An Epstein-Barr virus positive natural killer lymphoma xenograft derived for drug testing.
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.
Loong
Susan Li Er
SL
Division of Cellular and Molecular Research, Department of Radiation Oncology, National Cancer Centre, Singapore.
Hwang
Jacqueline Siok Gek
JS
Lim
Soon-Thye
ST
Yap
Swee Peng
SP
Tao
Miriam
M
Chong
Tsung-Wen
TW
Tan
Leonard Hwan Cheong
LH
Huynh
Hung
H
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
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