Activity in Animal Models

The antiproliferative activity of Glivec has been confirmed in animal models. Once-daily intraperitoneal treatment with 2.5 to 50 mg/kg of Glivec starting 1 wk after injection of Bcr-Abl-transformed 32D cells in syngeneic mice caused dose-dependent inhibition of tumor growth (14). In contrast, Glivec showed no anti-tumor activity against tumors derived from v-src-transformed 32D cells, in line with the lack of inhibition of Src kinase by the compound. The in vivo activity of Glivec against Bcr-Abl-driven tumors was confirmed using the KU812 cell line derived from a CML patient in blast crisis injected into nude mice. Oral treatment with 160 mg/kg daily in three divided doses for 11 consecutive days was associated with continuous blockage of p210bcr-abl tyrosine phosphorylation and resulted in tumor-free survival of the animals (24). These data suggested that continuous exposure to Glivec would be important for optimal anti-leukemic effects. The anti-tumor effect of Glivec was specific for Bcr-Abl-expressing cells as no growth inhibition occurred in mice given injections of U937, a Bcr-Abl-negative myeloid cell line. Glivec has also been shown to have oral activity in a murine model of CML based on retroviral p210bcr-abl transduction of transplanted bone marrow, where survival of animals was significantly prolonged, together with a marked improvement in peripheral white blood counts and splenomegaly (28).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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