title: An Epstein-Barr virus positive natural killer lymphoma xenograft derived for drug testing.
abstract: Natural killer (NK) lymphomas occurring more frequently in the Far East and South America respond poorly to anthracycline-based regimens. Here we report an in vivo NK lymphoma xenograft (NK-S1) derived from the testicular metastasis of a patient with an extranodal NK lymphoma (nasal type). The NK-S1 xenograft, established in severe combined immune deficient (SCID) mice retained the same imunophenotypic features as the original tumor. NK-S1 disseminated intra-abdominally to the testis, intestine and liver. Although doxorubicin, rapamycin, bevacizumab, rapamycin-doxorubicin, and bevacizumab-doxorubicin had no effects on the growth of subcutaneous NK-S1 xenografts, intraperitoneal (IP) delivery of cyclophosphamide caused complete tumor regression; this tumor regression was associated with apoptosis, upregulation of activated caspase-3, and cleaved Poly(ADP-ribose) polymerase (PARP). In an IP model of NK lymphoma, cyclophosphamide also prolonged the survival of mice and potently inhibited tumor dissemination and ascites formation. Our data suggest that the NK-S1 xenograft is a useful tool for screening preclinical drugs, and cyclophosphamide may be a useful drug for the treatment of this disease.
authors.affiliation: Division of Cellular and Molecular Research, Department of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Susan Li Er
authors.initials: SL
authors.lastname: Loong
authors.forename: Jacqueline Siok Gek
authors.initials: JS
authors.lastname: Hwang
authors.forename: Soon-Thye
authors.initials: ST
authors.lastname: Lim
authors.forename: Swee Peng
authors.initials: SP
authors.lastname: Yap
authors.forename: Miriam
authors.initials: M
authors.lastname: Tao
authors.forename: Tsung-Wen
authors.initials: TW
authors.lastname: Chong
authors.forename: Leonard Hwan Cheong
authors.initials: LH
authors.lastname: Tan
authors.forename: Hung
authors.initials: H
authors.lastname: Huynh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000068258:Bevacizumab; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004789:Enzyme Activation / Q000187:drug effects; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000821:virology; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000821:virology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D004317:Doxorubicin; D003520:Cyclophosphamide; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020123:Sirolimus