Clinical significance of the expression of endothelial-monocyte activating polypeptide II (EMAPII) in the treatment of glioblastoma with recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2).
BACKGROUND
The application of human mutant recombinant TNF-alpha (TNF-SAM2) to glioblastoma has shown that there is marked variation in its sensitivity to TNF. To determine whether the production of endothelial-monocyte activating polypeptide II (EMAPII) by tumors confers TNF sensitivity and whether EMAPII expression in glioblastoma can predict the clinical response to TNF therapy, we evaluated EMAPII expression and the efficacy of TNF in patients with glioblastoma.


METHODS
We analyzed EMAPII mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) of frozen tissue sections of glioblastoma and evaluated if there was any correlation between EMAPII expression and the response to TNF therapy in patients with glioblastoma.


RESULTS
Amplified bands corresponding to EMAPII were obtained by RT-PCR in 8 out of 11 glioblastomas. There was a significant correlation between the time to tumor progression after TNF-SAM2 treatment and the expression of EMAPII (p < 0.05). Patients with positive expression of EMAPII in their tumor tissues tended to have longer progression-free survival.


CONCLUSIONS
Variable responses to combined chemotherapy with mutant TNF-alpha (TNF-SAM2) might be explained by EMAPII expression in glioblastoma. EMAPII expression in glioblastoma might predict the clinical response to TNF therapy and potentially identify patients with cytokine-responsive tumors.
Yamamoto
M
M
Department of Neurosurgery, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan. masaaki@fukuoka-u.ac.jp
Fukushima
T
T
Ueno
Y
Y
Hayashi
S
S
Kimura
H
H
Soma
G
G
Tomonaga
M
M
D000368:Aged; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D003131:Combined Modality Therapy; D016207:Cytokines; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000627:therapeutic use*
D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C109083:TNF-SAM2; D014409:Tumor Necrosis Factor-alpha; C077219:small inducible cytokine subfamily E, member 1