Targeting the PI3K-Akt pathway in human cancer: rationale and promise.
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Biomedical subjects
Publications and source records attributed to Ji Luo.
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OBJECTIVE: To investigate the efficacy of the specific murine anti-human CD(3) T lymphocyte monoclonal antibody (CD(3) MoAb) for severe aplastic anemia (SAA). METHODS: 13 SAA patients were chosen with a medium age of 22 years, including 4 untreated patients and 9 nonresponding to previous management. They were treated with 5 mg of CD(3) MoAb per day for a total 10 days. RESULTS: The response rate was 11/13, including 2 cured and 2 remission cases during a follow up of 3 to 15 months. As compared with the pretreatment condition the proliferation of bone marrow in 8 cases become better; the leukocytes, granulocytes, hemoglobin and platelets of peripheral blood increased 1.59 x 10(9)/L, 0.72 x 10(9)/L, 40 g/L and 47 x 10(9)/L respectively (P < 0.01, respectively); the ratio of CD(4)/CD(8) of T cell subsets increased from 1.12 to 1.42 while the expression of HLA-DR antigen decreased from 29.2 to 15.2 (P < 0.01, respectively); TNF alpha, IFN gamma and IL-2 secreted by peripheral blood mononuclear cells (PBMNCs) decreased obviously from 267, 784 and 92 to 152, 570 and 51 U/ml on the average respectively (P < 0.01, respectively). The main side effects were fever in all the patients and shortness of breath in 4 cases, but none died during the therapy. CONCLUSIONS: In contrast to other kinds of common immune suppressor, CD(3) MoAb showed better response and probably higher efficacy and safety for SAA. It is necessary to have more cases and to follow up longer to estimate its long term effect and side effects.
Based on the theory of fractal geometry, branching patterns of primitive Abies fabri in the dark coniferous forest ecosystem at the upper reach of Yangtze River were studied. The results showed that the maximum crown width was appeared at inferior 20% of the crown height, and its volume could be simulated by the combination of a round table and a cone. The surface of the crown and their branching patterns of Abies fabri had the common typical fractal characters, the fractal dimensions (FD) were 2.3232 and 1.8119, and the correlation coefficient was 0.99.
The key role played by PI3 kinase in cancer, hormone action, and a host of other biological functions suggests that specific inhibitors whose disposition could be ascertained in vivo would be useful in biological research or, potentially, for imaging PI3K in a clinical setting. Wortmannin (Wm, 1) is an inhibitor of PI3 kinase with high specificity for this enzyme. We synthesized three modified Wm probes, a biotinylated Wm (7a), a 4-hydroxy-3-iodophenylated Wm, which was obtained both unlabeled (7b) and labeled with (125)I (8), and a fluoresceinated Wm (7c), through modification at C-11, and evaluated their inhibitive activity as inhibitors of PI3 kinase. Biotinylated (7a) and 4-hydroxy-3-iodophenylated Wm's (7b) had IC(50)s for PI3K of 6.11 and 11.02 nM, respectively, compared to an IC(50) for Wm of 1.63 nM. Fluoresceinated Wm (7c) lost considerably more activity than the other derivatives, with an IC(50) of 64.9 nM. The (125)I labeled 4-hydroxy-3-iodophenylated Wm (8) could be detected after reaction with an immunoprecipitate of PI3 kinase. The activity of these reporter Wm's is discussed in relationship to earlier findings on the pharmacological activity of Wm derivatives and the ability of inhibitors to fit into the ATP pocket of PI3 kinase.