Astrocyte elevated gene-1 serves as a target of miR542 to promote glioblastoma proliferation and invasion.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle. METHODS: The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored. RESULTS: MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT. CONCLUSION: The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.

Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles.

Aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate are commonly used human vaccine adjuvants. In an effort to improve the adjuvant activity of aluminum salts, we previously showed that the adjuvant activity of aluminum oxyhydroxide nanoparticles is significantly more potent than that of aluminum oxyhydroxide microparticles. The present study was designed to (i) understand the mechanism underlying the potent adjuvant activity of aluminum oxyhydroxide nanoparticles, relative to microparticles, and (ii) to test whether aluminum hydroxyphosphate nanoparticles have a more potent adjuvant activity than aluminum hydroxyphosphate microparticles as well. In human THP-1 myeloid cells, wild-type and NLRP3-deficient, both aluminum oxyhydroxide nanoparticles and microparticles stimulate the secretion of proinflammatory cytokine IL-1ß by activating NLRP3 inflammasome, although aluminum oxyhydroxide nanoparticles are more potent than microparticles, likely related to the higher uptake of the nanoparticles by the THP-1 cells than the microparticles. Aluminum hydroxyphosphate nanoparticles also have a more potent adjuvant activity than microparticles in helping a model antigen lysozyme to stimulate specific antibody response, again likely related to their stronger ability to activate the NLRP3 inflammasome.

Applications of bacillus Calmette-Guerin and recombinant bacillus Calmette-Guerin in vaccine development and tumor immunotherapy.

Bacillus Calmette-Guerin (BCG) vaccines are attenuated live strains of Mycobacterium bovis and are among the most widely used vaccines in the world. BCG is proven to be effective in preventing severe infant meningitis and miliary tuberculosis. Intravesical instillation of BCG is also a standard treatment for non-muscle invasive bladder cancer. In the past few decades, recombinant BCG (rBCG) technology had been extensively applied to develop vaccine candidates for a variety of infectious diseases, including bacterial, viral, and parasite infections, and to improve the efficacy of BCG in bladder cancer therapy. This review is intended to show the vast applications of BCG and recombinant BCG (rBCG) in the prevention of infectious diseases and cancer immunotherapy, with a special emphasis on recent approaches and trends on both pre-clinical and clinical levels.

Biodistribution and in vivo activities of tumor-associated macrophage-targeting nanoparticles incorporated with doxorubicin.

Tumor-associated macrophages (TAMs) are increasingly considered a viable target for tumor imaging and therapy. Previously, we reported that innovative surface-functionalization of nanoparticles may help target them to TAMs. In this report, using poly(lactic-co-glycolic) acid (PLGA) nanoparticles incorporated with doxorubicin (DOX) (DOX-NPs), we studied the effect of surface-modification of the nanoparticles with mannose and/or acid-sensitive sheddable polyethylene glycol (PEG) on the biodistribution of DOX and the uptake of DOX by TAMs in tumor-bearing mice. We demonstrated that surface-modification of the DOX-NPs with both mannose and acid-sensitive sheddable PEG significantly increased the accumulation of DOX in tumors, enhanced the uptake of the DOX by TAMs, but decreased the distribution of DOX in mononuclear phagocyte system (MPS), such as liver. We also confirmed that the acid-sensitive sheddable PEGylated, mannose-modified DOX-nanoparticles (DOX-AS-M-NPs) targeted TAMs because depletion of TAMs in tumor-bearing mice significantly decreased the accumulation of DOX in tumor tissues. Furthermore, in a B16-F10 tumor-bearing mouse model, we showed that the DOX-AS-M-NPs were significantly more effective than free DOX in controlling tumor growth but had only minimum effect on the macrophage population in mouse liver and spleen. The AS-M-NPs are promising in targeting cytotoxic or macrophage-modulating agents into tumors to improve tumor therapy.

[Cervical lymph node metastasis of hypopharyngeal carcinoma].

OBJECTIVE: To investigate the characteristic of cervical lymph node metastasis of hypopharyngeal carcinoma and its influence to the prognosis. METHODS: One hundred and eight hypopharyngeal carcinoma patients who accepted treatments in the 1st Affiliated Hospital of China Medical University from 1985 to 2000 were reviewed retrospectively. All of them accepted surgical treatment without pre-operative chemotherapy or radiotherapy. Stage was made according to the standard of International Union Against Cancer (UICC) in 1992. Specimens of the patients were carefully examined to confirm the primary site of the tumor and the distribution of cervical lymph node metastasis. Pathological differentiations of the tumor were classified into high, middle and low category. Kaplan-Meier method was used to estimate the 3rd, 5th years survival. RESULTS: The rates of lymph node metastasis of was 45.8% for patients with TI and T2 disease, 79.8% for those with T3 and T4, and 75.0% (81/108)for the whole patients(P < 0.05). Patients with pyriform sinus cancer occupied 92.6% (100/108) of all the cases. Cervical lymph node metastasis rate of pyriform sinus cancer and posterior pharyngeal wall cancer were 74. 0% and 87. 5% respectively (P > 0.05). Cervical lymph node metastasis rate of patients with the high, middle and low differentiation tumor were 72. 2% , 67.6% and 85.7% respectively (P > 0.05). The 3rd and 5th years survival rates of all patients were 67.53% and 29.87% respectively. The occurrence of cervical lymph node metastasis was 76.5% in the level II and III, and 8.6% in the level V and VI. CONCLUSIONS Cervical lymph node metastasis rate of hypopharyngeal carcinoma is high. Cervical lymph node metastasis was one of the most significant prognostic factors of hypopharyngeal carcinoma. With the increase of the cervical node metastasis, the 3rd and 5th years survival of the patients declined gradually.