Cationic liposome co-encapsulation of SMAC mimetic and zVAD using a novel lipid bilayer fusion loaded with MLKL-pDNA for tumour inhibition in vivo

The increase in multidrug resistance among colon cancer cells presents a challenge for the development of effective therapies. Small-molecule analogues of second mitochondria-derived activator of caspase (SMAC) mimetic in association with mixed lineage kinase domain-like protein (MLKL)-pDNA and z-VAD-fmk have shown ideal antitumor effects in colon cancer cells in vitro via induction of RIP3-dependent necroptosis. To achieve synergistic antitumor effects in vivo, liposomes loaded with SMAC mimetic, MLKL-pDNA and z-VAD-fmk have been developed using novel lipid fusion methods to co-localise the molecules of interest within the tumour cells. The co-encapsulation liposome (MLKL-zVAD-BV6-LP) had a high entrapment efficiency of approximately 95% for both zVAD and BV6 and was able to condense MLKL-pDNA very well. The vectors showed good biocompatibility, tumour targeting and small-molecule co-localisation. In a CT26 mouse model, the MLKL-zVAD-BV6-LP exhibited a tumour-suppression rate of over 60% in vivo, which was significantly higher than that of both the null-liposome and coadministration groups. Above all, the co-encapsulation system provided a novel approach to combination tumour therapy.     

The anti-tumor effect of pachymic acid on osteosarcoma cells by inducing PTEN and Caspase 3/7-dependent apoptosis

Pachymic acid (PA) is a lanostane type triterpenoid isolated from Poria cocos, which possesses an anti-tumor effect in breast cancer, prostate cancer, lung cancer, and bladder cancer cells. In this study, we investigated the effect of PA on the growth and apoptosis of human immortalized cell line (HOS) and primary osteosarcoma cells by a Cell Counting Kit-8 (CCK-8) and Annexin V and propidium iodide (PI) staining, respectively. Western blot was used to measure the expression of cleaved Caspase 3, PTEN, and AKT, as well as the AKT phosphorylation. The Caspase 3 activity was determined using the Caspase-3 Colorimetric Assay Kit. From the results, PA significantly reduced cell proliferation in a concentration- and time-dependent manner. PA also induced cell apoptosis in a dose-dependent fashion. PA treatment led to increased Caspase 3 activation and PTEN expression, as well as reduced AKT phosphorylation. Moreover, Ac-DEVD-CHO (a Caspase 3/7 inhibitor) pre-treatment or PTEN knockdown partially blocked the effects of PA on cell proliferation and apoptosis. Caspase 3/7 inhibitor had an additive effect with PTEN knockdown. Collectively, our results suggested that induction of apoptosis by PA was mediated in part by PTEN/AKT signaling and Caspase 3/7 activity. This study provides evidence that PA might be useful in the treatment of human osteosarcoma.     

New,Immunomodulatory, Oral Nutrition Formula for Use Prior to Surgery in Patients With Head and Neck Cancer: An Exploratory Study

Background: The perioperative use of immunomodulatory nutrition formulas in patients with head and neck cancer reduces the number of postoperative infections and the length of hospital stay. Objective: An exploratory, randomized, controlled, blind, clinical trial was designed to examine the effect of the preoperative consumption of a new, immunomodulatory, oral nutrition formula in patients with head and neck cancer. Methods: Thirty‐eight patients were randomized to receive either 400 mL/d of either the new immunomodulatory formula (IF) or that commonly used in clinical practice (CF) over 10 days prior to surgery. Thirty‐three patients completed the study. Compliance, tolerance, the length of hospital stay, the incidence of infections and noninfectious complications before discharge, and the same up to 15 and 30 days after discharge were recorded. Results: The percentage of patients who developed infections before discharge was significantly lower in the IF than in the CF group (P = .013), as was the number of infections/100 patients/d (P = .035). The length of hospital stay was significantly shorter in the IF group (P = .001). Both formulas were safe and well tolerated. No other differences were detected. These results suggest preoperative consumption of the new formula to be beneficial for patients with neck and head cancer. Further trials are needed to confirm these results and to test the efficacy of the formula in patients with other conditions. Conclusion: The new formula can be safely prescribed as part of the preoperative treatment of patients with head and neck cancer and might reduce the problem of postoperative infection.