Phenyl-tert-butylnitrone induces tumor regression and decreases angiogenesis in a C6 rat glioma model.
The prognosis of patients who are diagnosed with glioblastoma multiforme is very poor, due to the difficulty of an early and accurate diagnosis and the lack of currently efficient therapeutic compounds. The efficacy of phenyl-tert-butylnitrone (PBN) as a potential anti-glioma therapeutic drug was assessed by magnetic resonance (MR) imaging (T(1)/T(2)-weighted imaging) and MR angiography (time-of-flight imaging, in conjunction with a Mathematica-based program) methods by monitoring morphologic properties, growth patterns, and angiogenic behaviors of a moderately aggressive rat C6 glioma model. MR results from untreated rats showed the diffusive invasiveness of C6 gliomas, with some associated angiogenesis. PBN administration as a pretreatment was found to clearly induce a decrease in growth rate and tumor regression as well as preventing angiogenesis. This compound even had a 40% efficiency in reducing well-established tumors. MR findings rivaled those from histology and angiogenesis marker immunostaining evaluations. In this study we demonstrated the efficiency of PBN as a potential anti-glioma drug and found it to inhibit tumor cell proliferation and prevent vascular alterations in early stages of glioma progression. The MR methods that we used also proved to be particularly suitable in following the angiogenic behavior and treatment response of a potential anti-glioma agent in a rat C6 glioma model.
Oklahoma University Bioengineering Center, Norman, OK, USA.
Sabrina
S
Doblas
Debbie
D
Saunders
Preeti
P
Kshirsagar
Quentin
Q
Pye
Jenny
J
Oblander
Brian
B
Gordon
Stanley
S
Kosanke
Robert A
RA
Floyd
Rheal A
RA
Towner
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005910:Glioma / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D007150:Immunohistochemistry; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D012984:Software; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; C029217:phenyl-N-tert-butylnitrone