentina).

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Wearing, Oliver H; Conner, Justin; Nelson, Derek; Crossley, Janna; Crossley, Dane A

2017-07-15

Reduced oxygen availability (hypoxia) is a potent stressor during embryonic development, altering the trajectory of trait maturation and organismal phenotype. We previously documented that chronic embryonic hypoxia has a lasting impact on the metabolic response to feeding in juvenile snapping turtles ( Chelydra serpentina ). Turtles exposed to hypoxia as embryos [10% O 2 (H10)] exhibited an earlier and increased peak postprandial oxygen consumption rate, compared with control turtles [21% O 2 (N21)]. In the current study, we measured central blood flow patterns to determine whether the elevated postprandial metabolic response in H10 turtles is linked to lasting impacts on convective transport. Five years after hatching, turtles were instrumented to quantify systemic ([Formula: see text]) and pulmonary ([Formula: see text]) blood flows and heart rate ( f H ) before and after a ∼5% body mass meal. In adult N21 and H10 turtles, f H was increased significantly by feeding. Although total stroke volume ( V S,tot ) remained at fasted values, this tachycardia contributed to an elevation in total cardiac output ([Formula: see text]). However, there was a postprandial reduction in a net left-right (L-R) shunt in N21 snapping turtles only. Relative to N21 turtles, H10 animals exhibited higher [Formula: see text] due to increased blood flow through the right systemic outflow vessels of the heart. This effect of hypoxic embryonic development, reducing a net L-R cardiac shunt, may support the increased postprandial metabolic rate we previously reported in H10 turtles, and is further demonstration of adult reptile cardiovascular physiology being programmed by embryonic hypoxia. © 2017. Published by The Company of Biologists Ltd.

Advanced cell-based modeling of the royal disease: characterization of the mutated F9 mRNA.

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Martorell, L; Luce, E; Vazquez, J L; Richaud-Patin, Y; Jimenez-Delgado, S; Corrales, I; Borras, N; Casacuberta-Serra, S; Weber, A; Parra, R; Altisent, C; Follenzi, A; Dubart-Kupperschmitt, A; Raya, A; Vidal, F; Barquinero, J

2017-11-01

Essentials The Royal disease (RD) is a form of hemophilia B predicted to be caused by a splicing mutation. We generated an iPSC-based model of the disease allowing mechanistic studies at the RNA level. F9 mRNA analysis in iPSC-derived hepatocyte-like cells showed the predicted abnormal splicing. Mutated F9 mRNA level was very low but we also found traces of wild type transcripts. Background The royal disease is a form of hemophilia B (HB) that affected many descendants of Queen Victoria in the 19th and 20th centuries. It was found to be caused by the mutation F9 c.278-3A>G. Objective To generate a physiological cell model of the disease and to study F9 expression at the RNA level. Methods Using fibroblasts from skin biopsies of a previously identified hemophilic patient bearing the F9 c.278-3A>G mutation and his mother, we generated induced pluripotent stem cells (iPSCs). Both the patient's and mother's iPSCs were differentiated into hepatocyte-like cells (HLCs) and their F9 mRNA was analyzed using next-generation sequencing (NGS). Results and Conclusion We demonstrated the previously predicted aberrant splicing of the F9 transcript as a result of an intronic nucleotide substitution leading to a frameshift and the generation of a premature termination codon (PTC). The F9 mRNA level in the patient's HLCs was significantly reduced compared with that of his mother, suggesting that mutated transcripts undergo nonsense-mediated decay (NMD), a cellular mechanism that degrades PTC-containing mRNAs. We also detected small proportions of correctly spliced transcripts in the patient's HLCs, which, combined with genetic variability in splicing and NMD machineries, could partially explain some clinical variability among affected members of the European royal families who had lifespans above the average. This work allowed the demonstration of the pathologic consequences of an intronic mutation in the F9 gene and represents the first bona fide cellular model of HB allowing the

Inhibition of H3K9 methyltransferase G9a induces autophagy and apoptosis in oral squamous cell carcinoma

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Ren, Aishu; Qiu, Yu [Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, 401147 (China); Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, 401147 (China); Cui, Hongjuan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400716 (China); Fu, Gang, E-mail: fg.ras@hotmail.com [Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, 401147 (China); Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, 401147 (China)

2015-03-27

Objective: To explore whether inhibition of H3K9 Methyltransferase G9a could exert an antitumoral effect in oral squamous cell carcinoma (OSCC). Materials and methods: First we checked G9a expression in two OSCC cell lines Tca8113 and KB. Next we used a special G9a inhibitor BIX01294 (BIX) to explore the effect of inhibition of G9a on OSCC in vitro. Cell growth was tested by typlan blue staining, MTT assay and Brdu immunofluorescence staining. Cell autophagy was examined by monodansylcadaverine (MDC) staining, LC3-II immunofluorescence staining and LC3-II western blot assay. Cell apoptosis was checked by FITC Annexin-V and PI labeling, tunnel staining and caspase 3 western blot assay. Finally, the effect of inhibition of G9a on clonogenesis and tumorigenesis capacity of OSCC was analyzed by soft agar growth and xenograft model. Results: Here we showed that G9a was expressed in both Tca8113 and KB cells. Inhibition of G9a using BIX significantly reduced cell growth and proliferation in Tca8113 and KB. Inhibition of G9a induced cell autophagy with conversion of LC3-I to LC3-II and cell apoptosis with the expression of cleaved caspase 3. We also found that inhibition of G9a reduced colony formation in soft agar and repressed tumor growth in mouse xenograph model. Conclusion: Our results suggested that G9a might be a potential epigenetic target for OSCC treatment. - Highlights: • Inhibition of G9a reduced cell growth and proliferation in OSCC cells. • Inhibition of G9a induces autophagy and apoptosis in OSCC cells. • Inhibition of G9a repressed tumor growth in mouse xenograph model.

Role of 18F-FDG PET/CT in Posttreatment Evaluation of Anal Carcinoma.

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Houard, Clémence; Pinaquy, Jean-Baptiste; Mesguich, Charles; Henriques de Figueiredo, Bénédicte; Cazeau, Anne-Laure; Allard, Jean-Baptiste; Laharie, Hortense; Bordenave, Laurence; Fernandez, Philippe; Vendrely, Véronique

2017-09-01

The aim of this study was to evaluate the relevance of PET/CT and 18 F-FDG as a strategy for response evaluation after chemoradiotherapy for anal cancer. For this, the performance of posttreatment 18 F-FDG PET/CT, the impact on patient care, and the predictive value of metabolic response were assessed. Methods: This was a retrospective and multicenter analysis of 87 patients treated by chemoradiotherapy for anal squamous cell carcinoma between October 2007 and October 2013. All patients underwent systematic posttreatment 18 F-FDG PET/CT and were followed with at least a clinical examination every 4 mo for 2 y and every 6 mo thereafter. Disease progression was confirmed by biopsy for all patients in the case of local recurrence before surgery. Kaplan-Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and progression-free survival (PFS) or cause-specific survival (CSS). Results: The median follow-up was 25 mo. 18 F-FDG PET/CT was performed 1-8 mo (median, 4 mo) after completion of chemoradiotherapy. Overall, 25 patients relapsed and 13 died. The posttherapy 18 F-FDG PET/CT did not show any abnormal 18 F-FDG uptake (complete metabolic response [CMR]) in 55 patients whereas 32 displayed incomplete response (non-CMR): 15 patients with partial response and 17 with disease progression. The sensitivity of 18 F-FDG PET/CT to detect residual tumor tissue was 92% (95% confidence interval [CI], 75%-97%), specificity was 85% (95% CI, 75%-92%), positive predictive value was 72% (95% CI, 61%-90%), and negative predictive value was 96.4% (95% CI, 90%-98.7%). The 2-y PFS was 96% (95% CI, 90-100) for patients with CMR and 28% (95% CI, 14-47) for non-CMR patients ( P PET/CT changed patient management in 14 cases (16%), with relevant modifications in 12 (14%). A Cox proportional hazards model of survival outcome indicated that a CMR was the only significant predictor of PFS and CSS ( P PET/CT shows good accuracy in posttreatment

A clinical study of nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Ito, Zenya; Wada, Tetsuro; Senarita, Masamitsu

1999-01-01

Forty-four patients of nasopharyngeal carcinoma, treated in Tsukuba University Hospital between March 1988 and March 1998, were reviewed in order to assess the adequacy of our treatment protocol. Most of the cases except 5 were histologically diagnosed as squamous cell carcinoma including 25 of lymphoepithelioma (poorly-differentiated squamous cell carcinoma). Thirty-two out of 39 squamous cell carcinoma cases have fallen into Stage IV category (UICC, 1987) , and all of the non-squamous cell carcinoma cases were also categorized as Stage IV. The basic protocol for nasopharyngeal squamous cell carcinoma was the combination of full-dose irradiation and chemotherapy using cisplatin/carboplatin and peplomycin. The metastatic cervical lymphnodes in 9 cases, too massive to control by this treatment, were surgically dissected after the treatment. Recurrence was noted in 9 cases who were rehospitalized and salvaged medically and/or surgically. As a consequence, the overall 5-year survival rate was 71.4% for squamous cell carcinoma. On the other hand, only one of the 5 non-squamous cell carcinoma cases died of the disease. (author)

Pseudomonas orientalis F9: A Potent Antagonist against Phytopathogens with Phytotoxic Effect in the Apple Flower

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Veronika Zengerer

2018-02-01

Full Text Available In light of public concerns over the use of pesticides and antibiotics in plant protection and the subsequent selection for spread of resistant bacteria in the environment, it is inevitable to broaden our knowledge about viable alternatives, such as natural antagonists and their mode of action. The genus Pseudomonas is known for its metabolic versatility and genetic plasticity, encompassing pathogens as well as antagonists. We characterized strain Pseudomonas orientalis F9, an isolate from apple flowers in a Swiss orchard, and determined its antagonistic activity against several phytopathogenic bacteria, in particular Erwinia amylovora, the causal agent of fire blight. P. orientalis F9 displayed antagonistic activity against a broad suite of phytopathogenic bacteria in the in vitro tests. The promising results from this analysis led to an ex vivo assay with E. amylovora CFBP1430Rif and P. orientalis F9 infected detached apple flowers. F9 diminished the fire blight pathogen in the flowers but also revealed phytotoxic traits. The experimental results were discussed in light of the complete genome sequence of F9, which revealed the strain to carry phenazine genes. Phenazines are known to contribute to antagonistic activity of bacterial strains against soil pathogens. When tested in the cress assay with Pythium ultimum as pathogen, F9 showed results comparable to the known antagonist P. protegens CHA0.

Pseudomonas orientalis F9: A Potent Antagonist against Phytopathogens with Phytotoxic Effect in the Apple Flower.

Science.gov (United States)

Zengerer, Veronika; Schmid, Michael; Bieri, Marco; Müller, Denise C; Remus-Emsermann, Mitja N P; Ahrens, Christian H; Pelludat, Cosima

2018-01-01

In light of public concerns over the use of pesticides and antibiotics in plant protection and the subsequent selection for spread of resistant bacteria in the environment, it is inevitable to broaden our knowledge about viable alternatives, such as natural antagonists and their mode of action. The genus Pseudomonas is known for its metabolic versatility and genetic plasticity, encompassing pathogens as well as antagonists. We characterized strain Pseudomonas orientalis F9, an isolate from apple flowers in a Swiss orchard, and determined its antagonistic activity against several phytopathogenic bacteria, in particular Erwinia amylovora , the causal agent of fire blight. P. orientalis F9 displayed antagonistic activity against a broad suite of phytopathogenic bacteria in the in vitro tests. The promising results from this analysis led to an ex vivo assay with E. amylovora CFBP1430 Rif and P. orientalis F9 infected detached apple flowers. F9 diminished the fire blight pathogen in the flowers but also revealed phytotoxic traits. The experimental results were discussed in light of the complete genome sequence of F9, which revealed the strain to carry phenazine genes. Phenazines are known to contribute to antagonistic activity of bacterial strains against soil pathogens. When tested in the cress assay with Pythium ultimum as pathogen, F9 showed results comparable to the known antagonist P. protegens CHA0.

Ab Initio f values for Fe II J=9/2 ->9/2^o transitions

Science.gov (United States)

Beck, Donald

2005-05-01

Relativistic configuration interaction f values have been obtained for 264 transitions between the lowest 12 J=9/2 and the 22 J=9/2^o levels. Length and velocity gauges agree to 3.8% for in-shell transitions and 10.0% for shell jump transitions. Two J=9/2^o levels are so nearly degenerate that it was necessary to introduce a semi-empirical correction to produce the correct level ordering. The results are in overall good agreement with the semi-empirical results of Kurucz ootnotetextR. L. Kurucz, http://kurucz.harvard.edu/atoms/2601/ and Raassen ootnotetextA. J. J. Raasen, ftp://ftp.wins.uva.nl/pub/orth/iron/FeII.E1 (1999). An efficient method of including magnetic Breit effects in the energy matrix is presented.

Primary squamous cell carcinoma of the thyroid. Initial assessment and follow-up using 18F-FDG PET/CT.

Science.gov (United States)

Caballero Gullón, L; Carmona González, E; Martínez Estévez, A; Gómez Camarero, M P; Corral, J J; Borrego Dorado, I

Squamous cell carcinoma of thyroid is an uncommon, very aggressive neoplasm, having a poor prognosis and poor response to chemotherapy and radiotherapy. Surgery is the initial treatment of choice, although it often presents as a widespread disease at the time of diagnosis, usually with cervical swelling that causes most of the symptoms due to local infiltration or metastasis. Local infiltration from adjacent tumour and metastatic disease needs to be excluded from other primary epidermoid carcinomas, in order to make a correct diagnosis. This also requires the typical cytokeratin pattern seen in histological studies. The case is presented of a 53 year-old man with a medical history of hepatocarcinoma, with a cervical hypermetabolic lesion detected in an 18 F-FDG PET/CT performed to exclude widespread disease. The follow-up of this lesion with this technique and its usefulness is also described. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

Directory of Open Access Journals (Sweden)

Deepika Kanojia

Full Text Available BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9 in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042 and low grade tumors (P = 0.002 suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets

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Tropé Claes G

2007-07-01

Full Text Available Abstract Background The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52 and their in vitro models (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3 by methylation-specific polymerase chain reaction (MSP. Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features. Results Eight out of the 13 genes were hypermethylated among the ovarian carcinomas, and altogether 40 of 52 tumours were methylated in one or more genes. Promoter hypermethylation of HOXA9, RASSF1A, APC, CDH13, HOXB5, SCGB3A1 (HIN-1, CRABP1, and MLH1 was found in 51% (26/51, 49% (23/47, 24% (12/51, 20% (10/51, 12% (6/52, 10% (5/52, 4% (2/48, and 2% (1/51 of the carcinomas, respectively, whereas ADAMTS1, MGMT, NR3C1, p14ARF, and p16INK4a were unmethylated in all samples. The methylation frequencies of HOXA9 and SCGB3A1 were higher among relatively early-stage carcinomas (FIGO I-II than among carcinomas of later stages (FIGO III-IV; P = 0.002, P = 0.020, respectively. The majority of the early-stage carcinomas were of the endometrioid histotype. Additionally, HOXA9 hypermethylation was more common in tumours from patients older than 60 years of age (15/21 than among those of younger age (11/30; P = 0.023. Finally, there was a significant difference in HOXA9 methylation frequency among the histological types (P = 0.007. Conclusion DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis and HOXA9, HOXB5, SCGB3A1, and CRABP1 are identified as novel hypermethylated target genes in this tumour type.

Clinical Observation on Thyroid Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Park, Seon Yang; Shin, Yong Tae; Cho, Bo Yun; Kim, Byung Kuk; Koh, Chang Soon; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1978-09-15

Clinical features of 147 patients with biopsy-proven thyroid carcinomas were investigated from January, 1972 to April, 1978 at the Seoul National University Hospital with the following results. 1) The incidence of thyroid carcinomas according to their histopathological classification revealed 76.2% of papillary carcinoma, 19.0% of follicular carcinoma, and 3 cases of occult sclerozing carcinoma, 1 case of giant cell carcinoma and 1 case of metastatic melanoma. 2) The ratio of male to female patients was 1:8.3 and showed no difference between papillary and follicular carcinomas. 3) The age distribution showed the peak incidence in the fourth decade (29.3%) followed by the fifth and sixth decades. 4) The average duration of illness from the onset of symptoms was about 5 years while it was 4.4 years and 7.6 years in the papillary and follicular carcinomas respectively. 5) The diameter of the thyroid masses was smaller than 5 cm in 53.6% of the patients, from 5 cm to 10 cm in 40.0% and larger than 10 cm in 6.4%. 6) In 36.4% of the patients with thyroid carcinomas the thyroid masses were fixed to adjacent tissues. 7) Metastasis to the regional lymph nodes was noted in 40.0% of the total cases, and in 45.2% and 17.6% of the papillary and follicular carcinomas respectively, while the lung and bone metastases were found in 10.0% and 4.4% in each type respectively. 8) 88.9% of the patients showed cold areas in the thyroid scans using {sup 131}I. 9) Typical psammoma bodies were observed in 21.3% of the cases in the microscopic examination of the pathological specimens. 10) The initial diagnosis of thyroid malignancy could be made before histological confirmation in 64.5% of the patients. 11) The clinical staging slightly modified from Schulz method revealed 43.6% of the patients in stage I, 26.4% in stage II, 20.9% in stage III and 9.1% in stage IV. 12) The association with Hashimoto's thyroiditis was noted in 4 cases, with nodular goiter in 3 cases, and with follicular

Female parthenogenetic apomixis and androsporogenetic parthenogenesis in embryonal cells of Araucaria angustifolia: interpolation of progenesis and asexual heterospory in an artificial sporangium.

Science.gov (United States)

Durzan, Don J

2012-09-01

Cell fate, development timing and occurrence of reproductive versus apomictic development in gymnosperms are shown to be influenced by culture conditions in vitro. In this study, female parthenogenetic apomixis (fPA), androsporogenetic parthenogenesis (mAP) and progenesis were demonstrated using embryonal initials of Araucaria angustifolia in scaled-up cell suspensions passing through a single-cell bottleneck in darkness and in an artificial sporangium (AS). Expression was based on defined nutrition, hormones and feedforward-adaptive feedback process controls at 23-25 °C and in darkness. In fPA, the nucleus of an embryonal initial undergoes endomitosis and amitosis, forming a diploid egg-equivalent and an apoptotic ventral canal nucleus in a transdifferentiated archegonial tube. Discharge of egg-equivalent cells as parthenospores and their dispersal into the aqueous culture medium were followed by free-nuclear conifer-type proembryogenesis. This replaced the plesiomorphic and central features of proembryogenesis in Araucariaceae. Protoplasmic fusions of embryonal initials were used to reconstruct heterokaryotic expressions of fPA in multiwell plates. In mAP, restitutional meiosis (automixis) was responsible for androsporogenesis and the discharge of monads, dyads, tetrads and polyads. In a display of progenesis, reproductive development was brought to an earlier ontogenetic stage and expressed by embryonal initials. Colchicine increased polyploidy, but androspore formation became aberrant and fragmented. Aberrant automixis led to the formation of chromosomal bouquets, which contributed to genomic silencing in embryonal initials, cytomixis and the formation of pycnotic micronucleated cells. Dispersal of female and male parthenospores displayed heteromorphic asexual heterospory in an aqueous environment.

Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation.

LENUS (Irish Health Repository)

Curry, Sarah

2012-02-01

The 2004 World Health Organization classification includes the new entity "neuroblastoma-associated renal cell carcinoma." The pathogenetic link between these entities is unknown as yet. The patient reported herein developed renal cell carcinoma after anaplastic embryonal rhabdomyosarcoma, a previously unknown association. The 2nd malignancy developed very soon after the 1st one, prompting concern for inherent cancer predisposition rather than a therapy-induced 2nd malignancy. A variety of features raised suspicion for Tp53 mutation, and indeed a pathogenic germline Tp53 mutation was identified in this child, despite a negative family history for Li-Fraumeni syndrome. Consideration of underlying predisposition is advocated in the context of rapid evolution of 2nd childhood malignancy.

Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection

International Nuclear Information System (INIS)

El-Mokadem, Ismail; Lim, Alison; Kidd, Thomas; Garret, Katherine; Pratt, Norman; Batty, David; Fleming, Stewart; Nabi, Ghulam

2016-01-01

Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on

Efficacy of {sup 18}F-FDG PET/CT in the evaluation of patients with recurrent cervical carcinoma

Energy Technology Data Exchange (ETDEWEB)

Mittra, Erik; Rodriguez, Cesar A.; Quon, Andrew; Ross McDougall, I.; Iagaru, Andrei [Stanford Hospitals and Clinics, Division of Nuclear Medicine, Stanford, CA (United States); El-Maghraby, Tarek [Cairo University, Nuclear Medicine, Cairo (Egypt); Saad Specialist Hospital, Nuclear Medicine, Al Khobar (Saudi Arabia); Gambhir, Sanjiv S. [Stanford Hospitals and Clinics, Division of Nuclear Medicine, Stanford, CA (United States); Stanford Hospital and Clinics, Division of Nuclear Medicine, Departments of Radiology and Bioengineering, Stanford, CA (United States)

2009-12-15

Only a limited number of studies have evaluated the efficacy of {sup 18}F-FDG PET/CT for recurrent cervical carcinoma, which this study seeks to expand upon. This is a retrospective study of 30 women with cervical carcinoma who had a surveillance PET/CT after initial therapy. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated using a 2 x 2 contingency table with pathology results (76%) or clinical follow-up (24%) as the gold standard. The Wilson score method was used to perform 95% confidence interval estimations. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for the detection of local recurrence at the primary site were 93, 93, 93, 86, and 96%, respectively. The same values for the detection of distant metastases were 96, 95, 95, 96, and 95%, respectively. Seventy-one percent of the scans performed in symptomatic patients showed true-positive findings. In comparison, 44% of scans performed in asymptomatic patients showed true-positive findings. But, all patients subsequently had a change in their management based on the PET/CT findings such that the effect was notable. The maximum standardized uptake value ranged from 5 to 28 (average: 13 {+-} 7) in the primary site and 3 to 23 (average: 8 {+-} 4) in metastases which were significantly different (p = 0.04). This study demonstrates favorable efficacy of {sup 18}F-FDG PET/CT for identification of residual/recurrent cervical cancer, as well as for localization of distant metastases. (orig.)

Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

International Nuclear Information System (INIS)

Huang, L.-H.; Shiao, N.-H.; Hsuuw, Y.-D.; Chan, W.-H.

2007-01-01

Previous studies have established that ethanol induces apoptosis, but the precise molecular mechanisms are currently unclear. Here, we show that 0.3-1.0% (w/v) ethanol induces apoptosis in mouse blastocysts and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, prevents ethanol-induced apoptosis and inhibition of cell proliferation. Moreover, ethanol-treated blastocysts show normal levels of implantation on culture dishes in vitro but a reduced ability to reach the later stages of embryonic development. Pretreatment with resveratrol prevented ethanol-induced disruption of embryonic development in vitro and in vivo. In an in vitro cell-based assay, we further found that ethanol increases the production of reactive oxygen species in ESC-B5 embryonic stem cells, leading to an increase in the intracellular concentrations of cytoplasmic free Ca 2+ and NO, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c, activation of caspase-9 and -3, and apoptosis. These changes were blocked by pretreatment with resveratrol. Based on these results, we propose a model for the protective effect of resveratrol on ethanol-induced cell injury in blastocysts and ESC-B5 cells

{sup 18}F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Archier, Aurelien; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Heimburger, Celine [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); Guerin, Carole; Palazzo, Fausto F.; Henry, Jean-Francois; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Morange, Isabelle [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Schneegans, Olivier [Paul Strauss Cancer Center, Department of Nuclear Medicine, Strasbourg (France); Abdullah, Ahmad Esmaeel [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Imperiale, Alessio [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); ICube, UMR 7357 University of Strasbourg/CNRS and FMTS, Faculty of Medicine, Strasbourg (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France)

2016-06-15

To evaluate the performance of {sup 18}F-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone {sup 18}F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. {sup 18}F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of {sup 18}F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. {sup 18}F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by {sup 18}F-DOPA PET/CT. (orig.)

In vitro metabolism studies of 18F-labeled 1-phenylpiperazine using mouse liver S9 fraction

International Nuclear Information System (INIS)

Ryu, Eun Kyoung; Choe, Yearn Seong; Kim, Dong Hyun; Ko, Bong-Ho; Choi, Yong; Lee, Kyung-Han; Kim, Byung-Tae

2006-01-01

The in vitro metabolism of 1-(4-[ 18 F]fluoromethylbenzyl)-4-phenylpiperazine ([ 18 F]1) and 1-(4-[ 18 F]fluorobenzyl)-4-phenylpiperazine ([ 18 F]2) was investigated using mouse liver S9 fraction. Results were compared to those of in vivo metabolism using mouse blood and bone and to in vitro metabolism using mouse liver microsomes. Defluorination was the main metabolic pathway for [ 18 F]1 in vitro and in vivo. Based on TLC, HPLC and LC-MS data, [ 18 F]fluoride ion and less polar radioactive metabolites derived from aromatic ring oxidation were detected in vitro, and the latter metabolites were rapidly converted into the former with time, whereas only the [ 18 F]fluoride ion was detected in vivo. Similarly, the in vitro metabolism of [ 18 F]2 using either S9 fraction or microsomes showed the same pattern as the in vivo method using blood; however, the radioactive metabolites derived from aromatic ring oxidation were not detected in vivo. These results demonstrate that liver S9 fraction can be widely used to investigate the intermediate radioactive metabolites and to predict the in vivo metabolism of radiotracers

Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

Science.gov (United States)

Schierz, Jan-Henning; Opfermann, Thomas; Steenbeck, Jörg; Lopatta, Eric; Settmacher, Utz; Stallmach, Andreas; Marlowe, Robert J; Freesmeyer, Martin

2013-06-01

In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. This pilot study

pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

DEFF Research Database (Denmark)

Struckmann, K; Mertz, Kd; Steu, S

2008-01-01

Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship to...

Kinetics and tissue distribution of the radiolabeled chimeric monoclonal antibody MOv18 IgG and F(ab')2 fragments in ovarian carcinoma patients

NARCIS (Netherlands)

Buist, M. R.; Kenemans, P.; den Hollander, W.; Vermorken, J. B.; Molthoff, C. J.; Burger, C. W.; Helmerhorst, T. J.; Baak, J. P.; Roos, J. C.

1993-01-01

Twenty-four patients suspected of having ovarian carcinoma received i.v. injection with a combination of radiolabeled intact IgG (1 mg) and F(ab')2 fragments (1 mg) of the chimeric monoclonal antibody MOv18, each form labeled with 1.85 MBq 131I or 125I. Laparotomy was performed either 2 or 6 days

F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity.

Science.gov (United States)

Miller, C H; Benson, J; Ellingsen, D; Driggers, J; Payne, A; Kelly, F M; Soucie, J M; Craig Hooper, W

2012-05-01

Both genetic and treatment-related risk factors contribute to the development of inhibitors in haemophilia. An inhibitor surveillance system piloted at 12 US sites has the goal of assessing risk factors through prospective data collection. This report examines the relationship of genotype and race/ethnicity to history of inhibitor in a large cohort of US haemophilia patients. Mutation analysis was performed on 676 haemophilia A (HA) and 153 haemophilia B (HB) patients by sequencing, Multiplex Ligation-dependent Probe Amplification, and PCR for inversions in F8 introns 22 (inv22) and 1 (inv1). Two HB patients with deletions had history of inhibitor. In severe HA, frequency of history of inhibitor was: large deletion 57.1%, splice site 35.7%, inv22 26.8%, nonsense 24.5%, frameshift 12.9%, inv1 11.1% and missense 9.5%. In HA, 19.6% of 321 White non-Hispanics (Whites), 37.1% of 35 Black non-Hispanics (Blacks) and 46.9% of 32 Hispanics had history of inhibitor (P = 0.0003). Mutation types and novel mutation rates were similar across ethnicities. When F8 haplotypes were constructed, Whites and Hispanics showed only H1 and H2. Within H1, history of inhibitor was 12.4% in Whites, 40.0% in Blacks (P = 0.009) and 32.4% in Hispanics (P = 0.002). Inhibitor frequency is confirmed to vary by mutation type and race in a large US population. White patients with history of inhibitor did not exhibit rare F8 haplotypes. F8 gene analysis did not reveal a cause for the higher inhibitor frequencies in Black and Hispanic patients. © 2011 Blackwell Publishing Ltd.

18F-FDG-PET for evaluation of the response to concurrent chemoradiation therapy with intensity-modulated radiation technique for Stage T4 nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Yen, T.-C.; Lin, C.-Y.; Wang, H.-M.; Huang, S.-F.; Liao, C.-T.; Kang, C.-J.; Ng, S.-H.; Chan, S.-C.; Fan, K.-H.; Chen, I.-H.; Lin, W.-J.; Cheng, A.-J.; Chang, Joseph Tung-Chieh

2006-01-01

Purpose: This article evaluates [ 18 F] fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) findings as a predictor for local responders (R) vs. nonresponders (NR) in nasopharyngeal carcinoma (NPC) patients with Stage T4 lesions, before and at 3 months after completion of concurrent chemotherapy and radiation therapy (CCRT). Methods and Materials: From January 2002 to November 2003, 39 T4 NPC patients were enrolled. All had magnetic resonance imaging and 18 F-FDG-PET, both before and 3 months after CCRT. Any residual/recurrent lesions were confirmed histopathologically. Results: Of the 39 eligible patients, after a follow-up of 24.2 ± 9.5 months, 35 became disease-free and 4 had residual or recurrent disease. Marginal differences in standard uptake values (SUV) were observed (10.9 ± 5.3 vs. 15.6 ± 3.4, p = 0.058) between R and NR before treatment, and value changes of SUV before and after CCRT were not significantly different. However, highly significantly lower values of SUV were noted for R than for NR 3 months after completion of CCRT (2.1 ± 0.8 vs. 5.5 ± 3.2, p 0.001). One hundred percent positive and negative predictive values were observed for SUV values of 4.0, set 3 months after completion of CCRT. Conclusions: Neither the pretreatment SUV nor the changes of SUV between pretreatment and posttreatment were significant predictors for local response. SUV at 3 months after completion of CCRT was a significant determinator for local response. The cutoff of 4.0 for SUV at 3 months after completion of CCRT was useful to be offered as a diagnostic reference for recurrent or residual tumor for NPC treatment

Giant seminoma case with very small yolk sac and embryo carcinoma components, detected by intensive histopathological examination

Directory of Open Access Journals (Sweden)

Takeo Nakaya, MD

2016-09-01

Full Text Available We experienced the giant seminoma with 18 × 10 × 10 cm sized and about 2.6 kg weight of 25 year old patient. We intensively examined the histological tissue type distributions in this giant seminoma. Most of the tumor consisted of seminoma components. In addition, the tumor included the very small fragments of yolk sac tumor and embryonal carcinoma component at the root part of the seminoma mass. This shows that intensive histological examination may contribute to the finding of other embryonic component of the large seminoma. This may show that leaving the seminoma growing may generate the other embryonic tumor component, not always big enough to find out in a routine procedure, during the growth, in the different way from the original mixed cell germ tumor.

Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

DEFF Research Database (Denmark)

Gao, S.; Worm, J.; Guldberg, P.

2004-01-01

The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours...

[Immunohistochemical study of the specific features of expression of matrix metalloproteinases 1, 9 in the photoaged skin, the foci of actinic keratosis and basal cell carcinoma].

Science.gov (United States)

Kuznetsova, E V; Snarskaya, E S; Zavalishina, L E; Tkachenko, S B

Matrix metalloproteinases (MMPs) mediate the degradation of all types of collagens and other extracellular matrix components (elastin, proteoglycans, and laminin), their synthesis and accumulation play a key role in the hydrolysis of basement membrane. MMPs are involved in a wide range of proteolytic processes in the presence of different physiological and pathological changes, including inflammation, wound healing, angiogenesis, and carcinogenesis. to study the specific features of MMP-1 and MMP-9 expression in different stages of skin photoaging, in the foci of actinic keratosis and basal cell carcinoma by immunohistochemical examination. 12 samples of the healthy skin (6 samples of the eyelid skin with Glogau grade II photoaging; 6 ones of eyelid skin with Glogau grades III-IV photoaging) and biopsies from 8 foci of actinic keratosis and from 8 ones of basal cell carcinoma were examined. A positive reaction to MMPs was shown as different brown staining intensity in the cytoplasm of keratinocytes/tumor cells. MMP-1 and MMP-9 expression was recorded in 67% of the histological specimens of the Glogau grade III photoaged skin and in 100% of those of Glogau grade IV. In the foci of actinic keratosis, the expression of MMP-1 was observed in 62.5% of cases and that of MMP-9 was seen in 87.5%. In basal cell carcinoma, the expression of MMP-1 and MMP-9 was detected in all investigated samples. The immunomorphological findings are indicative of the important role of the level of MMP-1 and MMP-9 expression that is associated with the degree of progression of skin photoaging processes. Minimal MMP-1 and MMP-9 expression was recorded even in grades III-IV photoaging and in the foci of actinic keratosis. Intense MMP-1 and MMP-9 expression was detected in malignant skin epithelial neoplasms as different clinicomorphological types of basal cell carcinoma.

Systematic Kinase Inhibitor Profiling Identifies CDK9 as a Synthetic Lethal Target in NUT Midline Carcinoma

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Johannes Brägelmann

2017-09-01

Full Text Available Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC cells are specifically killed by CDK9 inhibition (CDK9i and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells. Finally, RNA-seq and ChIP-based analyses reveal a BRD4-NUT-specific CDK9i-induced perturbation of transcriptional elongation. Thus, our data provide a mechanistic basis for the genotype-dependent vulnerability of NMC cells to CDK9i that may be of relevance for the development of targeted therapies for NMC patients.

Contribution of autophagy inhibitor to radiation sensitization in nasopharyngeal carcinoma cells

International Nuclear Information System (INIS)

Zhou Zhirui; Zhu Xiaodong; Zhao Wei; Qu song; Pan Wenyan; Guo Ya; Su Fang; Li Xiaoyu

2012-01-01

Objective: To investigate the role of autophagy in radiation-induced death response of human nasopharyngeal carcinoma cells. Methods: MTT method was used to detect cell viability of CNE-2 cells in different time after irradiation. Clonogenic survival assay was used to evaluate the effect of autophagy inhibitor (chloroquine phosphate) and autophagy inductor (rapamycin) on radiosensitivity of nasopharyngeal carcinoma cells.Cell apoptosis was assessed by flow cytometry. The expressions of LC3 and P62 were measured with Western blot. Cell ultrastructural analysis was performed under an electron microscope.Results Irradiation with 10 Gy induced a massive accumulation of autophagosomes accompanied with up-regulation of LC3-Ⅱ expression in CNE-2 cells. Compared with radiation alone, chloroquine phosphate (CDP) enhanced radiosensitivity significantly by decreasing cell viability (F=25.88, P<0.05), autophagic ratio (F=105.15, P<0.05), and LC3-Ⅱ protein level (F=231.68, P<0.05), while up-regulating the expression of P62 (F=117.52, P<0.05). Inhibition of autophagy increased radiation-induced apoptosis (F=143.72, P<0.05). Rapamycin (RAPA) also significantly decreased cell viability, but increased autophagic ratio and LC3-Ⅱ protein level while down-regulated the expression of P62. Induction of autophagy increased radiation-induced apoptosis (F=167.32, P<0.05). Conclusions: Blockage of autophagy with CDP could enhance radiosensitivity in human nasopharyngeal carcinoma cells, suggesting that inhibition of autophagy could be used as an adjuvant treatment to nasopharyngeal carcinoma. (authors)

Detection of distant metastasis and prognostic prediction of recurrent salivary gland carcinomas using 18 F-FDG PET/CT.

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Lee, S H; Roh, J-L; Kim, J S; Lee, J H; Choi, S-H; Nam, S Y; Kim, S Y

2018-04-24

To compare the diagnostic accuracy of 18 F-FDG PET/CT and conventional contrast-enhanced CT for the re-staging of recurrent salivary gland carcinoma (SGC). This study included 58 consecutive patients who underwent recurrent SGCs after definitive treatment. The recurrences were evaluated by 18 F-FDG PET/CT and contrast-enhanced CT of the neck and chest. McNemar's test was used to compare the diagnostic accuracy of 18 F-FDG PET/CT with standard neck and chest CT imaging, and a Cox proportional hazards model was used to assess the prognostic value of PET/CT. Of 58 patients with recurrent SGCs, 17 (29%) had a local recurrence, 17 (29%) had a regional recurrence, and 38 (66%) had a distant metastasis, with these classifications showing overlap. The sensitivity and accuracy of 18 F-FDG PET/CT for the detection of distant metastases were significantly higher than those of CT (P 0.1). The 18 F-FDG PET/CT-positive findings at distant sites were predictors of poor progression-free and overall survival outcome (all P PET/CT is a more effective method than CT for detecting distant site recurrences of SGC. This may lead to prognostic prediction for recurrent SGCs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Critical windows in embryonic development: Shifting incubation temperatures alter heart rate and oxygen consumption of Lake Whitefish (Coregonus clupeaformis) embryos and hatchlings.

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Eme, J; Mueller, C A; Manzon, R G; Somers, C M; Boreham, D R; Wilson, J Y

2015-01-01

Critical windows are periods of developmental susceptibility when the phenotype of an embryonic, juvenile or adult animal may be vulnerable to environmental fluctuations. Temperature has pervasive effects on poikilotherm physiology, and embryos are especially vulnerable to temperature shifts. To identify critical windows, we incubated whitefish embryos at control temperatures of 2°C, 5°C, or 8°C, and shifted treatments among temperatures at the end of gastrulation or organogenesis. Heart rate (fH) and oxygen consumption ( [Formula: see text] ) were measured across embryonic development, and [Formula: see text] was measured in 1-day old hatchlings. Thermal shifts, up or down, from initial incubation temperatures caused persistent changes in fH and [Formula: see text] compared to control embryos measured at the same temperature (2°C, 5°C, or 8°C). Most prominently, when embryos were measured at organogenesis, shifting incubation temperature after gastrulation significantly lowered [Formula: see text] or fH. Incubation at 2°C or 5°C through gastrulation significantly lowered [Formula: see text] (42% decrease) and fH (20% decrease) at 8°C, incubation at 2°C significantly lowered [Formula: see text] (40% decrease) and fH (30% decrease) at 5°C, and incubation at 5°C and 8°C significantly lowered [Formula: see text] at 2°C (27% decrease). Through the latter half of development, [Formula: see text] and fH in embryos were not different from control values for thermally shifted treatments. However, in hatchlings measured at 2°C, [Formula: see text] was higher in groups incubated at 5°C or 8°C through organogenesis, compared to 2°C controls (43 or 65% increase, respectively). Collectively, these data suggest that embryonic development through organogenesis represents a critical window of embryonic and hatchling phenotypic plasticity. This study presents an experimental design that identified thermally sensitive periods for fish embryos. Crown Copyright �

Clinical Significance of 18F-FDG-PET in Invasive Lobular Carcinoma.

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Fujii, Takaaki; Yajima, Reina; Kurozumi, Sasagu; Higuchi, Toru; Obayashi, Sayaka; Tokiniwa, Hideaki; Nagaoka, Rin; Takata, Daisuke; Horiguchi, Jun; Kuwano, Hiroyuki

2016-10-01

The diagnostic utility of 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for breast cancer is controversial. The histological type or tumor size of breast cancer has been reported to be associated with a greater likelihood of positive FDG uptake. Compared to invasive ductal carcinomas (IDCs), invasive lobular carcinomas (ILCs) have a lower level of FDG uptake and are detected at a significantly lower sensitivity. The role of preoperative FDG-PET for ILCs may, thus, be limited. Few data evaluating the significance of FDG-PET in ILCs are available. Here, we evaluated the clinical significance of FDG-PET for ILC patients. We retrospectively investigated the cases of 196 consecutive patients with primary breast cancer who were diagnosed as having ILC (n=15) or IDC (n=181) and underwent FDG-PET preoperatively. Fifteen (7.7%) of patients were histopathologically diagnosed as ILC. A univariate analysis revealed that tumor size, extent of tumor, estrogen receptor (ER) expression and progesterone receptor (PgR) expression were significantly different between the ILC and IDC groups. The maximum standardized uptake value (SUV max ) values of the primary tumors were not significantly different between the two groups but, regardless of the larger size of tumor or ductal spread, the SUV max was relatively lower in the ILC group compared to the IDC group. The tumors in two ILC cases showed no FDG uptake. Among the ILC cases, there were linear associations between SUV max and tumor size and between SUV max and the nuclear grade by Pearson correlation (r=0.447, p=0.048 and r=0.519, p=0.024, respectively). Our findings imply that the preoperative FDG uptake in ILC may be reflective of the tumor size and the nuclear grade of the tumor. FDG uptake may be useful and predictive of aggressive features or prognosis in ILC patients. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

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Liu, Feng-Yuan; Su, Tzu-Pei; Wang, Chun-Chieh; Chao, Angel; Chou, Hung-Hsueh; Chang, Yu-Chen; Yen, Tzu-Chen; Lai, Chyong-Huey

2018-07-01

To assess the clinical roles of [ 18 F]fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial. Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT. PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN.

Research advances in Hedgehog signaling pathway in hepatocellular carcinoma

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LIU Jia

2015-02-01

Full Text Available Hedgehog (Hh signaling pathway is present in many animals and plays an important role in regulating embryonic development and differentiation. Aberrant activation of Hh signaling contributes to the pathogenesis of many malignancies. Recent studies have shown that dysregulated Hh signaling pathway participates in the tumorigenesis, tumor invasion, and metastasis of hepatocellular carcinoma (HCC. Investigation of the relationship between Hh signaling pathway and HCC will help elucidate the molecular mechanism of pathogenesis of HCC and provide a new insight into the development of novel anticancer therapy and therapeutic target.

Septin9 is involved in septin filament formation and cellular stability

DEFF Research Database (Denmark)

Füchtbauer, Annette C.; Lassen, Louise Berkhoudt; Jensen, Astrid Bøgh

2011-01-01

in embryonic lethality around day 10 of gestation whereas mice homozygous for the conditional allele develop normally. Here we report the consequences of homozygous loss of Sept9 in immortalized murine embryonic fibroblasts. Proliferation rate was not changed but cells without Sept9 had an altered morphology...

Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance in patients with advanced T-stage oropharyngeal squamous cell carcinoma.

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Cheng, Nai-Ming; Fang, Yu-Hua Dean; Chang, Joseph Tung-Chieh; Huang, Chung-Guei; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Lin, Chien-Yu; Liao, Chun-Ta; Yen, Tzu-Chen

2013-10-01

Previous studies have shown that total lesion glycolysis (TLG) may serve as a prognostic indicator in oropharyngeal squamous cell carcinoma (OPSCC). We sought to investigate whether the textural features of pretreatment (18)F-FDG PET/CT images can provide any additional prognostic information over TLG and clinical staging in patients with advanced T-stage OPSCC. We retrospectively analyzed the pretreatment (18)F-FDG PET/CT images of 70 patients with advanced T-stage OPSCC who had completed concurrent chemoradiotherapy, bioradiotherapy, or radiotherapy with curative intent. All of the patients had data on human papillomavirus (HPV) infection and were followed up for at least 24 mo or until death. A standardized uptake value (SUV) of 2.5 was taken as a cutoff for tumor boundary. The textural features of pretreatment (18)F-FDG PET/CT images were extracted from histogram analysis (SUV variance and SUV entropy), normalized gray-level cooccurrence matrix (uniformity, entropy, dissimilarity, contrast, homogeneity, inverse different moment, and correlation), and neighborhood gray-tone difference matrix (coarseness, contrast, busyness, complexity, and strength). Receiver-operating-characteristic curves were used to identify the optimal cutoff values for the textural features and TLG. Thirteen patients were HPV-positive. Multivariate Cox regression analysis showed that age, tumor TLG, and uniformity were independently associated with progression-free survival (PFS) and disease-specific survival (DSS). TLG, uniformity, and HPV positivity were significantly associated with overall survival (OS). A prognostic scoring system based on TLG and uniformity was derived. Patients who presented with TLG > 121.9 g and uniformity ≤ 0.138 experienced significantly worse PFS, DSS, and OS rates than those without (P 121.9 g or uniformity ≤ 0.138 were further divided according to age, and different PFS and DSS were observed. Uniformity extracted from the normalized gray

Wind-Tunnel Investigation at Low Speed of the Rolling Stability Derivatives of a 1/10-Scale Model of the Grumman F9F-9 Airplane, TED No. NACA AD 3109

Science.gov (United States)

Wolhart, Walter D.; Thomas, David F., Jr.

1955-01-01

An experimental investigation has been made in the Langley stability tunnel to determine the low-speed yawing, pitching, and static stability characteristics of a 1/10-scale model of the Grumman F9F-9 airplane. Tests were made to determine the effects of duct-entrance-fairing plugs on the static lateral and longitudinal stability characteristics of the complete model in the clean condition. The remaining tests were concerned with determining tail contributions as well as the effect of duct-entrance-fairing plugs, slats, flaps, and landing gear on the yawing and pitching stability derivatives. These data are presented without analysis in order to expedite distribution.

Clinical Application of {sup 18}F-FDG PET in Nonmelanomatous Skin Cancer

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Yoon, Joon Kee [Ajou University School of Medicine, Suwon (Korea, Republic of)

2008-12-15

Nonmelanomatous skin cancer includes basal cell carcinoma, squamous cell carcinoma, merkel cell carcinoma and dermatofibrosarcoma protuberance. So far, there have been a few reports that {sup 18}F-FDG PET was useful in the evaluation of metastasis and therapeutic response in nonmelanomatous skin cancer, however, those are very weak evidences. Therefore, further studies on the usefulness of {sup 18}F-FDG PET in nonmelanomatous skin cancer are required.

Tensile Strength of the Al-9%Si Alloy Modified with Na, F and Cl Compounds

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T. Lipiński

2010-01-01

Full Text Available The modification of the Al-9%Si alloy with the use of a complex modifier containing Na, F and Cl was investigated in the study. The modifier was composed of NaCl, Na3AlF6 and NaF compounds. The modifier and the liquid Al-Si alloy were kept in the crucible for 15 minutes. The modifier's effect relative to the weight of the processed alloy on its tensile strength was presented in graphic form. The results of the study indicate that the complex modifier altered the investigated properties of the eutectic Al-9%Si alloy.

Expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder.

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Ai, Xing; Zhang, Xu; Wu, Zhun; Ma, Xin; Ju, Zhenghua; Wang, Baojun; Shi, Taoping

2007-02-01

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (PMRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P>0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (PMRP-1/CD9 expression was statistically significant (r=0.316, PMRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells.

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Roman J Krawetz

Full Text Available The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK play pivotal roles in cell migration, apoptosis (membrane blebbing, cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the

Thyroid Metastasis from Breast Carcinoma Accompanied by Papillary Thyroid Carcinoma

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Song-I Yang

2014-07-01

Full Text Available Metastasis to the thyroid gland is very rare. Recently, we experienced a case of thyroid metastasis from breast cancer accompanying a papillary thyroid. A 51-year-old female patient presented with a palpated lymph node on her left lateral neck. The patient had undergone a left modified radical mastectomy followed by chemotherapy and hormonal therapy 12 years prior. Ultrasonography of the neck revealed a malignant looking nodule at the left thyroid lobe, measuring 0.9 × 0.9 cm, and several cystic nodules at the right thyroid lobe. Ultrasonography of the neck additionally revealed a malignant looking lymph node at the right level VI. Fine-needle aspiration of the left thyroid lobe resulted in a diagnosis of papillary thyroid carcinoma and that of the right level VI in Hurthle cell lesion. The patient had a total thyroidectomy with selective dissection of the left neck node. Pathologic assessment of the specimen revealed metastatic carcinoma from the breast carcinoma and papillary thyroid carcinoma. Although the thyroid gland is highly vascularized, metastasis of malignant tumors to the thyroid is relatively rare and detection of metastasis shows a low frequency. So a careful evaluation of thyroid tumor should be considered in a patient with a history of other malignancy.

Evaluation of 18F-labeled exendin(9-39) derivatives targeting glucagon-like peptide-1 receptor for pancreatic β-cell imaging.

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Kimura, Hiroyuki; Ogawa, Yu; Fujimoto, Hiroyuki; Mukai, Eri; Kawashima, Hidekazu; Arimitsu, Kenji; Toyoda, Kentaro; Fujita, Naotaka; Yagi, Yusuke; Hamamatsu, Keita; Murakami, Takaaki; Murakami, Atsushi; Ono, Masahiro; Nakamoto, Yuji; Togashi, Kaori; Inagaki, Nobuya; Saji, Hideo

2018-01-15

β-cell mass (BCM) is known to be decreased in subjects with type-2 diabetes (T2D). Quantitative analysis for BCM would be useful for understanding how T2D progresses and how BCM affects treatment efficacy and for earlier diagnosis of T2D and development of new therapeutic strategies. However, a noninvasive method to measure BCM has not yet been developed. We developed four 18 F-labeled exendin(9-39) derivatives for β-cell imaging by PET: [ 18 F]FB9-Ex(9-39), [ 18 F]FB12-Ex(9-39), [ 18 F]FB27-Ex(9-39), and [ 18 F]FB40-Ex(9-39). Affinity to the glucagon-like peptide-1 receptor (GLP-1R) was evaluated with dispersed islet cells of ddY mice. Uptake of exendin(9-39) derivatives in the pancreas as well as in other organs was evaluated by a biodistribution study. Small-animal PET study was performed after injecting [ 18 F]FB40-Ex(9-39). FB40-Ex(9-39) showed moderate affinity to the GLP-1R. Among all of the derivatives, [ 18 F]FB40-Ex(9-39) resulted in the highest uptake of radioactivity in the pancreas 30 min after injection. Moreover, it showed significantly less radioactivity accumulated in the liver and kidney, resulting in an overall increase in the pancreas-to-organ ratio. In the PET imaging study, pancreas was visualized at 30 min after injection of [ 18 F]FB40-Ex(9-39). [ 18 F]FB40-Ex(9-39) met the basic requirements for an imaging probe for GLP-1R in pancreatic β-cells. Further enhancement of pancreatic uptake and specific binding to GLP-1R will lead to a clear visualization of pancreatic β-cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanobiology of embryonic limb development.

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Nowlan, Niamh C; Murphy, Paula; Prendergast, Patrick J

2007-04-01

Considerable evidence exists to support the hypothesis that mechanical forces have an essential role in healthy embryonic skeletal development. Clinical observations and experimental data indicate the importance of muscle contractions for limb development. However, the influence of these forces is seldom referred to in biological descriptions of bone development, and perhaps this is due to the fact that the hypothesis that mechanical forces are essential for normal embryonic skeletal development is difficult to test and elaborate experimentally in vivo, particularly in humans. Computational modeling has the potential to address this issue by simulating embryonic growth under a range of loading conditions but the potential of such models has yet to be fully exploited. In this article, we review the literature on mechanobiology of limb development in three main sections: (a) experimental alteration of the mechanical environment, (b) mechanical properties of embryonic tissues, and (c) the use of computational models. Then we analyze the main issues, and suggest how experimental and computational fields could work closer together to enhance our understanding of mechanobiology of the embryonic skeleton.

{alpha}{sub v}{beta}{sub 3} imaging can accurately distinguish between mature teratoma and necrosis in {sup 18}F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

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Aide, Nicolas [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Centre Francois Baclesse, Service de Medecine Nucleaire, Caen (France); Briand, Melanie; Dutoit, Soizic; Deslandes, Edwiges; Poulain, Laurent [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Bohn, Pierre; Rouvet, Jean; Modzelewski, Romain; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Department of Nuclear Medicine, Rouen (France); Lasnon, Charline [Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Chasle, Jacques [Francois Baclesse Cancer Centre and Caen University, Pathology Department, Caen (France); Vela, Antony [Francois Baclesse Cancer Centre and Caen University, Radiophysics Unit, Caen (France); Carreiras, Franck [Universite de Cergy Pontoise, UFR Sciences et Techniques, ERRMECe, EA 1391, Institut des materiaux, Cergy-Pontoise (France)

2011-02-15

We assessed whether imaging {alpha}{sub v}{beta}{sub 3} integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).{sup 18}F-Fluorodeoxyglucose ({sup 18}F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of {alpha}{sub v}{beta}{sub 3} expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [{sup 99m}Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse {alpha}{sub v}{beta}{sub 3} expression were performed. Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for {sup 18}F-FDG [mean standardised uptake value (SUV{sub mean}) = 0.48 {+-} 0.05] compared to untreated embryonal carcinoma (SUV{sub mean} = 0.92 {+-} 0.13) (p = 0.005). {alpha}{sub v}{beta}{sub 3} imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 {+-} 1.57) from necrosis (tumour to muscle ratio = 1.3 {+-} 0.26) (p = 0.0002). Immunohistochemistry studies showed that {alpha}{sub v}{beta}{sub 3} integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. Imaging {alpha}{sub v}{beta}{sub 3} integrin accurately distinguished mature teratoma from

Diagnostic accuracy of (18) F-methylcholine positron emission tomography/computed tomography for intra- and extrahepatic hepatocellular carcinoma.

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Bieze, Matthanja; Klümpen, Heinz-Josef; Verheij, Joanne; Beuers, Ulrich; Phoa, Saffire S K S; van Gulik, Thomas M; Bennink, Roelof J

2014-03-01

Diagnosis of hepatocellular carcinoma (HCC) primarily involves imaging. The aim of this study was to assess the accuracy of (18) F-fluorocholine ((18) F-FCH) positron emission tomography (PET) for detection of HCC and evaluation of extent of disease. Patients with HCC >1 cm were included between 2009 and July 2011, and follow-up closed in February 2013. Diagnosis was based on American Association for the Study of Liver Diseases criteria, and all patients underwent (18) F-FCH PET/computed tomography (CT) at baseline before treatment, 6 underwent a second PET/CT posttreatment, and 1 a third during follow-up. Whole-body PET and low-dose CT imaging were performed 15 minutes after (18) F-FCH injection. Evaluation of imaging was done with standardized uptake value (SUV) ratios: SUV maximum of the lesion divided by the SUV mean of surrounding tissue. Statistical analyses included descriptive analyses, receiver operating characteristic curve, McNemar's test, and Kaplan-Meier's test at 5% level of significance. Twenty-nine patients revealed 53 intrahepatic lesions. In 48 of 53 lesions, (18) F-FCH PET was positive (SUVratio , 1.95 ± 0.66; sensitivity, 88%; specificity, 100%). PET/CT showed uptake in 18 extrahepatic lesions and no uptake in 3 lesions affirmed non-HCC lesions; all lesions were confirmed with additional investigation (accuracy, 100%). In 17 of 29 patients, additional lesions were found on PET/CT imaging, with implications for treatment in 15 patients. Posttreatment PET/CT showed identical results, compared with standard treatment evaluation. This study shows additional value of (18) F-FCH PET/CT for patients with HCC. (18) F-FCH PET/CT has implications for staging, management, and treatment evaluation because of accurate assessment of extrahepatic disease. © 2014 by the American Association for the Study of Liver Diseases.

Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population.

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Kavanaugh, Gina; Williams, Jason; Morris, Andrew Scott; Nickels, Michael L; Walker, Ronald; Koglin, Norman; Stephens, Andrew W; Washington, M Kay; Geevarghese, Sunil K; Liu, Qi; Ayers, Dan; Shyr, Yu; Manning, H Charles

2016-12-01

Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[ 18 F]fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [ 18 F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [ 11 C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [ 18 F]FSPG PET/CT and present the first comparison to [ 11 C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. x C- transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [ 18 F]FSPG PET/CT, with seven patients also imaged with [ 11 C]acetate PET/CT. x C- transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [ 18 F]FSPG PET/CT demonstrated a detection rate of 75 %. [ 18 F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [ 18 F]FSPG and [ 11 C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [ 18 F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [ 11 C]acetate PET/CT. [ 18 F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [ 18 F]FSPG PET/CT impact on diagnosis and management of HCC. [ 18 F

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Full Text Available His.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 Histone Liver Carcinoma, Hepatocellu...lar http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

Inference of Transcriptional Network for Pluripotency in Mouse Embryonic Stem Cells

International Nuclear Information System (INIS)

Aburatani, S

2015-01-01

In embryonic stem cells, various transcription factors (TFs) maintain pluripotency. To gain insights into the regulatory system controlling pluripotency, I inferred the regulatory relationships between the TFs expressed in ES cells. In this study, I applied a method based on structural equation modeling (SEM), combined with factor analysis, to 649 expression profiles of 19 TF genes measured in mouse Embryonic Stem Cells (ESCs). The factor analysis identified 19 TF genes that were regulated by several unmeasured factors. Since the known cell reprogramming TF genes (Pou5f1, Sox2 and Nanog) are regulated by different factors, each estimated factor is considered to be an input for signal transduction to control pluripotency in mouse ESCs. In the inferred network model, TF proteins were also arranged as unmeasured factors that control other TFs. The interpretation of the inferred network model revealed the regulatory mechanism for controlling pluripotency in ES cells

Genomic instability in human actinic keratosis and squamous cell carcinoma

Science.gov (United States)

Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

2011-01-01

OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

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SU-E-I-85: Exploring the 18F-Fluorodeoxyglucose PET Characteristics in Staging of Esophageal Squamous Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Ma, C; Yin, Y [Shandong Cancer Hospital, Jinan, Shandong (China)

2014-06-01

Purpose: The aim of this study was to explore the characteristics derived from 18F-fluorodeoxyglucose (18F-FDG) PET image and assess its capacity in staging of esophageal squamous cell carcinoma (ESCC). Methods: 26 patients with newly diagnosed ESCC who underwent 18F-FDG PET scan were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, texture features and shape feature were considered. Taken the histopathologic examination as the gold standard, the extracted capacities of indices in staging of ESCC were assessed by Kruskal-Wallis test and Mann-Whitney test. Specificity and sensitivity for each of the studied parameters were derived using receiver-operating characteristic curves. Results: 18F-FDG SUVmax and SUVmean showed statistically significant capability in AJCC and TNM stages. Texture features such as ENT and CORR were significant factors for N stages(p=0.040, p=0.029). Both FDG PET Longitudinal length and shape feature Eccentricity (EC) (p≤0.010) provided powerful stratification in the primary ESCC AJCC and TNM stages than SUV and texture features. Receiver-operating-characteristic curve analysis showed that tumor textural analysis can capability M stages with higher sensitivity than SUV measurement but lower in T and N stages. Conclusion: The 18F-FDG image-derived characteristics of SUV, textural features and shape feature allow for good stratification AJCC and TNM stage in ESCC patients.

Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

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Zong-yu XIAO

2015-04-01

Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

Diagnostic value of combining {sup 11}C-choline and {sup 18}F-FDG PET/CT in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Castilla-Lievre, Maria-Angela [University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Department of Nuclear Medicine, Hopital Antoine Beclere, Clamart (France); IMIV - UMR 1023 Inserm/CEA/Universite Paris Sud - ERL 9218 CNRS, Orsay (France); Franco, Dominique [Universite Paris-Sud, Department of Surgery, Hopital Antoine Beclere, University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clamart (France); Gervais, Philippe; Kuhnast, Bertrand; Desarnaud, Serge; Helal, Badia-Ourkia [IMIV - UMR 1023 Inserm/CEA/Universite Paris Sud - ERL 9218 CNRS, Orsay (France); CEA, DSV, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Agostini, Helene [University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clinical Research Unit of Hopitaux universitaires Paris-Sud, Hopital Kremlin Bicetre (France); Marthey, Lysiane [Universite Paris-Sud, Department of Gastroenterology, Hopital Antoine Beclere, University Department Hepatinov, Assistance-Publique Hopitaux de Paris, Clamart (France)

2016-05-15

In this prospective study, our goal was to emphasize the diagnostic value of combining {sup 11}C-choline and {sup 18}F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease. Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death). Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of {sup 11}C-choline, {sup 18}F-FDG and combined {sup 11}C-choline and {sup 18}F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with {sup 18}F-FDG-positive lesions than those with {sup 18}F-FDG-negative lesions (p < 0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with {sup 18}F-FDG-positive lesions than in those with {sup 18}F-FDG-negative lesions (p < 0.05). The combined use of {sup 11}C-choline and {sup 18}F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation. (orig.)

Evaluation of renal cell carcinoma histological subtype and fuhrman grade using {sup 18}F-fluorodeoxyglucose-positron emission tomography/computed tomography

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Nakajima, Reiko; Nozaki, Sayumi; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan); Nagashima, Yoji [Tokyo Women' s Medical University, Department of Surgical Pathology, Tokyo (Japan)

2017-11-15

We evaluated {sup 18}F-fluorodeoxyglucose (FDG) uptake by renal cell carcinomas (RCCs) to determine whether different histological subtypes and Fuhrman grades can be distinguished. We retrospectively reviewed the records and maximum standardised uptake value (SUVmax) of 147 patients with 154 RCCs who underwent FDG-positron emission tomography (PET)/computed tomography (CT) prior to tumour resection. The SUVmax was significantly lower in chromophobe RCC (chRCC) tumours than in clear cell RCC (ccRCC; p = 0.003) and papillary RCC (pRCC; p = 0.034) tumours. The mean tumour SUVmax was 4.58 ± 4.1 (range, 1.29-30.4) for ccRCC, 3.98 ± 1.9 (range, 0.49-6.72) for pRCC, and 1.93 ± 0.9 (range, 0.89-3.41) for chRCC. The SUVmax was not significantly different between the ccRCC and pRCC groups. In ccRCC and pRCC tumours, high-grade tumours had a significantly greater SUVmax (p < 0.001 and p < 0.05) than low-grade tumours by analysis of variance (ANOVA) and the Mann-Whitney U test. In ccRCC, multivariate regression analysis indicated that the SUVmax was a significant indicator of Fuhrman grade. No significant differences in uptake were observed between high- and low-grade chRCC tumours. The SUVmax obtained using FDG-PET/CT may be an important indicator for predicting tumour grade in ccRCC and pRCC. (orig.)

Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

Science.gov (United States)

Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

2014-01-01

Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

PET imaging of EGF receptors using [{sup 18}F]FBEM-EGF in a head and neck squamous cell carcinoma model

Energy Technology Data Exchange (ETDEWEB)

Li, Weihua [Harbin Medical University, Department of Medical Imaging and Nuclear Medicine, Fourth Affiliated Hospital, Harbin (China); National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States); Niu, Gang; Lang, Lixin; Guo, Ning; Ma, Ying; Kiesewetter, Dale O.; Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States); Backer, Joseph M. [SibTech Inc., Brookfield, CT (United States); Shen, Baozhong [Harbin Medical University, Department of Medical Imaging and Nuclear Medicine, Fourth Affiliated Hospital, Harbin (China)

2012-02-15

To prepare and evaluate a new radiotracer for molecular imaging of cell surface receptors for epidermal growth factor (EGF). Cys-tagged EGF (cEGF) was labeled with {sup 18}F by coupling the free thiol group of the Cys tag with N-[2-(4-[{sup 18}F]fluorobenzamido)ethyl]maleimide ([{sup 18}F]FBEM) to form [{sup 18}F]FBEM-cEGF. Cell uptake, internalization and efflux of [{sup 18}F]FBEM-cEGF were tested in human head and neck squamous carcinoma UM-SCC1 cells. In vivo tumor targeting and pharmacokinetics of the radiotracers were evaluated in UM-SCC1 tumor-bearing athymic nude mice by static and dynamic microPET imaging. Ex vivo biodistribution assays were performed to confirm the noninvasive imaging results. The radiolabeling yield for [{sup 18}F]FBEM-cEGF was over 60%, based on starting [{sup 18}F]FBEM. [{sup 18}F]FBEM-cEGF exhibited rapid blood clearance through both hepatobiliary and renal excretion. UM-SCC1 tumors were clearly visualized and showed modest tracer uptake of 2.60 {+-} 0.59 %ID/g at 30 min after injection. Significantly higher tumor uptake of [{sup 18}F]FBEM-cEGF (5.99 {+-} 1.61%ID/g at 30 min after injection, p < 0.01) and tumor/nontumor ratio were achieved by coinjection of 50 {mu}g of unlabeled EGF. Decreased liver uptake of [{sup 18}F]FBEM-cEGF was observed when unlabeled EGF was coadministered. With optimized liver blocking, [{sup 18}F]FBEM-cEGF has the potential to be used in a noninvasive and quantitative manner for detection of malignant lesions and evaluation of EGFR activity. (orig.)

Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography

International Nuclear Information System (INIS)

Lee, Jong Doo; Yun, Mijin; Lee, Jae Myun; Choi, Youjeong; Choi, Youn-Hee; Kim, Ji Su; Kim, Se Jong; Park, Jeon Han; Kim, Kyung Sik; Lee, Woo Jung; Yang, Woo Ick; Park, Young Nyun; Han, Kwang-Hyub; Yoo, Naechun; Lim, Sang Moo

2004-01-01

18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumour aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of hepatocellular carcinomas (HCCs) were evaluated to determine whether HCCs with high 18 F-FDG uptake have more aggressive biological potential than those with low uptake. Surgical specimens were obtained from ten patients with HCC (six males and four females, age range 38-68 years). The tumour samples were divided into two groups based on the 18 F-FDG PET scan findings: high 18 F-FDG uptake (n=4) and low 18 F-FDG uptake (n=6). The pathological tumour grade was closely correlated with the 18 F-FDG uptake pattern: HCCs with high 18 F-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were either grade II or grade II with a focal area of grade III. The total RNA was extracted from the frozen tissues of all HCCs (n=10) and adjacent non-cancerous tissue (n=7). The gene expression profiles were evaluated using an oligoDNA microarray. The HCCs with high 18 F-FDG uptake showed increased expression of 11 genes - including vascular cell adhesion molecule-1, vinexin beta and core 1 UDP-galactose: N-acetylgalactosamine-alpha-R-beta 1,3-galactosyltransferase and the natural killer cell inhibitory receptor - compared to those with low uptake (p 18 F-FDG uptake appear to have more aggressive biological properties than those with low uptake. (orig.)

The 18F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

International Nuclear Information System (INIS)

Wu Jinchang

2002-01-01

In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18 F-Deoxyglucose (FDG) by PET prior to surgery and the DNA content and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46(93.88%) were aneuploidy and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18 F-FDG PET as a non-invasive metabolic imaging technique, may also provide information correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction

File list: Oth.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

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Full Text Available Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

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Full Text Available Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients

Directory of Open Access Journals (Sweden)

Gallagher Michael F

2009-12-01

Full Text Available Abstract Background Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-like populations within malignancies. We aim to identify molecular mechanism associated with the generation of tumours with differing grades from malignant stem cell populations with different differentiation potentials. In this study we assessed microRNA (miRNA regulation in two populations of malignant Embryonal Carcinoma (EC stem cell, which differentiate (NTera2 or remain undifferentiated (2102Ep during tumourigenesis, and compared this to miRNA regulation in ovarian serous carcinoma (OSC patient samples. Methods miRNA expression was assessed in NTera2 and 2102Ep cells in the undifferentiated and differentiated states and compared to that of OSC samples using miRNA qPCR. Results Our analysis reveals a substantial overlap between miRNA regulation in 2102Ep cells and OSC samples in terms of miRNA biosynthesis and expression of mature miRNAs, particularly those of the miR-17/92 family and clustering to chromosomes 14 and 19. In the undifferentiated state 2102Ep cells expressed mature miRNAs at up to 15,000 fold increased levels despite decreased expression of miRNA biosynthesis genes Drosha and Dicer. 2102Ep cells avoid differentiation, which we show is associated with consistent levels of expression of miRNA biosynthesis genes and mature miRNAs while expression of miRNAs clustering to chromosomes 14 and 19 is deemphasised. OSC patient samples displayed decreased expression of miRNA biosynthesis genes, decreased expression of mature miRNAs and prominent clustering to chromosome 14 but not 19. This indicates that miRNA biosynthesis and levels of miRNA expression, particularly from chromosome 14, are tightly regulated both in progenitor cells and in tumour samples. Conclusion miRNA biosynthesis and

Clinic results of 121 nasopharyngeal carcinoma patients treated by helical tomotherapy

International Nuclear Information System (INIS)

Du Lei; Ma Lin; Feng Linchun; Zhou Guixia; Qu Baolin; Ren Gang; Xu Shouping; Xie Chuanbin; Zhang Xinxin; Li Fang

2012-01-01

Objective: To summarize the outcome of nasopharyngeal carcinoma (NPC) treated by helical tomotherapy in the Chinese PLA general hospital. Methods: Between September 2007 and August 2010, 121 newly diagnosed NPC patients were treated by radiotherapy with Tomotherapy system, with (n =90) or without (n = 31) concurrent chemotherapy or molecular target therapy. The prescription dose was 70 - 74 Gy/33f to primary tumor and positive lymph node planning target volume, 60.0 - 62.7 Gy/33f to high risk planning target volume, and 52 -56 Gy/33f to low risk planning target volume. Acute side-effects were evaluated with RTOG/EORTC criteria. Results: The remission rate of primary lesion and positive lymph nodes was 95.0% and 99.0%, respectively. The follow-up rate was 100%. The number of patients with 1, 2 and 3 years followed-up were 99, 49, and 7. The 1-, 2-and 3-year local relapse-free survival rates were 97.30%, 97.3% and 97.3%, respectively. The 1-, 2-and 3-year nodal relapse-free survival rates were 100%, 100% and 100%, respectively. The 1-, 2-and 3-year distant metastasis-free survival rates were 98.4%, 96.3% and 96.3%, respectively. The 1-, 2-and 3-year overall survival rates were 96.5%, 92.6% and 86.8%, respectively. Acute toxicities of skin, oral mucosa and xerostomia with grade 0, 1, 2 and 3 were 5.0%, 74.4%, 15.7% and 4.9%; 0.8%, 37.2%, 57.9% and 4.1%; 3.3%, 53.7%, 43.0% and 0%, respectively. Xerostomia restored with time, no grade 2 or more xerostomia was observed 1 year after radiation therapy. Concurrent chemotherapy significantly increased incidence of mucositis, esophagitis and tracheitis. Conclusion: Helical tomotherapy is efficient, secure and effective modality for the treatment of nasopharyngeal carcinoma. (authors)

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Remaining Sites Verification Package for the 100-F-26:9, 1607-F2 Sanitary Sewer Pipelines. Attachment to Waste Site Reclassification Form 2008-029

International Nuclear Information System (INIS)

Capron, J.M.

2008-01-01

The 100-F-26:9 underground pipeline subsite consists of the sanitary sewers servicing the 105-F, 108-F, 184-F, 185-F, and 190-F buildings, and the 1700-F administration and service buildings (1704-F, 1707-F, 1707-FA, 1713-F, 1717-F, 1719-F, and 1722-F). In accordance with this evaluation, the confirmatory and verification sampling results support a reclassification of this site to Interim Closed Out. The current site conditions achieve the remedial action objectives and the corresponding remedial action goals established in the Remaining Sites ROD. The results of verification sampling show that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River

Characterization of glycolipid galactosyltransferases from embryonic chicken brain

International Nuclear Information System (INIS)

Kyle, J.W.

1985-01-01

Glycolipid galactosyltransferases (GalT-3 and GalT-4) were solubilized from a membrane fraction isolated from embryonic chicken brain. The profiles of specific activity and total units per brain of GalT-3 and GalT-4 varied with embryonic age. GalT-4 had the highest specific activity at 9 days of embryonic development and showed a steady decrease until hatching. GalT-3 showed a gradual increase in specific activity. Both GalT3 and GalT-4 showed a steady increase in total units per brain throughout embryonic development. The solubilized enzymes could be separated using gel filtration, ion exchange chromatography or affinity chromatography on α-lactalbumin-agarose. Data obtained in the study imply that GalT-4 is involved in both glycoprotein and glycolipid biosynthesis. Glycosphingolipid products from GalT-3 and GalT-4 catalyzed reactions labeled with [ 14 C]galactose comigrated with authentic GMI and nLcOse 4 Cer, when examined by thin layer chromatography and autoradiography. Studies with galactosidases revealed that all of the enzyme products formed by GalT-3 and GalT-4 contained a [ 14 C]-galactose in a β anomeric linkage. Periodate oxidation studies of Gal-[ 14 C]GlcNAc, formed by purified GalT-4 using [ 14 C]GlcNAc as the acceptor, demonstrated that approximately 70% of the linkage formed was Galβ1-4GlcNAc and 30% was Galβ1-3GlcNAc. Studies on the susceptibility of [ 14 C]Gal-GlcNAc to base catalyzed β-elimination also suggested the presence of approximately 30% Galβ1-3GlcNAc

Wnt and Hedgehog Signaling Regulate the Differentiation of F9 Cells into Extraembryonic Endoderm

Directory of Open Access Journals (Sweden)

Gurjoth S. J. Deol

2017-10-01

Full Text Available Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE when treated with retinoic acid (RA, and this is accompanied by an up-regulation of Gata6. The role of the GATA6 network in PrE differentiation is known, and we have shown it directly activates Wnt6. Canonical Wnt/β-catenin signaling is required by F9 cells to differentiate to PrE, and this, like most developmental processes, requires input from one or more additional pathways. We found both RA and Gata6 overexpression, can induce the expression of Indian Hedgehog (Ihh and a subset of its target genes through Gli activation during PrE induction. Chemical activation of the Hh pathway using a Smoothened agonist (SAG also increased Gli reporter activity, and as expected, when Hh signaling was blocked with a Smoothened antagonist, cyclopamine, this RA-induced reporter activity was reduced. Interestingly, SAG alone failed to induce markers of PrE differentiation, and had no effect on Wnt/β-catenin-dependent TCF-LEF reporter activity. The expected increase in Wnt/β-catenin-dependent TCF-LEF reporter activity and PrE markers induced by RA was, however, blocked by cyclopamine. Finally, inhibiting GSK3 activity with BIO increased both TCF-LEF and Gli reporter activities. Together, we demonstrate the involvement of Hh signaling in the RA-induced differentiation of F9 cells into PrE, and while the activation of the Hh pathway itself is not sufficient, it as well as active Wnt/β-catenin are necessary for F9 cell differentiation.

Mucinous carcinoma of the breast: mammographic features with histologic correlation

International Nuclear Information System (INIS)

Cui Chunyan; Zhang Ling; Wu Yaopan; Li Shuqin

2011-01-01

Objective: To correlate the mammographic findings of mucinous carcinoma with histologic features. Methods: Retrospective analysis of the mammographic and pathologic findings of 37 patients with mucinous carcinomas of the breasts was performed. Results: Mammograms of ten (52.6%) women with mucinous carcinomas showed masses with well-defined, lobu-lated margins correlating well with the pure histologic type. Thirteen (81.3%) mixed type of mucinous carcinomas demonstrated poorly defined or spiculated margins (P<0.05). Most of the pure type carcinomas were hyperdense similar to most of mixed type carcinomas (P<0.05). Of 34 mucinous carcinomas tested, there were 25 ER-positive, 29 PR-positive, 24 C-erbB-2 negative expressions with pure type carcinomas accounting for 78.9%, 89.5% and 78.9%, respectively. Conclusion: The mammographic features of pure type are different from those of mixed type of mucinous breast carcinomas. The most common mammographic appearance of pure mucinous carcinoma is a well-defined mass without calcification whereas the mixed type carcinomas have more aggressive imaging characteristics. (authors)

Diagnostic usefulness of 18F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Nobusawa, Aiko; Kim, Mai; Kaira, Kyoichi; Miyashita, Go; Negishi, Akihide; Yokoo, Satoshi; Oriuchi, Noboru; Higuchi, Tetsuya; Tsushima, Yoshito; Kanai, Yoshikatsu; Oyama, Tetsunari

2013-01-01

l-[3- 18 F]-α-Methyltyrosine ( 18 F-FAMT) was developed as an amino acid tracer for PET imaging to provide better specificity than 2-[ 18 F]fluoro-2-deoxy-d-glucose ( 18 F-FDG) PET for cancer diagnosis. We investigated the diagnostic usefulness of 18 F-FAMT in oral squamous cell carcinoma (OSCC). The correlation between tumour uptake of 18 F-FAMT and L-type amino acid transporter 1 (LAT1) expression was determined. The study group comprised 68 OSCC patients who underwent both 18 F-FAMT and 18 F-FDG PET. Resected tumour sections were stained by immunohistochemistry for LAT1, CD98 and Ki-67, and microvessel density was determined in terms of CD34 and p53 expression. The sensitivity of primary tumour detection by 18 F-FAMT and 18 F-FDG PET was 98 % and 100 %, respectively. The sensitivity, specificity and accuracy of 18 F-FAMT PET for detecting malignant lymph nodes were 68 %, 99 % and 97 %, respectively, and equivalent values for 18 F-FDG PET were 84 %, 94 % and 94 %, respectively. The specificity and accuracy of 18 F-FAMT were significantly higher than those of 18 F-FDG. The uptake of 18 F-FAMT was significantly correlated with LAT1 expression, cell proliferation and advanced stage. The expression of LAT1 in OSCC cells was closely correlated with CD98 levels, cell proliferation and angiogenesis. 18 F-FAMT PET showed higher specificity for detecting malignant lesions than 18 F-FDG PET. The uptake of 18 F-FAMT by OSCC cells can be determined by the presence of LAT1 expression and tumour cell proliferation. (orig.)

Molecular Conversations and the Development of the Hair Follicle and Basal Cell Carcinoma

OpenAIRE

Harris, Pamela Jo; Takebe, Naoko; Ivy, S. Percy

2010-01-01

The understanding of the anatomy and development of fetal and adult hair follicles and molecular study of the major embryonic pathways that regulate the hair follicle have led to exciting discoveries concerning the development of basal cell carcinoma (BCC). These studies have shed light on the major roles of Sonic hedgehog (Shh) signaling and its interactions with the insulin-like growth factor (IGF) axis in BCC development. New work, for example, explores a link between Shh signaling and IGF...

Clinical utility of simultaneous whole-body 18F-FDG PET/MRI as a single-step imaging modality in the staging of primary nasopharyngeal carcinoma.

Science.gov (United States)

Chan, Sheng-Chieh; Yeh, Chih-Hua; Yen, Tzu-Chen; Ng, Shu-Hang; Chang, Joseph Tung-Chieh; Lin, Chien-Yu; Yen-Ming, Tsang; Fan, Kang-Hsing; Huang, Bing-Shen; Hsu, Cheng-Lung; Chang, Kai-Ping; Wang, Hung-Ming; Liao, Chun-Ta

2018-03-03

Both head and neck magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) play a crucial role in the staging of primary nasopharyngeal carcinoma (NPC). In this study, we sought to prospectively investigate the clinical utility of simultaneous whole-body 18F-FDG PET/MRI for primary staging of NPC patients. We examined 113 patients with histologically confirmed NPC who underwent pretreatment, simultaneous whole-body PET/MRI and PET/CT for primary tumor staging. The images obtained with the different imaging modalities were interpreted independently and compared with each other. PET/MRI increased the accuracy of head and neck MRI for assessment of primary tumor extent in four patients via addition of FDG uptake information to increase the conspicuity of morphologically subtle lesions. PET/MR images were more discernible than PET/CT images for mapping tumor extension, especially intracranial invasion. Regarding the N staging assessment, the sensitivity of PET/MRI (99.5%) was higher than that of head and neck MRI (94.2%) and PET/CT (90.9%). PET/MRI was particularly useful for distinguishing retropharyngeal nodal metastasis from adjacent nasopharyngeal tumors. For distant metastasis evaluation, PET/MRI exhibited a similar sensitivity (90% vs. 86.7% vs. 83.3%), but higher positive predictive value (93.1% vs. 78.8% vs. 83.3%) than whole-body MRI and PET/CT, respectively. For tumor staging of NPC, simultaneous whole-body PET/MRI was more accurate than head and neck MRI and PET/CT, and may serve as a single-step staging modality.

Distant metastases and synchronous second primary tumors in patients with newly diagnosed oropharyngeal and hypopharyngeal carcinomas: evaluation of 18F-FDG PET and extended-field multi-detector row CT

International Nuclear Information System (INIS)

Ng, Shu-Hang; Ko, Sheung-Fat; Chin, Shu-Chyn; Chan, Sheng-Chieh; Yen, Tzu-Chen; Liao, Chun-Ta; Huang, Shiang-Fu; Chang, Joseph Tung-Chieh; Lin, Chin-Yu.; Wang, Hung-Ming

2008-01-01

Patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) have a high risk of having distant metastases or second primary tumors. We prospectively evaluate the clinical usefulness of 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET), extended-field multi-detector computed tomography (MDCT), and their side-by-side visual correlation for the detection of distant malignancies in these two tumors at presentation. A total of 160 patients with SCC of the oropharynx (n = 74) or hypopharynx (n=86) underwent 18 F-FDG PET and extended-field MDCT to detect distant metastases or second primary tumors. Suspected lesions were investigated by means of biopsy, clinical, or imaging follow-up. Twenty-six (16.3%) of our 160 patients were found to have distant malignancy. Diagnostic yields of 18 F-FDG PET and MDCT were 12.5% and 8.1%, respectively. The sensitivity of 18 F-FDG PET for detection of distant malignancies was 1.5-fold higher than that of MDCT (76.9% vs. 50.0%, P=0.039), while its specificity was slightly lower (94.0% vs. 97.8%, P=0.125). Side-by-side visual correlation of MDCT and 18 F-FDG PET improved the sensitivity and specificity up to 80.8% and 98.5%, respectively, leading to alteration of treatment in 13.1% of patients. A significant difference in survival rates between its positive and negative results was observed. 18 F-FDG PET and extended-field MDCT had acceptable diagnostic yields for detection of distant malignancies in untreated oropharyngeal and hypopharyngeal SCC. 18 F-FDG PET was 1.5-fold more sensitive than MDCT, but had more false-positive findings. Their visual correlation improved the diagnostic accuracy, treatment planning, and prognosis prediction. (orig.)

Prognostic significance of standardized uptake value and metabolic tumour volume on {sup 18}F-FDG PET/CT in oropharyngeal squamous cell carcinoma

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Kim, Ji Won; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Centre, Seoul (Korea, Republic of); Oh, Jungsu S.; Kim, Jae Seung [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Centre, Seoul (Korea, Republic of); Kim, Sang Yoon [University of Ulsan College of Medicine, Department of Otolaryngology, Asan Medical Centre, Seoul (Korea, Republic of); Biomedical Research Institute, Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2015-08-15

Standardized uptake value (SUV) and metabolic tumour volume (MTV) measured by {sup 18}F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers. However, their prognostic significance in oropharyngeal squamous cell carcinoma (OPSCC) has been investigated in only a few studies and with small cohorts. In the present study we evaluated the ability of SUV, MTV, and total lesion glycolysis (TLG) measured on pretreatment {sup 18}F-FDG PET/CT to predict recurrence and survival outcomes in OPSCC. The study included 221 patients with OPSCC who underwent pretreatment {sup 18}F-FDG PET/CT imaging and received definitive treatment at our tertiary referral centre. The PET imaging parameters SUV{sub max}, SUV{sub peak}, MTV and TLG were measured in primary tumours with focal {sup 18}F-FDG uptake. Clinical and imaging variables significantly associated with overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate analyses using the Cox proportional hazards model. Overall 5-year OS and DFS rates were 72.0 % and 79.5 %, respectively, during a median follow-up of 61 months (range 18 - 122 months). The cut-off values of tumour SUV{sub max}, SUV{sub peak}, MTV and TLG for prediction of DFS were 7.55, 6.80, 11.06 mL and 78.56 g, respectively. Univariate analyses showed that age >60 years, advanced tumour stage, and high tumour SUV{sub max}, SUV{sub peak}, MTV and TLG were significantly associated with decreased OS and DFS (P < 0.05 each). Age, tumour SUV{sub max} and MTV remained independent variables for OS and DFS (P < 0.05 each) in the multivariate analyses. SUV{sub max} and MTV measured on pretreatment {sup 18}F-FDG PET/CT may be useful in predicting the clinical outcomes in OPSCC patients. This study investigated the clinical prognostic value of imaging parameters from pretreatment {sup 18}F-FDG PET/CT in 221 patients who underwent definitive treatment for oropharyngeal squamous cell carcinoma. High maximum standardized

Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

International Nuclear Information System (INIS)

Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J.; Davenport, Matthew S.; Caoili, Elaine M.; Else, Tobias

2015-01-01

There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

Energy Technology Data Exchange (ETDEWEB)

Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J. [University of Michigan Health System, Section of Pediatric Radiology, C. S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Davenport, Matthew S.; Caoili, Elaine M. [University of Michigan Health System, Division of Abdominal Imaging, Department of Radiology, Ann Arbor, MI (United States); Else, Tobias [University of Michigan Health System, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Ann Arbor, MI (United States)

2015-08-15

There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

Prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma

Science.gov (United States)

Wang, Wei; Chen, Xiao-Long; Zhao, Shen-Yu; Xu, Yu-Hui; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

2016-01-01

The prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma (GC) has been widely reported and is still under debate. Here, we evaluated the prognostic significance of preoperative serum CA125, CA19-9 and CEA in patients with GC. 1692 patients with GC who underwent gastrectomy were divided into the training (from January 2005 to December 2011, n = 1024) and the validation (from January 2012 to December 2013, n = 668) cohorts. Positive groups of CA125 (> 13.72 U/ml), CA19-9 (> 23.36 U/ml) and CEA (> 4.28 ng/ml) were significantly associated with more advanced clinicopathological traits and worse outcomes than that of negative groups (all P tumor size (P tumor markers (NPTM) were more accurate in prognostic prediction than TNM stage alone. Our findings suggested that elevated preoperative serum CA125, CA19-9 and CEA were associated with more advanced clinicopathological traits and less favorable outcomes. In addition, CA125 as an independent prognostic factor should be further investigated. Nomogram based on NPTM could accurately predict the prognosis of GC patients. PMID:27097114

A 9 years boy with MEN-2B variant of medullary thyroid carcinoma.

Science.gov (United States)

Sattar, M A; Hadi, H I; Ekramuddoula, F M; Hasanuzzaman, S M

2013-04-01

To highlight a rare disease like multiple endocrine neoplasia (MEN)-2B variant of medullary thyroid carcinoma and to optimize the management option in such cases, we present a nine year old boy with thyroid swelling, cervical lymphadenopathy and thick lips. His calcitonin level was raised. Investigation's results of the boy were as following fine needle aspiration cytology (FNAC) was medullary carcinoma of thyroid, preoperative calcitonin was >2000pg/ml, post operative histopathological report was medullary carcinoma. Total thyroidectomy with aggressive initial neck surgery may reduce the recurrence and increase better prognosis and survival rate. Calcitonin is used as diagnostic and follow-up marker.

Neck ultrasound in staging squamous oesophageal carcinoma - a high yield technique

International Nuclear Information System (INIS)

Griffith, J.F.; Chan, A.C.W.; Ahuja, A.T.; Leung, S.F.; Chow, L.T.C.; Chung, S.C.S.; Metreweli, C.

2000-01-01

AIM: This study evaluates the use of neck ultrasound in staging squamous oesophageal carcinoma. MATERIALS AND METHODS: A prospective analysis of the clinical, neck ultrasound (US) and thoraco-abdominal computed tomography (CT) findings in 121 patients with squamous oesophageal carcinoma at presentation was performed. The relationship between malignant neck nodes, mediastinal and abdominal adenopathy, location and size of the primary tumour was analysed. RESULTS: Ten of 121 patients (8%) had clinically palpable neck nodes which were deemed malignant in six (5%) following US and fine-needle aspiration for cytology. Of those 111 patients with no palpable neck nodes, 31 (28%) had malignant nodes shown on US. The more cephalad the location of the primary tumour, the higher the frequency of malignant neck nodes which were found in 80%, 52%, 29% and 9% of cervical, upper thoracic, mid-thoracic and lower thoracic oesophageal tumours, respectively. Eleven (29%) of the 38 patients with malignant neck nodes shown on US had no CT evidence of additional adenopathy in the mediastinum or upper abdomen. Neck US altered TNM staging in 22/121 (18%) patients at presentation. CONCLUSION: Neck US frequently detects clinically impalpable metastatic nodes leading to altered TNM staging in patients with squamous oesophageal carcinoma. We advocate its routine use when staging squamous oesophageal carcinoma. Griffith, J.F. 2000

How the embryonic chick brain twists

OpenAIRE

Chen, Zi; Guo, Qiaohang; Dai, Eric; Forsch, Nickolas; Taber, Larry A.

2016-01-01

During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left–right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of in vitro experiments, a physical model of the embryonic m...

Adenosquamous carcinoma arising within a retrorectal tailgut cyst: Report of a case

Institute of Scientific and Technical Information of China (English)

Zoran Krivokapic; Ivan Dimitrijevic; Goran Barisic; Velimir Markovic; Miodrag Krstic

2005-01-01

Retrorectal, developmental tail gut cysts, include dermoid cysts, rectal duplication cysts and retrorectal cyst-hamartomas. Retrorectal cyst-hamartomas (RCH) are derived from remnants of the tail gut, the most caudal part of the embryonic hind gut, which normally involutes by the 8th wk of embryonic development (3-8 mm stage). They have specific radiological and histopathological features that distinguish them from other similar formations (dermoid cysts, enteric duplication cysts and teratomas). We report a patient with adenosquamous carcinoma arising within RCH, who underwent complete resection of the cyst through anterior laparotomy, and reached complete (recurrencefree for 14 mo, so far) functional recovery. The cyst was incidentally discovered during hysterectomy 12 years ago.Diagnostic, therapeutic and histopathological aspects of this rare case are discussed. The mentioned period between diagnosis and surgical treatment suggests that RCH, given enough time, can develop malignant degeneration, and should be resected at the time of diagnosis.

File list: Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung mm9 Unclassified Lung Carcinoma, Lewis Lung ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung.bed ...

Unusual presentation of metastatic carcinoma cervix with clinically silent primary identified by 18F-flouro deoxy glucose positron emission tomography/computed tomography

International Nuclear Information System (INIS)

Senthil, Raja; Mohapatra, Ranjan Kumar; Srinivas, Shripriya; Sampath, Mouleeswaran Koramadai; Sundaraiya, Sumati

2016-01-01

Carcinoma cervix is the most common gynecological malignancy among Indian women. The common symptoms at presentation include abnormal vaginal bleeding, unusual discharge from the vagina, or pain during coitus and postmenopausal bleeding. Rarely, few patients may present with distant metastases without local symptoms. We present two patients with an unusual presentation of metastatic disease without any gynecological symptoms, where 18 F-flouro deoxy glucose positron emission tomography/computed tomography helped in identifying the primary malignancy in the uterine cervix

Sox9

DEFF Research Database (Denmark)

Seymour, Philip A

2014-01-01

Over the last decade, it has been discovered that the transcription factor Sox9 plays several critical roles in governing the development of the embryonic pancreas and the homeostasis of the mature organ. While analysis of pancreata from patients affected by the Sox9 haploinsufficiency syndrome...... endocrine differentiation and maintaining pancreatic ductal identity, and it has recently been unveiled as a key player in the initiation of pancreatic cancer. These functions of Sox9 are discussed in this article, with special emphasis on the knowledge gained from various loss-of-function and lineage...

[Expression of embryonic markers in pterygium derived mesenchymal cells].

Science.gov (United States)

Pascual, G; Montes, M A; Pérez-Rico, C; Pérez-Kohler, B; Bellón, J M; Buján, J

2010-12-01

Destruction of the limbal epithelium barrier is the most important mechanism of pterygium formation (conjunctiva proliferation, encroaching onto the cornea). It is thought to arise from activated and proliferating limbal epithelial stem cells. The objective of this study is to evaluate the presence of undifferentiated mesenchymal cells (stem cells) in cultured cells extracted from human pterygium. Cells from 6 human pterygium were isolated by explantation and placed in cultures with amniomax medium. Once the monolayer was reached the cells were seeded onto 24 well microplates. The cells were studied in the second sub-culture. The immunohistochemical expression of different embryonic stem cell markers, OCT3/4 and CD9, was analysed. The differentiated phenotypes were characterised with the monoclonal antibodies anti-CD31, α-actin and vimentin. All the cell populations obtained from pterygium showed vimentin expression. Less than 1% of the cells were positive for CD31 and α-actin markers. The majority of the cell population was positive for OCT3/4 and CD9. The cell population obtained from pterygium expressed mesenchymal cell phenotype and embryonic markers, such us OCT3/4 and CD9. This undifferentiated population could be involved in the large recurrence rate of this type of tissue after surgery. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Racial influence on the prevalence of prostate carcinoma in Brazilian volunteers

Directory of Open Access Journals (Sweden)

Edson L Paschoalin

2003-08-01

Full Text Available PURPOSE: To investigate the prevalence of prostate carcinoma in a sample of volunteers known to have a large proportion of Bantu African ancestors, and the performance of total PSA (tPSA, PSA density (PSAD and free-to-total PSA ratio (f/tPSA on the diagnosis. MATERIALS AND METHODS: A total of 473 volunteers (range: 40 - 79 years were screened for prostate carcinoma. Those with tPSA >2 ng/ml and/or abnormal digital rectal examination were submitted to a transrectal ultrasound-directed biopsy (10 cores. The volunteers were classified as White, Mulatto or Black according to physical characteristics and to ancestors race reference. The following variable number of tandem repeats (VNTR were analyzed in the blood of 120 volunteers without cancer and in 27 patients with prostate cancer: D4S43, PAH, F13A1, APOB and vW-1. RESULTS: The biopsies performed in 121 volunteers revealed cancer in 27 (5.7% of 473. The proportions of cancer in White, Mulatto and Black were respectively: 0.6% (1/148, 6.7% (6/90 and 8.5% (20/235 (p = 0.006. The VNTRs analysis revealed heterogeneity in White, Mulatto and Black anthropologic phenotypes with the following admixture of Caucasian, African and Amerindian gene lineages: 67.5 ± 8%, 20.8 ± 8%, 11.7 ± 7%; 54.8 ± 9%, 36.3 ± 5%, 8.9 ± 7%; and, 45.3 ± 3%, 45.9 ± 4%, 8.8 ± 7%. Such a mixture was 50.5 ± 9%, 49 ± 8% and 0.5 ± 4% in volunteers bearing cancer, and 59.1 ± 7%, 31.7 ± 8% and 9.2 ± 5% in those without cancer. The sensitivity and specificity of tPSA at cut-off levels of 2, 2.5 and 4 ng/ml for volunteers with tPSA <= 10 ng/ml were respectively: 100% and 6,6%, 100% and 36,6%, 69,2% and 62,2%. PSAD at a cut-off level of 0.08 or 0.10, and f/tPSA at a cut-off level of 20% were able to increase significantly tPSA specificity without loss on sensitivity. CONCLUSIONS: The tumor prevalence was higher in Non-White than in White phenotype. The association of tPSA at a cut-off level of 2.5 ng/ml with a PSAD of 0.08 or

Enhanced activation of matrix metalloproteinase-9 correlates with the degree of papillary thyroid carcinoma infiltration

Science.gov (United States)

Marečko, Ilona; Cvejić, Dubravka; Šelemetjev, Sonja; Paskaš, Svetlana; Tatić, Svetislav; Paunović, Ivan; Savin, Svetlana

2014-01-01

Aim To determine whether matrix metalloproteinase-9 (MMP-9) may be a useful adjunctive tool for predicting unfavorable biological behavior of papillary thyroid carcinoma (PTC) by evaluating the expression profile and proteolytic activity of MMP-9 in PTC by different techniques and correlating the findings with clinicopathological prognostic factors. Methods Immunohistochemical localization of MMP-9 was analyzed with antibodies specific for either total or active MMP-9. Activation ratios of MMP-9 were calculated by quantifying gel zymography bands. Enzymatic activity of MMP-9 was localized by in situ zymography after inhibiting MMP-2 activity. Results Immunostaining of total and active MMP-9 was observed in tumor tissue and occasionally in non-neoplastic epithelium. Only active MMP-9 was significantly associated with extrathyroid invasion, lymph-node metastasis, and the degree of tumor infiltration (P zymography revealed a correlation between the MMP-9 activation ratio and nodal involvement, extrathyroid invasion, and the degree of tumor infiltration. In situ zymography showed that gelatinases exerted their activity in tumor parenchymal and stromal cells. Moreover, after application of MMP-2 inhibitor, the remaining gelatinase activity, corresponding to MMP-9, was highest in cancers with the most advanced degree of tumor infiltration. Conclusions This is the first report suggesting that the evaluation of active MMP-9 by immunohistochemistry and determination of its activation ratio by gelatin zymography may be a useful adjunct to the known clinicopathological factors in predicting tumor behavior. Most important, in situ zimography with an MMP-2 inhibitor for the first time demonstrated a strong impact of MMP-9 activity on the degree of tumor infiltration during PTC progression. PMID:24778099

File list: NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Unc.Bld.10.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.10.AllAg.Carcinoma,_Squamous_Cell mm9 Unclassified Blood Carcinoma, Squamou...s Cell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.10.AllAg.Carcinoma,_Squamous_Cell.bed ...

File list: Unc.Bld.05.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.05.AllAg.Carcinoma,_Squamous_Cell mm9 Unclassified Blood Carcinoma, Squamou...s Cell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.Carcinoma,_Squamous_Cell.bed ...

The expression of Toll-like receptors 2, 4, 5, 7 and 9 in Merkel cell carcinoma.

Science.gov (United States)

Jouhi, Lauri; Koljonen, Virve; Böhling, Tom; Haglund, Caj; Hagström, Jaana

2015-04-01

We sought to clarify whether the expression of toll-like receptors (TLR) in Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics, especially the presence of Merkel cell polyoma virus (MCV). The study comprised of 128 patients with data on Merkel cell polyomavirus (MCV) status and clinical features were included in the study. Immunohistochemistry for TLR expression was performed on tissue microarray (TMA) slides. TLR 2, 4, 5, 7 and 9 expression was noted in most of the tumor specimens. Decreased expression of TLR 9 correlated strongly with MCV positivity. Cytoplasmic TLR 2 expression correlated with small tumor size, while nuclear TLR 2 and TLR 5 expressions with larger tumors. Increased nuclear TLR 4 expression and decreased TLR 7 expression were associated with older age. TLR 2, 4, 5, 7 and 9 appear to reflect certain clinicopathological variables and prognostic markers of MCC tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

Science.gov (United States)

Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

2017-03-01

The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (Pepithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

F9 fimbriae of uropathogenic Escherichia coli are expressed at low temperature and recognise Galβ1-3GlcNAc-containing glycans.

Directory of Open Access Journals (Sweden)

Daniël J Wurpel

Full Text Available Uropathogenic Escherichia coli (UPEC is the leading causative agent of urinary tract infections (UTI in the developed world. Among the major virulence factors of UPEC, surface expressed adhesins mediate attachment and tissue tropism. UPEC strains typically possess a range of adhesins, with type 1 fimbriae and P fimbriae of the chaperone-usher class the best characterised. We previously identified and characterised F9 as a new chaperone-usher fimbrial type that mediates biofilm formation. However, the regulation and specific role of F9 fimbriae remained to be determined in the context of wild-type clinical UPEC strains. In this study we have assessed the distribution and genetic context of the f9 operon among diverse E. coli lineages and pathotypes and demonstrated that f9 genes are significantly more conserved in a UPEC strain collection in comparison to the well-defined E. coli reference (ECOR collection. In the prototypic UPEC strain CFT073, the global regulator protein H-NS was identified as a transcriptional repressor of f9 gene expression at 37°C through its ability to bind directly to the f9 promoter region. F9 fimbriae expression was demonstrated at 20°C, representing the first evidence of functional F9 fimbriae expression by wild-type E. coli. Finally, glycan array analysis demonstrated that F9 fimbriae recognise and bind to terminal Galβ1-3GlcNAc structures.

File list: DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: DNS.Bld.05.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Bld.05.AllAg.Carcinoma,_Squamous_Cell mm9 DNase-seq Blood Carcinoma, Squamous C...ell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.05.AllAg.Carcinoma,_Squamous_Cell.bed ...

File list: DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: Pol.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Lng.50.AllAg.Carcinoma,_Lewis_Lung mm9 RNA polymerase Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.50.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: Pol.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Lng.05.AllAg.Carcinoma,_Lewis_Lung mm9 RNA polymerase Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.05.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: Pol.Bld.50.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Bld.50.AllAg.Carcinoma,_Squamous_Cell mm9 RNA polymerase Blood Carcinoma, Squam...ous Cell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.AllAg.Carcinoma,_Squamous_Cell.bed ...

File list: DNS.Bld.50.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Bld.50.AllAg.Carcinoma,_Squamous_Cell mm9 DNase-seq Blood Carcinoma, Squamous C...ell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.50.AllAg.Carcinoma,_Squamous_Cell.bed ...

File list: Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung mm9 RNA polymerase Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung.bed ...

Follicular carcinoma

International Nuclear Information System (INIS)

Shah, D.H.; Samuel, A.M.

1999-01-01

Follicular thyroid carcinoma (FTC) is considered as a disease of the elderly with a higher incidence in females as compared to papillary thyroid carcinoma (PTC). Some studies have reported its occurrence at an early age, which may be attributed to early diagnosis because of the availability of advanced techniques. The prognosis of the disease is considered poor as compared to that of PTC. The conclusions drawn in this review are based on 663 cases in whom adequate data was available for meaningful analysis followed for a mean period of 9.2 years, median, 7.8 years; range, 1-32 years

File list: Oth.Bld.05.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Bld.05.AllAg.Carcinoma,_Squamous_Cell mm9 TFs and others Blood Carcinoma, Squam...ous Cell http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.AllAg.Carcinoma,_Squamous_Cell.bed ...

File list: InP.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: InP.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

File list: Oth.Bld.20.AllAg.Carcinoma,_Squamous_Cell [Chip-atlas[Archive

Lifescience Database Archive (English)