AURKB promotes colorectal cancer progression by triggering the phosphorylation of histone H3 at serine 10 to activate CCNE1 expression.

Aurora kinase B (AURKB) initiates the phosphorylation of serine 10 on histone H3 (pH3S10), a crucial process for chromosome condensation and cytokinesis in mammalian mitosis. Nonetheless, the precise mechanisms through which AURKB regulates the cell cycle and contributes to tumorigenesis as an oncogenic factor in colorectal cancer (CRC) remain unclear. Here, we report that AURKB was highly expressed and positively correlated with Ki-67 expression in CRC. The abundant expression of AURKB promotes the growth of CRC cells and xenograft tumors in animal model. AURKB knockdown substantially suppressed CRC proliferation and triggered cell cycle arrest in G2/M phase. Interestingly, cyclin E1 (CCNE1) was discovered as a direct downstream target of AURKB and functioned synergistically with AURKB to promote CRC cell proliferation. Mechanically, AURKB activated CCNE1 expression by triggering pH3S10 in the promoter region of CCNE1. Furthermore, it was showed that the inhibitor specific for AURKB (AZD1152) can suppress CCNE1 expression in CRC cells and inhibit tumor cell growth. To conclude, this research demonstrates that AURKB accelerated the tumorigenesis of CRC through its potential to epigenetically activate CCNE1 expression, suggesting AURKB as a promising therapeutic target in CRC.

Silencing of UBE2D1 inhibited cell migration in gastric cancer, decreasing ubiquitination of SMAD4.

BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer-related deaths. Because it is hard to diagnose at early stage, the overall 5 years survival rate is lower than 25%. High migration is the main hallmark of malignant cells at advanced stage of GC. Thus, it is urgent to find biomarkers for early diagnosis and more effective therapy of GC. METHODS: In this study, lentivirus-mediated silencing and overexpression lentiviruses targeting the ubiquitin-conjugating enzyme E2 D1 (UBE2D1), transwell, wound healing, and pulmonary metastasis mouse model were applied to analyze the function of UBE2D1 in vitro and in vivo. Real-time PCR and immunohistochemistry were used to elucidate the level of UBE2D1 in GC samples. RESULTS: Silencing of UBE2D1 inhibited cell migration and the levels of epithelial-mesenchymal transition makers (MMP2 and MMP9) in AGS and MKN45 cells. Silencing of UBE2D1 inhibited cell metastasis in mouse model. On the contrary, UBE2D1 overexpression increased cell migration and the levels of MMP2 and MMP9 in MGC-803 cells. Further, silencing of UBE2D1 decreased the ubiquitination level of mothers against decapentaplegic homolog 4 (SMAD4), and the increase of cell migration induced by UBE2D1 overexpression could be reversed by SMAD4. CONCLUSION: Silencing of UBE2D1 inhibited cell migration through transforming growth factor ß (TGF-ß)/SMAD4 signaling pathway in GC.

Two postoperative chemotherapies for gastric cancer: FOLFOX4 vs. TPF.

Clinical effects of FOLFOX4 and TPF chemotherapy regimen on postoperative gastric cancer patients were investigated. A total of 60 patients admitted to the First People's Hospital of Changzhou receiving gastric cancer operation were selected and they were divided into two groups at random. Thirty patients in the FOLFOX4 group were treated with oxaliplatin, fluorouracil and leucovorin, while 30 patients in the TPF group were treated with paclitaxel, fluorouracil and cisplatin. The therapeutic effects, adverse reactions, quality of life and survival time of patients in the two groups were observed. The total effective rate of the FOLFOX4 group was 73.3%, which was significantly higher than that of the TPF group (43.3%), and the difference was statistically significant (P<0.05). The proportions of neurotoxicity and thrombocytopenia in the FOLFOX4 group were 56.7 and 33.3%, while those in the TPF group were 26.7 and 60%, respectively, and the differences were statistically significant (P<0.05). The increasing proportion of postoperative scores of the FOLFOX4 group was 46.7%, which was significantly higher than that of the TPF group (20%), and the difference was statistically significant (P<0.05). The 2- and 3-year survival rates of the FOLFOX4 group were 63.3 and 50%, which were significantly higher than those of the TPF group (36.7 and 23.3%), and the differences were statistically significant (P<0.05). Therefore, the effective rate of FOLFOX4 regimen is high in the treatment of gastric cancer with relatively fewer adverse reactions, which has a certain advantage.

Effects of probiotics combined with enteral nutrition on immune function and inflammatory response in postoperative patients with gastric cancer.

PURPOSE: To explore the therapeutic effect of probiotics combined with enteral nutrition (ΕΝ) in postoperative patients with gastric cancer (GC). METHODS: 140 GC patients were enrolled in this study and randomly assigned into the test group and the control group, with 70 patients in each group. Patients in the test group were treated with probiotics combined with ΕΝ, while those in the control group were treated with common ΕΝ. Patients' conditions were observed for 8 days. IgG, IgA, IgM, IL-6, IL- 8, TNF-α, hemoglobin, albumin, pre-albumin, time to relief of abdominal distension, time to first flatus, length of hospital stay and adverse events were recorded and analyzed. RESULTS: The factors related to immune function in patients of the test group, such as IgG, IgA and IgM, were higher than those of the control group. Moreover, the improvements of inflammatory cytokines including IL-6, IL-8 and TNF-α in patients of the test group were better than those of the control group. However, no obvious difference was found in the nutritional status before and after treatment between the two groups (p>0.05). In the comparison of clinical symptoms, time to relief of abdominal distention and time to first flatus were both earlier in patients of the test group than in those of the control group (p=0.002, p=0.03, respectively). Additionally, the diarrhea caused by ΕΝ was also significantly less in the test group compared with the probiotics control (p=0.03). CONCLUSIONS: Probiotics combined with ΕΝ could improve the immune function and reduce the inflammatory response and the incidence of diarrhea in postoperative patients with gastric cancer.

[Analysis of clinical characteristics and prognosis of perineural invasion in patients with gastric carcinoma].

OBJECTIVE: To investigate the association between perineural invasion(PNI) and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma. METHODS: A total of 178 patients with gastric carcinoma from January 2004 to May 2008 were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent gastric resection were stained with laminin. PNI-positive was defined as infiltration of carcinoma cells into the perineurium or neural fascicles. The association of PNI with clinicopathologic features and prognosis of gastric carcinoma was studied. RESULTS: PNI was positive in 78 of 178 patients(43.8%). The proportions of T stage, lymph node metastasis and TNM stage were significantly higher in PNI-positive group than those in PNI-negative group(all P<0.01). The PNI positive rate was correlated with the depth of gastric mural invasion and clinical stage. The overall survival in PNI-positive group was significantly lower than that in PNI-negative group by univariate analysis(P<0.01). The mean survival of PNI-positive patients(28.6 months) was significantly shorter than that of PNI-negative patients (44.3 months, P<0.01), which was also influenced by pN stage, pT stage, and clinical stage(P<0.01). By multivariable Cox proportional hazards model of overall survival, the positivity of PNI appeared to be an independent prognostic factor (hazards ratio=2.257, 95% CI:1.268-4.019, P=0.006). CONCLUSIONS: PNI is associated with the degree of malignancy in gastric cancer. PNI can be a candidate of new prognostic factor.