tbuckley/cabot-search huggingface dataset:
Abstract 589: Expression levels of ABCA6 or ABCA7 predict primary Ewing sarcoma progression at diagnosis
Authors: Michela Pasello, Marilù Fanelli, Valentina Mularoni, Sonia Ciotti, Piero Picci, Massimo Serra, Katia Scotlandi
Journal: Cancer Research (2015)

Abstract Introduction: Ewing Sarcoma (EWS), the second most common bone tumor occurring in children and young adults, is a clinically very aggressive tumor with high metastatic tendency. EWS therapy is still firmly based on chemotherapy and development of chemoresistance is a major cause of disease progression. The mechanisms of chemoresistance are, however, still poorly defined. In this study, we analyzed the prognostic value of 21 ABC transporters with different mechanisms of action. Materials and methods: Gene expression of 21 ABC transporters was determined by RT-PCR in two different series of EWS patients with primary localized tumor at diagnosis (training set: 30 pts; validation set: 109 pts) and in human EWS cell lines. Association with patient outcome was determined by log-rank test and Kaplan-Meier survival curves (EFS and OVS). Sensitivity to conventional chemotherapeutic agents, such as Doxorubicin, Vincristine, Etoposide, Actinomicin-D and Ifosfamide, was tested in a representative panel of human EWS cell lines. Results: Among the 21 ABC transporters that were analyzed in the training set, expression of ABCA2, ABCA6, ABCA7, ABCB9 and ABCC4 was found to be associated with differential prognosis. Of these genes, only ABCA6 and ABCA7 were confirmed to be significant indicators of EWS progression when the analysis was extended to a new series of 109 patients with localized primary tumor (validation set): high expression of ABCA6 or ABCA7 was associated with a better prognosis. Correlative in vitro studies on EWS cell lines showed that the high expression of ABCA7 was not associated with higher response to conventional drugs, indicating a more complex role in the regulation of EWS aggressiveness. Conclusions: The study validated the impact of ABCA6 or ABCA7, the still poorly understood members of ABC transporters, on EWS progression. However, since high expression of these two transporters is related to better prognosis rather that worse, a different role from the canonical function of drug extruders should be supposed. We are currently testing the association between ABCA7 expression and ceramide levels, which are known to induce cell apoptosis, and macrophage-mediated phagocytosis as indicated in the literature (Kielar D. et al. J Invest Dermatol. 2003 Sep;121(3):465-74; Jehle AW et al. J Cell Biol. 2006 Aug 14;174(4):547-56). Funded by: AIRC to KS IG 14049. Citation Format: Michela Pasello, Marilù Fanelli, Valentina Mularoni, Sonia Ciotti, Piero Picci, Massimo Serra, Katia Scotlandi. Expression levels of ABCA6 or ABCA7 predict primary Ewing sarcoma progression at diagnosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 589. doi:10.1158/1538-7445.AM2015-589
551. Longitudinal High Resolution 3-D Imaging of AAV Gene Expression In Vivo
Authors: Linh Pham, Lukkana Suksanpaisan, Kah-Whye Peng, Margaret M. Redfield, Stephen J. Russell
Journal: Molecular Therapy (2015)

Adeno-associated viral (AAV) are small non-integrating vectors that are being developed for a number of gene therapy applications. Different AAV serotypes, armed with constitutive or tissue specific promoters, capable of infecting various tissue types have been engineered to enable preferential transduction of the target tissues. In order to rapidly screen and evaluate the best AAV serotype and promoter for high levels of transgene expression in a specific organ, we have been developing the sodium iodide symporter (NIS) as a reporter gene for screening the biodistribution of AAV vectors. NIS is expressed endogenously in thyroid follicular cells where its role is to concentrate iodine for the synthesis of thyroid hormones. For more than 70 years, thyroidal NIS expression has been provided the basis for I-123 gamma camera or SPECT/CT imaging in thyroid disorders and for I-131 tumor ablation of metastatic thyroid cancer. Using NIS imaging, we would be able to longitudinally monitor gene expression in the same animal over time, from rodents, dogs, nonhuman primates and in human subjects. In this study, we have generated a panel of AAV vectors of serotype 1, 2, 5, 8, and 9 and administered the vectors via various routes of delivery. The mice and rats were imaged using SPECT (I-125 or Tc99m pertechnetate) isotopes on a high resolution microSPECT/CT scanner. Results indicate robust AAV gene expression by 2 weeks post vector administration. [Figure 1: AAV mediated NIS gene expression in the liver and heart of mice post IV administration of vector]. For example, AAV9-CMV-NIS gave high levels of cardiac gene expression and interestingly, of subcutaneous brown fat (scapular region). In contrast AAV1-CMV-NIS resulted in highest gene expression in the subcutaneous brown fat only whereas AAV-LST-NIS (liver specific promoter) gave only NIS expression in the liver. When the regions of interests were quantitated, we found that AAV-NIS gene expression was maintained over 90 days in immunocompetent rats and over 200 days in immunocompromised mice. Using NIS as the reporter gene, we are able to use the same vector construct and perform similar noninvasive NIS imaging studies in large animal models using the same SPECT isotopes in combination with clinical SPECT/CT scanners. In contrast to traditional biodistribution studies utilizing PCR analysis or luciferase imaging, NIS imaging enables rapid identification of the organs supporting high levels of transgene expression.
Abstract 5228: mTORC2 mediates SDF-1α/CXCL12-induced angiogenesis
Authors: Mary E. Ziegler, Michaela M.S. Hatch, Christopher C.W. Hughes
Journal: Cancer Research (2015)

Abstract Angiogenesis occurs when new blood vessels sprout from the existing vasculature and mature into an organized and functional circulatory system. Physiological angiogenesis is stringently regulated and occurs transiently. Numerous disease states, including chronic inflammation and cancer, induce pathological angiogenesis, which disrupts the stable vascular network by altering both positive and negative angiogenic regulators. The chemokine stromal-cell derived factor-1 (SDF-1α, also called CXCL12) and its receptor CXCR4 promote endothelial cell (EC) migration and tube formation. PI3K is a key downstream regulator of CXCR4-mediated chemotaxis and mammalian target of rapamycin (mTOR) is at the center of PI3K-mediated signal transduction. mTOR exists in two complexes: mTOR complex 1 (mTORC1) and 2 (mTORC2). Receptor induced mTORC1 signal transduction has been widely studied. In contrast, the signaling upstream of mTORC2 remains elusive. We hypothesized that the SDF-1 α/CXCR4/mTOR signaling axis contributes to the molecular mechanism of tumor angiogenesis. This study illustrates that SDF-1α activates a distinct molecular signaling cascade in EC that involves CXCR4, G protein, PI3K and mTORC2, but not mTORC1. CXCR4 inhibition blocks sprouting in a 3D in vitro angiogenesis model, and specific inhibition of each of the mTOR complexes reveals that sprouting angiogenesis requires mTORC2 signal transduction. In a mouse model, tumor angiogenesis is significantly reduced only when mTORC2 is targeted. An analysis of targets downstream of mTORC2 indicates that 6-phosphofructo-2-kinase (PFKFB3), which is a key regulator of glycolytic flux and sprouting angiogenesis, is reduced in vivo when mTORC2 is targeted and tumor angiogenesis is inhibited. This study provides evidence that mTORC2 is an important regulator of angiogenesis that is downstream of GPCR signaling and upstream of metabolic regulation. In addition, these data present a potential link between mTORC2, metabolism and angiogenesis. Citation Format: Mary E. Ziegler, Michaela M.S. Hatch, Christopher C.W. Hughes. mTORC2 mediates SDF-1α/CXCL12-induced angiogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5228. doi:10.1158/1538-7445.AM2015-5228
Abstract 1946: Activating transcription factor 5 (ATF5) in highly expressed in Stage 4, MYCN-amplified neuroblastoma
Authors: Debarshi Banerjee, Shuobo Zhang, Gonzalo Lopez, Andrea Califano, Angela Kadenhe-Chiweshe, Darrell Yamashiro
Journal: Cancer Research (2015)

Abstract Background: Activating transcription factor 5 (ATF5), a member of the ATF/CREB family transcription factor, has been shown to regulate the differentiation of neuroprogenitor cells into mature neurons. ATF5 has also been implicated in progression of glioblastoma multiforme. We have recently identified ATF5 as a potential synthetic lethal gene to MYCN-amplified neuroblastoma (NB) through a whole genome shRNA screen. In the present study we investigate the role of ATF5 in NB tumorigenesis. Methods: We analyzed the human NB patient data GEO (GSE45480, Kocak et al.) to investigate and correlate the expression of ATF5 with different stages of NB. Immunohistochemical staining for ATF5 was performed on primary human NB tumors. Quantitative RT-PCR and western blot for ATF5 were conducted on a panel of NB cell lines. Immunocytochemistry was performed to determine the intercellular localization of ATF5. ATF5 was silenced by a tetracycline inducible (tet-on) shRNA construct in BE(2)-C and SK-N-DZ cells. The cells were subjected to cell viability assay and soft agar colony formation assay to assess the function of ATF5. Results: Analysis of NB patient data GEO (GSE45480) from Kocak et al., demonstrated that ATF5 is highly expressed in Stage 4 MYCN-amplified tumors compared to Stage 4, MYCN-non-amplified tumors (P = 2.56e-10) or Stage 1 tumors (P = 7.30e-18). ATF5 is also highly expressed in Stage 4, MYCN-non-amplified tumors vs. Stage 1 tumors (P = 2.8e-7). High expression of ATF5 strongly correlated with poor survival of NB patients (P = 2.88e-6, NCI Oncogenomics, Obertheur data set). Quantitative PCR detected ATF5 transcript in all eight NB cell lines tested. Western blot analyses demonstrated high expression of ATF5 in the MYCN-amplified neuroblastoma cell lines BE(2)-C, SK-N-DZ, and IMR32. Nuclear ATF5 staining was detected in all three cell lines as well as in Stage 4 NB tumors. Silencing of ATF5 reduced BE(2)-C cell viability to 30%, 48 hr after the addition of doxycycline. Silencing of ATF5 significantly reduced the colony formation of BE(2)-C and SK-N-DZ cells in soft agar (p&amp;lt;0.05) Conclusions: Our study demonstrates that ATF5 is highly expressed in Stage 4 MYCN-amplified tumors, and that silencing of ATF5 inhibits proliferation. These results suggest that ATF5 has a role in NB tumorigenesis and it represents a potential therapeutic target in MYCN-amplified neuroblastoma. Citation Format: Debarshi Banerjee, Shuobo Zhang, Gonzalo Lopez, Andrea Califano, Angela Kadenhe-Chiweshe, Darrell Yamashiro. Activating transcription factor 5 (ATF5) in highly expressed in Stage 4, MYCN-amplified neuroblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1946. doi:10.1158/1538-7445.AM2015-1946
Bacillus Cereus: A Leukemia-Specific, Neuroinvasive Pathogen?
Authors: Chanu Rhee, Veronica Manzo, Terrance Shea, Christopher Desjardins, Geraldine Van der Auwera, Sarah Young, Ann Marie Riley, Daniel J. DeAngelo, Lindsey R Baden, Jay Gee, Matthew Meyerson, Michael Klompas, Deborah Yokoe, Linda Weiser, Chandra Sekhar Pedamallu, Ami S. Bhatt
Journal: Blood (2014)
Abstract 2735: Tributyltin alters the production and secretion of inflammatory cytokines from human and mouse immune cells
Authors: Shanieek T. Lawrence, Margaret Whalen, Samuel Pellom, Anil Shanker
Journal: Cancer Research (2015)

Abstract Tributyltin (TBT) is an environmental contaminant that has been used for several industrial, agricultural and household purposes. Despite limited bans on the usage of Tributyltin, the stability and toxicity of the compound may prove to have negative effects on immune function in terrestrial mammals. Studies show that there is an increase in the incidences of tumors and decreased immune cell function in TBT-exposed mammals. TBT interferes with the ability of human natural killer (NK) cells to lyse target cells; it also alters the secretion of the pro-inflammatory cytokines Interferon gamma (IFNγ) and Tumor necrosis factor alpha (TNFα) from human immune cells ex vivo. Any dysregulation of the cytokine communication network may have detrimental effects on immune function, as cytokines play a key role in the regulation of immune responsiveness. There have been no in vivo studies on the effects of exposure to TBT on the cytokine communication network. The effects of 24 hour exposure to TBT on the production of IFNγ and TNFα from human immune cells were analyzed in an ex vivo system using western blotting. The serum of TBT-exposed mice was analyzed for changes in the levels of cytokine secretion and production using a Milliplex mouse cytokine/chemokine magnetic bead premixed 32 plex kit and western blotting; the effects of TBT-exposure was assessed using a time curve of 6h, 12h, 24h, 48h and control. TBT increased the levels of the cytokines IFNγ, TNFα, IL1β, IL5, IL7, IL12βp40, IL13, IL15, MIP1β, MIP2 and RANTES in the serum at a minimum of one time point. IFNγ and TNFα secretion and production from human cells also increased, showing striking agreement in the response to TBT between the human and mouse systems. Supported by: NIH grant 5U54CA163066-03 Citation Format: Shanieek T. Lawrence, Margaret Whalen, Samuel Pellom, Anil Shanker. Tributyltin alters the production and secretion of inflammatory cytokines from human and mouse immune cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2735. doi:10.1158/1538-7445.AM2015-2735
The structure of the mite allergen Blo t 1 explains the limited antibody cross-reactivity to Der p 1
Authors: K. H. Meno, J. S. Kastrup, I.-C. Kuo, K. Y. Chua, M. Gajhede
Journal: Allergy (2016)

The Blomia tropicalis (Blo t) mite species is considered a storage mite in temperate climate zones and an important source of indoor allergens causing allergic asthma and rhinitis in tropical and subtropical regions. Here, we report the crystal structure of one of the allergens from Blo t, recombinant proBlo t 1 (rproBlo t 1), determined at 2.1 Å resolution. Overall, the fold of rproBlo t 1 is characteristic for the pro-form of cysteine proteases from the C1A class. Structural comparison of experimentally mapped Der f 1/Der p1 IgG epitopes to the same surface patch on Blo t 1, as well as of sequence identity of surface-exposed residues, suggests limited cross-reactivity between these allergens and Blo t 1. This is in agreement with ELISA inhibition results showing that, although cross-reactive human IgE epitopes exist, there are unique IgE epitopes for both Blo t 1 and Der p 1.
Community-wide outbreaks of haemolytic uraemic syndrome associated with Shiga toxin-producing Escherichia coli O26 in Italy and Romania: a new challenge for the European Union
Authors: Ettore Severi, Flavie Vial, Emilie Peron, Otilia Mardh, Taina Niskanen, Johanna Takkinen
Journal: Eurosurveillance (2016)

Preview this article: Community-wide outbreaks of haemolytic uraemic syndrome associated with Shiga toxin-producing Escherichia coli O26 in Italy and Romania: a new challenge for the European Union, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/21/49/eurosurv-21-30420-3-1.gif
Clinical and Epidemiological Observations on Tropical Typhus in the Federated Malay States.
Journal: JAMA (1931)

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Abstract 3158: Ex vivo expansion and activation of human lymphocytes with a selective activator of effector cells
Authors: Jared E. Lopes, Jan L. Fisher, Heather C. Losey, Marc S. Ernstoff, Juan C. Alvarez
Journal: Cancer Research (2015)

Abstract RDB 1450 is an engineered fusion protein of circularly permuted IL-2 and IL-2Rα that is selective for the intermediate-affinity IL-2 receptor. The intermediate-affinity receptor is comprised of the IL-2 receptor beta chain (CD122) and common gamma chain (CD132) expressed on lymphocytes with effector function, whereas the high-affinity receptor, which additionally includes the alpha chain (CD25), is expressed primarily on immunosuppressive CD4+CD25+ regulatory T cells (Tregs). Ex vivo proliferation of subsets of human lymphocytes in response to RDB 1450 or rhIL-2 were evaluated. RDB 1450 supports the selective activation and expansion of effector lymphocytes based on higher observed memory CD8 T/Treg and NK/Treg ratios. Both RDB 1450 and IL-2 drive expansion of NK cells, however, a greater proportion of CD25+ NK cells are observed in response to RDB 1450. Furthermore, unlike IL-2, RDB 1450 does not effectively expand highly suppressive ICOS+ Tregs. The immunological profile resulting from the ex vivo treatment of human PBMCs with RDB 1450 supports its use as a novel immunotherapy for cancer. Citation Format: Jared E. Lopes, Jan L. Fisher, Heather C. Losey, Marc S. Ernstoff, Juan C. Alvarez. Ex vivo expansion and activation of human lymphocytes with a selective activator of effector cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3158. doi:10.1158/1538-7445.AM2015-3158
Erythropoietin Therapy Does Not Benefit Transfusion-Dependent Primary Myelofibrosis Patients and Treatment Response Is Infrequent with a Baseline Hemoglobin Level ≥ 10 g/dL.
Authors: Jocelin Huang, Terra L. Lasho, Chin Yang Li, Animesh D. Pardanani, Ruben A. Mesa, Ayalew Tefferi
Journal: Blood (2007)
High Density SNP Array Analysis of Tyrosine Kinase Inhibitor (TKI) Resistant Chronic Myeloid Leukemia (CML) Shows Secondary Genomic Alterations
Authors: Daniel Nowak, Norihiko Kawamata, Tadayuki Akagi, Ryoko Okamoto, Nils Thoennissen, Wolf-Karsten Hofmann, Motohiro Kato, Torsten Haferlach, Seishi Ogawa, H. Phillip Koeffler
Journal: Blood (2008)
Reactivation of Cured Hepatitis B Virus after Allogeneic Hematopoietic Stem Cell Transplantation and Its Asociation with Liver Graft Versus Host Disease.
Authors: Mariana Bastos Oreiro, Ana Lopez de la Guia, Miguel Canales, Raquel de Paz, Monica Martin Salces, Rosa Arrieta Gallastegui, Fernando Hernandez Navarro
Journal: Blood (2008)
Abstract 5064: EGFR and HER3 are important in the interaction between lung cancer cells and fibroblasts
Authors: Christina Demuth, Kristine Raaby Jakobsen, Peter Meldgaard, Anders Lade Nielsen, Boe Sandahl Sorensen
Journal: Cancer Research (2015)

Abstract Introduction: The cancer microenvironment has been recognised as a major factor in the development and treatment of lung cancer. Fibroblasts have gained attention owing to their ability to stimulate the growth of cancer cells and to change the response to chemotherapy. Though, not much is known about the underlying mechanisms. Methods: Lung cancer cell lines (H1568, Calu-3 and HCC827) and a lung fibroblast cell line (WI-38) were grown in co-culture using a Boyden chamber assay. Results: The presence of lung fibroblasts markedly increased growth of the lung cancer cells during co-culture. We investigated the activation of 49 different receptor tyrosine kinases and found that H1568 activated only EGFR and HER3. Activation of EGFR and HER3 was confirmed in Calu-3 and HCC827 after co-culture with fibroblasts. To account for this activation, we measured the expression of all EGFR ligands in the cell lines. We found that all lung cancer cell lines had increased levels of amphiregulin mRNA after co-culture with fibroblasts. ELISA confirmed increased protein production. We also found that the amount of available amphiregulin in the media of the co-culture is increased compared to controls. Conclusion: Lung fibroblasts stimulate the growth of lung cancer cells lines. We suggest that this effect is obtained by activation of EGFR and HER3. Furthermore we show that co-culture induce increased amphiregulin production in the cancer cells. This study identifies EGFR and HER3 as important components in the interaction between lung cancer cells and fibroblasts. Citation Format: Christina Demuth, Kristine Raaby Jakobsen, Peter Meldgaard, Anders Lade Nielsen, Boe Sandahl Sorensen. EGFR and HER3 are important in the interaction between lung cancer cells and fibroblasts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5064. doi:10.1158/1538-7445.AM2015-5064
Study on the Mechanism of ‘ei’formation in the Bone Marrow Smears of the Patients with BMMNC-Coombs Test(+) Hematocytopenia
Authors: Rong Fu, Yi hao Wang, Zonghong Shao, Jin Chen, Lijuan Li, Hui Liu, Huaquan Wang, Limin Xing, Hong Liu
Journal: Blood (2008)