Lysyl Oxidase Promotes the Formation of Vasculogenic Mimicry in Gastric Cancer through PDGF-PDGFR Pathway.

Objective: Vasculogenic mimicry (VM) generates an important supplementary form of blood supply in cancer, which many factors regulate. However, the effect of lysyl oxidase (LOX) on VM formation is unclear. In this study, gastric cancer tissues and cells were used to investigate the role of LOX in the formation of VM. Materials and Methods: The samples were collected from 49 patients with a final diagnosis of gastric cancer. According to metastasis (including lymph node metastases and distant metastases), gastric cancer samples were divided into metastasis and non-metastasis groups. Based on the degree of invasion, gastric cancer specimens were divided into T1 + T2 and T3 + T4 groups. The relative expression of LOX was detected using Western blot. The formation of VM was measured by double staining with CD34 and Periodic acid-Schiff (PAS) in gastric cancer tissue slices, and the correlation between LOX and VM was analyzed with Pearson's correlation analysis. Gastric cancer cell line BGC-803 was treated with LOX, ß-aminopropionitrile (BAPN, an inhibitor of LOX), and AG1295 or AG1296 (inhibitors of the platelet-derived growth factor receptor). The formation of VM was then measured using PAS staining. The expression of platelet-derived growth factor receptor (PDGFR)α and PDGFRß in gastric cancer cells was detected by Western blot. Results: In gastric cancer samples, the level of LOX was higher in the metastasis group than in the non-metastasis group (P < 0.05) and in the T3 + T4 group than in the T1 + T2 group (P < 0.05). VM formation was greater in the T3+T4 group than in the T1+T2 group (P < 0.05) and in the metastasis group than in the non-metastasis group (P < 0.05). The expression level of LOX was positively correlated with VM formation (P < 0.01). In gastric cancer cells, LOX concentration was positively correlated with the degree of VM, and BAPN concentration was negatively correlated with the degree of VM (P <0.05). PDGFR levels in the T3+T4 and metastasis groups were relatively higher (P <0.01) and positively correlated with LOX levels in gastric cancer specimens (P < 0.01). The relative expression of PDGFRα and PDGFRß in gastric cancer cells was up-regulated with increasing LOX and downregulated with increasing BAPN (P < 0.05). With inhibition of PDGFRα and PDGFRß using AG1295 or AG1296, VM formation in gastric cancer cells decreased (P <0.05), but the number of VM structures increased while LOX was added (P < 0.05). Conclusion: LOX partially promotes the formation of VM in gastric cancer through the PDGF-PDGFR signaling pathway.

Effect of Simvastatin on 5-HT and 5-HTT in a Rat Model of Pulmonary Artery Hypertension.

BACKGROUND/AIMS: To investigaterole of serotonin (5-HT) and serotonin transporter (5-HTT) in a rat model of cigarette smoke-induced pulmonary artery hypertension (PAH) and the effect of statins on regulating 5HT and 5-HTT. METHODS: A rat model of COPD comorbid with PAH was established by cigarette smoke exposure with or without simvastatin administration. The smoking and the simvastatin plus smoking groups were exposed to cigarette smoke daily, and the latter received simvastatin at 5mg/kg, once a day. After 16 weeks of cigarette smoke exposure, body weight and mean pulmonary arterial pressure (mPAP) were measured, bronchoalveolar lavage (BAL) was performed, and lung tissues and blood samples were collected to determine cardiopulmonary pathology, physiological indices, blood levelof 5-HT and expression of 5-HTT in the lung. RESULTS: In addition to alveolar structural damage (COPD-like injury), chronic cigarette smoke exposure lead to pulmonary artery remodeling and PAH as evidenced by significant elevation of mPAP, RVHI, WT%and WA%. Cigarette smoke exposure resulted in significant reduction in animal body weight, and simvastatin significantly prevented smoke-induced weight loss. The number of inflammatory cells in BALF was dramatically increased in smoke exposed rats, and simvastatin dampened the number of leukocytes, neutrophils, lymphocytes, and macrophages. In addition, circulating 5-HTand expression of 5-HTT in the lung were significantly increased in the smoked rats compared to control rats, and it was significantly reduced by simvastatin. Alteration of BALF inflammatory cells, 5-HT and 5-HTT was significantly correlated with changes of mPAP, RVHI, WT% and WA%. CONCLUSIONS: Cigarette smoke exposure could result in not only COPD, but also PAH, which may attribute to the alteration of blood 5-HT and lung tissue 5-HTT. Simvastatin could significantly inhibited 5-HT and 5-HTT expression, and by which mechanism, it may protect animals from development of PAH.

Association of atherosclerotic cerebral infarction and human leukocyte antigen-DRB in a North Chinese Han population.

BACKGROUND AND OBJECTIVES: Evidence from experimental and genetic studies suggest the existence of a potential link between the polymorphisms of human leukocyte antigen class II gene (HLA-DR) and ischemic stroke. This study addressed the association of HLA-DR gene with atherosclerotic cerebral infarction (ACI) in a North Chinese Han population. MATERIAL AND METHODS: The genotyping of HLA-DRB1 was determined by standard techniques based on polymerase chain reaction and sequence-specific oligonucleotides hybridization in a gene chip. RESULTS: The relative risk (RR) of HLA-DRB1 FNx01 04 and HLA-DRB1 FNx01 03 (17) in patients with ACI and their first-degree relatives were significantly higher than those in the control group (RR=2.56 and 18.77, respectively; P <0.05). In contrast, the RR of HLA-DRB1 FNx01 12 was dramatically reduced in patients with ACI in relation to healthy controls (RR=0.17; P <0.01). CONCLUSIONS: These data indicate that the polymorphisms in HLA-DRB1 may influence the risk of ACI in the North Han population of China. Further studies are necessary to validate the observation in larger samples.

[Effect of lysyl oxidase on migration and adhesion of human gastric cancer HGC-27 cells in vitro].

OBJECTIVE: To study the effects of lysyl oxidase (LOX) on the migration and adhesion of the human gastric cancer cell line HGC-27 cells in vitro. METHODS: The human gastric cancer cell line HGC-27 cells were cultured in vitro, and treated with different concentration of ß-aminopropionitrile (BAPN). The ability of migration was assessed by wound-healing assay. The ability of adhesion was detected by homogenous and heterogeneous adhesion experiments. RESULTS: Compared that with 0 mmol/L BAPN, the ability of migration of the cells after treatment with 0.2 mmol/L BAPN was descended at 8, 24, 32 and 48 h; the number of cells with homogeneous adhesion was increased from (6.97 ± 0.07) × 10(3)/ml to (7.78 ± 0.11) × 10(3)/ml; and the number of cells with heterogeneous adhesion was decreased from (8.98 ± 0.15) × 10(3)/ml to (8.35 ± 0.10) × 10(3)/ml, both < 0.05. Compared with that of cells treated with 0 mmol/L and 0.2 mmol/L BAPN, the migration ability of cells after treatment with 0.3 mmol/L BAPN was descended at 8, 24, 32 and 48 h; the number of cells with homogeneous adhesion was raised to (8.02 ± 0.11) × 10(3)/ml and the number of cells with heterogeneous adhesion was down to (7.93 ± 0.07) × 10(3)/ml (P < 0.05). CONCLUSION: LOX may promote the metastasis of cancer cells by enhancing invasion, increasing heterogeneous adhesion and decreasing homogeneous adhesion.

[Expression of LOX and MMP-2 in gastric cancer tissue and the effects of LOX and MMP-2 on tumor invasion and metastasis].

OBJECTIVE: To compare the expressions of lysyl oxidase (LOX) and matrix metalloproteinases-2 (MMP-2) in gastric cancer and pericancerous tissues, in gastric cancers with and without lymph node metastasis, and to analyze the effects of LOX and MMP-2 on tumor invasion and metastasis. METHODS: Gastric cancer and pericancerous tissues were collected from 46 patients who underwent surgery. Levels of LOX and MMP-2 mRNA were detected by RT-PCR. Protein abundance of LOX and MMP-2 was examined using Western blot. RESULTS: Expressions of LOX and MMP-2 mRNA, and protein in 46 gastric cancers were significantly higher than that in 46 pericancerous tissues. In gastric cancer with lymph node metastasis, the levels of LOX and MMP-2 mRNA and protein were higher than those in gastric cancers without lymph node metastasis (P < 0.05). In the groups of gastric cancer with lymph node metastasis, expression of LOX was positively correlated with MMP-2 protein expression (P < 0.01). CONCLUSIONS: Expressions of LOX and MMP-2 in gastric cancer tissues are significantly higher than that in pericancerous tissues. The expressions of LOX and MMP-2 in gastric cancer with lymph node metastasis are higher than that in gastric cancer without lymph node metastasis. Expressions of LOX and MMP-2 are positively correlated. The results suggest that LOX and MMP-2 may promote the growth and metastasis of gastric cancer.

Quality of life and its influencing factors in patients with post-traumatic epilepsy.

OBJECTIVE: To observe the quality of life in patients with post-traumatic epilepsy and discuss the influencing factors. METHODS: We assessed 105 patients with post-traumatic epilepsy and 100 healthy people as control using Quality of Life Scale-31 (QOL-31), Self-rating Depressing Scale (SDS) and Self-rating Anxiety Scale (SAS), and conducted retrospective analysis on the depression, anxiety, site of trauma, control of seizure, EEG and therapeutic compliance. RESULTS: Patients with post-traumatic epilepsy scored much lower than the control group on QOL-31 (P less than 0.01), but higher than the control group on SDS and SAS (P less than 0.01). Multiple regression analysis indicated that major influencing factors on the quality of life were anxiety, therapeutic compliance, depression, poor control of epileptic seizure and site of trauma. CONCLUSIONS: The quality of life in patients with post-traumatic epilepsy has significantly declined. Doctors should pay attention to psychological and mental problems of patients with epilepsy, such as depression and anxiety, enhancing therapeutic compliance and controlling epileptic seizure, which are the keys to improving prognosis.