Su Chongyu

The aim of the present study was to explore the potential role of cluster of differentiation CD68+ tumor‑associated macrophages (TAMs) induced by interleukin (IL)-6 in the progression of gastric cancer (GC) and patient prognosis. The expression levels of IL‑6 and CD68 were detected by immunohistochemical staining in 60 samples of tumor and non‑tumor gastric tissues. CD14+ monocytes were isolated from peripheral blood mononuclear cells and stimulated with macrophage colony stimulation factor (M‑CSF) and IL‑6, and the expression levels of IL‑10, IL‑12, vascular endothelial growth factor (VEGF)‑C and transforming growth factor (TGF)‑β were measured by reverse transcription polymerase chain reaction and ELISA. The GC MGC‑803 cell line was co‑cultured with monocytes stimulated by M‑CSF and IL‑6 and the invasion ability of the MGC‑803 was evaluated by Transwell analysis. The levels of STAT3, P‑STAT3 and interferon‑regulatory factor 4 (IRF4) in the monocytes stimulated by M‑CSF and IL‑6 were detected by western blotting. The results demonstrated that the frequencies of IL‑6+ macrophages (Mφs) and CD68+ Mφs were significantly higher in tumor regions compared with the corresponding non‑tumor regions of GC tissues. Kaplan‑Meier analysis revealed that the densities of tumor‑infiltrating CD68+ or IL‑6+ Mφs were inversely associated with the overall survival rates of the patients. In vitro, the expression levels of IL‑10, VEGF‑C and TGF‑β significantly increased in CD14+ monocytes subsequent to M‑CSF and IL‑6 stimulation. The invasion abilities of MGC‑803 were increased by the monocytes stimulated with M‑CSF and IL‑6. The levels of STAT3, P‑STAT3 and IRF4 proteins increased in the monocytes stimulated by M‑CSF and IL‑6. In conclusion, the results from the present study suggest that a high density of CD68+ TAMs predicts a poor prognosis in GC. IL‑6 may polarize the Mφs and promote tumor invasion through the IL-6/STAT3/IRF4 signaling pathway.

BACKGROUND AND AIM: Tubulointerstitial nephritis antigen-like 1 (TINAGL1), as a novel matricellular protein, has been demonstrated to participate in cancer progression, whereas the potential function of TINAGL1 in gastric cancer (GC) remains unknown. METHODS: The expression pattern of TINAGL1 in GC was examined by immunohistochemistry, ELISA, real-time polymerase chain reaction, and Western blot. Correlation between TINAGL1 and matrix metalloproteinases (MMPs) was analyzed by the GEPIA website and Kaplan-Meier plots database. The lentivirus-based TINAGL1 knockdown, CCK-8, and transwell assays were used to test the function of TINAGL1 in vitro. The role of TINAGL1 was confirmed by subcutaneous xenograft, abdominal dissemination, and lung metastasis model. Microarray experiments, ELISA, real-time polymerase chain reaction, and Western blot were used to identify molecular mechanism. RESULTS: TINAGL1 was increased in GC tumor tissues and associated with poor patient survival. Moreover, TINAGL1 significantly promoted GC cell proliferation and migration in vitro as well as facilitated GC tumor growth and metastasis in vivo. TINAGL1 expression in GC cells was accompanied with increasing MMPs including MMP2, MMP9, MMP11, MMP14, and MMP16. GEPIA database revealed that these MMPs were correlated with TINAGL1 in GC tumors and that the most highly expressed MMP was MMP2. Mechanically, TINAGL1 regulated MMP2 through the JNK signaling pathway activation. CONCLUSIONS: Our data highlight that TINAGL1 promotes GC growth and metastasis and regulates MMP2 expression, indicating that TINAGL1 may serve as a therapeutic target for GC.

We employed a previously described procedure, based on circular dichroism (CD) spectroscopy, to quantify the distribution of conformational states adopted by equimolar mixtures of complementary G-rich and C-rich DNA strands from the promoter regions of the VEGF and Bcl-2 oncogenes. Spectra were recorded at different pHs, concentrations of KCl, and temperatures. The temperature dependences of the fractional populations of the duplex, G-quadruplex, i-motif, and coiled conformations of each promoter were then analyzed within the framework of a thermodynamic model to obtain the enthalpy and melting temperature of each folded-to-unfolded transition involved in the equilibrium. A comparison of the conformational data on the VEGF and Bcl-2 DNA with similar results on the c-MYC DNA, which we reported previously, reveals that the distribution of conformational states depends on the specific DNA sequence and is modulated by environmental factors. Under the physiological conditions of room temperature, neutral pH, and elevated concentrations of potassium ions, the duplex conformation coexists with the G-quadruplex conformation in proportions that depend on the sequence. This observed conformational diversity has biological implications, and it further supports our previously proposed thermodynamic hypothesis of gene regulation. In that hypothesis, a specific distribution of duplex and tetraplex conformations in a promoter region is fine-tuned to maintain the healthy level of gene expression. Any deviation from a healthy distribution of conformational states may result in pathology stemming from up- or downregulation of the gene.

BACKGROUND AND OBJECTIVE: Laparoscopy-assisted total gastrectomy (LATG) has not gained popularity due to the technical difficulty of esophagojejunostomy (EJ) and the high incidence of EJ-related complications. Herein, we compared two types of EJ for Roux-en-Y reconstruction to determine whether semi-end-to-end (SETE) EJ is more convenient than the end-to-side (ETS) procedure and is capable of reducing stricture and leakage. METHODS: A total of 268 patients who underwent LATG with Roux-en-Y reconstruction were included in this study. Two types of EJ were applied for LATG: conventional ETS EJ and SETE EJ. The surgical outcomes and postoperative complications were compared. RESULTS: The mean reconstruction time in the SETE group was shorter than that in the ETS group (41.6 ± 8.0 min vs 51.3 ± 9.2 min, P = 0.000). The incidences of total EJ-related complications, EJ leakage, and EJ stricture in the SETE group and ETS group were 1.1% (1/92) and 10.2% (18/176), 1.1% (1/92) and 4.0% (7/176), and 0 and 6.2% (11/176), respectively. The incidence of total EJ-related complications in the SETE group was lower than that of the ETS group (P = 0.006), and the incidence of EJ stricture in the SETE group was lower than that of the ETS group (P = 0.034). CONCLUSIONS: SETE EJ is more convenient than the conventional ETS procedure and is associated with a shorter reconstruction time and a lower incidence of EJ stricture and leakage.