Tripartite motif protein 11 (TRIM11), an oncogene for human lung cancer via the DUSP6-mediated ERK1/2 signaling pathway.

Evidence suggests that Tripartite Motif Containing 11 (TRIM11) has pro-tumor activity in human non-small cell lung cancer (NSCLC). However, the roles and underlying mechanisms of TRIM11 in NSCLC have not yet been fully elucidated. In this work, human lung cancer cell lines (A549, H446, and H1975) were transfected with siRNA or lentiviruses to knockdown or overexpress TRIM11 and dual-specificity phosphatase 6 (DUSP6). The cell tumor response was assessed by determining the rate of proliferation, apoptosis, the uptake of 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose (2-NBDG), and the secretion of lactic acid (LD). Dominant-negative (dn)-MEK1 was used to block the ERK1/2 pathway. The mechanism was investigated by assessing the protein levels of pyruvate kinase isozymes M2 (PKM2) and DUSP6, as well as the activation of ERK1/2 pathway. Our data confirmed the anti-cancer effect of siTRIM11 in human lung cancer by demonstrating inhibition of cancer cell proliferation, induction of apoptosis, prevention of 2-NBDG uptake, suppression of LD production, and prevention of lung cancer cell (A549) tumorigenicity in nude mice. The underlying mechanism involved the up-regulation of DUSP6 and the inhibition of ERK1/2 activity. Overexpression of TRIM11 induced tumorigenesis of NSCLC in vitro, and the activation of ERK1/2 was significantly reversed by DUSP6 overexpression or additional dn-MEK1 treatment. Interestingly, we confirmed TRIM11 as a deubiquitinase that regulated DUSP6 accumulation, indicating that lung cancer progression is regulated via the DUSP6-ERK1/2 pathway. In conclusion, TRIM11 is an oncogene in NSCLC, likely through the DUSP6-mediated ERK1/2 signaling pathway.

Knockdown of TRIM65 inhibits lung cancer cell proliferation, migration and invasion: A therapeutic target in human lung cancer.

Lung cancer is the most commonly diagnosed type of cancer worldwide. Although TRIM65 is an important protein involved in white matter lesion, the role of TRIM65 in human cancer remains less understood. Here, we reported that TRIM65 was significantly overexpressed in lung cancer tissues compared with adjacent normal lung tissues. Furthermore, TRIM65 expression was closely related to overall survival of patients with lung cancer. Knock down of TRIM65 in two lung cancer cell lines, SPC-A-1 and NCI-H358, resulted in a significant reduction in cell proliferation, migration, invasion and adhesion and a dramatic increase in G0-G1 phase arrest and apoptosis. In vivo tumorigenesis experiment also revealed that depletion of TRIM65 expression inhibited NCI-H358 cell growth. Moreover, based on gene set enrichment analysis (GSEA) with The Cancer Genome Atlas (TCGA) dataset, we found that TRIM65 was positive related to cell cycle, metastasis up and RHOA-REG pathways, which was further validated by RT-PCR and Western blot in TRIM65 knockdown lung cancer cells and indicated a possible mechanism underlying its effects on lung cancer. In summary, our study suggests that TRIM65 may work as an oncogene and a new effective therapeutic target for lung cancer treatment.

Effect of short hairpin RNA-induced CXCR4 silence on ovarian cancer cell.

This study was aimed to investigate the effect of down-regulating the CXC chemokine receptor-4 (CXCR4) expression on cell proliferation, invasion and migration of human ovarian cancer cell line SW626. The CXCR4 specific short hairpin RNA (shRNA) plasmid vector was constructed and then transfected into the SW626 cells. The expression of CXCR4 mRNA and protein was detected by real-time RT-PCR and western blot respectively. Cell proliferation was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell invasion and migration was assayed in Biocoat Matrigel invasion chambers. The expression level of CXCR4 in SW626 cell transfected with CXCR4-siRNA was inhibited, leading to significant decrease in SW626 cell proliferation, invasion and migration. We conclude that CXCR4 is essential for tumor cell proliferation and invasion. The CXCR4 molecule is a potential therapeutic target to control ovarian cancer cell growth or metastasis.

[Clinical application of MC + PEEK cage in traumatic cervical disc herniation].

OBJECTIVE: To explore the clinical outcomes of surgical treatment for traumatic cervical disc herniation with MC + PEEK cage. METHODS: A total of 51 patients with traumatic cervical disc herniation in mono-segment were surgically treated. The patients in group A (n = 20) were treated by MC + PEEK cage while those in group B (n = 31) by anterior cervical plate with PEEK cage or titanium mesh. Various parameters of operative duration, blood loss volume, operative complications, bone union, height of intervertebral space and Japanese Orthopedic Association (JOA) score were recorded and compared. RESULTS: Fifty-one patients were followed up for an average time of 26 months (range: 6 - 40). Operative duration, blood loss volume and operative complications of group A were better than group B with statistical significance (P < 0.05). Bone union, height of intervertebral space and recovery of spinal cord function were satisfactory with no statistical difference (P > 0.05). CONCLUSION: With this new cage, traumatic cervical disc herniation may be safely and micro-invasively treated without the need of anterior cervical plate.

Effect of yiqi huoxue formula on healing quality and recurrence rate of peptic ulcer / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of yiqi huoxue formula (YHF) on healing and recurrence of peptic ulcer.</p><p><b>METHODS</b>Adopting randomized and controlled principle, the 46 patients with active peptic ulcer were randomly allocated into the treated group and the control group, they received respectively the treatment of YHF + Omeprazole and Omeprazole alone for 5 weeks. If exhibiting positive Hp, the Trigeminy one-week eradicating treatment, using Omeprazole, Clarithromycin and Amoxicillin, was applied firstly, after then, followed with the prescriptive treatment. Gastroscopy was performed before and after treatment to assess the status of Hp eradicating and the endoscopic and histological maturity of regenerated mucosa. Meanwhile, the changes of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels were detected with ELISA. Patients with ulcer healed were followed up for 6 months to observe the condition of recurrence.</p><p><b>RESULTS</b>The percentage of Sc phase maturity and excellent histological maturity of regenerated mucosa obtained in the treated group were more than those in the control group respectively (P < 0.05), and levels of VEGF and bFGF increased significantly in the treated group after treatment (P < 0.05). But the difference of ulcer recurrence rate between the two groups in the 6-month follow-up study showed no statistically significance. However, the recurrence rate in patients with excellent histological maturity of regenerated mucosa was lower than that with good histological maturity (P < 0.05); and it was decreasing along with the progressing of regenerated mucosa endoscopic maturity, i.e., Sc < Sb < Sa (P < 0.01).</p><p><b>CONCLUSION</b>YHF can improve the quality of ulcer healing, and its mechanism is possibly related to the increase of VEGF and bFGF expressions. The higher the quality of ulcer healing, the lower the recurrence rate.</p>

Short-term safety and curative effect of recombinant adenovirus carrying hepatocyte growth factor gene on ischemic cardiac disease.

BACKGROUND: Adenovirus-mediated angiogenic growth factor gene transfer provides a new therapeutic strategy for treatment of coronary heart disease. Preclinical studies showed that direct intramyocardial injection of recombinant adenovirus with hepatocyte growth factor gene (Ad-HGF) was able to promote neovascularization, improve heart function and abate the area of ischemic myocardia in animal models. However, the safety and therapeutic effect of Ad-HGF were not evaluated in clinical trials. PATIENTS AND METHODS: A open-label, safety and tolerance trial of Ad-HGF in 18 patients suffering from coronary heart disease was performed. Three groups, each with 6 patients, received 5x10(8) (low dosage), 1.5 x 10(9) (medium dosage) and 5x10(9) (high dosage) pfu of Ad-HGF/person respectively, by direct multipoint injection into the myocardium while accepting coronary artery bypass surgery. The changes of vital symptoms, blood and urea routine analyses, as well as myocardial perfusion before and after treatment were analyzed. RESULTS: There was no evidence of systemic or cardiac-related adverse events after intramyocardial administration of the Ad-HGF. Myocardial perfusion of the Ad-HGF-injected area was improved in 3 cases of the low-dose group, 5 cases of the medium-dose group, and all of the high-dose group. CONCLUSION: These preliminary clinical data indicate that direct intramyocardial administration of Ad-HGF was well tolerated and could improve myocardial perfusion with a dose-effect relationship, encouraging larger and randomized efficacy trials.