Effective prevention of thrombocytopenia in mice using adenovirus-mediated transfer of HST-1 (FGF-4) gene.
HST-1 (FGF-4) gene product is a member of the fibroblast growth factor family with a signal peptide and plays a crucial role in limb development. We showed previously that an intraperitoneal injection of replication-deficient adenovirus containing the HST-1 gene (Adex1HST-1) into normal mice caused a twofold increase in peripheral platelet count. To investigate whether Adex1HST-1 could effectively prevent experimentally induced thrombocytopenia in mice, we injected Adex1HST-1 intraperitoneally into thrombocytopenic mice induced by administration of a chemotherapeutic agent and/or by irradiation. A single Adex1HST-1 injection caused continuously increased levels of serum HST-1 protein for at least 30 d and increased the count of large megakaryocytes in bone marrow, which specifically recovered platelet counts and more efficiently diminished the extent and duration of thrombocytopenia than any other reported cytokine or any combination of cytokines so far. In the other peripheral hematological parameters, no discernible differences were detected. No other apparent side effects were observed. Therefore, this method could be useful for treatment and/or prevention of thrombocytopenia induced by chemotherapy and/or irradiation for cancer treatment.
Konishi
H
H
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
Ochiya
T
T
Sakamoto
H
H
Tsukamoto
M
M
Saito
I
I
Muto
T
T
Sugimura
T
T
Terada
M
M
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation; D010976:Platelet Count / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011833:Radiation Injuries, Experimental / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013921:Thrombocytopenia / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*
C496445:FGF4 protein, human; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D005346:Fibroblast Growth Factors; D002945:Cisplatin