BCL11B suppresses tumor progression and stem cell traits in hepatocellular carcinoma by restoring p53 signaling activity.

Accumulating evidence indicates that hepatocellular carcinoma (HCC) tumorigenesis, recurrence, metastasis, and therapeutic resistance are strongly associated with liver cancer stem cells (CSCs), a rare subpopulation of highly tumorigenic cells with self-renewal capacity and differentiation potential. Previous studies identified B cell leukemia/lymphoma-11b (BCL11B) as a novel tumor suppressor with impressive capacity to restrain CSC traits. However, the implications of BCL11B in HCC remain unclear. In this study, we found that low BCL11B expression was an independent indicator for shorter overall survival (OS) and time to recurrence (TTR) for HCC patients with surgical resection. In vitro and in vivo experiments confirmed BCL11B as a tumor suppressor in HCC with inhibitory effects on proliferation, cell cycle progression, apoptosis, and mobility. Furthermore, BCL11B could suppress CSC traits, as evidenced by dramatically decreased tumor spheroid formation, self-renewal potential and drug resistance. A Cignal Finder Array and dual-luciferase activity reporter assays revealed that BCL11B could activate the transcription of P73 via an E2F1-dependent manner. Thus, we concluded that BCL11B is a strong suppressor of retaining CSC traits in HCC. Ectopic expression of BCL11B might be a promising strategy for anti-HCC treatment with the potential to cure HBV-related HCC regardless of P53 mutation status.

CD73 promotes hepatocellular carcinoma progression and metastasis via activating PI3K/AKT signaling by inducing Rap1-mediated membrane localization of P110ß and predicts poor prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD73-expressing tumor cell is implicated in development of several types of cancer. However, the role of CD73 in HCC cell has not been systematically investigated and its underlying mechanism remains elusive. METHODS: CD73 expression in HCC cell was determined by RT-PCR, Western blot, and immunohistochemistry staining. Clinical significance of CD73 was evaluated by Cox regression analysis. Cell counting kit-8 and colony formation assays were used for proliferation evaluation. Transwell assays were used for motility evaluations. Co-immunoprecipitation, cytosolic and plasma membrane fractionation separation, and ELISA were applied for evaluating membrane localization of P110ß and its catalytic activity. NOD/SCID/γc(null) (NOG) mice model was used to investigate the in vivo functions of CD73. RESULTS: In the present study, we demonstrate that CD73 was crucial for epithelial-mesenchymal transition (EMT), progression and metastasis in HCC. CD73 expression is increased in HCC cells and correlated with aggressive clinicopathological characteristics. Clinically, CD73 is identified as an independent poor prognostic indicator for both time to recurrence and overall survival. CD73 knockdown dramatically inhibits HCC cells proliferation, migration, invasion, and EMT in vitro and hinders tumor growth and metastasis in vivo. Opposite results could be observed when CD73 is overexpressed. Mechanistically, adenosine produced by CD73 binds to adenosine A2A receptor (A2AR) and activates Rap1, which recruits P110ß to the plasma membrane and triggers PIP3 production, thereby promoting AKT phosphorylation in HCC cells. Notably, a combination of anti-CD73 and anti-A2AR achieves synergistic depression effects on HCC growth and metastasis than single agent alone. CONCLUSIONS: CD73 promotes progression and metastasis through activating PI3K/AKT signaling, indicating a novel prognostic biomarker for HCC. Our data demonstrate the importance of CD73 in HCC in addition to its immunosuppressive functions and revealed that co-targeting CD73 and A2AR strategy may be a promising novel therapeutic strategy for future HCC management.

Dual-Stimuli-Responsive Paclitaxel Delivery Nanosystems from Chemically Conjugate Self-Assemblies for Carcinoma Treatment.

Diselenide-bond-linked poly(N-isopropylacrylamide)-paclitaxel chemical conjugates are synthesized as a drug release carrier. The conjugates can self-assemble into "core-shell" nanoscaled micelles in aqueous solution and show thermal and redox dual-responsiveness. The conjugates can afford a high encapsulation efficiency of up to 72.3%, and deliver hydrophobic anticancer drug paclitaxel in a temperature and oxidization or reduction stress-mode. The in vitro 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and in vivo anticancer assays are performed to assess the cytotoxicity and anticancer activity of the conjugates, suggesting that the developed conjugates can be used to treat carcinoma as a novel and highly efficient drug delivery system.

Genetic Record for a Recent Invasion of Phenacoccus solenopsis (Hemiptera: Pseudococcidae) in Asia.

The cotton mealybug Phenacoccus solenopsis Tinsley is an emerging invasive insect pest. Since its first report as a pest in the United States in 1991, it has invaded and colonized more than 23 countries over the past century. It was first recorded from Pakistan in 2006 and from China in 2008. In this study, we performed field surveys from 2010 to 2012 and obtained mtCOI sequences from specimens across China and Pakistan, then compared them with already available mtCOI sequences from additional Asian and North American countries. Our genetic analysis provides evidence that P. solenopsis should be classified into two groups, one of which is found only in the United States, and the other found only in Asia. The Asian group contains nine unique haplotypes, two of which have invaded and spread across China, Pakistan, India, and Vietnam over the last 4-6 yr. Our genetic analysis also indicates that P. solenopsis has a close relationship with the parasitoid wasp Aenasius bambawalei Hayat, providing preliminary evidence of a congruent spread of this mealybug and its parasitoids across China.

Preparation and biological evaluation of a novel selenium-containing exopolysaccharide from Rhizobium sp. N613.

In order to obtain a low toxic antitumor agent and an organic selenium source, an exopolysaccharide obtained from Rhizobium sp. N613 (REPS) was modified by selenious acid using barium chloride as the catalyst. The reaction conditions were optimized by response surface methodology (RSM), and the optimal conditions for preparation of selenium-containing REPS (Se-REPS) were obtained. The selenium content of Se-REPS was 790 µg/g under these conditions. The molecular structure of Se-REPS was confirmed by FTIR. In vitro antitumor activity of Se-REPS was evaluated by MTT assay, and the results indicated that Se-REPS could significantly inhibit the growth of S180 and HepG2 cells. Furthermore, Se-REPS exhibited comparable in vivo antitumor efficacy to cyclophosphamide at same concentrations. In addition, Se-REPS could substantially elevate the thymus and spleen indices in tumor-bearing mice. This study demonstrates that Se-REPS holds great potential to be a desirable antitumor agent for therapeutic and immunomodulatory applications.

(E)-N'-(3-Nitro-benzyl-idene)-4-(8-quinol-yloxy)butano-hydrazide.

In the title Schiff base compound, C(20)H(18)N(4)O(4), the conformation along the bond sequence linking the benzene and quinoline rings is trans-(+)gauche-trans-trans-(+)gauche-trans-trans. The dihedral angle between the aromatic ring systems is 80.3 (6)°. In the crystal, a pair of inter-molecular N-H⋯N hydrogen bonds link the mol-ecules into centrosymmetric R(2) (2)(20) dimers, which are aggregated via π-π inter-actions into sheets [quinoline-benzene ring centroid-centroid separation = 3.572 (2)-3.773 (3) Å].