Ge et al. and Suppiah et al. studied genetic variants associated with SVR to PEG-IFN/RBV therapy in individuals infected with HCV genotype 1.17,18 McHutchison et al. found genetic factors using patients from the IDEAL trial,21 a large randomized controlled trial involving Caucasian, American-African, and Hispanic individuals

in North America (n = 1137) (Table 1). The latter study group analyzed Caucasians consisting of 293 Australians of Northern European learn more ancestry with HCV genotype 1, and also validated the results in an independent replication cohort consisting of 555 Europeans from the UK, Germany, Italy and Australia. These two study groups mainly investigated GWAS in Caucasians, and analyze host factors associated with SVR. Tanaka et al. examined 142 Japanese patients with chronic hepatitis C infected with HCV genotype 1 for GWAS, and prepared an independent replication cohort of 172 Japanese (Table 1).20 Especially, Tanaka et al. divided patients into three groups, SVR, TVR, or NVR, and NVR versus virological responder (VR) consisting of SVR and TVR was also used for the predication of NVR factors (Fig. 1). Rauch et al. investigated

465 Caucasians infected with HCV genotypes 1, 2, 3 or 4 to reveal genetic variations associated with response to the combination therapy.19 A case-control study was designed to detect genetic variations related selleckchem to SVR in European individuals. Three study groups except Suppiah et al. selected patients receiving at least 80% of the recommended treatment dose to emphasize genetic associations. Ge et al. identified a genetic see more polymorphism (rs12979860)

near the IL-28B gene on chromosome 19, encoding IFN-λ3 (IFN-λ3). Individuals with the CC genotype showed the association with an approximately twofold better response to PEG-IFN/RBV treatment compared with those with the TT genotype, both among patients of European ancestry (P = 1.06 × 10−25) and African-Americans (P = 2.06 × 10−3). Both Suppiah et al. and Tanaka et al. revealed the most significant SNPs, rs8099917 (8 kb upstream of IL-28B) associated with SVR in patients of European and Japanese. Suppiah et al. also identified the association of rs8099917 in European ancestry with HCV genotype 1 based on the determination of SVR factors (combined P = 9.25 × 10−9, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.57–2.52) (Table 1).17 The population with risk allele rs8099917 showed low levels of IL-28A/B mRNA by real-time polymerase chain reaction (PCR).17,20 Rauch et al. involved patients infected with HCV genotypes 1, 2, 3, or 4. They also identified several SNPs around the IL-28B gene on chromosome 19.19 The strongest association with treatment failure was found with rs8099917 (P = 5.47 × 10−8; OR = 5.19). Interestingly, rs8099917 did not associate with the response to PEG-IFN&RBV therapy in genotype 2 or 3 patients.

However, little is known about whether and how YAP and CREB interact with each other. In this study, we found that YAP-CREB interaction is critical for liver cancer cell survival and maintenance of transformative phenotypes, both in vitro and in vivo. Moreover, both CREB and YAP proteins are highly expressed in a subset of human liver cancer samples and are closely MDV3100 chemical structure correlated. Mechanistically, CREB promotes YAP transcriptional

output through binding to −608/−439, a novel region from the YAP promoter. By contrast, YAP promotes protein stabilization of CREB through interaction with mitogen-activated protein kinase 14 (MAPK14/p38) and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC). Rucaparib price Gain-of-function and loss-of-function studies demonstrated that phosphorylation of CREB by MAPK14/p38 at ser133 ultimately leads to its degradation. Such effects can be enhanced by BTRC through

phosphorylation of MAPK14/p38 at Thr180/Tyr182. However, YAP negatively controls phosphorylation of MAPK14/p38 through inhibition of BTRC expression. Conclusion: There is a novel positive autoregulatory feedback loop underlying the interaction between YAP and CREB in liver cancer, suggesting that YAP and CREB form a nexus to integrate the protein kinase A, Hippo/YAP, and MAPK14/p38 pathways in cancer cells and thus selleck chemicals llc may be helpful in the development of effective diagnosis and treatment strategies against liver cancer. (Hepatology 2013;53:1011–1020) Liver cancer is the fifth-most common cancer worldwide and the third-leading cause of cancer death.[1] The treatment options for these hepatic malignancies are extremely limited, mainly because the mechanisms of pathogenesis of these cancers are

not completely known. Recently, the dysfunctional Hippo/Yes-associated protein (YAP)-signaling pathway has been linked to hepatocarcinogenesis.[2] Transgenic mice with liver-targeted YAP overexpression demonstrated a dramatic increase in liver size and eventually developed tumors.[3] In addition, clinical studies revealed that YAP was overexpressed in 62% of hepatocellular carcinoma (HCC) patients and was an independent predictor associated with poor disease-free survival and overall survival in HCC.[4] In view of the vital roles that YAP plays in the development of liver cancer, it was extremely important to understand how YAP is up-regulated in tumor. Numerous studies have shown that cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) may be involved in liver cancer development. CREB is a ubiquitous transcription factor that activates the transcriptional activity of various promoters through its binding site.

However, little is known about whether and how YAP and CREB interact with each other. In this study, we found that YAP-CREB interaction is critical for liver cancer cell survival and maintenance of transformative phenotypes, both in vitro and in vivo. Moreover, both CREB and YAP proteins are highly expressed in a subset of human liver cancer samples and are closely check details correlated. Mechanistically, CREB promotes YAP transcriptional

output through binding to −608/−439, a novel region from the YAP promoter. By contrast, YAP promotes protein stabilization of CREB through interaction with mitogen-activated protein kinase 14 (MAPK14/p38) and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC). selleck Gain-of-function and loss-of-function studies demonstrated that phosphorylation of CREB by MAPK14/p38 at ser133 ultimately leads to its degradation. Such effects can be enhanced by BTRC through

phosphorylation of MAPK14/p38 at Thr180/Tyr182. However, YAP negatively controls phosphorylation of MAPK14/p38 through inhibition of BTRC expression. Conclusion: There is a novel positive autoregulatory feedback loop underlying the interaction between YAP and CREB in liver cancer, suggesting that YAP and CREB form a nexus to integrate the protein kinase A, Hippo/YAP, and MAPK14/p38 pathways in cancer cells and thus selleck compound may be helpful in the development of effective diagnosis and treatment strategies against liver cancer. (Hepatology 2013;53:1011–1020) Liver cancer is the fifth-most common cancer worldwide and the third-leading cause of cancer death.[1] The treatment options for these hepatic malignancies are extremely limited, mainly because the mechanisms of pathogenesis of these cancers are

not completely known. Recently, the dysfunctional Hippo/Yes-associated protein (YAP)-signaling pathway has been linked to hepatocarcinogenesis.[2] Transgenic mice with liver-targeted YAP overexpression demonstrated a dramatic increase in liver size and eventually developed tumors.[3] In addition, clinical studies revealed that YAP was overexpressed in 62% of hepatocellular carcinoma (HCC) patients and was an independent predictor associated with poor disease-free survival and overall survival in HCC.[4] In view of the vital roles that YAP plays in the development of liver cancer, it was extremely important to understand how YAP is up-regulated in tumor. Numerous studies have shown that cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) may be involved in liver cancer development. CREB is a ubiquitous transcription factor that activates the transcriptional activity of various promoters through its binding site.

With genotypes 4, 5, and 6 representing a substantial proportion of all HCV infections worldwide and with 4a and 6a also being poorly responsive to conventional therapy,2 it is crucial that these genotypes are considered in the future development of PIs and other antiviral therapy. Although not as potent as BILN 2061, telaprevir has been shown to be clinically effective in genotype 1-infected patients.12 In

a phase IIa clinical trial, telaprevir also demonstrated substantial activity in genotype 2-infected patients but only limited efficacy in genotypes 3- and 4-infected individuals, for whom as a result treatment was stopped.13, 14 As buy Small molecule library demonstrated by our in vitro studies, telaprevir also shows considerable differences in click here potency against different genotypes, observations that highlight again the potential value of evaluating PIs on all genotypes

before clinical assessment. We found that genotypes 1b and 6a were the most susceptible to telaprevir, followed by 2a, then 3a, and genotypes 4a and 5a being the most resistant. Based on the in vitro findings, genotype 6a- but not 4a- and 5a-infected patients might therefore be effectively treated by this antiviral in the future. However, in this specific case where relatively smaller genotype-associated differences in IC50 values for telaprevir have been found, it is necessary to investigate the extent of within-subtype variability in susceptibility and whether this might have a significant impact on clinical effectiveness. For example, in previous studies, catalytic efficiencies within a subtype were shown to vary widely (by up to 7-fold), especially within genotypes 1a and 1b.30, 31 We have shown that different isolates of genotype 3a exhibited at least 3-fold variability in IC50 values (130 nM to 310 nM) against BILN 2061, attributable to naturally occurring amino acid changes in the protease domain of NS3.16 These strain-associated differences may indeed account for the discrepancies between genotype 3 and 4 susceptibilities in the in vitro system with clinical susceptibility data.13, 14 However, the chimera model correctly reports

their much poorer response compared to genotype 1 and 2. The rapid selection of drug-resistant genetic variants is a major problem substantially limiting the effectiveness of antiviral therapy for HCV.21 Mathematical modeling selleck screening library has suggested that all possible single- and double-mutant viruses already preexist before treatment32 and can be rapidly selected at the start of antiviral therapy. Identification of potential resistance mutations within the individual genotypes towards the different PIs is crucial to preidentify individuals with preexisting resistant variants and adjust treatment options accordingly. We induced resistance mutations in vitro through passaging the intra- and intergenotypic recombinants under subinhibitory concentrations of PIs. Several new potential resistance loci were identified (Fig. 4; Tables 2, 3).

Blood tests revealed a minor elevation of aspartate aminotransferase (133 u/l) and alanine aminotransferase (103 u/l). Serum levels of various tumor markers were within the reference range and she had negative serological tests for hepatitis B and C. An abdominal computed tomography scan showed a nodular lesion in segment 3 of the liver that showed a target-like appearance with a low-attenuation rim (Figure 1). With magnetic resonance imaging (MRI), there was a drop in signal in the peripheral area of the lesion

on the opposed-phase T1-weighted image (Figure 2, left) but not on the in-phase T1-weighted image (Figure 2, right). The patient underwent a percutaneous biopsy with ultrasound control. Histological high throughput screening assay evaluation revealed macrovesicular and microvesicular RO4929097 datasheet steatosis, ballooning degeneration with Mallory bodies and perisinusoidal fibrosis consistent with focal steatohepatitis. Over recent years, there has been increasing interest in the effect of cancer therapy on the non-tumor bearing liver. These changes are more common with chemotherapy but have also been described with drugs such as tamoxifen. The most frequent change is that of a diffuse fatty liver.

However, fatty change can also be focal and may mimic a metastasis as in the above patient. These areas of focal steatosis are mostly found in segments 3 and 4. This distribution has been attributed to small areas in the liver that lack portal venous inflow. However, lack of portal venous inflow has also been used to explain areas of “fat-sparing”. After cessation of chemotherapy, diffuse fatty change is at check details least partially reversible in the majority of patients but the natural history of focal fatty change remains unclear. Images in the above patient illustrate the helpful role of CT and MRI in the differentiation of focal steatosis from liver metastases. With focal steatosis, there is a low attenuation area on unenhanced

CT while, with MRI, opposed-phase T1-weighted images show signal loss when compared with the in-phase images. In contrast, there is no signal loss with opposed-phase T1 images in patients with typical metastases. Contributed by “
“We read with great interest the article by Bruce et al. regarding the effect in a mouse model of maternal high-fat feeding on the development of nonalcoholic fatty liver disease (NAFLD) in adult offspring.1 The authors observed that maternal fat intake contributes toward the NAFLD progression in adult offspring, which is mediated through impaired hepatic mitochondrial metabolism. Although the authors reported only female mice data because their data from males and females showed the same pattern, we consider that some issues deserve further discussion.

Several evidences indicated that single nucleotide polymorphisms (SNPs) in STATs gene such as rs2293152 and rs1053004 at STAT3 and rs7574865 at STAT4 have been associated with chronic hepatitis B (CHB) induced hepatocellular carcinoma (HCC). Objective: This study aims to describe the association between these SNPs and HCC in Thai patients with CHB. Method: Study subjects were enrolled and divided into 3 groups including

CHB-re- lated HCC (n=192), CHB without HCC (n=200) and healthy controls (n=190). The rs2293152 and rs7574865 SNPs were genotyped using polymerase chain reaction – restriction fragment length polymorphism whereas the rs1053004 SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Results: Data analysis revealed that the distribution of rs2293152 and rs1053004 DAPT cell line at STAT3 and rs7574865 at STAT4 genotypes were in Hardy-Weinberg equilibrium (P > 0.05). rs2293152 SNP on STAT3 gene was not significantly associated with the risk of HCC

(P > 0.05) whereas the CC genotype of rs1053004 SNP was significantly associated with an increased risk of HCC compared with the CHB without HCC (odds ratio=1.85, 95 %confidence interval=1.00-3.43, P=0.049). In addition, the genotype of rs7574865 SNP at STAT4 (GG versus TT+GT) was significantly associated with a reduced risk of HCC AZD1208 molecular weight when compared with the healthy controls (odds ratio=1.71, 95 %confidence interval=1.13-2.59, P=0.011). Conclusion: Therefore, these findings provided important

evidence that the rs1053004 SNP at STAT3 and rs7574865 SNP at STAT4 were significantly associated with HCC risk and might be used as a novel genetic marker for HCC in Thai population. Disclosures: The following people have nothing to disclose: Nawin Chanthra, Sunchai Payungporn, Natthaya Chuaypen, Pisit Tangkijvanich Background and Aim: Hepatitis B virus (HBV) has been classified into at find more least eight genotypes, and the proportion of genotypes varies depending on region. In Japan, HBV genotype C was a most common genotype, while HBV genotype A was rare. But nowadays, the proportion of HBV genotype A is increasing in Japan. Upon infection in adults, HBV genotype A develops chronic infection more often than HBV genotype C. However, the mechanism by which such the difference occur remain unclear. In this study, we investigated the mechanism of the difference of chronicity rates in genotype A and C by using hydrodynamic injection mouse model. Methods: Immu-no-competent NOD mice, NOD-scid mice which are deficient of B and T cells on NOD mice and NOG mice which are further deficient of NK cells on NOD-scid mice, were used. Plasmid pHBA1.2 and pHBC1.2 containing an overlength (1.2-mer) copy of HBV genotype A and genotype C, respectively were transfected by hydrodynamic injection into these mice. Results: Hydrodynamic injection of pHBA1.2 and pHBC1.2 successfully transfected hepatocytes in mice leading to HBV viremia.

003; to the first defection 3.1 ± 0.7 vs. 3.6 ± 0.8 day, P = 0.01; start of ambulation time 2.6 ± 0.9 vs. 3.1 ± 1.0 day, P = 0.04; were all significantly less in patients assigned to the fast track surgery protocol compared with those in the conventional care programme. The mean hospital stay was 8.3 ± 1.3 and 9.9 ± 1.1 day for the Fast track surgery group and the conventional care group, respectively. We found no statistical difference in postoperative complications in the two groups. No readmitted cases or mortalities were reported during the follow-up

period. Conclusion: Fast-track rehabilitation was considered as a safe and feasible measures in advanced gastric cancer patients. Moreover, it results in decreased find more hospital stay. Key Word(s): 1. fast-track surgery;

2. laparoscopic gastrectomy; 3. advanced gastric cancer Presenting Author: OSAMA ELGEMAABI Additional Authors: OMAYMA M SABIR, AHMED B ALI Corresponding Author: OSAMA ELGEMAABI Affiliations: Al Neelain University, Al Neelain University Objective: The blind liver biopsy technique has been widely used in Sudan as the availability of the ultra sound machines and the committed Pediatrics Radiologist were not always at hands. Liver biopsy is an essential tool in the diagnosis Idasanutlin cost of liver diseases and subsequently, initiating the appropriate treatment. The aim of the

study was to observe the safety of blind liver biopsy in our children. Methods: One hundred fifteen consecutive liver biopsies in hospitalized children were evaluated retrospectively. Using a standard percussion technique biopsy sites were chosen and selleckchem through intercostals space blind liver biopsies were performed by TruCut biopsy needle. The study was conducted at Gafaar Ibn Oaf Specialized Children Hospital, Khartoum Sudan, over the last five years, between January 2005-January 2010. Results: The first biopsy sample was considered macroscopically adequate in 94.8% of cases. A definitive histological diagnosis was possible in 99.1% of cases. seventy children were more than 5 years of age and of these 8 (11.4%) complained of pain at the biopsy site, External hemorrhage from the biopsy site was seen in 1 (0.6%) case but no sign of internal hemorrhage was detected during the 24 hours follow up period. No child died following the procedure. Conclusion: Blind liver biopsy in the studied hospitalized children was found to be a safe procedure. Key Word(s): 1. blind liver biopsy; 2.

Results:  The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109–142) and 16.2 (range: 6–38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6–51) and the area under the receiver–operator

curve of that (c-statistics: 0.867) was higher than MELD score Adriamycin and sodium concentration (c-statistics: 0.820 and

0.842, respectively). Conclusion:  Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT. “
“The aim of this study was to examine the distribution of interferon lambda-3 www.selleckchem.com/products/PD-0332991.html (IFN-λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-λ3 genotype frequency among the different ethnic populations. This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN-λ3 single nucleotide polymorphisms

were genotyped by the Applied Biosystems’s Taqman single nucleotide polymorphism genotyping assay. Between May 2012 and June 2012, selleck 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high-dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN-λ3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN-λ3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN-λ3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001). The distribution of IFN-λ3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America.

In all cases informed consent was obtained from the patients or their relatives before the procedure. All procedures were performed under our institutional mild sedation protocol. Using a transfemoral approach, an 8-Fr balloon guide catheter was placed in the ICA and an angiogram was performed to locate the occluding

clot. A heparinized saline solution was continuously perfused through the catheter during the procedure. When the carotid siphon and terminal ICA appeared very tortuous a 4.3F or 3.9F catheter (Concentric DAC) could be advanced through the guiding catheter to increase system stability. With the balloon of the guide catheter deflated, a .014-inch guide wire (Transend) and microcatheter .018 inch (Rebar) were Decitabine advanced (through the guiding catheter or the DAC catheter when used) within the occluded intracranial vessel passing through the clot. Once the distal end of the microcatheter was positioned

a few millimeters beyond the distal aspect of the clot the guide wire was exchanged by the TR embolectomy device. The TR device was held in place when 3 mm were out of the microcatheter. Then the microcatheter was slowly pulled back in order to deploy the TR device over the clot. At that point a contrast injection through the balloon-guiding catheter could show contrast filling of some distal branches previously occluded. The stent was kept deployed for 1 or 2 minutes to allow the clot to be embedded PI3K inhibitor in the stent mesh. Then, the guiding catheter balloon was inflated to occlude the ICA proximal to the clot. The microcatheter and the embolectomy TR device were gently withdrawn through the guide catheter under selleck inhibitor continuous proximal aspiration with a 50 cc syringe to create a reverse flow. If recanalization did not occur the procedure could be repeated up to 6 passes. The procedure was terminated when recanalization was achieved or according to the treating physician criteria (usually 8 hours after symptom onset). A final control angiogram was performed to confirm recanalization and reperfusion. After successful recanalization of the proximal occlusion, if distal occlusion in M2-M3 branches

was observed intra-arterial (IA) tPA could be used as adjuvant therapy to complete recanalization. Vascular recanalization was defined as TICI grade 2a, 2b, or 3.9 Established device-related complications namely: vascular perforation, arterial dissection, or embolization, were systematically collected. Symptomatic intracranial hemorrhage was defined as hemorrhagic transformation on the 24-hour CT scan that was related to deterioration in the patient’s clinical condition in the judgment of the clinical investigator.10 Dramatic clinical improvement was defined as a ≥ 10 points decrease in the NIHSS at 24 hours.11 Functional outcome was assessed by modified Rankin Scale (mRS) at 3 months. Functional independence was defined as mRS score ≤ 2 at 3 months. In-hospital mortality was recorded.

31 The developing tumors were observed over the next 5 to 6 weeks, and the mice were then sacrificed at the end of follow-up. All animal studies were approved by the Institutional Animal and Committee at the National Defense

Medical Center. Details regarding generation of plasmid constructs, stably or inductively expressing SOX1 clones, cell proliferation, invasion, colony formation, glutathione selleckchem S-transferase pull-down, co-immunoprecipitation, immunocytochemistry and senescence-associated β-galactosidase staining, and statistical analysis are provided in the Supporting Information. AIG, anchorage-independent growth; DOX, doxycycline; GST, glutathione S-transferase; HCC, hepatocellular carcinoma; LEF, lymphocyte-enhanced factor; NOD/SCID, nonobese diabetic/severe combined immunodeficiency; QMS-PCR, quantitative methylation-specific polymerase chain reaction; RT-PCR, reverse-transcription polymerase

chain reaction; SOX, SRY (sex determining IWR1 region Y)-box; TCF, T cell factor; TLCN, Taiwan Liver Cancer Network. First, we examined the messenger RNA (mRNA) and protein expression of SOX1 in eight HCC cell lines. SOX1 transcript and protein was undetectable in 100% of the HCC cell lines, but was expressed in normal liver tissue (Fig. 1A). We then checked the mRNA level of 60 primary HCCs and their corresponding adjacent nontumor tissues using quantitative RT-PCR and found that SOX1 mRNA expression was significantly downregulated

in primary HCCs compared with the adjacent nontumor tissues (P < 0.01) (Fig. 1B). There was no significant correlation between SOX1 mRNA expression and clinical characteristics (Supporting Table 2). Based on our previous data, promoter hypermethylation of SOX1 might contribute to downregulation of SOX1 in HCC. Next, we checked the methylation status of the HCC cell lines and clinical HCC tissues by QMS-PCR. Hypermethylation was confirmed in the HCC cell lines (HepG2, Hep3B, Huh7, SK-Hep-1, HA22T, Mahlauv, and Tong) and HCC tissues, which showed downregulated or silenced SOX1 expression, whereas methylation was not found in the nontumor liver tissues (P < 0.01) (Fig. 1C,D). The methylation status in the SOX1 promoter region was then validated by bisulfite sequencing. The selleck chemicals llc bisulfite sequencing results were consistent with QMS-PCR (data not shown). To validate whether promoter methylation is involved in the regulation of SOX1, three HCC cell lines (HepG2, Hep3B, and TONG) with silenced SOX1 expression were treated with 5-AZA-2′-deoxycytidine (5-Aza-CdR) combined with or without trichostatin A. The data showed the decreased methylation status of SOX1 and re-expression of SOX1 mRNA in all cell lines examined (Fig. 1E), further implying that the transcriptional silencing of SOX1 was mediated by promoter methylation and/or histone modification.