Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent

Gliomas are the most common primary brain tumors with a usually fatal malignancy. They are associated with a poor prognosis although multiple therapeutic options have been available. Trimebutine is one of the prokinetic agents and it has been mainly used for treatment of disorders of the gastrointestinal (GI) tract such as irritable bowel syndrome. However, its effects on glioma cells remain unknown. Here, we used various concentrations of trimebutine to treat SHG44, U251, and U-87 MG human glioma/glioblastoma cells. And combined experiments of MTT, colony formation assay, and wound healing assay, as well as western blot and immunofluorescence staining were used to evaluate the effects of trimebutine on glioma cells. The results demonstrated that trimebutine significantly inhibited cell viability and colony formation. A significant inhibition of glioma cell migration was also indicated by wound healing assay. In addition, trimebutine promoted cell apoptosis and induced Bcl-2 downregulation, accompanied with Bax upregulation. Both immunofluorescence staining and western blot results showed that trimebutine increased the level of active Caspase-3. Moreover, trimebutine reduced the activation of both AKT and ERK signaling pathways. In subcutaneous U-87 MG cell xenograft tumors in nude mice, trimebutine significantly inhibited tumor growth. More TUNEL-positive apoptotic cells in tumor sections were observed in trimebutine-treated mice when compared to the vehicle control. Reduced Bcl-2 and upregulated Bax, as well as perturbed p-AKT and p-ERK signaling pathways were also observed in trimebutine-treated xenograft tissues. Our combined data indicated that trimebutine may be potentially applied for the clinical management of glioma/glioblastoma

Short-term surgical and long-term survival outcomes after laparoscopic distal gastrectomy with D2 lymphadenectomy for gastric cancer

BACKGROUND: Laparoscopic distal gastrectomy (LDG) for gastric cancer has gradually gained popularity. However, the long-term oncological outcomes of LDG have rarely been reported. This study aimed to investigate the survival outcomes of LDG, and evaluate the early surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG). METHODS: Clinical outcomes of 240 consecutive patients with gastric cancer who underwent LDG at our institution between October 2004 and April 2013 were analyzed. Early surgical outcomes of LADG and TLDG were compared and operative experiences were evaluated. RESULTS: Of the 240 patients, 93 underwent LADG and 147 underwent TLDG. There were 109 T1, 36 T2, 31 T3, and 64 T4a lesions. The median follow-up period was 31.5 months (range: 4–106 months). Tumor recurrence was observed in 40 patients and peritoneal recurrence was observed most commonly. The 5-year disease-free survival (DFS) and overall survival (OS) rates according to tumor stage were 90.3% and 93.1% in stage I, 72.7% and 67.6% in stage II, and 34.8% and 41.5% in stage III, respectively. No significant differences in early surgical outcomes were noted such as operation time, blood loss and postoperative recovery between LADG and TLDG (P >0.05). CONCLUSIONS: LDG for gastric cancer had acceptable long-term oncologic outcomes. The early surgical outcomes of the two commonly used LDG methods were similar

Polo-like kinase 1 regulates mitotic arrest after UV irradiation through dephosphorylation of p53 and inducing p53 degradation

AbstractUltraviolet (UV) irradiation can result in cell cycle arrest. The reactivation of Polo-like kinase 1 (Plk1) is necessary for cell cycle reentry. But the mechanism of how Plk1 regulates p53 in UV-induced mitotic arrest cells remained elusive. Here we find that UV treatment leads HEK293 cells to inverse changes of Plk1 and p53. Over-expression of Plk1 rescue UV-induced mitotic arrest cells by inhibiting p53 activation. Plk1 could also inhibit p53 phosphorylation at Ser15, thus facilitates its nuclear export and degradation. Further examination shows that Plk1, p53 and Cdc25C can form a large complex. Plk1 could bind to the sequence-specific DNA-binding domain of p53 and active Cdc25C by hyperphosphorylation. These results hypothesize that Plk1 and Cdc25C participate in recovery the mitotic arrest through binding to the different domain of p53. Cdc25C may first be actived by Plk1, and then its phosphatase activity makes p53 dephosphorylated at Ser15

Sperm Quality and DNA Integrity of Coke Oven Workers Exposed to Polycyclic Aromatic Hydrocarbons

Objectives: The objective of this study was to assess sperm quality and deoxyribonucleic acid (DNA) integrity of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) as compared to control subjects. Material and Methods: The coke oven workers (N = 52) and administrative staff (N = 35) of a steel plant served as the exposed and control groups, respectively. Exposure to PAHs was assessed by measuring 1-hydroxypyren. Analysis of sperm quality (concentration, motility, vitality, and morphology) was performed simultaneously with sperm DNA integrity analysis, including DNA fragmentation, denaturation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2\u27-deoxyguanosine (8-oxo-dGuo). A questionnaire was conducted to collect demographic and potential confounding data. Results: The coke oven workers had lower percentages of sperm motility, vitality and normal morphology than the control group, but the difference was not significant. For DNA integrity, the coke oven workers had significantly higher concentrations of bulky DNA adducts and 8-oxo-dGuo than the control subjects (p = 0.009 and p = 0.048, respectively). However, DNA fragmentation percentages did not significantly increase as compared to those in the subjects from the control group (p = 0.232). There was no correlation between sperm quality parameters and DNA integrity indicators. Conclusions: Occupational exposure of the coke oven workers to PAHs was associated with decreased sperm DNA integrity