METHODS AND RESULTS: We synthesized superparamagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe3O4 nanoparticles could be successfully coated with active drug, and thermogravimetric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe3O4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe3O4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate "burst release" and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line.

Materials and methods: QOS collagen nanofibers were electrospun by incorporating various concentrations of QOS (0.1%-10% w/w) and were cross-linked in situ after exposure to ammonium carbonate. The QOS cross-linked scaffolds were characterized and their biological properties were evaluated in terms of their biocompatibility, cellular adhesion and metabolic activity for primary human dermal fibroblasts and human fetal osteoblasts.

Results and discussion: The study revealed that 1) QOS cross-linking increased the flexibility of otherwise rigid collagen nanofibers and improved the thermal stability; 2) QOS cross-linked mats displayed potent antibacterial activity and 3) the biocompatibility of the composite mats depended on the amount of QOS present in dope solution - at low QOS concentrations (0.1% w/w), the mats promoted mammalian cell proliferation and growth, whereas at higher QOS concentrations, cytotoxic effect was observed.

MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.

METHODS: Primary cultures of young, pre-senescent, and senescent fibroblast cells were incubated with γ-tocotrienol for 24 h. The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction. Cell cycle profiles were determined using a FACSCalibur Flow Cytometer.

RESULTS: The cell cycle was arrested in the G(0)/G(1) phase, and the percentage of cells in S phase decreased with senescence. CCND1, RB1, MMP1, and IL6 were upregulated in senescent fibroblasts. A similar upregulation was not observed in young cells. Incubation with γ-tocotrienol decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell populations in the G(0)/G(1) phase and increased cell populations in the G(2)/M phase. γ-Tocotrienol treatment also upregulated ELN and COL1A1 and downregulated MMP1 and IL6 expression in young and senescent fibroblasts.

MATERIALS AND RESULTS: Thirty-five paraffin-embedded ameloblastoma cases, ameloblastoma-derived cell lines (AM-1), and primary cultures of ameloblastoma stromal fibroblasts (ASF) were used. Immunohistochemistry, MTT assay, Western blotting, and RT-PCR were performed on these samples. Parenchyma-stromal CCN2 overexpression correlated significantly with fibrous-type stroma, but not with myxoid-type stroma, suggesting a role of CCN2 in fibrosis (P < 0.05). Recombinant CCN2 induction of enhanced ASF proliferation in AM-1 medium supports this view. Conversely, BMP4 and TGF-β were expressed in myxoid-type fibroblasts, but little expression was found in parenchyma. RANKL-positive and CD68-positive stromal cell populations were significantly greater in myxoid-type tumor areas than in fibrous-type tumor areas, while a higher Ki-67 labeling index was recorded in ameloblastoma with fibrous-type stroma. These data suggest that stromal properties influence bone resorption-related activities and growth rates, respectively.