Preparation and characterization of paclitaxel palmitate albumin nanoparticles with high loading efficacy: an in vitro and in vivo anti-tumor study in mouse models.

BACKGROUND: Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. METHODS: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). RESULTS: Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane®), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles. CONCLUSIONS: This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.

Clinical diagnostic values of transfer RNA-derived fragment tRF-19-3L7L73JD and its effects on the growth of gastric cancer cells.

Background and aim: Medicine has made great progress, but gastric cancer is still one of the most common malignant tumors worldwide. tRNA-derived fragments (tRFs), a type of small non-coding RNA, have been found to play important roles in cancers. Due to an abundance of modifications, tRFs have the potential to serve as cancer biomarkers. However, the relationship between tRFs and gastric cancer is still largely unclear. We have identified a new tRF, tRF-19-3L7L73JD, found to be expressed at a lower level in gastric cancer patients than healthy controls. Our study aims to explore the diagnostic value of tRF-19-3L7L73JD screening in gastric cancer and to investigate its effects on the growth of gastric cancer cells. Methods: Using quantitative reverse transcription-polymerase chain reaction, we identified tRF-3L7L73JD as differentially expressed in plasma from gastric cancer patients compared to healthy controls. We measured tRF-3L7L73JD levels in plasma from 40 gastric cancer patients and healthy controls. Furthermore, we tested another cohort containing 89 gastric cancer patients and 98 healthy controls to validate our findings. Next, we analyzed the relationship between levels of tRF-19-3L7L73JD in plasma and clinicopathological data of gastric cancer patients, and then evaluated the effects of tRF-19-3L7L73JD on gastric cancer cell growth. Cell proliferation was measured by the Cell Counting Kit-8 and clone formation experiments after transfer with tRF-19-3L7L73JD mimics. The changes in cell migration ability were explored through the scratch and Transwell experiments. Finally, we explored changes in apoptosis and cell cycle by flow cytometry. Results: tRF-19-3L7L73JD showed lower expression in the tested gastric cancer patients. In the validation cohort tRF-19-3L7L73JD was also expressed at low levels in the pre-operative plasma group compared with healthy plasma and post-operative plasma groups. Additionally, a comparison of gastric cancer cell lines with normal gastric epithelial cell lines produced the same result. We found that tRF-19-3L7L73JD expression in patients was related to tumor size. The area under the curve (AUC) was 0.6230, with sensitivity and specificity of 0.4045 and 0.7959, respectively. Cellular function studies revealed that tRF-19-3L7L73JD inhibited cell proliferation and migration, induced apoptosis, and arrested cells at G0/G1 phases, suggesting it may suppress the development of gastric cancer. Conclusion: The results suggest that tRF-19-3L7L73JD may be useful as a biomarker of gastric cancer.

Evaluation of fasting metabolism of growing water buffalo (Bubalus, Bubalis).

The objectives of the present study were to evaluate fasting metabolism (FM) of water buffalo (Bubalus, Bubalis) at three stages of growth (12, 18 and 24 months) in Guangxi, China. Five female water buffalo were used for each age group and their live weight was on average 254, 326 and 338 kg, respectively. All animals were of average body condition, healthy and de-wormed before start of the study. Prior to a 6-day fasting period, buffalo were offered a mixed diet of forage and concentrates (70% and 30%, dry matter basis) on a restricted nutritional level (419 kJ/kg(0.75) of metabolizable energy, ME) for 15 days. Gas exchanges for each animal were determined for 3 days from day 4 of starvation, using open-circuit respiratory head hoods. Fasting body weight was 0.918 of live weight (P < 0.001, r(2) = 0.99). Both fasting heat production (FHP) and FM (MJ/day) increased significantly with increased age of animals (P < 0.05). Linear regression analysis indicated a positive relationship between fasting body weight (kg(0.75)) and FHP (MJ/day, P < 0.01, r(2) = 0.49) or FM (MJ/day P < 0.01, r(2) = 0.52) when using individual animal data across three groups. However, when expressed as kJ/kg(0.75) of fasting body weight, the differences in FHP or FM between three groups of animals were not significant. The present average FHP and FM (322 and 347 kJ/kg(0.75) of fasting body weight) were compatible to those published in the literature for water buffalo, beef and dairy cattle. The present FM data were also used to estimate net energy (NE(m)) and ME (ME(m)) requirements for maintenance for water buffalo. The results for these two parameters were similar to those for FHP and FM. There was no significant difference between three groups of buffalo in NE(m) or ME(m) when expressed as kJ/kg(0.75) of live weight. The present average NE(m) and ME(m) values (347 and 506 kJ/kg(0.75) of live weight) are close to those proposed by the Agricultural and Food Research Council adopted in UK for beef and dairy cattle. The results indicate that the present FM data can be used as a basis for rationing water buffalo in China.