Ribozyme mediated down-regulation of thrombospondin receptor CD36 inhibits the growth of the human osteosarcoma cell line.

Thrombospondin-1 (TSP1) is known to possess tumor suppressor functions. In contradiction, TSP1 enhances the stromal vascularization and growth of certain cancers. A cell adhesion receptor, CD36, has been shown to interact with a ligand TSP1.

Establishment of a new model of human multiple myeloma using NOD/SCID/gammac(null) (NOG) mice.

We developed a new experimental animal model of human multiple myeloma using immunodeficient NOD/SCID/gammac(null) (NOG) mice. A human myeloma cell line, U266, was intravenously inoculated into 20 NOG mice, all of which developed hind leg paralysis and distress around 6 weeks after transplantation. Pathological studies showed that only the bone marrow was infiltrated with U266 cells, and no cells were present in other organs.

The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer.

It is unclear whether a subunit of glutamate cysteine ligase [a modifier subunit (GCLM) and a catalytic subunit (GCLC)] is an effective target for ameliorating cisplatin (CDDP)-resistance. We inhibited each subunit of GCL mRNA using a specific ribozyme (M-Rz and C-Rz) in the pulmonary adenocarcinoma cell line A549. GCL activity was suppressed by the ribozyme.

Mutation analysis of vinyl carbamate or urethane induced lung tumors in rasH2 transgenic mice.

Previous studies showed that significant differences in mutation frequency of the human c-Ha-ras transgene between vinyl carbamate (VC)- and ethyl carbamate (urethane)-induced lung tumors were observed in rasH2 mice. It remains unclear why the point mutation frequency is extremely low in VC-induced lung tumors, although this compound is much more carcinogenic than urethane. In this study, we examined the somatic point mutations of the transgene at the RNA level in VC- and urethane-induced lung tumors of rasH2 mice.

Ribozyme mediated cleavage of cell-associated isoform of vascular endothelial growth factor inhibits liver metastasis of a pancreatic cancer cell line.

Stromal angiogenesis is an important factor for progression of malignant neoplasms. We used hammerhead ribozymes against vascular endothelial growth factor (VEGF) gene transcripts to down-regulate cell-associated VEGF189 isoform function in the pancreatic cancer cell line MIA PaCa2. MIA PaCa2 transfected with anti-VEGF189 ribozyme did not show any alteration of growth rate under tissue culture.

Transgene stability and features of rasH2 mice as an animal model for short-term carcinogenicity testing.

The transgenic mouse rasH2 line, in which the mouse carries the human c-Ha-ras gene under the control of its own enhancer and promoter, has been proposed as one of the alternative short-term models for carcinogenicity testing. To apply this purpose, we have produced a genetically homogeneous population as C57BL/6JJic-TgN(RASH2) (Tg-rasH2) by continuous backcrossing. In this study, we examined the transgene stability between different generations and the detailed transgene architecture of the integrated human c-Ha-ras gene.