Effect of Tacrolimus Time in Therapeutic Range on Postoperative Recurrence in Patients Undergoing Liver Transplantation for Liver Cancer.

BACKGROUND AND OBJECTIVE: Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines. METHODS: A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus. RESULT: Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation. CONCLUSIONS: TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.

Circadian clock protein CRY1 prevents paclitaxel­induced senescence of bladder cancer cells by promoting p53 degradation.

Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first­line treatment is cisplatin­based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy­induced senescence can act as a 'back­up' response to chemotherapy in cancer types that are resistant to apoptosis­based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)­induced senescence in cisplatin­resistant bladder cancer cells. Cisplatin­resistant bladder cancer cells were established via long­term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA­ß­Gal staining, but this was not observed in the cisplatin­resistant cells. The cisplatin­resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin­resistant cells, and that CRY1 knockdown restored PTX­induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto­oncogene. These data suggested that the accumulated CRY1 in cisplatin­resistant cells could prevent PTX­induced senescence by promoting p53 degradation.

Resistin Gene Polymorphism Is an Influencing Factor of Postoperative Pain for Chinese Patients.

BACKGROUND: Gene polymorphism is an important factor affecting the efficacy and dosage of opioids. A recent study showed RETN rs3745367 was associated with postoperative pain intensity. OPRM1 gene was confirmed to affect the postoperative analgesic consumption of morphine and other opioids. OBJECTIVE: In this study, we investigated the association between single nucleotide polymorphisms (SNPs) in the RETN, OPRM1 gene and postoperative pain intensity, analgesics consumption, and ADR. The haplotype analysis focus on OPRM1 was also implemented. STUDY DESIGN: This was a prospective, observational study. SETTING: Patients undergoing spinal fusion and correction operation were recruited. Genotypes of rs3745367, rs1799971, rs2075572, and rs9322447 were tested. Pain assessment was performed to measure postoperative pain intensity, postoperative fentanyl and pethidine consumption was recorded to calculate analgesics consumption, and adverse reactions were recorded. METHOD: We recruited 142 patients undergoing spinal correction and fusion. Genotyping was performed by using a real-time polymerase chain reactions (PCRs) system and validated with allelic discrimination assays. The pain was assessed using a numerical rating scale (NRS). Statistical analyses were performed using SPSS software. LD test and the construction and analysis of haplotype were using Haploview software. RESULTS: Rs3745367 demonstrated a significant association with postoperative average pain intensity in 24h (P = 0.015) and 48h (P = 0.001) after surgery. Rs2075572 and rs9322447 influenced postoperative maximal pain intensity in 48h after surgery (P = 0.042, 0.033, respectively). No correlation was found between OPRM1 SNPs and analgesics consumption and adverse reaction. According to the results of this study, a strong LD was observed between rs1799971 and rs9322447 (Block 1, LD parameters: D' = 0.82, r2 = 0.14), rs2075572 and rs9322447 (Block 2, LD parameters: D' = 0.92, r2 = 0.51). LIMITATIONS: The association between rs3745367 with serum resistin levels was not investigated in this research, serum resistin levels of the incision part should be investigated in future studies. CONCLUSION: RETN rs3745367 was associated with postoperative average pain intensity, OPRM1 rs2075572 and rs9322447 may influence postoperative maximal pain intensity.