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Andrew E Greenstein, Mouhammed Amir Habra, Subhagya A Wadekar, and Andreas Grauer

pathway' and 'natural killer cell-mediated cytotoxicity') were assessed by GC status. Unsupervised clustering of normalized gene expression for these two KEGG pathways showed lower gene expression in GC+ cases ( Fig. 2A ). When clustering GC+ and GC

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Courtney A Dreyer, Kacey VanderVorst, Savannah Free, Ashley Rowson-Hodel, and Kermit L Carraway III

progression . Trends in Molecular Medicine 20 332 – 342 . ( ) Nieswandt B Hafner M Echtenacher B Männel DN 1999 Lysis of tumor cells by natural killer cells in mice is impeded by platelets . Cancer

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R Zhang and L J DeGroot

To explore a more efficient multi-gene antitumor treatment, we developed an adenoviral vector expressing both herpes simplex virus thymidine kinase (HSVtk) and human interleukin-2 (hIL-2) (AdCMVTKhIL2). Production of hIL-2 is expected to augment antitumor T cell and natural killer cell activity. Two separate cassettes expressing HSVtk and hIL-2, each under the control of the human cytomegalovirus (CMV) immediate early gene promoter, were inserted into the early 1 region of adenovirus type 5. This vector showed similar direct cytotoxicity towards infected rat medullary thyroid carcinoma (rMTC) cells as did the single gene vector, AdCMVtk. rMTC cells infected with the virus in vitro showed high sensitivity to ganciclovir. After infection with AdCMVTKhIL2 at 100 m.o.i. for 1 h, more than 20 000 U hIL-2 were produced during 24 h by 1 &times 10(6) rMTC cells on day 2 and day 3. hIL-2 was also detected in the supernatants of primary cultures from tumors treated in vivo by the AdCMVTKhIL2 vector. Infected cells lost their tumorigenicity when transplanted subcutaneously into syngeneic rats, whereas all control animals developed tumors. More than 63% of tumors (19 out of 30 treated tumors) were destroyed when AdCMVTKhIL2 was injected intratumorally, compared with 38% when tumors were treated with AdCMVIL2, and 12% when treated with AdCMVtk, indicating an antitumor effect superior to that of each single vector given alone at the same dosage. These results indicate that the AdCMVTKhIL2 vector efficiently produces both HSVtk and hIL-2, and provides an enhanced antitumor activity.

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D Engelmann, D Koczan, P Ricken, U Rimpler, J Pahnke, Z Li, and B M Pützer

G Mantovani A 1997 IL-15 is chemotactic for natural killer cells and stimulates their adhesion to vascular endothelium . Journal of Leukocyte Biology 61 729 – 735 . Bonni A Brunet A West AE Datta SR Takasu MA Greenberg ME

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Nevena Gajovic, Milena Jurisevic, Jelena Pantic, Gordana Radosavljevic, Nebojsa Arsenijevic, Miodrag L Lukic, and Ivan Jovanovic

37 S81 – S90 . ( ) 10.2337/dc14-S081) Berrou J Fougeray S Venot M Chardiny V Gautier JF Dulphy N Toubert A Peraldi MN 2013 Natural killer cell function, an important target for infection and tumor protection

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Tiffany Scully, Carolyn D Scott, Sue M Firth, Lisa M Sedger, John E Pintar, Stephen M Twigg, and Robert C Baxter

with T cells and natural killer cells. (A) Intratumoural expression of Gzmb is not different overall between wild-type and BP3KO mice but is reduced with HFD in BP3KO mice ( P  = 0.024 for interaction). Intratumoural gene expression of the regulatory

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S Latteyer, S Christoph, S Theurer, G S Hönes, K W Schmid, D Führer, and L C Moeller

3 is expressed on malignant cells and in inflammatory sites, especially in activated macrophages, monocytes, neutrophils, natural killer cells, naive T lymphocytes and endothelial cells ( Piali et al. 1995 , Eliceiri & Cheresh 1998 , Wilder 2002

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Robert C Mould, Jacob P van Vloten, Amanda W K AuYeung, Khalil Karimi, and Byram W Bridle

and malignant lesions ( Liu et al. 2013 ). Natural killer cells Natural killer (NK) cells can spontaneously kill cells deemed to be dangerous to the host, including cancer cells and are, therefore, presumed to be important in cancer

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Lucas Leite Cunha, Marjory Alana Marcello, and Laura Sterian Ward

.1146/annurev.immunol.18.1.767 ). Baume DM Robertson MJ Levine H Manley TJ Schow PW Ritz J 1992 Differential responses to interleukin 2 define functionally distinct subsets of human natural killer cells . European Journal of Immunology 22 1

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Chiachen Chen, Yuan-Ching Chang, Chien-Liang Liu, Tsang-Pai Liu, King-Jen Chang, and Ing-Cherng Guo

cells ( Elinav et al. 2006 ). We address the possibility whether the reported anti-tumor effect actually resulted from the natural killer cell-mediated immune defense of mouse host to reject human Hep3B xenograft, rather than an inhibitory effect of