Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.

CONTEXT: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. OBJECTIVE: Our study explores the effect and mechanism of STS against LUAD. MATERIALS AND METHODS: LUAD cells were treated with 100 µM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. RESULTS: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. DISCUSSION AND CONCLUSIONS: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

STS â ¡A inhibited angiogenesis of lung adenocarcinoma by activating FOXO3 to inhibit CXCL1/STAT3/VEGF pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Sulfotanshinone IIA sodium (STS IIA) has been proven to have an anticancer effect. However, its role in LUAD and its underlying mechanism remain unclear. OBJECTIVE: To investigate the role and mechanism of STS IIA in LUAD angiogenesis. METHODS: The mRNA levels of genes, including forkhead box O3 (FOXO3) and chemokine C-X-C motif ligand 1 (CXCL1), were detected by qRT-PCR. The levels of proteins, including FOXO3, CXCL1, and vascular endothelial growth factor (VEGF), were measured by Western blot. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by the EdU assay and the tubule formation assay, respectively. The binding relationship between FOXO3 and CXCL1 was detected by dual-luciferase reporter assay. RESULTS: Our results illustrated that different concentrations of STS IIA inhibited the proliferation and angiogenesis of HUVECs. FOXO3 regulated the proliferation and angiogenesis of HUVECs inhibited by STS ⅡA via targeting CXCL1. Subsequently, we proved that exogenous CXCL1 alleviated the inhibition of proliferation and angiogenesis of HUVECs regulated by STS IIA via activating the STAT3/VEGF pathway. Finally, we found that STS IIA inhibited the angiogenesis of lung adenocarcinoma though FOXO3 to inhibit the CXCL1/STAT3/VEGF pathway. CONCLUSION: Our study finally elucidated the underlying molecular mechanism by which STS ⅡA inhibits LUAD angiogenesis.

Efficacy and Side Effects of Combined Capecitabine Plus Intensity Modulated Radiotherapy as an Effective Adjuvant Therapy for Gastric Cancers.

This study aims to evaluate the clinical outcomes and the toxicities associated with intensity modulated radiotherapy (IMRT) administered in combination with capecitabine for gastric cancer. This study was conducted between July 2009 and October 2011, and included 31 patients (23 female and eight male patients; mean age: 57 years old) with pathologically confirmed gastric cancer (pathological staging T3 or T4 or positive lymph node). All patients underwent D2 surgery and adjuvant chemoradiotherapy, followed by combined treatment with IMRT and capecitabine. All patients received follow-up examinations every 3-6 months by physical examination, magnetic resonance imaging (MRI), and assays for tumor markers. The Kaplan-Meier method was used to calculate the rates for locoregional control (LRC) and disease-free survival (DFS). Only two patients could not complete the planned treatment regimen. Patients treated with IMRT and capecitabine tolerated their treatment well, and displayed few significant side effects. The mean follow-up, disease-free survival (DFS) and survival times were 33.0, 27.5, and 32.9 months, respectively.This study confirmed that the combined administration of IMRT and capecitabine can be used as an adjuvant therapy for gastric cancer patients, with few toxic side effects.

Effect of tetramethylpyrazine combined with cisplatin on VEGF, KLF4 and ADAMTS1 in Lewis lung cancer mice.

OBJECTIVE: To further explore the function of combine use of tetramethylpyrazine (TMP) and cisplatin (DDP) in lung carcinoma. METHODS: We used the combination drug to treat Lewis lung cancer mice, investigated the expression level of vascular endothelial growth factor (VEGF), Kruppel-like factor 4 (KLF4) and A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and to further explore the inhibitory effects and potential mechanism of TMP combined with DDP on tumor angiogenesis. RESULTS: The tumor growth was suppressed in TMP group, DDP group and TMP combined with DDP group. Furthermore, the weights and volume of tumor, the expression level of VEGF, KLF4 and ADAMTS1 were found significantly changed between experiment group and control group. These findings suggest that TMP with DDP had additional or synergistic effects to inhibit the tumor growth effectively, might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expression of angiogenesis inhibitors KLF4 and ADAMTS1. CONCLUSION: KLF4 and ADAMTS1 may be synergically involved in the angiogenesis in mouse Lewis lung cancer through the different signal ways.

Evaluation of intraoperative radiotherapy for gastric carcinoma with D2 and D3 surgical resection.

AIM: To study the proper sites and doses of intraoperative radiotherapy (IORT) for gastric carcinoma and the effects of this treatment. METHODS: A total of 106 patients with stage I-IV gastric carcinoma who received D2 or D3 radical operation combined with IORT were analyzed. Sixty-seven patients with gastric cancer of the antrum and body underwent distal gastrectomy. The sites of irradiation were at the celiac artery and hepatoduodenal ligment area. Another 39 patients with carcinoma of the cardia and upper part of the gastric body and whole stomach underwent proximal gastrectomy or total gastrectomy. The sites of irradiation for this group were the upper margin of the pancreas and the regional para-aorta. The therapeutic effects (including survival and complications) of these 106 cases received operation combined with IORT (IORT group) were compared with 441 cases treated during the same time period by a radical operation alone (operation group). RESULTS: The radiation dose below 30 Gy was safe. The therapeutic method of the operation combined with IORT did not prolong the survival of patients with stage I and IV gastric cancer, but the 5-year survival rates of patients with stage II and III gastric cancers were significantly improved. The 5-year survival rates of the stages III cancer patients receiving D2 resection combined with IORT were markedly improved, while for those receiving D3 radical resection, only the postoperative 3- or 4-year survival rates were improved (P < 0.005-0.001). The 5-year survival rate for those patients was raised only by 4.7% (P > 0.05). CONCLUSION: The 5-year survival rates of patients with stages II and III gastric carcinoma who received D2 lymphadenectomy combined with IORT were improved, and there was no influence on the postoperative complications and mortality.

Effect of endostar combined with cisplatin on expression of VEGF and Sema3A of Lewis lung cancer rats.

OBJECTIVE: To evaluate the therapeutic effect of endostar (ED) combined with cisplatin(DDP) on model of C57BL/6 rats, and to further investigate the inhibiting mechanism of endostar from tumor angiogenesis. METHODS: Lewis lung cancer cells were inoculated in C57BL/6 mouse, then the mouse were randomized into control group (group A), ED (group B), DDP (group C) and ED/DDP (group D). They were treated according to the plan. And the expressions of VEGF and Sema3A were evaluated by immunhistochemisty. RESULTS: The weight of tumor increased in group A and B. It was decreased in group C and D. The tumor volume was increased in all the 4 groups. The VEGF expression of group D was obviously lower than the other group 3, but the Sema3A expressed of group D was significantly strengthener than the other group 3. The VEGF expression of group B and group D were obviously low especially in the 4th-8th days. Pearson correlated analysis showed that the expression VEGF and Sema3A were negatively correlated (r=-0.72, P<0.05). CONCLUSIONS: ED combined with DDP could control the tumor growth effectively, and avoid weight loss. ED could reduce VEGF expression, and enhance Sema3A expression. Tumor vessel presents transient normalization. It is easy for DDP perfusion, and to kill tumor cells.

Cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on QSG-7701 hepatocytes.

OBJECTIVE: To investigate the cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on cultured QSG-7701 cells lines. METHODS: Isoniazid, rifampicin, mixture of rifampicin and isoniazid, acetylhydrazine, hydrazine were added in cultural media of QSG-7701 cells and cultured for 48 hours. The survival rate of cells was determined by MTT method. The cultural media and cells were collected and the activity of lactate dehydrogenase was detected by chromatometry. RESULTS: Compared with control group, the survival rate decreased significantly and the lactate dehydrogenase released from cell increased significantly in cells treated with isoniazid, rifampicin, acetylhydrazine, hydrazine. Hydrazine, the metabolite of isoniazid produced significant damage on hepatocytes in low concentration. CONCLUSIONS: Rifampicin together with rifampicin and metabolites of isoniazid produce cellular toxic effects and hydrazine may be the most toxiferous metabolite.

Diagnostic value of tumor marker pro-gastrin-releasing peptide in patients with small cell lung cancer: a systematic review.

BACKGROUND: Lung cancer is one of the most common malignancies in the world and one of the leading cancers that result in death. The aim of this study was to evaluate and compare the diagnostic value of the serum tumor marker pro-gastrin-releasing peptide 31-98 (ProGRP31-98) to pathological diagnosis as reference standard in patients with suspected small cell lung cancer (SCLC). METHODS: Literature searches covering 1978 through to 2009 were performed in Pubmed, OVID, MEDLINE, EMbase, Cancerlit, China National Knowledge Infrastructure (CNKI), and CBM using the key search words; 'small cell lung cancer', 'tumor marker', 'ProGRP31-98' and 'diagnostic tests', 'ELISA', 'EIA' and 'diagnostic accuracy'. Studies were collected and data analyzed to evaluate the diagnostic value of serum ProGRP31-98 levels for the diagnosis of SCLC compared with pathology. Eligibility criteria for inclusion in the analysis were based on criteria for diagnostic research published by the Cochrane Screening and Diagnostic Tests METHODS: Group (SDTMG). The characteristics of the included articles were appraised and the data were extracted from the original articles for further statistical analysis of study heterogeneity using Review Manager 4.2 software. Based on study heterogeneity analysis, a suitable 'effect' model was selected to calculate pooled sensitivity and specificity by meta-analysis. A Summary Receiver Operating Characteristic (SROC) curve and the area under the curve (AUC) were generated and sensitivity analysis conducted. RESULTS: A total of 22 articles were entered into this meta-review, including 11 English articles with a quality at level C. In total, the studies involved 6759 subjects, of which 1470 were diagnosed with SCLC by pathology, and 5289 subjects diagnosed with non-SCLC (NSCLC). The meta-analysis showed that heterogeneity among studies was high (P = 0.00001, I(2) = 86.8%). With ELISA, the pooled sensitivity was 0.72 (0.70 to 0.75 at 95%CI) and the pooled specificity was 0.93 (0.92 to 0.94 at 95%CI); the SROC and the AUC were 0.8817. These data suggest that ProGRP31-98 has a relatively high rate of missed diagnosis (28%), but a relatively low rate of misdiagnosis (7%). CONCLUSION: From meta-analysis, we concluded that serum ProGRP31-98 is a valuable marker with a high specificity for diagnosis of SCLC with a similar diagnostic accuracy to pathology.