M-443

Control mice survive with a median of 32 days after tumor cell implantation. Treatment with M443 alone adds 5.5 days to this survival, whereas the chosen low dose of radiation does not significantly increase survival. In contrast, the combination of M443 and IR extend survival with a median of 16 days longer than control. Treatment with M443 does not affect the animal weight, as the weight loss observed is observed in all groups just a few days before the animals became moribund. It is showed that the tumor-containing fraction has elevated levels of both total and active MRK (lane RB in the vehicle-treated brain). In contrast, the tumor-containing fraction from the M443-treated brain shows total loss of MRK activity. Interestingly, the fractions containing normal brain, which in the control brain show some level of MRK protein, in the treated brain also has lost MRK, suggesting that diffusion of M443 across the whole cerebellum inhibit normal MRK as well^[1].