DNA-damaging drug-induced apoptosis sensitized by N-myc in neuroblastoma cells.

Neuroblastoma is one of the most common solid tumours in children (8-10% of all malignancies). Over 22% of cases have N-myc amplification associated with aggressively growing neuroblastomas. Oncogene-induced sensitization of cells to apoptosis is an important mechanism for suppression of tumorigenesis. Tumour suppressors often play a critical role in linking oncogenes to apoptotic machinery. For example, activated p53 then targets both intrinsic and extrinsic pathways to promote apoptosis through transcription-dependent and -independent mechanisms. Understanding of the involved mechanisms has important clinical implications. We have employed DNA-damaging drug-induced apoptosis sensitized by oncogene N-myc as a model. DNA damaging drugs trigger high levels of p53, leading to caspase-9 activation in neuroblastoma cells. Inactivation of p53 protects cells from drug-triggered apoptosis sensitized by N-myc. These findings thus define a molecular pathway for mediating DNA-damaging drug-induced apoptosis sensitized by oncogene, and suggest that inactivation of p53 or other components of this apoptotic pathway may confer drug resistance in neuroblastoma cells. The data also suggests that inactivation of apoptotic pathways through co-operating oncogenes may be necessary for the pathogenesis of neuroblastoma with N-myc amplification.

[Intervention effect of tongfei mixture on nocturnal hypoxia in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the effect of tongfei mixture (TFM, a Chinese recipe mainly consisted of angelica and rehmannia root) on nocturnal hypoxia in patients with chronic obstructive pulmonary disease (COPD). METHODS: Sixty patients with COPD of remission phase were randomly divided into 3 groups, 20 in each group. Group A was the control group; Group B, the group simply treated with oxygen; Group C, treated with oxygen and TFM. Changes of pulmonary function, diaphragm muscle mobility (DMM), 6 min walk distance (6MWD), morning arterial blood gas, nocturnal lowest oxygen saturation (LSaO2), mean blood oxygen saturation (MSaO2), the percentage of saturation lower than 90% time account for total sleeping time (SLT90%) and ultrasonocardiogram before and after treatment were observed. RESULTS: Levels of LSaO2, MSaO2 and SLT90% in Groups B and C were significantly higher than those in Group A (P<0.05, P<0.01). The lowering of PaCO2 in Group C was more significant than that in Group B (P<0.05). The mPAP level in Group C was lower, FEV1, 6MWD and DMM were improved than those in Group A and B, showing significant difference (P<0.05). CONCLUSION: Combined use of oxygen therapy and TFM could not only improve the nocturnal hypoxia, but also lower PaCO2. TFM is an important supplement of oxygen therapy.

Essential role for p53 and caspase-9 in DNA damaging drug-induced apoptosis in neuroblastoma IMR32 cells.

Neuroblastoma is a solid tumor of the sympathetic nervous system accounting for up to 10% of pediatric cancers and 15% of cancer-related deaths. It is a useful system for investigation of stress signal-mediated apoptosis as a tumor suppression mechanism. In this study, we present evidence that p53 mediates DNA damaging drug-induced apoptosis in IMR32 cells through the caspase-9 pathway. In summary, we define a molecular pathway for mediating DNA damaging drug-induced apoptosis in human neuroblastoma IMR32 cells and suggest that inactivation of essential components of this apoptotic pathway may confer drug resistance on neuroblastoma cells.