Notch signaling inhibits the growth of the human chronic myeloid leukemia cell line K562.

Notch signaling functions in the development of some types of leukemia and lymphoma, but the relationship between Notch signaling and chronic myeloid leukemia (CML) remains to be elucidated. In this study, we examined the expression of Notch receptors and ligands in the human CML cell line K562. When the active form of Notch1, the Notch intra-cellular domain (NIC), was over-expressed in K562, the proliferation of K562 was mildly but significantly inhibited, accompanied by increased Hes1 mRNA level. On the other hand, when Notch signaling was attenuated by over-expression of a dominant-negative RBP-J, RBP-J(R218H), in K562 cells, the proliferation of K562 was increased. Moreover, we found that activation of Notch signaling inhibited while repression of Notch signaling promoted the colony-forming activity of K562 cells. We examined cell cycle-related molecules in K562 transfected with NIC or RBP-J(R218H), and found that the protein level of the retinoblastoma gene product (the Rb protein) was induced in K562 expressing NIC, and down-regulated in K562 expressing RBP-J(R218H). These data suggest that the Notch signaling may function as a tumor inhibitor in human CML cells.

[Changes of lipid levels in mice with hypoxic pulmonary arterial hypertension].

OBJECTIVE: To observe the changes of lipid levels in mice with pulmonary hypertension induced by hypoxia. METHODS: The animal model of hypoxic pulmonary hypertension was established by exposing the mice to isobaric hypoxic chamberfor 3 weeks (23 h/d, regular chow feed). Twenty male C57BL/6 mice were randomlydivided into normoxia group and hypoxia group (n=10). The concentrations of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) in plasma were detected by Elisa method.The mRNA levels of HMG-CoAreductase (HMGCR), low density lipoprotein receptor (LDLR), scavenger receptor class B1 (SR-B1), and sterol regulatory element-binding factor-2 (SREBF2) in liverwere measured by real-time PCR. RESULTS: ① The right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group (P<0.05).② The concentrations of HDL and HDL/LDL in plasma were significantly higher in hypoxia group, compared with normoxia group (P<0.05).③The mRNA levels of LDLR and SR-B1in liver were significantly down-regulated in hypoxia group(P<0.05).④RVSP were significantly negative correlated with HDL/LDL, the gene expression of LDLR and SR-B1 (P<0.05). CONCLUSIONS: Abnormal lipid metabolism participates in the pathological proceeding of pulmonary hypertension induced by hypoxia.

Brain metastasis: experience of the Xi-Jing hospital.

BACKGROUND: The management of metastatic brain tumors is an important issue in patients with malignant tumors or cancer. The authors summarize the results of patients with brain metastases treated at the Xi-Jing Hospital during a 10-year period, in order to assess the best modality of treatment for patients with brain metastases. METHODS: Between 1990 and 2000, 463 patients with brain-metastatic tumors were treated at the Xi-Jing Hospital of the Fourth Military Medical University, Xian, China. In most patients, the pathologic diagnosis of primary cancer was obtained before they were referred for their brain metastasis. There were 34 (8.42%) cases with an unknown primary cancer site at the time of initial presentation. Patients were grouped according to treatment methods, which included neurosurgical craniotomy (NS; 130 patients), whole-brain radiotherapy (WBRT; 120 patients). Linac XKnife radiosurgery (RS; 130 patients) and Linac XKnife radiosurgery plus WBRT (RT; 83 cases). Survival was measured from the time of treatment and was analyzed by the Kaplan-Meier product-limit method and then plotted. Differences between curves were evaluated using the log-rank test. Multivariate factors associated with survival were analyzed using the Cox proportional hazards model. RESULTS: The survival time was 68.4 +/- 7.20 weeks after NS, 51.3 +/- 5.04 weeks after WBRT, 67.9 +/- 3.68 weeks after RS and 89.7 +/- 4.50 weeks after RT. The presence of active systemic cancer in a larger number of metastatic tumors was associated with a poor survival (p = 0.0003 and 0.0000). The female patients showed better survival rates over the male ones (p = 0.0000). Patients treated with RT had a better survival than those treated with NS, WBRT and RS (p = 0.0048, 0.0000 and 0.1222, respectively), although the latter did not show statistical significance. CONCLUSIONS: RS was an effective modality for patients with brain metastases, and if combined with WBRT, survival was better. Progression of systemic cancer and the number of metastatic tumors were the most significant factors for a poor survival after treatment of the brain metastases.