Correlation between serum IGF-1 and blood lead level in short stature children and adolescent with growth hormone deficiency.

UNLABELLED: This study aimed to investigate correlation between serum insulin-like growth factor-1 (IGF-1) and blood lead level in short stature children with growth hormone deficiency (GHD), and IGF-1 signal molecules were investigated in lead exposed rats. Our findings may provide evidence for clarifying pathogenesis of lead induced short stature in children. METHODS: 880 short stature children were recruited from clinics and divided into GHD group and idiopathic short stature (ISS) group according to the GH peak in growth hormone stimulation test. The height, body weight, serum IGF-1 level and blood lead level were determined. A rat model of lead poisoning was used to establish and western blot assay was employed to detect the phosphorylation of signaling molecules (MAPK and PI3K/Akt) related to IGF-1 signaling pathway. RESULTS: In GHD group, the height, body weight and serum IGF-1 level were significantly lower, but the blood lead level was significantly higher than those in ISS group (P<0.05). Western blot assay confirmed that the protein expression of phosphorylated ERK1/2, JNK, p38, Akt473 and Akt308 increased significantly (P<0.01) in lead exposure rats. CONCLUSION: Our study suggesting that reduction in IGF-1 in children with GHD is associated with blood lead level. Lead exposure may induce expression of phosphorylated MAPK and Akt signaling molecules. The activation of these molecules may influence binding of IGF-1 and tyrosine kinase receptor IGFIR to regulate cell growth via the MAPK and Akt signaling pathways, which then interfere with growth-promoting effect of IGF-1 in short children.

[Effects of TFDP3 on regulating the autophagy and apoptosis of LNCaP cells].

AIM: To investigate the effect of TFDP3 on prostate cancer cell line LNCaP by transgenic method, and to explore the effect of TFDP3 on regulating the autophay and apoptosis by co-regulation with E2F1. METHODS: LNCaP cells were transfected with pcDNA3.1-TFDP3, pCMV-E2F1-HA or pcDNA3.1 empty vector.The expression of TFDP3, E2F1 and LC3B were detected by real-time PCR after transfection for 24 h. Western blotting was used to monitor the changes in autophagy-associated protein LC3B, Apoptosis of transfected cells were analyzed by flow cytometry. RESULTS: The results showed that activation of TFDP3 upregulates the expression of autophagy genes-microtubule-associated protein-1 light chain-3B (LC3B), and E2F1 antagonizes TFDP3-induced autophagy, and TFDP3 can inhibit E2F1-induced apoptosis. CONCLUSION: TFDP3 upregulates the expression of autophagy gene LC3B and inhibits E2F1-induced apoptosis, and may play an important role in prostate cancer.

[The clinical research of serum soluble CD40L and high sensitivie C-reactive protein in patients with acute coronary syndrome].

AIM: To explore the clinical significance and mechanism of soluble CD40 Ligand (sCD40L) and high sensitive C-reactive protein (hs-CRP) in patients with acute coronary syndrome(ACS). METHODS: A total of 86 consecutive patients with ACS were included in the study, according to the selection criteria for diagnosis of acute coronary syndrome (ACS), 86 patients were divided into two groups: normal and the ACS, In all patients, sCD40L and CRP levels were evaluated within 12 h. the incidence of acute cardiovascular events were observed after two months follow-up. RESULTS: The ACS group was obviously higher than control group (P<0.01), AMI group slightly higher than the UA group but had no significant difference (P>0.05). sCD40L and hs-CRP group of cardiovascular events increased more than the normal group. CONCLUSION: Acute coronary syndrome patients with early peripheral serum levels of sCD40L and hs-CRP were significantly increased, suggesting that CD40/CD40L system participate the occurrence of ACS, and the inflammatory factors such as C-reactive protein in collaboration, plays an important role on atherosclerotic plaque instability.

[Effect of As(2)O(3) on expressions of COX-2 and matrix metalloproteinases in SGC7901 and K562 cells].

This study was aimed to investigate on effect of As(2)O(3) on expressions of COX-2, MMP-2 and MMP-9 in SGC7901 and K562 cells. SGC7901 and K562 cells were cultured in RPMI 1640 medium and were inoculated in culture medium with different concentrations of As(2)O(3) and at different times. Expressions of COX-2, MMP-2 and MMP-9 in SGC7901 and K562 cells were measured by using Western blot, while the levels of COX-2 mRNA and MMP-2 mRNA were measured with fluorescence quantitative RT-PCR. The results showed that the expression of COX-2, MMP-2 and MMP-9 decreased in dose- and time-dependent manners after treating with As(2)O(3). The levels of COX-2 mRNA and MMP-2 mRNA reduced in groups treated with As(2)O(3). In conclusion, As(2)O(3) inhibits expressions of COX-2, MMP-2 and MMP-9 in K562 and SGC7901 cells, suggesting that As(2)O(3) inhibits tumor development through its effect on angiogenesis involved in solid and hematologic malignancies.

[Effect of arsenic trioxide on vascular endothelial growth factor-C and its receptor (VEGFR-3) in nude mice with gastric cancer].

This study was aimed to investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 in gastric cancer in order to clarify the role of As2O3 in lymphangiogenesis and metastasis of tumor. The gastric cancer model was established in nude mice by using gastric cancer cell line SGC-7901. As2O3 was injected to the two treatment groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected to the control group. Expression of VEGF-C and VEGFR-3 were detected by immunohistochemistry and were analyzed with QWin550cW image Acquiring & Analysis System. The results showed that the expression of VEGF-C and VEGFR-3 in cancer cells significantly reduced in the arsenic -treated groups. The expression of VEGF-C and VEGFR-3 in 5 mg/kg group was significantly less than that in 2.5 mg/kg group. The gray ratio analysis confirmed that there were significant difference between control group and two treated group, as well as between 2.5 mg/kg-treated group and 5 mg/kg-treated group. It is concluded that As2O3 can inhibit expression of VEGF-C and VEGFR-3 of human gastric cancer xenografts in nude mice, which suggests that As2O3 may inhibit the lymphangiogenesis by suppressing the expression of VEGF-C and VEGFR-3.

Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice.

AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells. METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy. SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry. RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 micromol/L, respectively. Early apoptosis in the As2O3-treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls. CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.

Inhibitory effect of arsenic trioxide on angiogenesis and expression of vascular endothelial growth factor in gastric cancer.

AIM: To investigate the inhibitory effect of As(2)O(3) on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro. METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As(2)O(3) was injected into the arsenic-treated groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected into the control group. Microvessel density (MVD) and expression of VEGF were detected with immunofluorescence laser confocal technology. Further expression of VEGF protein and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT- PCR in SGC-7901 cells treated with As(2)O(3). RESULTS: In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3) respectively, about 50% and 30% tumor growth inhibition were observed correspondingly (P<0.05, P<0.05). Decrease in MVD appeared in As(2)O(3)-treated tumors compared with control group (P<0.001, P<0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5 mg/kg group (P<0.01). The fluorescence intensity levels of VEGF in tumor cells were significantly lowered in the arsenic-treated groups (P<0.01, P<0.01). The fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5 mg/kg group (P<0.01). In vitro, the expression of VEGF protein decreased in dose- and time-dependent manner after the treatment with As(2)O(3), but in VEGF mRNA no significant difference was found between the control group and the treated groups. CONCLUSION: As(2)O(3) can inhibit solid tumor growth by inhibiting the formation of new blood vessels. One of the mechanisms is that As(2)O(3) can inhibit VEGF protein expression.

[Effect of realgar on expression of survivin in leukemia cell lines and its significance].

To study the effect of realgar on expression of survivin in leukemia cell lines, HL-60 and Jurket cell lines were used as in vitro models. The expression of survivin was detected by Western blot analysis and immunofluorescence, and the expressions of Fas and caspase-3 were examined by immunohistochemistry. The results showed that the expression of survivin was positive in the two cell lines. HL-60 cells did not express Fas and caspase-3, and Jurket cells were Fas-positive and caspase-3 was negative. Realgar induced a dose- and time-dependent down-regulation of survivin expression in Jurket cells, and especially in HL-60. Caspase-3 expression changed from negative to positive in HL-60 cell, but there still was no expression in Jurket cell. It is concluded that survivin expression level decreased during leukemia cell apoptosis induced by Realgar. The down-regulation of survivin expression may be an important mechanism in leukemia cell apoptosis induced by realgar through mitochondrial pathway.