Synergistic impact of resection margin and microscopic vascular invasion for patients with HBV-related intrahepatic cholangiocarcinoma.

OBJECTIVES: The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes. METHODS: A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus-related ICC were retrospectively analyzed. The different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive, +, or negative, -) on overall survival (OS) and recurrence-free survival (RFS) were analyzed. RESULTS: The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RM & MVI (-), 58.0%, 36.1%, and 26.5% in narrow RM & MVI (-), 51.0%, 27.0%, and 24.3% in wide RM & MVI (+), and 39.0%, 20.4% and 14.3% in narrow RM & MVI (+) (p < 0.001). Multivariate analysis showed that RM & MVI were independent risk factors for the OS and RFS. CONCLUSION: Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.

Synthesis and characterization of four process impurities in pazopanib.

Pazopanib (trade name Votrient®) is a potent and selective multi-targeted tyrosine kinase inhibitor that blocks tumor growth and inhibits angiogenesis. Based on a recently reported procedure, we herein report the first synthesis of four potential process impurities generated in the production of pazopanib. The structure of these impurities were synthesized and characterized by 1H NMR, 13C NMR and HRMS data. The possible formation mechanisms of these impurities were also elucidated. These findings should be useful for the quality control of pazopanib in manufacture.

Krüppel-like factor 8 promotes cancer stem cell-like traits in hepatocellular carcinoma through Wnt/ß-catenin signaling.

Krüppel-like factor 8 (KLF8) is highly expressed in hepatocellular carcinoma (HCC) and contributes to tumor initiation and progression by promoting HCC cell proliferation and invasion. However, the role of KLF8 in liver cancer stem cells (LCSCs) is not known. In the current study, we investigated the role of KLF8 in LCSCs to determine if KLF8 is a novel marker of these cells. We found that KLF8 was highly expressed in primary HCC tumors, distant migrated tissues, and LCSCs. Patients with high KLF8 expression had a poor prognosis. KLF8 promoted stem cell-like features through activation of the Wnt/ß-catenin signaling pathway. Cell apoptosis was significantly increased in HCC cells with knockdown of KLF8 compared with the control cells when treated with the same doses of sorafenib or cisplatin. Taken together, our study shows that KLF8 plays a potent oncogenic role in HCC tumorigenesis by maintaining stem cell-like features through activation of the Wnt/ß-catenin signaling pathway and promoting chemoresistance. Thus, targeting KLF8 may provide an effective therapeutic approach to suppress tumorigenicity of HCC. © 2016 Wiley Periodicals, Inc.

Vitamin D: preventive and therapeutic potential in Parkinson's disease.

Vitamin D is one of the important nuclear steroid transcription regulators that controls transcriptions of a large number of genes. Vitamin D supplement is commonly recommended for the elderly to prevent bone diseases. Amounting new evidence has indicated that vitamin D plays a crucial role in brain development, brain function regulation and neuroprotection. Parkinson's disease (PD) is a degenerative disorder commonly seen in the elderly, characterized by movement disorders including tremor, akinesia, and loss of postural reflexes. The motor symptoms largely result from the continued death of dopaminergic neurons in the substantia nigra, despite use of current therapeutic interventions. The cause and mechanism of neuron death is currently unknown. Vitamin D deficiency is common in patients with PD suggesting its preventive and therapeutic potential. Vitamin D may exert protective and neurotropic effects directly at cellular level, e.g. protection of dopamine system, and/or by regulating gene expression. This review summarizes the epidemiological, genetic and translational evidence implicating vitamin D as a candidate for prevention and treatment for PD.

Immunosuppressant utilization and cardiovascular complications among Chinese patients after kidney transplantation: a systematic review and analysis.

PURPOSE: Data on the utilization of immunosuppressants and incidences of cardiovascular complications after kidney transplantation are generally lacking in China. The objectives of this systematic review and analysis were to investigate the hypothesis that tacrolimus and cyclosporine have different effects on the incidences of cardiovascular complications among Chinese patients after kidney transplantation. METHODS: A comprehensive database research was performed in PubMed and CMB-disc. Random effect models and meta-regression were used for data analysis. Eleven eligible studies were retrieved (7 comparative studies and 4 conversion studies). RESULTS: There were 838 participants from the eligible studies. The incidences of drug-related hypertension, dyslipidemia and hyperglycemia were compared between tacrolimus and cyclosporine groups. Significant different odds ratios for dyslipidemia (40 vs. 20 %, OR 2.72) and hypertension (63 vs. 37 %, OR 2.93), but not for hyperglycemia (11 vs. 15 %, OR 0.705) were noted between patients receiving cyclosporine and tacrolimus containing regimens. The secondary analysis including comparative studies revealed a similar acute rejection rate, but significantly improved renal functions, lipid profiles and lower liver toxicity associated with tacrolimus. Significant reversal of hypertension and dyslipidemia was also noted in the analysis of the conversion studies. CONCLUSIONS: A significant association between immunosuppressant use and cardiovascular complications was identified among Chinese patients after kidney transplantation. Patients receiving cyclosporine-containing regimens and/or with chronic allograft nephropathy should be closely monitored for potential cardiovascular complications.

Eplerenone ethanol solvate.

EPLERENONE [SYSTEMATIC NAME: 7α-(methoxy-carbon-yl)-3-oxo-9α,11-ep-oxy-17α-pregn-4-ene-21,17-carbolactone], an aldo-sterone receptor antagonist, crystallizes from ethanol as a monosolvate, C(24)H(30)O(6)·C(2)H(6)O. The eplerenone mol-ecule has two five-membered rings, three six-membered rings and one three-membered ring. Both five-membered rings display envelope conformations, while the three six-membered rings assume envelope (cyclohexene), half-chair (cyclohexane sharing one edge with epoxy) and chair (other cyclohexane) conformations. The solvent mol-ecule is disordered equally over two sites. It is linked to the eplerenone mol-ecule by hydrogen bonds.