The molecular basis for enhanced chemosensitivity of testicular germ cell tumors （GCT） has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far,...The molecular basis for enhanced chemosensitivity of testicular germ cell tumors （GCT） has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of C＆T has been variously attributed to multiple factors -- an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-la （HIF-la） expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.展开更多
Objective: To explore the mRNA expression of the related genes of p53, MDM2, vascular endothelial growth factor (VEGF) and hypoxia inducible transcription factors-1 a (HIF-la) in villous samples of spontaneous abortio...Objective: To explore the mRNA expression of the related genes of p53, MDM2, vascular endothelial growth factor (VEGF) and hypoxia inducible transcription factors-1 a (HIF-la) in villous samples of spontaneous abortion mouse models and normal pregnancy models, and to discuss the effect of p53, MDM2 on the growth of villous trophoblast cells. Methods: The abortion-prone CBAXDBA/2 matings were established as the model of spontaneous abortion and the non-abortion-prone CBAXBALB/c matings as the model of normal pregnancy. Applied q Real-time PCR method to detect the mRNA expression levels of p53, MDM2, VEGF and HIF-la in villous samples of spontaneous abortion mouse models and normal pregnancy models. Results: The relationship of the mRNA expression level of p53, MDM2, VEGF and HIF-la in vinous samples of spontaneous abortion mouse models: in the villous samples of spontaneous abortion mouse models, the expression of p53 was positively correlated with the expression of MDM2, HIF-la (r = 0.35;r = 0.63), and the relationship was significant (P = 0.01;P < 0.001);but negatively correlated to the expression of VEGF (r = ?0.30), and the relationship was significant (P = 0.03). The expression of MDM2 was positively correlated with the expression of HIF-la (r = 0.28), and the relationship was significant (P = 0.04);and negatively correlated with the expression of VEGF (r = ?0.08), but the relationship was not significant (P = 0.57). The expression of HIF-la was negatively correlated with the expression of VEGF (r = ?0.37), and the relationship was significant (P = 0.007). The relationship of the mRNA expression level of p53,MDM2, VEGF and HIF-1 a in vinous samples of normal pregnancy models: in the vinous samples of normal pregnancy models, the expression of p53 was positively correlated with the expression of MDM2, VEGF and HIF-la (r = 0. 31;r = 0. 48;r = 0. 67), and the relationship was significant (P = 0.03;P = 0.003;P < 0.001). The expression of MDM2 was positively correlated with the expression of VEGF (r = 0. 23), but the relationship was not significant (P = 0.11);and negatively correlated with the expression of HIF-la (r = ?0.03), but the relationship was not significant (P = 0.84). The expression of HIF-la was positively correlated with the expression of VEGF (r = 0. 35), and the relationship was significant (P = 0.01). Conclusion: angiogenesis reduces in villous samples of spontaneous abortion mouse model, P53 and MDM2 involve in angiogenesis in villous samples, unlikely p53, and MDM2 have effects on normal early pregnancy villous angiogenesis and when the cell DNA damages or hypoxia exacerbates, it can induce high expression of p53, MDM2, inhibit angiogenesis in villous samples in early pregnancy. P53, MDM2 generegulate villous trophoblast cell growth by adjusting expression of HIF-1a and VEGF gene, finally influences pregnancy.展开更多
文摘The molecular basis for enhanced chemosensitivity of testicular germ cell tumors （GCT） has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of C＆T has been variously attributed to multiple factors -- an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-la （HIF-la） expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.
文摘Objective: To explore the mRNA expression of the related genes of p53, MDM2, vascular endothelial growth factor (VEGF) and hypoxia inducible transcription factors-1 a (HIF-la) in villous samples of spontaneous abortion mouse models and normal pregnancy models, and to discuss the effect of p53, MDM2 on the growth of villous trophoblast cells. Methods: The abortion-prone CBAXDBA/2 matings were established as the model of spontaneous abortion and the non-abortion-prone CBAXBALB/c matings as the model of normal pregnancy. Applied q Real-time PCR method to detect the mRNA expression levels of p53, MDM2, VEGF and HIF-la in villous samples of spontaneous abortion mouse models and normal pregnancy models. Results: The relationship of the mRNA expression level of p53, MDM2, VEGF and HIF-la in vinous samples of spontaneous abortion mouse models: in the villous samples of spontaneous abortion mouse models, the expression of p53 was positively correlated with the expression of MDM2, HIF-la (r = 0.35;r = 0.63), and the relationship was significant (P = 0.01;P < 0.001);but negatively correlated to the expression of VEGF (r = ?0.30), and the relationship was significant (P = 0.03). The expression of MDM2 was positively correlated with the expression of HIF-la (r = 0.28), and the relationship was significant (P = 0.04);and negatively correlated with the expression of VEGF (r = ?0.08), but the relationship was not significant (P = 0.57). The expression of HIF-la was negatively correlated with the expression of VEGF (r = ?0.37), and the relationship was significant (P = 0.007). The relationship of the mRNA expression level of p53,MDM2, VEGF and HIF-1 a in vinous samples of normal pregnancy models: in the vinous samples of normal pregnancy models, the expression of p53 was positively correlated with the expression of MDM2, VEGF and HIF-la (r = 0. 31;r = 0. 48;r = 0. 67), and the relationship was significant (P = 0.03;P = 0.003;P < 0.001). The expression of MDM2 was positively correlated with the expression of VEGF (r = 0. 23), but the relationship was not significant (P = 0.11);and negatively correlated with the expression of HIF-la (r = ?0.03), but the relationship was not significant (P = 0.84). The expression of HIF-la was positively correlated with the expression of VEGF (r = 0. 35), and the relationship was significant (P = 0.01). Conclusion: angiogenesis reduces in villous samples of spontaneous abortion mouse model, P53 and MDM2 involve in angiogenesis in villous samples, unlikely p53, and MDM2 have effects on normal early pregnancy villous angiogenesis and when the cell DNA damages or hypoxia exacerbates, it can induce high expression of p53, MDM2, inhibit angiogenesis in villous samples in early pregnancy. P53, MDM2 generegulate villous trophoblast cell growth by adjusting expression of HIF-1a and VEGF gene, finally influences pregnancy.
