Results.— Incision-only control mice showed no changes from baseline periorbital von Frey mechanical thresholds.

CCI significantly reduced mean periorbital von Frey thresholds (periorbital allodynia) compared with baseline and craniotomy-only at each endpoint, analysis of variance P < .0001. Craniotomy significantly reduced periorbital threshold at 14 days but not 7, 21, or 28 days compared with baseline threshold, P < .01. CCI significantly increased SP immunoreactivity in the brainstem at 7 and 14 days but not 28 days compared with craniotomy-only and controls, P < .001. CGRP levels in brainstem tissues were significantly increased IWR-1 manufacturer in CCI groups compared with controls (incision-only and naïve mice) or craniotomy-only mice at each endpoint examined, P < .0001. There was a significant correlation between CGRP and periorbital allodynia (P < .0001,

r = −0.65) but not for SP (r = 0.20). CCI significantly increased the number of macrophage/microglia in the injured cortex at each endpoint up to 28 days, although cell numbers declined over weeks post-injury, P < .001. GFAP+ immunoreactivity was significantly find more increased at 7 but not 14 or 28 days after CCI, P < .001. Craniotomy resulted in transient periorbital allodynia accompanied by transient increases in SP, CGRP, and GFAP immunoreactivity compared with control mice. There was no increase in the number of macrophage/microglia cells compared with controls after craniotomy. Conclusion.— Injury to the somatosensory cortex results in persistent periorbital allodynia

and increases in brainstem nociceptive neuropeptides. Findings suggest that persistent allodynia and increased neuropeptides are maintained by mechanisms other than activation of macrophage/microglia or astrocyte in the injured somatosensory cortex. “
“Individually, both obesity and headache are conditions associated with a substantial personal and societal impact. Recent data support that obesity is Epothilone B (EPO906, Patupilone) comorbid with headache in general and migraine specifically, as well as with certain secondary headache conditions such as idiopathic intracranial hypertension. In the current manuscript, we first briefly review the epidemiology of obesity and common primary and secondary headache disorders individually. This is followed by a systematic review of the general population data evaluating the association between obesity and headache in general, and then obesity and migraine and tension-type headache disorders. Finally, we briefly discuss the data on the association between obesity and a common secondary headache disorder that is associated with obesity, idiopathic intracranial hypertension. Taken together, these data suggest that it is important for clinicians and patients to be aware of the headache/migraine-obesity association, given that it is potentially modifiable.

Treatment started 1 week after development of ascites and stopping CCl4 administration

in a setting of advanced cirrhosis or after 2 weeks of BDL, in a precirrhotic stage. Experiments were performed 1 hour after the last dose of terutroban or vehicle. Treatments were prepared by a third person and experimental studies were realized blindly. The code was kept sealed until the final analysis of the results. find protocol The dose of terutroban used has been previously shown to have antivasoconstricting and antiatherosclerotic properties.[16, 22, 23] The animals were kept in environmentally controlled animal facilities at the Institut d’Investigacions Biomèdiques August Pi i Sunyer. All procedures were approved by the Laboratory Animal Care and Use Committee of the University of Barcelona and were conducted in accordance with European Community guidelines for the protection of animals used for experimental and other scientific purposes (EEC Directive 86/609). Cirrhotic rats were anesthetized with intraperitoneal ketamine hydrochloride (100 mg/kg; Merial Laboratories, Barcelona, Spain) plus midazolam (5 mg/kg intraperitoneally; Laboratorios Reig Jofré, Barcelona, Spain). The femoral artery and the ileocolic vein were cannulated with PE-50 catheters to measure mean arterial pressure

(MAP; mmHg) and portal pressure (PP; mmHg), respectively. Perivascular ultrasonic transit-time flow probes connected to a flow meter (Transonic Systems, Ithaca, NY) were placed around the portal vein, as close as possible to the liver to measure portal blood flow perfusing the Roscovitine nmr liver (PBF; mL/min/g liver) and around the superior mesenteric artery, in BDL cirrhotic rats, to measure superior mesenteric artery blood flow (SMABF, mL/min/100g body weight). Hepatic vascular resistance (HVR, mmHg/mL/min/g liver) was calculated as: PP/PBF; and superior mesenteric artery resistance (SMAR, mmHg/mL/min/100g

body weight) was calculated as (MAP-PP)/SMABF. Blood pressures and flows were registered on a multichannel computer-based recorder (PowerLab; AD Instruments, Colorado Springs, CO). The temperature of the animals was RNA Synthesis inhibitor maintained at 37 ± 0.5°C. Hemodynamic data were collected after a 20-minute stabilization period. To determine if terutroban correctly blocked the TP receptor in a subgroup of CCl4 and BDL cirrhotic rats (n = 3) treated with terutroban (30 mg/kg) or vehicle for 2 weeks, measurements of MAP and PP were performed before and after the intravenous infusion of 10 μg/kg U46619.[24] U46619 (9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid; Cayman Chemical, Tallin, Estonia) is a synthetic TXA2 analog that specifically activates the TP-receptor. An additional group of cirrhotic rats were randomized to receive terutroban (30 mg/kg; n = 8 in CCl4; n = 8 in BDL) or vehicle (n = 9 in CCl4; n = 9 in BDL) for 3 days.

Hypothetically, vitamin D levels might be assessed before starting antiviral therapy, which should be initiated only in the presence

of normal serum vitamin D values; in the presence of vitamin D deficiency, it might be preferable to correct the deficiency before starting antiviral therapy. The supposed relationship between the rapid slope of the HCV RNA level after therapy initiation and vitamin D suggests that the latter could Target Selective Inhibitor Library cell line amplify the immunological effect of IFN. In fact, beyond the classical actions related to calcium homeostasis and bone metabolism, vitamin D has emerged as a key regulator of the innate immunity response in humans.23, 29, 30 Can pretreatment serum vitamin D determination be a useful adjunct to IL-28B rs12979860 C/T polymorphism

evaluation in managing the treatment options for patients with chronic hepatitis C? This study demonstrated that the vitamin D level and the IL-28B rs12979860 C/T polymorphism are two independent predictors of SVR achievement in difficult-to-treat HCV genotypes. Moreover, our results clearly illustrate that these two predictors, being completely independent of each other, may be usefully Selleck Tanespimycin combined to enhance the ability to identify patients who will respond to treatment. Compared with patients carrying the IL-28B rs12979860 C/C genotype and who have a normal vitamin D level, vitamin D deficiency identifies patients with a lower probability of SVR attainment. Furthermore, carrying at least one T allele along with vitamin D deficiency was associated with the lowest probability of attaining the same viral endpoint. Although promising, this study has some limitations. First, it is retrospective. Second, Vildagliptin only a baseline vitamin D determination was available, and no further vitamin D levels could be included in the analysis. Therefore, we cannot

exclude that during antiviral treatment, vitamin D levels vary in relationship with a number of factors capable of influencing its level. However, in accordance with the data presented, vitamin D plays its major role during the initial phases of viral decline soon after initiating treatment, and although dependent on several environmental factors, vitamin D levels are probably at least in part genetically predetermined.31 In conclusion, the present study confirms a possible role for the serum vitamin D level in predicting the outcome of antiviral therapy in HCV chronic infection. Vitamin D deficiency is associated with a reduced probability of RVR attainment. The determination of this vitamin may be complementary to that of the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of SVR achievement in treatment-naïve patients with chronic hepatitis C.

We conducted a prospective study in consecutively admitted patients with cirrhosis and ascites in any of the following clinical situations: patients with SBP (Group I), patients admitted for the treatment of uncomplicated ascites without bacterial infections (ASC), as determined by negative microbiological culture and no presence of bacterial DNA in blood and ascitic fluid (AF), who were not receiving long-term SID with norfloxacin as secondary prophylaxis of SBP (Group II) and patients

undergoing SID with norfloxacin as secondary prophylaxis of SBP (Group III). No patient included in the study showed multinodular hepatocellular Lumacaftor mw carcinoma, portal selleckchem thrombosis, alcoholic hepatitis, previous liver transplantation, or previous transjugular intrahepatic portosystemic shunt.

SBP was defined as the presence of >250 polymorphonuclear (PMN) cells/μL in AF. The ethics committee of the hospital approved the study protocol, and all patients gave informed consent to participate in the study. Blood and AF were obtained from all patients at admission and were analyzed for routine biochemical and cytological studies. In patients with SBP, samples were obtained at the time of SBP diagnosis. Blood and

AF cultures were performed in all cases, as described elsewhere.11 Aliquots of blood and AF were inoculated under aseptic conditions in sterile, rubber-sealed Vacutainer SST Org 27569 II tubes (BD Diagnostics, Belgium) that were never exposed to free air. To detect the presence of bacterial DNA fragments in blood and AF, a broad-range polymerase chain reaction (PCR) was performed according to the methodology described elsewhere.12 A quantitative chromogenic limulus amoebocyte lysate test (BioWhittaker, Nottingham, UK) was followed to evaluate endotoxin levels in blood and AF samples as previously described.13 Samples and reagents were handled in an airflow chamber and processed with pyrogen-free material tested by the manufacturers. PMN cells from peripheral blood samples were isolated with PolymorphPrep (Axis-Shield PoC, Oslo, Norway) according to manufacturer’s instructions. After PMN cell isolation, cells were washed twice with freshly made phosphate-buffered saline (PBS) at 4°C. Cell viability was evaluated by trypan blue (Sigma, Madrid, Spain).

5A). We also compared the necrosis areas in liver induced by

CCl4. As shown in Fig. 5B and Supporting Fig. 2, CCl4 caused more severe liver injury in ΔIN-FXR mice than in FXR Fl/Fl mice. Although the CYP7a1 expression levels were decreased in both ΔIN-FXR and FXR Fl/Fl mice after CCl4 injection, the expression levels of CYP7a1 in the ΔIN-FXR mice were significantly higher compared to that in FXR Fl/Fl PLX3397 cost mice (Fig. 5C). This confirms that intestine FXR plays an important role in the regulation of CYP7a1 expression. We next measured the FGF15 expression levels in intestine and found that the induction of the FGF15 in the FXR Fl/Fl mice was blocked in ΔIN-FXR mice (Fig. 5D). FGF15 is a hormone that can mediate the effect of intestine FXR to regulate

bile acid levels in liver. Because we observed that intestine-specific deletion of FXR resulted in greater Transmembrane Transporters modulator defective liver regeneration/repair induced by 70% PH and CCl4, we therefore used both of the models to ask whether FGF15 plays a role in promoting liver regeneration/repair. ΔIN-FXR and FXR KO mice were injected with either a recombinant adenovirus that expresses FGF15 or a control adenovirus, and then 70% PH was performed or a single dose of CCl4 was administered. We first confirmed that the FGF15 adenovirus infection increased FGF15 expression in ΔIN-FXR and FXR KO mice (Fig. 6A,B). We then observed that hepatic BrdU incorporation was significantly increased in ΔIN-FXR and FXR KO mice after FGF15 adenovirus injection compared with

the control mice receiving the adenovirus alone after 70% PH at 40 h (Fig. 6C). Similar Anidulafungin (LY303366) results were also observed in a toxic CCl4-induced liver injury model (Fig. 6D; Supporting Fig. 3). BrdU incorporation was significantly increased in adenovirus FGF15 expression group comparing with the control group in ΔIN-FXR and FXR KO mice. CYP7a1 expression levels were down-regulated in the FGF15-infected mice compared to the controls in either the 70% PH model (Fig. 6E) or CCl4 model (Fig. 6F). These results indicate that FGF15 activated by intestine FXR indeed participates in promoting liver regeneration/repair. We previously showed that FXR was required for normal liver regeneration and liver repair after injury. However, the mechanism by which FXR regulates this process is still unclear. In this report we show that hepatic and intestine FXR use distinct mechanisms to promote liver regeneration/repair. Liver regeneration is regulated by many signals from the hepatic environment. Different signal pathways will lead to the activation of transcription factors that either stimulate hepatocyte proliferation or promote cell survival to promote liver regrowth.5, 20 We previously showed that FXR bound to an FXRE in Foxm1b intron 3 and induced Foxm1b gene transcription during liver regeneration.6 In FXR KO mice, this Foxm1b induction was blocked and liver regeneration was delayed.

The Asn-87 Selleck Acalabrutinib mutation seems to be an important determinant of failure of fluoroquinolone-containing triple eradication therapy

based on eradication results. “
“Background:  The eradication rate of first-line Helicobacter pylori treatment is only 70–85% and has been decreasing due to the increase in antibiotic resistance. The aim of this study was to evaluate the efficacy of bismuth-containing quadruple therapy as second-line treatment for H. pylori infection based on treatment duration. Methods:  We prospectively enrolled 227 patients that were found to have persistent H. pylori infection after first-line proton-pump inhibitor-clarithromycin-amoxicillin triple therapy. Patients were randomized to 1-week (112 patients) and 2-week (115 patients) quadruple therapy with tripotassium dicitrate buy MG-132 bismuthate 300 mg q.i.d., meteronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. and esomeprazole 20 mg b.i.d. The eradication rate, drug compliance, and adverse events were compared based on treatment duration. Results:  The eradication rates were 72/112

(64.3%, 95% CI: 0.504–0.830) and 71/92 (77.2%, 0.440–0.749) with 1-week group, and 95/115 (82.6%, 1.165–2.449) an 88/94 (93.6%, 1.213–5.113) with 2-week group by intention-to-treat therapy (p = .002) and per-protocol analysis (p = .001), respectively. The adverse events increased as the treatment durations increased from 7 to 14 days (20.0 and 42.5%, respectively, p < .001). However, there was no significant difference in the patient compliance or the rate of major adverse events between the 1- and 2-week groups (6.3 and 12.5%, respectively, p = .133). Conclusion:  Two-week bismuth-containing Adenosine triphosphate quadruple therapy was more effective than the 1-week treatment, and should be considered for second-line treatment in Korea. “
“Background: 

Long-term Helicobacter pylori infection leads to chronic gastritis, peptic ulcer, and gastric malignancies. Indigenous microflora in alimentary tract maintains a colonization barrier against pathogenic microorganisms. This study is aimed to observe the gastric and duodenum microflora alteration after H. pylori infection in Mongolian Gerbils model. Materials and Methods:  A total of 18 Mongolian gerbils were randomly divided into two groups: control group and H. pylori group that were given H. pylori NCTC J99 strain intragastrically. After 12 weeks, H. pylori colonization was identified by rapid urease tests and bacterial culture. Indigenous microorganisms in stomach and duodenum were analyzed by culture method. Histopathologic examination of gastric and duodenum mucosa was also performed. Results:  Three of eight gerbils had positive H. pylori colonization. After H. pylori infection, Enterococcus spp. and Staphylococcus aureus showed occurrences in stomach and duodenum. Lactobacillus spp. showed a down trend in stomach. The levels and localizations of Bifidobacterium spp., Bacteroides spp., and total aerobes were also modified. Bacteroides spp.

There were 3 adverse events. MWT (n = 1), one patient had a retroperitoneal perforation after pancreatoscopy (treated with laparotomy) and one had moderate pancreatitis. All patients had uneventful discharges within 48 hours. Conclusion: Cholangiopancreatoscopy has a high negative predictive value for

non-malignant lesions. There is a high concordance rate observed between macroscopic and microscopic findings in benign lesions, however significant discrepancies in malignant lesions. Cholangiopancreatoscopy was safe with low morbidity and no mortality. It is an important tool for stricture assessment and EHL therapy for difficult CBD stones. “
“The key factors in the pathogenesis of liver fibrosis are the activation and proliferation

of hepatic stellate cells (HSCs), which express integrin αvβ3 after activation. This study aimed HER2 inhibitor to explore the potential of 99mTc-labeled cyclic arginine-glycine-aspartic acid pentapeptide (cRGD) as a single photon emission computed tomography (SPECT) radiotracer to image hepatic integrin αvβ3 expression to reflect HSC activity in fibrotic livers. Rat models of liver fibrosis caused by thioacetamide Erlotinib datasheet or carbon tetrachloride (CCl4) treatment were employed to examine the expression and distribution of integrin αvβ3 during fibrotic progression or regression. The binding activity of radiolabeled cRGD to integrin αvβ3 was assessed in liver sections. SPECT was performed to determine hepatic integrin αvβ3 expression in rats with different stages of liver fibrosis. Protein and messenger RNA (mRNA) levels

of integrin αv and β3 subunits were increased with the progression of liver fibrosis and reduced with its regression. The cell type that expressed the majority of integrin αvβ3 in fibrotic livers was found to be activated HSCs. The cRGD binding to activated HSCs displayed a high receptor-coupling affinity and an abundant receptor capacity. Iodine-125 (125I)-labeled cRGD bound to fibrotic liver sections and the binding activity was the highest in advanced fibrosis. Intravenously administered carboxyfluorescein-labeled cRGD was accumulated in fibrotic liver, and the accumulation amount was increased with the progression and reduced with the regression of fibrosis. A SPECT imaging study mafosfamide with 99mTc-labeled cRGD as a tracer demonstrated that the radioactivity ratio of liver to heart increased progressively along with severity of hepatic fibrosis. Conclusion: Hepatic integrin αvβ3 expression in fibrotic liver reflects HSC activity and its imaging using 99mTc-labeled cRGD as a SPECT radiotracer may distinguish different stages of liver fibrosis in rats. (HEPATOLOGY 2011;) Liver fibrosis and its endstage cirrhosis are major world health problems arising from chronic liver injury by a variety of etiological factors, including hepatitis B, hepatitis C, alcohol, etc.1 The prognosis and management of chronic liver disease often depends on the degree of liver fibrosis.

Discuss a potential role of the brain histaminergic system in migraine. Unstructured literature

search with a no specific hypothesis-driven approach. There is substantial evidence that systemically given histamine may elicit, maintain, and aggravate headache. The mechanisms for this are not known, and histamines do not penetrate the blood–brain barrier (BBB). However, circulating histamine may influence hypothalamic activity via the circumventricular organs that lack BBB. In the rat, prolonged activation of meningeal nociceptors induced by dural mast cell degranulation has been observed. Subcutaneous injections of N-alpha-methyl histamine, a catabolite of histamine with high affinity to the histamine H3 receptor, GSK126 probably have some migraine preventive effect. A negative feedback on histamine release from mast cells in proximity to C-fiber endings has been a postulated mechanism. Most antihistamines have shown to be ineffective as acute medication for migraine. Two centrally acting potent H1 receptor antagonists (cinnarizine and cyproheptadine) have been reported to be efficacious

in preventing migraine. However, the proof for this is limited, and their efficacy has been ascribed other actions than the antihistaminergic. In general, lack of specificity and side effects limit the potential use of centrally acting H1 and H2 antagonists. Brain histamine is synthesized by neurons that are restricted to the posterior basal hypothalamus, more specific to the tuberomamillary nucleus (TMN), and that find more project practically to the whole central

nervous system. The posterior hypothalamus is a suspected locus in quo in several primary headaches. Recently, a positron emission tomography study performed in the prodromal phase of migraine attacks supported the idea of initial involvement of this area. In another recent study, the thalamic nuclei receiving trigeminal output was also shown to have direct connections with the ventral TMN. The central histaminergic system plays an important role in the complex sleep–wake cycle, promoting cortical excitability during wakening and attention, Phosphoprotein phosphatase and it consolidates the wake state. The period of the day, in the evenings and during the night, when there is reduced susceptibility for migraine attacks corresponds with less central histaminergic firing. Activation of both the H3 and the H4 receptor promotes inhibitory actions on neurons. The H3 receptor causes autoinhibition of the histaminergic neurons themselves, and centrally acting H3 receptor agonist prodrugs have shown to both inhibit neurogenic inflammation in dura, to induce sleep, and to produce antinociception. There are no registered ongoing studies on H3 and H4 receptor ligands in migraine. The role of the central histaminergic system in migraine is largely unexplored, but findings from preclinical research may be linked to several aspects of the disorder.

reported that serum PG I and II level, but not PG I/II ratio, were significantly higher in serum CagA antibody positive compared with negative children.[26] Serum PG was reported to be correlated with gastric inflammatory score.[27] In addition, the cagA status was reported to be associated with various kinds of cytokines including interleukin-8 (IL-8) and may cause severe inflammation

in the stomach.[28] It is also possible that gastritis increases Navitoclax permeability of the gastric epithelial surface, enabling back diffusion of PGs after secretion.[27] These findings suggest that serum CagA antibody titer was associated with gastric inflammation, but not atrophy. Shimoyama et al. reported that inflammation in the antrum and the corpus was more significant in serum CagA antibody positive when they examined the presence of serum CagA antibody by

immunoblot.[29] In the present study, although there were no significant differences of each histological score between serum CagA antibody positive and negative Selleckchem EPZ-6438 group, the mucosal inflammation in the corpus was significantly correlated with serum CagA antibody titer. This finding also supported that different level of antibody production from lymphocytes induced by H. pylori infection can contribute to the various serum CagA antibody level. Interestingly, positive correlation between the inflammatory score and serum CagA antibody titer was found only in the corpus but not in the antrum. Corpus dominant gastritis rather than antrum dominant gastritis was a risk factor to develop gastric ulcer and gastric cancer.[3, 30] In addition, even when only serum CagA antibody positive group was selected, serum CagA antibody titer was significantly correlated with inflammation and activity in the corpus. Therefore, antibody titer rather than the presence of antibody can be a useful marker for advanced inflammation in the stomach in Japan. This suggests that serum CagA antibody titer might be an available marker to predict Metformin manufacturer a gastric cancer in Japan. It has also been reported that measurement of serum levels of C-reactive protein (CRP) using a high-sensitivity assay (hs-CRP) can reveal

subclinical inflammatory states that may reflect vascular inflammation.[31] Recent report showed that the mean serum level of hs-CRP was significantly higher in H. pylori-positive group than H. pylori-negative group, although the level of hs-CRP was not different between CagA antibody positive and negative group in Iran.[32] It is better to examine the association between serum CagA antibody and hs-CRP in Japan in the further study. In our study, in spite of cagA positive by PCR, the prevalence of serum CagA antibody was 75.0%, which was consistent with previous studies from Japan.[17, 33] The cagA gene is located at one end of the cag pathogenicity island (PAI), an approximately 40-kbp region that is thought to have been incorporated into the H. pylori genome by horizontal transfer from an unknown source.

Conclusions: As a result of our integrative analysis using our GWAS and public eQTL data, we suggest that somatic mutations but not germ line variants of reported highly point-mutated genes may be associated with HCV-related hepatocarcinogenesis. Disclosures:

Kazuaki Chayama – Consulting: Abbvie; Grant/Research Support: Dainippon Sumitomo, Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, Toray, BMS, MSD; Speaking and Teaching: Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, KYO-RIN, Nihon Medi-Physics, BMS, Dainippon Sumitomo, MSD, selleck inhibitor ASKA, Astellas, AstraZeneca, Eisai, Olympus, GlaxoSmithKline, ZERIA, Bayer, Minophagen, JANSSEN, JIMRO, TSUMURA, Otsuka, Taiho, Nippon Kayaku, Nippon Shin-yaku, Takeda, AJINOMOTO, Meiji Seika, Toray The following people have nothing to disclose: Daiki Miki, Hidenori Ochi, C. Nelson Hayes, Atsushi Ono, Sakura Akamatsu, Yuji Urabe, Keiichi Masaki, Hiromi Abe, Tomokazu Kawaoka, Takashi Nakahara, Noriaki Seki, Eisuke Murakami, Yizhou Zhang, Takuro Uchida,

Yohji Honda, Hiromi Kan, Masataka Tsuge, Nobuhiko Hiraga, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Michiaki Kubo Background and aims Statins inhibit or delay the development of hepatocellular carcinoma (HCC), although the molecular mechanisms have not been established yet (El-Serag HB et al. Gastroenterology, AZD6244 datasheet 2009). The PI3K/AKT/mTOR pathway is frequently deregulated in cancer, and represents a suitable therapeutic target for HCC (Porta C et al. Front Oncol, 2014). The aim of this study is to evaluate the effect of commonly used statins on PI3K/AKT/MTOR pathway, using an in vitro model. Methods HepG2 and Huh7.5 cell lines were grown in supplemented DMEM culture medium and incubated at 37C, 5% CO2. Human hepatocytes were prepared from the liver biopsies obtained from patient submitted to a surgical resection of a liver tumor and hepatocyte isolation was based on the two-step collagenase procedure. Doxacurium chloride Simvastatin (1.9UM) were added 3 hours after cell seeding. Total RNA and protein were extracted at 72 hours. Gene expression was analyzed by qRT-PCR (Quantace, Bioline) and protein analysis was performed by Western-blot. Results

Statins could inhibit cell proliferation in a dose-dependent manner (S: 0.95UM, 1.9UM and 3.8UM) after 48-72 h of treatment. Huh7.5 cells treated with simvas-tatin showed a significant reduction of TCTP gene expression (1.69±0.2 fold inhibition). PI3K and mTOR protein expression were inhibited in both cell lines when treated with simvastatin (HepG2 PI3K: 2.1, MTOR: 2.30; Huh7.5 PI3K:2.38, MTOR: 5.56). Human hepatocytes treated with simvastatin had lower levels for PI3K, AKT and TCTP proteins as analyzed by western blot (PI3K: 1.57, AKT: 1.45, TCTP: 1.69 fold inhibiton). CONCLUSION Simvastatin inhibited cell proliferation through deregulation of the PI3K/AKT/MTOR pathway. Statins could be useful in the management of the hepatocellular carcinoma.