PNAEmu can significantly reduce Burkitt's lymphoma tumor burden in a SCID mice model: cells dissemination similar to the human disease.
In human Burkitt's Lymphoma (BL) BRG cells, a t(8;14) translocation, placing c-myc near the Emu enhancer of the H chain locus, causes tumor expansion. Earlier, we showed that a peptide nucleic acid complementary to the Emu sequence (PNAEmu), specifically inhibited the expression of translocated c-myc and impaired the growth of BRG cells-induced subcutaneous tumors in mice suffering from severe combined immunodeficiency (SCID). In this study, the therapeutic potential of PNAEmu was evaluated in a systemic mouse model. BRG-BL cells transfected with the luciferase gene were inoculated intravenously into SCID mice resulting in a preferential expansion, similar to the one of human adult patients, in the abdominal cavity, central nervous system and bone marrow. The mice were chronically injected intraperitoneally either with PNAEmu or with control PNA. The treatment was stopped when the control animals developed severe neurological symptoms. As detected both by inspection at necropsy and imaging, overall tumor growth in PNAEmu-treated mice decreased by >80%. Histological and immunohistochemical studies showed, only in PNAEmu-treated mice, a substantially reduced BL cell growth at the major sites of invasion and vast areas of necrosis in the lymphomatous tissues, with concomitant c-myc expression downregulation. Altogether, the data support the therapeutic potential of PNAEmu in human adult BL.
S.C. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, 16132 Genova, Italy.
S
S
Matis
M R
MR
Mariani
G
G
Cutrona
M
M
Cilli
F
F
Piccardi
A
A
Daga
G
G
Damonte
E
E
Millo
M
M
Moroni
S
S
Roncella
F
F
Fedeli
L C
LC
Boffa
M
M
Ferrarini
D000818:Animals; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D005260:Female; D006801:Humans; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008163:Luminescent Measurements; D051379:Mice; D016513:Mice, SCID; D020135:Peptide Nucleic Acids / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D020135:Peptide Nucleic Acids; D016271:Proto-Oncogene Proteins c-myc; D049409:Luciferases, Firefly