Objective　To explore the expression and significance of p21WAF1 and p53 in HCC. Methods　Immunohistochemical method (IHC) was used to localize and semi-quantitate the proteins of p21WAF1 and p53 and to observe the relationship between the expression of p21WAF1 and the different histopathologic characters in 38 patients of HCC and their peri-cancer tissue as well as 5 normal liver tissue. Results　Of all 38 cases, both p21WAF1 and p53 expression were significantly higher in tumor than that in corresponding non-tumors liver tissue; 14 (36.8 %) of 38 cases showed p21WAF1 positive staining, 28 cases (73.7 %) were p53 positive, p21WAF1＋/p53＋ or p21WAF1-/p53－ were observed in 18, while 20 cases showed p53＋/p21WAF1－ or p53－/p21WAF1＋. p21WAF1＋ was seen in 1 of 38 (2.6 %) corresponding non-cancerous tissue and 2 of 5 normal liver tissue. p53 protein was not detected neither in the non-tumorous tissue nor in normal liver. No significant association was found between the expressions of p21WAF1 and p53(P＞0.05) in HCC. Their was no significant correlation between p21WAF1 or p53 expression and the different histopathologic characters of tumor (differentiating grades, intrahepatic metastasis and/or cancerous thrombi within portal veins). Conclusion　Both p21WAF1 and p53 proteins are over expressed in HCC than that in corresponding non-tumorous liver tissue, but there is no relationship between them. Both p53-independent and p53-dependent mechanism may play a role in regulating p21WAF1 expression in HCC. p21WAF1 immunostaining cannot be used to assess the status of p53 in any given cell or tissue.

Objective To establish an UPLC-MS/MS method for determinating content of three paclitaxel fatty acid esters such as paclitaxel myristate （PTX-MA）, paclitaxel palmitate （PTX-PA） and paclitaxel myristate （PTX-SA） in mouse plasma, and preliminarily investigate the pharmacokinetic characteristics of their liposomes in mice. Methods Eclipse Plus C8 chromatography column （2.1 mm×50 mm, 1.8 μm） was used with different proportions of 0.2% formic acid aqueous solution （A） and methanol （B） mixture as mobile phase for gradient elution at a flow rate of 0.3 ml/min. The collum temperature was 30℃. The sample injection volume was 10 μl. The triple quadrupole mass series spectrometer was used as multi-reaction monitoring （MRM）. Results PTX-MA, PTX-PA and PTX-SA all exhibited a good linear relationship in the range of 5.0~500.0 ng/ml （r>0.9950）. Their RSD of precision, stability, extraction recovery rate and matrix effect test results was all less than 10%. The half-lives （t_1/2） for liposomes of three paclitaxel fatty acid esters PTX-MA-L、PTX-PA-L and PTX-SA-L in mice were 14.78 h, 44.49 h and 69.32 h individually, and their clearance rates （CL） were 29.06 L·kg/h, 24.94 L·kg/h and 13.74 L·kg/h, respectively. Conclusion This method had high specificity, sensitivity, easy operation and good stability, which could be used for the determination of paclitaxel fatty acid esters in mouse plasma. The results of pharmacokinetic studies in mice showed that t_1/2 for paclitaxel fatty acid esters were significantly prolonged, and the clearance rate were significantly reduced with the length of fatty acid carbon chains increasement, which indicated that esterification of paclitaxel with different chain length saturated fatty acids could obviously alter its in vivo pharmacokinetic properties, which provided scientific basis for the research and development of nano formulations of paclitaxel fatty acid ester prodrug.

BACKGROUND: Chemotherapy is a common treatment for advanced hepatocellular carcinoma, but the effect is not satisfactory. The study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid (ATRA) to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) for advanced hepatocellular carcinoma (HCC). METHODS: We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, and Zhejiang Sian International Hospital and retrospectively compared for overall survival. The Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age, sex, and disease stage. RESULTS: From July 2013 to July 2018, 111 patients with HCC were included in this study. The median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group ( P  < 0.001). The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group (3.6 months vs. 1.8 months, P  < 0.001). Hazard ratios for overall survival and disease progression were 0.465 (95% confidence interval: 0.298-0.726; P  = 0.001) and 0.474 (0.314-0.717; P  < 0.001) after adjusting for potential confounders, respectively. CONCLUSION ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.
Humans ; Carcinoma, Hepatocellular/drug therapy* ; Retrospective Studies ; Liver Neoplasms/pathology* ; Oxaliplatin/therapeutic use* ; Fluorouracil/adverse effects* ; Disease Progression ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Leucovorin/adverse effects* ; Colorectal Neoplasms/drug therapy*