FBLN3 inhibited the invasion and metastasis of colorectal cancer through the AKT/mTOR pathway.

Fibulin-3(FBLN3) levels are different in different types of cancers. We found that fibulin-3 was downregulated in colorectal (CRC) cells, particularly in the SW480 cell line. By comparison, transfecting SW480 cells with a lentivirus overexpressing fibulin-3 RNA could inhibit proliferation, induce G1/S arrest, and promote cell apoptosis. Fibulin-3 overexpression further suppressed the invasion and metastasis of CRC. These effects were regulated through the AKT/mTOR signaling pathway.

[In vivo and in vitro experimental studies of remote digital control endovascular robotic system in interventional angiography].

Objective: To investigate the feasibility of the remote control endovascular robotic system in interventional angiography. Method: The endovascular robotic system Heifetz™ and the matched steerable catheter Mirage™ were used to cannulate all the target vessels in the vascular model and cerebral arteries originated from the aorta of Bama mini-pigs under fluoroscopic guidance. The technical success rate, cannulation time and exposure dose were all collected and compared with the result of using conventional techniques. Result: All the target vessels were successfully cannulated.The average cannulation time for the steerable catheter into left subclavian artery, left common carotid artery, brachiocephalic artery, right common carotid artery and right subclavian artery in the vascular model was (21.3±2.8)s, (28.8±5.2)s, (17.7±2.6)s, (31.5±5.1)s and (24.2±3.7) s, respectively, while the average exposure dose was (9.3±1.2)mGy, (12.4±2.2)mGy, (7.4±1.2)mGy, (14.2±2.5)mGy and( 10.4±1.9)mGy, respectively. The endovascular robotic system completed the cerebral angiography in Bama mini-pigs successfully. The average cannulation time for left innominate artery, right innominate artery, right subclavian artery, common internal carotid trunk, left internal carotid artery and right internal carotid artery was (41.5±6.8)s, (29.1±3.7)s, (40.7±5.5)s, (40.1±5.8)s, (59.6±9.0)s and( 60.3±10.1)s, respectively, while the average exposure dose was (40.6±6.5)mGy, (36.0±5.2)mGy, (39.8±6.1)mGy, (43.9±6.7)mGy, (51.0±7.4)mGy and( 50.1±7.8)mGy, respectively. There was no significant difference between robotic and conventional group in success rate, cannulation time and exposure dose. Conclusion: The remote digital control endovascular robotic system could cannulate the target vessel in both vascular model and complete the cerebral angiography in Bama mini-pigs, which shows the feasibility of using this robotic system in endovascular intervention procedures under remote control.

Clinical significance of carcinoembryonic antigen-, cytokeratin 19-, or survivin-positive circulating tumor cells in the peripheral blood of esophageal squamous cell carcinoma patients treated with radiotherapy.

Circulating tumor cells (CTCs) have been associated with clinical outcome in various malignancies. The aim of this study was to examine CTC status in the peripheral blood of patients with esophageal squamous cell carcinoma (ESCC) before and after radiotherapy, and to evaluate its clinical significance. A total of 72 ESCC patients treated with radical radiotherapy were enrolled in this study. The nested reverse-transcriptase polymerase chain reaction was used to detect the three representative markers of CTCs, namely carcinoembryonic antigen, cytokeratin 19, and survivin. The results showed that CTC(+), a status with positive expression of at least one of these three markers, in patients with ESCC pre- and post-radiotherapy were 54.2% (39/72) and 38.9% (28/72), respectively (P= 0.059). Furthermore, CTC (+) in patients pre- or post-radiotherapy was both correlated with lymph metastasis and adverse 2-year progression-free survival. It was also found that changes in CTC status after radiotherapy could reflect patients' response to radiotherapy. The response rates in cases with CTC status pre-radiotherapy(+)/post-radiotherapy(+), pre-radiotherapy(-)/post-radiotherapy(+), pre-radiotherapy(-)/post-radiotherapy(-), pre-radiotherapy(+)/post-radiotherapy(-) were 58.3% (21/36), 0% (0/3), 73.7% (14/19), and 85.7% (12/14), respectively. In a multivariate analysis of Cox proportional hazard model, only CTC (+) post-radiotherapy was an independent unfavorable prognostic factor for ESCC apart from subsequent chemotherapy and patients' Karnofsky performance status scores. In conclusion, positive detection of CTCs in patients with ESCC after radiotherapy may be a promising biomarker for radiation efficiency and prognosis assessment in ESCC.

Downregulation of fibulin-3 gene by promoter methylation in colorectal cancer predicts adverse prognosis.

Fibulin-3 gene has been identified as an antagonist of angiogenesis. We investigated the protein expression and promoter methylation status of fibulin-3 gene in colorectal cancer (CRC) and analyzed its correlation with clinicopathological factors. The study population enrolled 85 paired CRC specimens and adjacent normal tissues, as well as 32 cases of colorectal adenoma. Genomic DNA was extracted from paraffin-embedded samples using manual microdissection. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status and fibulin-3 gene expression was detected by immunohistochemistry. The results showed that, downregulation or silence of fibulin-3 protein was found in 57.6% (49/85) of CRC tissues, which was significantly higher than that of adjacent normal tissues (28.2%, 24/85) and colorectal adenoma (34.4%, 11/32) (P<0.05). Furthermore, 33 out of 85 (38.8%) CRC specimens showed hypermethylation in fibulin-3 promoter region, and fibulin-3 methylation was closely correlated with its loss of expression. Also, downregulation of fibulin-3 was associated with advanced stage (P=0.008) and lymph node metastasis (P=0.013). Survival analyses and Cox proportional hazard models indicated that fibulin-3 downregulation was an independent factor related to adverse overall survival (OS) and disease-free survival (DFS) of CRC. In conclusion, we found aberrant methylation caused fibulin-3 downregulation in CRC, and fibulin-3 downregulation was correlated with tumor stage, lymph node metastasis and poor survival, which maybe use as a potential prognostic factor for CRC.