[24] These results suggested that hepatic iron content was not related to greater ROS production in OVX transgenic mice than in OVX non-transgenic

mice. The increase in inflammatory cytokine production and the hepatic iron content after ovariectomy were comparable in transgenic and non-transgenic mice. Nevertheless, the serum ALT level, hepatic steatosis and ROS production were greater in OVX transgenic mice than in OVX non-transgenic mice. Therefore we measured dROM and BAP in serum to compare antioxidant potentials in OVX transgenic and OVX non-transgenic DNA Damage inhibitor mice. We confirmed the significant negative correlation between the ratio of BAP to dROM and hepatic content of superoxide (Fig. 5). As expected, the values for

dROM were higher in OVX mice than in sham-operated mice, regardless of whether they were transgenic or non-transgenic. However, Selleck Raf inhibitor a significant increase in the BAP value was found in OVX non-transgenic mice but not in OVX transgenic mice, which resulted in a lower ratio of BAP to dROM in the OVX transgenic mice than in the OVX non-transgenic mice (Table 2). The first line of defense against ROS is the detoxifying enzymes that scavenge ROS. These include SOD and GPx1. Therefore we next investigated the expression levels of SOD2 and GPx1. The hepatic expression levels of SOD2 mRNA and GPx1 mRNA were significantly greater in OVX non-transgenic mice than in sham-operated non-transgenic mice, but

were comparable in OVX transgenic mice and sham-operated transgenic mice (Fig. 6a). Western blot analysis of the hepatic mitochondria fractions also showed significant increases of SOD2 and GPx1 expression in OVX non-transgenic mice but not in OVX transgenic mice (Fig. 6b). These results suggested that antioxidant defense mechanisms may be induced against ovariectomy-related ROS production in non-transgenic mice but not in transgenic mice. Proliferator-activated receptor-γ co-activator-1α is a master regulator of mitochondrial biogenesis medchemexpress and respiration[25] and required for the induction of many ROS-detoxifying enzymes, including SOD2 and GPx1 upon oxidative stress.[26] SIRT3 is a member of a class III histone deacetylase and is reported to mediate PGC-1α-dependent induction of ROS-detoxifying enzymes.[27] In accordance with the changes in SOD2 and GPx1 levels after ovariectomy, the hepatic expression of SIRT3 mRNA was significantly greater in OVX non-transgenic mice than in sham-operated non-transgenic mice, but comparable in OVX transgenic mice and sham-operated transgenic mice (Fig. 7a). Western blot analysis of hepatic mitochondria showed a significant increase of SIRT3 expression in OVX non-transgenic mice but not in OVX transgenic mice (Fig. 7a).

We found some anticipated themes and some unexpected ones, confirming that true perspective can only be provided by the patients themselves. Knowledge of these important themes has informed the development of new programmes aimed at this growing segment of the patient population. “
“Over 25 years of follow-up is now available for HIV-infected haemophilia

patients. The aim of this study was to retrospectively asses the morbidity and mortality of HIV infection and the effects of HAART in these patients. Data on HIV infection, its treatment and all types of comorbidity were collected from medical records of all 60 HIV-positive haemophilia patients who were treated

at the Van Creveldkliniek since 1980 and compared with data from 152 HIV-negative patients with severe haemophilia and the general age-matched male selleck kinase inhibitor population. AIDS developed in 27 patients (45%), while 31 patients died (52%). Death was solely or partially AIDS-related in 71%. Development of AIDS and AIDS-related deaths declined strongly after the introduction of HAART. Only one major ischaemic cardiovascular event occurred in our study population. Of the 27 patients who were still treated at our clinic in 2010, 25 (93%) were on HAART. They had more often hypertension and diabetes, but less often overweight and obesity and lower cholesterol levels Cell Cycle inhibitor than the general population. The occurrence of spontaneous intracranial bleeding was higher in HIV-positive haemophilia patients on HAART than in HIV-negative patients with severe haemophilia (16.6 vs. 1.2 per 1000 patient years). Since the introduction of HAART, the impact of HIV infection medchemexpress on morbidity and survival has decreased. The increased prevalences of hypertension and diabetes, however, warrant regular screening. HIV-positive haemophilia

patients on HAART appear to have an increased risk of spontaneous intracranial bleeding. Infection with HIV (human immunodeficiency virus) was an important and often devastating complication of haemophilia treatment in the 1980s. Fortunately, since 1985, all clotting-factor products have been free of HIV. Of 335 Dutch haemophilia patients known at our haemophilia centre in 1995 who were at risk for HIV infection, 53 (15.8%) were actually infected [1]. Before the introduction of highly active antiretroviral therapy (HAART) in 1996, many of these patients died. HAART, today also called combined antiretroviral therapy (CART), nowadays consists of a combination of nucleoside reverse transcriptase inhibitors, protease inhibitors and/or non-nucleoside reverse transcriptase inhibitors. Because of HAART, life expectancy of HIV-positive patients has improved dramatically, and HIV-related complications have become rare.

When outcomes were evaluated beyond 40 years of follow-up, vaccination in infancy was the most cost-effective strategy,

with a cost per quality-adjusted life year of $17,684 at 50 years of follow-up. Even in the worst-case scenario, where vaccine efficacy was limited to 20% and highest costs were assumed, the cost per quality-adjusted life year remained less than $50,000. This suggests that prevention of H. pylori infection, via vaccination, would be a cost-effective strategy in the United States. These analyses did not take into account any potential savings occurring as a result of a reduction in the burden of other H. pylori-related diseases, such as duodenal ulcer, dyspepsia, and gastric lymphoma. Another modeling study identified by our search selleck compound estimated future trends in gastric cancer incidence in China and assessed the potential BIBW2992 impact of interventions to prevent or treat the infection, as well as the falling prevalence in H. pylori infection on this [33]. The authors reported that universal treatment of H. pylori may reduce the incidence of gastric cancer by 33%, while vaccination in childhood would lead to a 42% reduction. Despite a declining prevalence of infection overall, however, it was

estimated that the total number of cases of gastric cancer among men would nearly double between the years 2005 and 2050 owing to changing population demographics. These data suggest that although the prevalence of H. pylori

infection is falling, even in regions at high risk of gastric cancer, prevention strategies are still required in the medium- to long-term to reduce the number of cases of gastric cancer. MCE As yet, no country has adopted these. We conclude that in spite of the relatively large number of articles published on the epidemiology of H. pylori and the public health measures that might be desirable to control the infection, little has been added to our current understanding of the subject during the past year. Much that was known before has been confirmed. The risk factors for developing the infection are similar in most of the studies and are in concordance with previous data. The mode of transmission of H. pylori remains unknown, and this limits the opportunity to develop effective primary intervention. More depressingly, in spite of the projected increase in the incidence of gastric cancer, already the second commonest cause of cancer death world wide and the knowledge (for over two decades) that H. pylori is the underlying carcinogen, no public health measures have yet been instituted to treat infected individuals in the populations at risk. The authors declare no conflicts of interest. “
“Manfredi et al.

Defect or deficiency in FVIII causes haemophilia A, a severe hereditary bleeding disorder. PARP inhibitor Intravenous administration of plasma-derived FVIII or recombinant FVIII

concentrates restores normal coagulation in haemophilia A patients and is used as an effective therapy. In this work, we studied the biophysical properties of clinically potent recombinant FVIII forms: human FVIII full-length (FVIII-FL), human FVIII B-domain deleted (FVIII-BDD) and porcine FVIII-BDD bound to negatively charged phospholipid vesicles at near-physiological conditions. We used cryo-electron microscopy (Cryo-EM) as a direct method to evaluate the homogeneity and micro-organization of the protein-vesicle suspensions, which are important for FVIII therapeutic properties. Applying concurrent Cryo-EM, circular dichroism and dynamic light scattering studies to the three recombinant FVIII PD0325901 clinical trial forms when bound to phospholipid vesicles revealed novel properties for their functional, membrane-bound state. The three FVIII constructs have similar activity, secondary structure distribution and bind specifically to negatively charged phospholipid membranes. Human and porcine FVIII-BDD induce strong aggregation of the vesicles, but the human FVIII-FL form does not. The proposed methodology is effective in characterizing and identifying

differences in therapeutic recombinant FVIII membrane-bound forms near physiological conditions, because protein-containing aggregates are considered to be a factor in increasing the immunogenicity of protein therapeutics. This will provide better characterization and development of safer and more effective FVIII products with implications for haemophilia A treatment. “
“Summary.  Inhibitors of factor VIII (FVIII) have been studied for more than 50 years, but diagnostic MCE and therapeutic challenges remain. To describe the features that distinguish alloantibodies from autoantibodies, list predisposing factors, and review methods for tolerance induction and autoantibody suppression. Review of key articles published during the past half-century that have advanced knowledge in this field. Alloantibodies generally bind to the A2

or C2 domains of FVIII and disrupt the formation of the FVIII–FIX complex. They exhibit type 1 reaction kinetics, are saturable by FVIII, and display anamnesis. In contrast, autoantibodies usually bind to the C2 domain of FVIII, interfering with phospholipid and von Willebrand factor binding. They have type-2 kinetics and are poorly neutralized by FVIII. Repeated exposures to FVIII induce tolerance in 70–80% of haemophiliacs with inhibitors, whereas drugs that deplete B-lymphocytes restore self-tolerance to FVIII in a similar percentage of non-haemophiliacs. Future work should focus on improving assays that detect and quantify inhibitors, examining the pathophysiology of inhibitor formation using contemporary immunologic tools, and investigating new treatment modalities.

5E). Differential gene expression was examined using microarray. Supporting Fig. S5 shows the heat map generated from the microarray data demonstrating the NVP-BGJ398 in vivo striking difference in gene expression between KO and controls. Note the controls were very similar regardless of age. Microarray analysis (25,000 genes) revealed that 402 genes were up-regulated and 182 genes were down-regulated (fold-change > 2.0; P < 0.05) (see Supporting Tables 2 and 3 for complete list). Quantitative real-time PCR confirmed these changes in more than 15 genes (Table 2). Many of the genes differentially

expressed in Phb1 KO mice liver are involved in growth such as H19, CDC20, PRC1, IGF2B, cyclin D1 (CCND1), EGFR1, RASAL1, and SRC (Table 2). Several genes involved in fibrogenesis are also markedly up-regulated, including many collagen genes and tissue inhibitor of metalloproteinase 1 (TIMP1). Interestingly, 3-deazaneplanocin A cost many enzymes are markedly down-regulated, including several

cytochrome P450 (CYP450) family members and uridine diphosphoglucuronate (UDP) glycosyltransferase (Table 2). Genes differentially expressed fall into many different pathways including angiogenesis, cytoskeletal regulation, signaling pathways involved in epidermal growth factor receptor, heterotrimeric G-protein, inflammation, integrin, interleukin, p53, phosphoinositide 3-kinase (PI3K), platelet-derived growth factor (PDGF), Ras, and vascular endothelial growth factor (VEGF). Supporting Tables S6 to S19 describe changes in mRNA level based on different signaling pathways and biological functions. PHB1 subcellular localization in hepatocytes has not been examined. Using confocal microscopy, Supporting Fig. 6A shows that the bulk of PHB1 is 上海皓元 localized in the mitochondria but there is also staining in the nuclei of normal mouse hepatocytes. PHB1 staining is diminished in both compartments in the hepatocytes isolated from the KO mouse (Supporting Fig. 6B). Both mitochondrial and nuclear staining can also be seen in AML12 cells

(Supporting Fig. 6C). To better assess whether the changes observed in the KO mice are due to direct or indirect effects (compensatory proliferation in response to injury) of PHB1 deficiency, we employed acute knockdown with siRNA against Phb1 in nontransformed AML12 cells. After 18 hours of siRNA treatment, the efficiency of PHB1 knockdown is about 90% (Fig. 6A) at the mRNA level whereas PHB1 protein level fell by only 30% (Fig. 6B). After 18 hours of siRNA treatment, a number of the genes picked up on in vivo microarray analysis also exhibited a similar change, but with much smaller magnitude, for instance, cyclin D1 (CCND1) was increased 64% instead of four-fold. Some of the genes exhibited similar magnitude of change as in the in vivo microarray, such as KRT18, which increased by 69% and p53, which increased by 48%.

Both compounds improved histological parameters of liver cell death (a 60% decrease in the number of bile infarcts per 10 high power field). Serum ALT decreased by 80% and 66% for TDZD and CPT-2Me-cAMP treated mice, respectively. Biochemical indicators of cell death (caspase 3 cleavage

and JNK phosphorylation), and ER stress, (IRE1 and eIF2alpha Ivacaftor nmr phosphorylation and CHOP expression) were also significantly attenuated by both TDZD and CPT-2-Me-cAMP treatment. Collectively, these results suggest that GSK inhibition and EPAC activation mediate cytoprotective effects in cholestatic liver disease in vivo. Disclosures: The following people have nothing to disclose: Cynthia Leveille-Webster, Andrea Johnston, Mohammed S. Anwer Background & Aims: Acute liver failure (ALF) is characterized by severe hepatocyte death and impaired liver regeneration. Acetaminophen (APAP) overdose is a leading cause of ALF in Western countries. In APAP hepatotoxicity, it has been shown that mitochondrial dysfunction buy Deforolimus is critical and that mitochondrial translocation of a stress MAP kinase, JNK is associated with this process. We previously demonstrated that Grb2-associated

binder 1 (Gab1) adaptor protein transmits mitogenic signals via a MAP kinase, ERK in vitro and in vivo. However, the role of Gab1 in hepatocyte death during APAP-induced ALF has remained unclear. Here, we investigated the role of Gab1 in this process. Method: Hepatocyte specific Gab1 knock-out (KO) and wild-type (WT) mice were intraperitoneally injected with APAP (250 mg/kg bw) to induce ALF. Results: KO mice showed significantly higher mortality rate compared with WT mice at 72 hours after APAP treatment (75%

in KO n=12 vs. 25% in WT n=12, p<0.05). This increased mortality in KO mice was associated with elevated serum ALT levels (p<0.05), increased TUNEL positive hepatocytes (p<0.05), and severe centrilobular liver necrosis (p<0.01) at 6 hours after APAP treatment. KO mice also showed a 2.4-fold increase in serum 上海皓元医药股份有限公司 levels of high mobility group box 1 (HMGB-1) (p<0.01), a danger signaling molecule, indicating higher degree of hepatocyte necrosis in KO mice. To clarify the mechanisms of enhanced hepatocyte necrosis in KO mice, we next examined whether loss of Gab1 affected the mitochondrial function during APAP-induced ALF. At 1.5 hours after APAP treatment, KO mice showed enhanced mitochondrial translocation of JNK compared with WT mice, accompanied by increased release of mitochondrial enzymes such as Apoptosis-inducing factor and Endonuclease G into the cytosol. These data suggested that loss of Gab1 might cause hepatocyte necrosis through mitochondrial dysfunction and subsequent nuclear DNA fragmentation. Finally, we examined compensatory proliferation in hepatocytes surrounding necrotic areas after APAP treatment. Ki67 stating demonstrated that KO mice had a 2-fold decrease (p<0.05) in the number of proliferating hepatocytes.

Studies were excluded if DDAVP was used for treatment of OSI-906 manufacturer diabetes insipidus or in nonpregnant women. From the studies that met the selection criteria, the following information was extracted and tabulated: the author

and year of publication, underlying bleeding disorder, indication and stage of pregnancy at which treatment with DDAVP was initiated, dose of DDAVP and any other treatment given, clinical and relevant laboratory haemostatic values, mode of delivery, maternal side effects and neonatal outcome. Two reviewers (IS and PP) independently extracted data from the included articles. Evaluation of eligibility for inclusion of the extracted articles was performed by a third reviewer (RK). Using the search criteria above, 30 studies were found eligible for inclusion in this review. The main clinical characteristics

of these are summarized in Tables 1–3. There were a total of 216 pregnancies included in these studies: eight prospective studies with a total of 111 pregnancies (Table 1) [7–14] and six retrospective studies with a total of 85 pregnancies (Table 2) [15–20]. The most common study design case report, which accounted for 16 of the studies and 20 of the total pregnancies (Table 3) [3,5,21–34]. The most common bleeding disorder reported by these studies was ICG-001 order VWD with 168 pregnancies followed by carriers of haemophilia A with 31 pregnancies reported. DDAVP was used in 12 pregnancies with disorders of platelet function including 上海皓元医药股份有限公司 Bernard–Soulier syndrome (three pregnancies), Hermansky–Pudlak Syndrome (four pregnancies), storage pool disorder (three pregnancies) and unspecified functional platelet disorders (two pregnancies). Other disorders with reported DDAVP use were acquired factor VIII inhibitors (three pregnancies) and Ehlers–Danlos

syndrome (two pregnancies). Dosing regimes for DDAVP were mostly based on patient weight with an intravenous infusion of 0.3 μg kg−1 DDAVP being the most commonly used (166 cases). Other intravenous dosing regimes were 0.4 μg kg−1 (five cases), 0.2 μg kg−1 (one case), 12 μg (one case) and 20 μg (one case). Intranasal DDAVP was used in two studies (33 cases) at a dose of 300 μg and in nine cases the dose of DDAVP was not recorded. Desmopressin was used during the first and early second trimester in 51 pregnancies. DDAVP was reported for prevention of bleeding prior to invasive procedures including chorionic villus sampling (20 cases), amniocentesis (12 cases), cervical cerclage (four cases) and termination of pregnancy (14 cases) [8,15,24]. All these procedures had successful outcomes without significant complication or bleeding. DDAVP was also used as treatment for bleeding complications in one case of first trimester retroplacental haematoma [15]. There were no reported neonatal complications reported in those pregnancies that were carried to term. Maternal side effects associated with DDAVP were recorded in one study and were generally mild and included facial flushing and headache [8].

Marcin Krawczyk M.D.*, Monica Acalovschi M.D.†, Frank Lammert M.D.*, * Department of Medicine II, Saarland University Medical Center, Hamburg, Germany, † Department of selleck kinase inhibitor Medicine III, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. “
“We read with great interest the article by O’Shea et al. in the January issue of HEPATOLOGY, regarding the American Association for the Study of Liver

Diseases (AASLD) Practice Guidelines on alcoholic liver disease.1 The article is well written and informative. However, we would like to bring some points to your kind attention which may be of interest to the physicians, gastroenterologists, and hepatologists. In Table 2, the authors described how to calculate the quantity of alcohol in a standard drink. This is an important piece of information when taking a history NVP-BGJ398 of alcohol intake from the patients. However, what constitutes one drink should also be described as patients describe their history of alcohol intake as the amount (in milliliters) of wine, beer, or hard liquor. It is defined that 12 ounces of beer (360

mL), 4 ounces of wine (120 mL), and 1.5 ounces of hard liquor (45 mL) constitutes one drink.2 Antioxidants have been used in the treatment of alcoholic liver disease, based on data from animal models as well as in patients with alcoholic liver disease.3, 4 The authors did discuss the current status of vitamin E supplementation. However, another powerful antioxidant, N-acetylcysteine (NAC), has been studied. A randomized controlled study reported in abstract form at the AASLD 2009 meeting showed benefit of NAC in the treatment of severe

acute alcoholic hepatitis (AH). Patients with AH treated with a combination of steroids and NAC (n = 85) compared to patients with AH treated with steroids alone (n = 89) had a lower mortality at month 2 (15% versus 33%; P = 0.007) and lower complication rate at month 6 (19% versus 42%; P = 0.001).5 If these results are confirmed in subsequent studies from other centers, a combination of steroids and NAC may be a potential option to improve 上海皓元医药股份有限公司 the outcome of patients with severe AH. While discussing the role of liver transplantation (LT) in AH, the authors did point out the requirement of 6 months of abstinence from alcohol to be eligible for LT. However, in an acute setting such as AH, this may not be possible and 30%-40% of patients with nonresponse to steroids (Lille score ≥0.45) succumb to their illness.6 Louvet et al., in a case-control study reported at the AASLD 2009 meeting in patients with nonresponse to steroids at 1 week showed improved survival at 6 months after LT (n = 18) as compared to matched controls (n = 18) (83% ± 9% versus 44% ± 12%; P = 0.009).

Despite best efforts with medical and dietary therapy, hepatocellular cancer Angiogenesis inhibitor may still occur and hence regular surveillance with AFP and liver imaging is recommended.[286, 287] 64. Initial treatment of hereditary tyrosinemia type 1 is with NTBC when the diagnosis is established. (1-A) 65. Referral for LT evaluation should occur promptly if the child has progressive liver disease despite an adequate dose of and compliance with NTBC, rising AFP while on NTBC, a change in liver imaging with a single nodule exceeding 10 mm or an increase in the number or size of hepatic nodules, or if management with NTBC and diet cannot be adequately maintained. (1-B) There are now 11 glycogen storages

diseases (GSD) described and most have many subtypes.[288] GSDs can

have hepatic, muscular, cardiac, neurological, immunological, or mixed presentations that are increasingly identified within each class of GSD with the help of advancing metabolic and genetic techniques. The degree to which extrahepatic manifestations of GSD are evident will vary with each patient as enzymes necessary for glycogen metabolism are found in many tissues. Among the family of GSDs, LT has been performed predominantly in patients with GSD I, III, and IV.[289] Glycogen storage disease type I (GSDI) is comprised of two major subtypes[290]: GSD type Ia (glucose-6-phosphatase deficiency) and GSD 1b (glucose-6-phosphate translocase deficiency) click here that affect the liver, kidney, and intestinal mucosa causing excessive accumulation of glycogen and fat in these organs. With good metabolic control, clinical manifestations such as growth retardation, hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, and hyperlipidemia can

be managed. Nephrocalcinosis, glomerular hyperfiltration, proteinuria, and endstage renal disease can occur. Hepatic adenomas (HA) are common and the prevalence of HCC increases with age reaching an estimated 50%-80% by the third decade of life.[291] Histology is the only sure way to differentiate MCE公司 HA from HCC, but may not be possible when numerous HAs are present. GSD type Ib has additional features that include neutropenia and impaired neutrophil function, resulting in recurrent bacterial infections and oral and intestinal mucosa ulceration that resembles inflammatory bowel disease, particularly Crohn’s disease. The majority of patients with GSD III (debranching deficiency) have a disease that is generalized (type IIIa, 80% of cases) to involve liver, muscle, cardiac muscle, erythrocytes, and fibroblasts and a minority having disease that is restricted to the liver (Type IIIb).[292] The presence of fibrosis, ranging from minimal to cirrhosis, occurs in GSD III but not GSD I. Aminotransferase elevations can be marked in childhood,[293] but become less apparent with time. Despite the presence of fibrosis or cirrhosis, synthetic function is typically preserved.

3D). There was also a significant drop

in levels of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by at least 10% and 30%, respectively, in the C/EBPα-saRNA-dendrimer-treated group when compared to both control groups (Fig. 3E,F). Histological examination of the liver showed a significant reduction in tumor nodules from C/EBPα-saRNA-dendrimer-injected rats when compared to both control groups (Fig. 4A,B). These results were consistent with immunohistology studies of tissue sections from C/EBPα-saRNA-treated rat liver stained for placenta-form of glutathione S-transferase (GST-p). Independent conclusions by two pathologists suggested that there was evidence of reduced carcinogenesis by treatment of C/EBPα-saRNA-dendrimer when compared to the PBS control or scramble-saRNA-dendrimer learn more control groups. Furthermore, there were no differences in liver fibrosis between the PBS control,

scramble-saRNA-dendrimer, or C/EBPα-saRNA-dendrimer-treated groups (Fig. 4C). The average density of positive staining for GST-p from control groups was 70 (±5.0%), and that from C/EBPα-saRNA-dendrimer injected rats was 32 (±6.5%). Since overexpression of GST-p is observed during rat liver preneoplastic state and neoplastic transformation,[28, 29] these data suggest that C/EBPα-saRNA-dendrimer treatment may reduce this process. Total RNA extracted PF-02341066 research buy from liver biopsies of seven animals medchemexpress from each group were screened for transcript levels of albumin (Fig. 5A), C/EBPα (Fig. 5B), hepatocyte nuclear factor 4-alpha (HNF4α) (Fig. 5C), and hepatocyte nuclear factor 1-alpha (HNF1α) (Fig. 5D). A significant

increase in mRNA level was observed for all the factors, consistent with the role of HNF4α in hepatocyte differentiation together with C/EBPα and HNF1α in promoting expression of albumin. Taken together, lower mRNA levels of hepatocyte growth factor (HGF) (Fig. 5E) and increased levels of 4-hydroxyphenylpyruvic acid dioxygenase (HPD1) (Fig. 5F) and plasminogen (Fig. 5G) are suggestive of improved liver function in these cirrhotic rats treated with C/EBPα-saRNA-dendrimer.[30] To investigate other liver-specific factors that might be affected in response to C/EBPα-saRNA;, we analyzed the gene expression profile of a panel of 84 liver cancer-specific genes (Qiagen/SABiosciences Human Liver Cancer RT2 Profiler) in C/EBPα-saRNA-transfected HepG2 cells (Fig. 6). Of particular interest was the observed up-regulation of 20 genes (Supporting Table 1), 18 of which are known tumor suppressor genes in HCC (Supporting Table 3) including RB. The most significantly up-regulated (over-3 fold) included the death agonist gene BH3-interacting domain (BID), and tumor protein 53 gene (TP53), encoding p53.