Recent studies indicate that the long noncoding RNA ATB (lncATB) can induce the epithelial−mesenchymal transition (EMT) in cancer cells, but the specific cellular targets of lncATB require further investigation. In the present study, the upregulation of lncATB in breast cancer cells was validated in a TGF-β-induced EMT model. Gain- and loss-of-function studies demonstrated that lncATB enhanced cell migration, invasion and clonogenicity in vitro and in vivo. LncATB promoted the EMT by acting as a sponge for the miR-200 family and restoring Twist1 expression. Subsequently, the clinical significance of lncATB was investigated in a cohort of breast cancer patients (N = 131). Higher lncATB expression was correlated with increased nodal metastasis (P = 0.036) and advanced clinical stage (P = 0.011) as well as shorter disease-free survival (P = 0.043) and overall survival (P = 0.046). These findings define Twist1 as a major target of lncATB in the induction of the EMT and highlight lncATB as a biomarker in breast cancer patients.
Surgical site infection (SSI) continues to be an issue in abdominal surgery, especially for contaminated (class III) and dirty-infected (class IV) wounds. Vacuum sealing drainage (VSD) was reported effective in the management of various types of wounds or skin grafts. Our goal was to investigate the efficacy of prophylactic VSD to better orient their medicosurgical care of high-risk incisions following laparotomy in a pediatric population.A total of 331 pediatric patients with contaminated (class III) and dirty-infected (class IV) wounds following emergency laparotomy were retrospectively reviewed between January 2005 and January 2013. Among them, 111 cases were placed with prophylactic VSD when incisions were closed. Clinical outcomes, including, overall surgical site complication, device effectiveness, and mean postoperative LOS were evaluated based on VSD usage or not.VSD was applied for an average of 5.8 days (range, 5–7 days), with 3 to 15 mL sucked fluid. The overall SSIs rate was 3% for patients with prophylactic VSD and 17% for patients with convention dressing (OR, 0.27; 95% CI, 0.10–0.71, P = 0.004). In patients with prophylactic VSD, only 1 of 96 wound developed postoperative incision dehiscence, which is significant reduced compared with patients for conventional dressings (OR, 0.12; 95% CI, 0.01–0.95; P = 0.017) (Table 2). It also exhibited a decreased mean postoperative LOS (P < 0.001) for prophylactic VSD over conventional dressings.Our study demonstrated beneficial postoperative clinical effects of prophylactic VSD for high-risk laparotomy incisions following emergency laparotomy, such as shorter length of hospitalization, which may be attributed to the reduced overall SSIs rate.
Background Angiogenesis is an indispensable step in the growth and invasiveness of breast cancers involving a series of exquisite molecular steps. Pro-angiogenic factors, including vascular endothelial growth factor (VEGF), have been recognized as pivotal therapeutic targets in the treatment of breast cancer. More recently, a highly conserved transcription factor Twist has been reported to be involved in tumor angiogenesis and metastasis. Methods The expression of VEGF-C and Twist was immunohistochemically determined in tissue samples of primary tumors from 408 patients undergoing curative surgical resection for breast cancer. The correlations of VEGF-C and Twist expressions with clinicopathologic parameters as well as survival outcomes were evaluated. Results Of the 408 patients evaluated, approximately 70% had high expression of VEGF-C which was significantly associated with advanced tumor stages (P = 0.019). Similarly, VEGF-C expression was associated with the proliferation index Ki67, N3 lymph node metastasis, and D2-40-positive lymphatic vessel invasion (LVI) in a univariate analysis. Furthermore, patients with high expressions of VEGF-C and Twist (V + T+) had significantly increased lymph node metastasis, higher clinical stage, and worse disease-free survival, DFS (P = 0.001) and overall survival, OS (P = 0.011). Conclusions Our results suggested that co-expression of VEGF-C and Twist was associated with larger tumor size, higher numbers of lymph node involvement, D2-40-positive LVI, higher risk of distant metastasis, and worse DFS or OS in breast cancer patients.
Resistance to radiotherapy remains a severe obstacle in the treatment of high-risk colorectal cancer patients. Recent studies have indicated that proteasome activator complex subunit 3 (PSME3) participates in the development and progression of various human malignancies and is proposed to play a role in tumor radioresistance. However, the impact of PSME3 on radioresistance of colorectal cancer has been largely unknown. In the present study, the enhanced expression of PSME3 was observed in colorectal cancer cells and tissue. Upregulation of PSME3 was significantly implicated in lymph node state, lymphovascular invasion, and Dukes' stage. Furthermore, high PSME3 expression was closely linked to poorer overall and progression-free survival in patients with colorectal cancer. The study further demonstrated that the proliferative, invasive and migratory potential of colorectal cancer cells was effectively inhibited in vitro after silencing PSME3. Our results verified that knockdown of PSME3 probably triggered cell cycle arrest at the G2/M phase by downregulation of cyclinB1 and CDK1, thereby enhancing the radiosensitivity of colorectal cancer cells. These data illustrated that PSME3 is a promising biomarker predictive of colorectal cancer prognosis and silencing of PSME3 may provide with a new approach for sensitizing the radiotherapy in colorectal cancer. Impact statement It is reported that colorectal cancer (CRC) is the third most common cancer worldwide and the fourth leading cause of cancer-related death. At present, the main treatment method of colorectal cancer is surgery, supplemented by radiotherapy and chemotherapy. Among them, radiotherapy plays an important role in the treatment of locally advanced colorectal cancer, surgery, and chemotherapy. Our study found that down-regulation of PSME3 may enhance the radiosensitivity of CRC cells by triggering cell cycle arrest, which suggests that silence PSME3 may provide a new method for improving the radiosensitivity of CRC. What’more, our research also demonstrated that PSME3 may promote proliferation, invasive and migratory potential of CRC cells, which implies that PSME3 might be a biomarker of CRC for early diagnosis and treatment.
Bioluminescence reporter proteins have been widely used in the development of tools for monitoring biological events in living cells. Currently, some assays like flow cytometry analysis are available for studying DNA synthetic phase (S-phase) targeted anti-cancer drug activity in vitro; however, techniques for imaging of in vivo models remain limited. Cyclin A2 is known to promote S-phase entry in mammals. Its expression levels are low during G1-phase, but they increase at the onset of S-phase. Cyclin A2 is degraded during prometaphase by ubiquitin-dependent, proteasome-mediated proteolysis. In this study, we have developed a cyclin A2-luciferase (CYCA-Luc) fusion protein targeted for ubiquitin-proteasome dependent degradation, and have evaluated its utility in screening S-phase targeted anti-cancer drugs. Similar to endogenous cyclin A2, CYCA-Luc accumulates during S-phase and is degraded during G2/M-phase. Using Cdc20 siRNA we have demonstrated that Cdc20 can mediate CYCA-Luc degradation. Moreover, using noninvasive bioluminescent imaging, we demonstrated accumulation of CYCA-Luc in response to 10-hydroxycamptothecin (HCPT), an S-phase targeted anti-cancer drug, in human tumor cells in vivo and in vitro. Our results indicate that a CYCA-Luc fusion reporter system can be used to monitor S-phase of cell cycle, and evaluate pharmacological activity of anti-cancer drug HCPT in real time in vitro and in vivo, and is likely to provide an important tool for screening such drugs.
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