Synergism of wt-p53 and synthetic material in local nano-TAE gene therapy of hepatoma: comparison of four systems and the possible mechanism.

BACKGROUND: TAE-gene therapy for hepatoma, incorporating the tumor-targeted therapeutic efficacy of trans-arterial embolization, hydroxyapatite nanoparticles (nHAP) and anti-cancer wild-type p53 gene (wt-p53), was presented in our former studies (Int J Nanomedicine 8:3757-68, 2013, Liver Int 32:998-1007, 2012). However, the incompletely antitumoral effect entails defined guidelines on searching properer materials for this novel therapy. METHODS: Unmodified nHAP, Ca(2+) modified nHAP, poly-lysine modified nHAP and liposome were separately used to form U-nanoplex, Ca-nanoplex, Pll-nanoplex, L-nanoplex respectively with wt-p53 expressing plasmid. The four nanoplexs were then applied in vitro for human normal hepacyte L02 and hepatoma HePG2 cell line, and in vivo for rabbits with hepatic VX2 tumor by injection of nanoplexs/lipiodol emulsion into the hepatic artery in a tumor target manner. The distribution, superficial potential, physical structure, morphology and chemical compositions of nanoplexs were evaluated by TEM, SEM, EDS etc., with the objective of understanding their roles in hepatoma TAE-gene therapy. RESULTS: In vitro, L-nanoplex managed the highest gene transferring efficiency. Though with the second highest transfection activity, Pll-nanoplex showed the strongest tumor inhibition activity while maintaining safe to the normal hepacyte L02. In fact, only Pll-nanoplex can combine both the antitumoral effect to HePG2 and safe procedure to L02 among the four systems above. In vivo, being the only one with successful gene transference to hepatic VX2 tumor, Pll-nanoplex/lipiodol emulsion can target the tumor more specifically, which may explain its best therapeutic effect and hepatic biologic response. Further physical characterizations of the four nanoplexs suggested particle size and proper electronic organic surface may be crucial for nano-TAE gene therapy. CONCLUSION: Pll-nanoplex is the most proper system for the combined therapy due to its selectively retention in liver cancer cells, secondary to its morphological and physico-chemical properties of nanometric particle size, steady emulsion, proper organic and electronic surface.

Untypical autoimmune pancreatitis and pancreatic cancer: differential diagnosis experiences extracted from misdiagnose of two cases.

BACKGROUND: Differentiation between pancreatic cancer (PC) and focal form of autoimmune pancreatitis (AIP) is very challenging, with similar clinical presentations, laboratory results and morphologic imagings of US, CT, EUS, MRI, ERCP, PET-CT. Even serum IgG4 and biopsy sometimes cannot give clear-cut differential accurate diagnostis. Considering the totally different management strategy of the two diseases, accurate diagnostic value is urgently needed to remind the clinicians of the rare diagnosis of untypical AIP among frequent PC-suspected patients. RESULTS: We present 2 laparotomy cases of AIP that had a high similar characteristic to PC and retrospectively extracted the warning signs that may help select untypical AIP in PC-suspected patients. CONCLUSIONS: We find that mild fluctuating jaundice with abdominal pain, young age, tumor marker of TPS, TPA and diverse results between variable radiological tests can help to differentiate AIP mass from PC, through retrospectively analyzing work-up process of AIP in two patients who underwent laparotomy for suspected PC.

Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR­206 and the role of miR­206 on TH­regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR­206 on lipid metabolism. Expression of miR­206 in serum and cells was determined by reverse transcription­quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR­206 was performed via transfection with a miR­206 mimic or miR­206 inhibitor. Serum miR­206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR­206 expression. Inhibition of endogenous miR­206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR­206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR­206 expression is reduced in patients with hyperthyroidism. In addition, miR­206 is involved in T3­mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR­206 in thyroid hormone­induced disorders of lipid metabolism in the liver.