Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are typical gastrointestinal tract neoplasms. Imatinib is the first-line therapy for GIST patients. Drug resistance limits the long-term effectiveness of imatinib. The regulatory effect of insulin-like growth factor 2 (IGF2) has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis. AIM: To further investigate the mechanism of IGF2 specific to GISTs. METHODS: IGF2 was screened and analyzed using Gene Expression Omnibus (GEO: GSE225819) data. After IGF2 knockdown or overexpression by transfection, the phenotypes (proliferation, migration, invasion, apoptosis) of GIST cells were characterized by cell counting kit 8, Transwell, and flow cytometry assays. We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition (EMT)-associated proteins. We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST. RESULTS: Data from the GEO indicated that IGF2 expression is high in GISTs, associated with liver metastasis, and closely related to drug resistance. GIST cells with high expression of IGF2 had increased proliferation and migration, invasiveness and EMT. Knockdown of IGF2 significantly inhibited those activities. In addition, OE-IGF2 promoted GIST metastasis in vivo in nude mice. IGF2 activated IGF1R signaling in GIST cells, and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis. GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance. Moreover, 2-deoxy-D-glucose (a glycolysis inhibitor) treatment reversed IGF2 overexpression-mediated imatinib resistance in GISTs. CONCLUSION: IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Vacuum sealing drainage to treat Fournier's gangrene.

BACKGROUND: Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier's gangrene (FG). METHODS: Data of patients surgically treated for FG were retrospectively analyzed. RESULTS: Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28-74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. CONCLUSION: VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.

AURKB Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT.

AIM: To investigate the function of Aurora kinase B (AURKB) in gastric cancer (GC). METHODS: Immunohistochemistry was used to assay the expression of AURKB in 50 pairs of GC and adjacent tissues, and qRT-PCR was conducted to test AURKB expression in normal gastric epithelial and GC cell lines. Two segments of small interference RNAs (siRNAs) targeting AURKB were synthesized and inserted into GV248 lentivirus vector. After transfected with LV-AURKB-RNAis, CCK8, wound healing, transwell and flow cytometric assays were performed to determine the influence of silencing AURKB on cell proliferation, invasion, migration, cell cycles and apoptosis of GC cells, and the expression of EMT (epithelial-mesenchymal transition)-related markers was demonstrated by Western blots (WB). RESULTS: AURKB was highly expressed in GC and closely associated with lymph node metastasis and advanced stages of GC. Down-regulating AURKB suppressed the proliferation and promoted the apoptosis of GC cells, arrested the cell cycle in G2/M phase, and inhibited the invasion and migration of GC cells. The expression levels of AKT1, mTOR, Myc, MMP2, and VEGFA were decreased, while the expression levels of OCLN and JUP were increased after knocking down of AURKB in both AGC and MKN45 cells. CONCLUSION: AURKB is overexpressed in GC and closely associated with clinicopathologic characteristics of GC. It is likely that by inhibiting VEGFA/Akt/mTOR and Wnt/ß-catenin/Myc pathways, silenced AURKB could inhibit the invasive and migratory abilities of GC cells. However, because of the small sample size and the absence of in-vivo experiments, these results should be verified by further studies.