Application of lanthanide-doped upconversion nanoparticles for cancer treatment: a review.

With the excellent ability to transform near-infrared light to localized visible or UV light, thereby achieving deep tissue penetration, lanthanide ion-doped upconversion nanoparticles (UCNP) have emerged as one of the most striking nanoscale materials for more effective and safer cancer treatment. Up to now, UCNPs combined with photosensitive components have been widely used in the delivery of chemotherapy drugs, photodynamic therapy and photothermal therapy. Applications in these directions are reviewed in this article. We also highlight microenvironmental tumor monitoring and precise targeted therapies. Then we briefly summarize some new trends and the existing challenges for UCNPs. We hope this review can provide new ideas for future cancer treatment based on UCNPs.

Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses.

BACKGROUND: Derivation of osteoblast-like cells from human pluripotent stem cells (hPSCs) is a popular topic in bone tissue engineering. Although many improvements have been achieved, the low induction efficiency because of spontaneous differentiation hampers their applications. To solve this problem, a detailed understanding of the osteogenic differentiation process of hPSCs is urgently needed. METHODS: Monolayer cultured human embryonic stem cells and human-induced pluripotent stem cells were differentiated in commonly applied serum-containing osteogenic medium for 35 days. In addition to traditional assays such as cell viability detection, reverse transcription-polymerase chain reaction, immunofluorescence, and alizarin red staining, we also applied studies of cell counting, cell telomerase activity, and flow cytometry as essential indicators to analyse the cell type changes in each week. RESULTS: The population of differentiated cells was quite heterogeneous throughout the 35 days of induction. Then, cell telomerase activity and cell cycle analyses have value in evaluating the cell type and tumourigenicity of the obtained cells. Finally, a dynamic map was made to integrate the analysis of these results during osteogenic differentiation of hPSCs, and the cell types at defined stages were concluded. CONCLUSIONS: Our results lay the foundation to improve the in vitro osteogenic differentiation efficiency of hPSCs by supplementing with functional compounds at the desired stage, and then establishing a stepwise induction system in the future.

Roles of ten-eleven translocation family proteins and their O-linked ß-N-acetylglucosaminylated forms in cancer development.

Members of the ten-eleven translocation (TET) protein family of which three mammalian TET proteins have been discovered so far, catalyze the sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine which serve an important role in embryonic development and tumor progression. O-GlcNAcylation (O-linked ß-N-acetylglucosaminylation) is a reversible post-translational modification known to serve important roles in tumorigenesis and metastasis especially in hematopoietic malignancies such as myelodysplastic syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia. O-GlcNAcylation activity requires only two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). OGT catalyzes attachment of GlcNAc sugar to serine, threonine and cytosine residues in proteins, while OGA hydrolyzes O-GlcNAc attached to proteins. Numerous recent studies have demonstrated that TETs can be O-GlcNAcylated by OGT, with consequent alteration of TET activity and stability. The present review focuses on the cellular, biological and biochemical functions of TET and its O-GlcNAcylated form and proposes a model of the role of TET/OGT complex in regulation of target proteins during cancer development. In addition, the present review provides directions for future research in this area.

[Effect of B4GALT1 on Proliferation of Its Co-cultured Human Acute Myeloid Leukemia Cell Line in Bone Marrow Stromal Cells].

OBJECTIVE: To investigate the effect of bone marrow stromal cell glycosyltransferase B4GALT1 expression on hematopoietic cell proliferation and its upstream regulation mechanism. METHODS: B4GALT1 was overexpressed in human bone marrow stromal cell line HS5, which was then co-cultured with acute myeloid leukemia cell line KG1a. And its effect on hematopoietic cell proliferation was detected by flow cytometry. Dual luciferase reporter assay, real-time PCR and Western blot were used to predict and validate upstream transcription factors that regulate stromal cell B4GALT1 expression. RESULTS: Overexpression of B4GALT1 in HS5 significantly promoted the proliferation of KG1a in the co-culture system. B4GALT1 expression in stromal cells positively correlated with upstream c-Jun expression, which was verified by JNK/c-Jun inhibitors. CONCLUSION: The differential expression of glycosyltransferases and their corresponding glycosylation in the hematopoietic microenvironment play an important role.

Novel triazolyl berberine derivatives prepared via CuAAC click chemistry: synthesis, anticancer activity and structure-activity relationships.

To search for novel anticancer agents, we designed and synthesized a series of new triazolyl berberine derivatives. The evaluation of all the synthesized compounds and their anticancer activities against a panel of four human cancer cell lines including MCF-7 (breast), MCF-7/ADR (breast), SW-1990 (pancreatic), SMMC-7721 (liver) and the noncancer cell line HUVEC (human umbilical vein endothelial cell). The results showed that most of the compounds displayed better anticancer activities against MCF-7 and SMMC-7721 compared with berberine. Among these derivatives, compounds 5p and 5a exhibited the most potent inhibitory activities against the SMMC-7721 and SW-1990 cell lines with IC50 values of 14.861 ± 2.4 µM and 16.798 ± 3.4 µM. Furthermore, compounds 5p, 5a and 5n exhibited much better selectivity toward the normal cell line HUVEC than berberine.

Novel Triazolyl berberine derivatives prepared via CuAAC click chemistry: Synthesis, Anticancer Activity and Structure-Activity Relationships.

To search for novel anticancer agents, we designed and synthesized a series of new triazolyl berberine derivatives. The evaluation of all the synthesized compounds and their anticancer activities against a panel of four human cancer cell lines including MCF-7 (breast), MCF-7/ADR (breast), SW-1990 (pancreatic), SMMC-7721 (liver) and the non-cancer cell line HUVEC (human umbilical vein endothelial cell). The results showed that most of the compounds displayed better anticancer activities against MCF-7 and SMMC-7721 compared with berberine. Among these derivatives, compounds 5p and 5a exhibited the most potent inhibitory activities against the SMMC-7721 and SW-1990 cell lines with IC50 values of 14.861 ± 2.4 µM and 16.798 ± 3.4 µM. Furthermore, compounds 5p, 5a and 5n exhibited much better selectivity toward the normal cell line HUVEC than berberine.

Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy.

AIM: To investigate the expression profile of microRNAs in inoperable advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the potential relevance of microRNAs to clinicopathological characteristics and prognosis. METHODS: Serum samples were taken from 260 inoperable advanced NSCLC patients and 260 healthy individuals. All the patients received cisplatin-based chemotherapy, including NP/NC regimens, GP/GC regimens, and TP/TC regimens. The serum levels of microRNAs (miR-125b, miR-10b, miR-34a and miR-155) were determined by quantitative real-time PCR. RESULTS: Serum levels of the 4 microRNAs examined in NSCLC patients were significantly increased as compared with healthy individuals. The levels of miR-125b and miR-155 were changed in a similar pattern: the patients with stage IV disease had the highest one, while the patients with stage III A and stage III B disease showed similar increased levels. The levels of miR-10b and miR-34a in the patients with different stages were increased to similar extent. The level of miR-125b in poorly differentiated cancer was significantly higher than those in well and moderately differentiated cancers, while the levels of miR-10b, miR-34a, and miR-155 did not significantly differ with cancer differentiation. Among the 4 microRNAs examined, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression levels in non-responsive patients. Furthermore, the high level of miR-125b was significantly correlated with poor patient survival. A multivariate Cox regression analysis showed that the expression level of miR-125b was an independent prognostic marker in NSCLC patients. CONCLUSION: Our results suggest that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC. This finding has important implications for development of targeted therapeutics to overcome chemotherapeutic resistance in NSCLC.