Pseudogene TDGF1P3 regulates the proliferation and metastasis of colorectal cancer cells via the miR-338-3p-PKM2 axis.

Research in the past decade has revealed significant roles of pseudogenes in colorectal cancer (CRC). Here, the role of teratocarcinoma-derived growth factor 1 pseudogene 3 (TDGF1P3) in regulating the proliferation and invasion of CRC cells was investigated; in addition, its downstream targets were analyzed, and the underlying mechanisms were elucidated. TDGF1P3 was determined to be upregulated in CRC cells and tissues. Silencing TDGF1P3 substantially repressed cell proliferation, migration, and invasion in vitro. Similarly, in vivo assays showed that TDGF1P3 knockdown attenuated tumor growth in nude mice. Mechanistic investigations revealed that TDGF1P3 directly bound to miR-338-3p, thereby preventing miR-338-3p from binding to its target mRNA pyruvate kinase M2 (PKM2). Functional rescue tests indicated that TDGF1P3 regulates CRC cell proliferation and invasion by restraining the miR-338-3p-PKM2 axis. Thus, these data illustrated that TDGF1P3 exerts its oncogenic activity by upregulating PKM2 via competitively binding miR-338-3p, which may be a therapeutic target for CRC.

GHR knockdown enhances the sensitivity of HCC cells to sorafenib.

Sorafenib is approved for treatment of advanced hepatocellular carcinoma (HCC) by the Drug Administration. However, the efficacy of sorafenib has become very limited because most tumors have developed resistance to this drug. In this study, we found that sorafenib stimulated GHR expression in HCC cell lines. Thus, GHR might be linked to sorafenib resistance. To verify this hypothesis, we researched the roles of GHR knockdown and sorafenib combination in cell viability, apoptosis, cycle, and migration. The results showed that GHR blockage enhanced sorafenib blocking of cell cycle progression, leading to inhibition of this drug on HCC cell viability, and the improved promoting ability of sorafenib on cell apoptosis. In addition, it was found that GHR knockdown enhanced sorafenib inhibition of cell migration. The synergistic antitumor effects of sorafenib and GHR knockdown combination may be attributed to inhibition of PI3K/AKT/ERK1/2 signaling pathway. In conclusion, the findings suggest that GHR knockdown enhances the sensitivity of HCC cells to sorafenib. and the inactivation of PI3K/AKT/ERK1/2 signaling pathway may be the underlying mechanisms. This highlights the absence of GHR as a promising way to enhance sorafenib efficacy in HCC.

Effects of medical adhesives in prevention of complications after endoscopic submucosal dissection.

AIM: To evaluate the use of medical adhesive spray in endoscopic submucosal dissection (ESD). METHODS: Patients who underwent ESD between January 2009 and June 2012 (n = 173) were enrolled in the prospective randomized study. Two patients undergoing surgery due to severe intraoperative hemorrhage and failed hemostasis were excluded, and the remaining 171 patients were randomly divided into two groups: group A (medical adhesive group, n = 89) and group B (control group, n = 82). In group A, a medical adhesive spray was evenly applied after routine electrocoagulation and hemostasis using hemostatic clip after ESD. Patients in group B only treated with routine wound management. Intraoperative and postoperative data were collected and compared. RESULTS: In all 171 patients, ESD was successfully completed. There was no significant difference in the average treatment time between groups A and B (59.4 min vs 55.0 min, respectively). The average length of hospital stay was significantly different between group A and B (8.89 d vs 9.90 d, respectively). The incidence of intraoperative perforation was 10.1% in group A and 9.8% in group B, and was not significantly different between the two groups. In all cases, perforations were successfully managed endoscopically and with conservative treatment. The incidence of postoperative delayed bleeding in group A was significantly lower than that in group B (0.00% vs 4.88%, respectively). CONCLUSION: ESD is an effective minimally invasive treatment for gastrointestinal precancerous lesions or early-stage gastrointestinal cancer. Medical adhesive spray is effective in preventing delayed bleeding after ESD, and can thus reduce the average length of hospital stay.

Effects of integrin-targeted photodynamic therapy on pancreatic carcinoma cell.

AIM: To investigate the effects of photodynamic therapy with quantum dots-arginine-glycine-aspartic acid (RGD) probe as photosensitizer on the proliferation and apoptosis of pancreatic carcinoma cells. METHODS: Construction of quantum dots-RGD probe as photosensitizer for integrin-targeted photodynamic therapy was accomplished. After cells were treated with photodynamic therapy (PDT), the proliferation of SW1990 cells were measured by methyl thiazolyl tetrazolium assay. Morphologic changes, cell cycle retardance and apoptosis were observed under fluoroscope and flow cytometry. The expression of myeloid cell leukemia-1 (Mcl-1), protein kinase B (Akt) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA were detected by reverse transcription-polymerase chain reaction. The amount of reactive oxygen species were also evaluated by fluorescence probe. RESULTS: The photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibited cell proliferation (P < 0.01). Apoptotic cells and morphologic changes could be found under optical microscope. The FCM revealed PDT group had more significant cell apoptosis rate compared to control cells (F = 130.617, P < 0.01) and cell cycle G0/G1 and S retardance (P < 0.05) compared to control cells. The expression of Mcl-1 and Akt mRNA were down-regulated, while expression of TRAIL mRNA was up-regulated after cells treated with PDT. PDT group had more significant number of cells producing reactive oxygen species compared to control cells (F = 3262.559, P < 0.01). CONCLUSION: The photodynamic therapy with quantum dots-RGD probe as photosensitizer significantly inhibits cell proliferation and increases apoptosis in SW1990 cells.

Antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline on bile duct ligation induced liver fibrosis in rats.

AIM: To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)-induced liver fibrosis in rats. METHODS: Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wk via a osmotic minipump (Alzet 2ML4) immediately after BDL operation. After scarifying, serum and liver specimens were collected. Hematoxylin and eosin staining, Sirius red staining, enzyme linked immunosorbent assay, Western blot or real-time polymerase chain reaction were used to determinate liver functions, histological alterations, collagen deposition, mRNA expression of markers for fibroblasts, transforming growth factor-ß1 (TGF-ß1) and bone morphogenetic protein-7 (BMP-7). RESULTS: When compared to model rats, chronic exogenous AcSDKP infusion suppressed profibrogenic TGF-ß1 signaling, α-smooth muscle actin positivity (α-SMA), fibroblast specific protein-1 (FSP-1) staining and collagen gene expression. Col I, Col III, matrix metalloproteinase-2, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10 vs. 14.16 ± 6.50, 2.02 ± 0.45 vs. 10.00 ± 3.35, 2.91 ± 0.30 vs. 7.83 ± 1.10, 4.64 ± 1.25 vs. 18.52 ± 7.61, 0.46 ± 0.16 vs. 0.34 ± 0.12, respectively, P < 0.05). Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury, inflammation and fibrosis. BDL caused a remarkable increase in alanine transaminase, aspartate transaminase, total bilirubin, and prothrombin time, all of which were reduced by AcSDKP infusion. Mast cells, collagen accumulation, α-SMA, TGF-ß1, FSP-1 and BMP-7 increased. The histological appearance of liver specimens was also improved. CONCLUSION: Infusion of exogenous AcSDKP attenuated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.