Body composition and risk of gastric cancer: A population-based prospective cohort study.

The recognition of adiposity as a risk factor for gastric cancer is mainly based on traditional anthropometric indices, such as body mass index, which are unable to discriminate between lean and fat mass. We undertook this study to examine body composition and subsequent risk of gastric cancer. This is a prospective analysis of participants free of cancer from the UK Biobank. We measured baseline body composition with electrical bioimpedance analysis and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. We documented 326 cases of cancer from 474,929 participants over a median follow-up of 6.6 years. Both male (HR 1.70, 95% CI 1.01 to 2.89) and female participants (HR 2.47, 95% CI 1.15 to 5.32) in the highest quartile of whole body fat-free mass were associated with increased risk of gastric cancer as compared with those in the lowest quartile.Whole body fat mass was associated with a decreased risk of gastric cancer (HR per 5-unit increase 0.86, 95% CI 0.74 to 0.99) in females, but not in males. We concluded that fat-free mass and fat mass may have different effects on gastric cancer risk. This study provided evidence for individualized weight management for the prevention of gastric cancer.

Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals.

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.