capsici resulted in the purification of a phytotoxic protein frac

capsici resulted in the purification of a phytotoxic protein fraction designated as p47f, capable of inducing wilting and necrosis on leaves of Capsicum chinense Jacq, and having a 47 kDa polypeptide with proteolytic activity as

the major component. The isolated p47f fraction induced DNA degradation and decreased cell survival of C. chinense cell suspension culture. Sequencing of p47f indicated the presence of 15 proteins, which could be grouped into seven classes including a protease group, cell wall remodelling proteins and the transglutaminase elicitor M81D, among others. This is the first report of P. capsici secreting proteins that modulate cell responses mediated by ROS in the host. “
“The effect of seed-borne pathogens of wheat and barley on crown and root rot diseases of seven barley cultivars (Jimah-6, Jimah-51, Jimah-54, Jimah-58, Omani, Beecher and Duraqi) and three wheat cultivars (Cooley, Maissani and Shawarir) BTK inhibitor was investigated. Bipolaris sorokiniana and Alternaria alternata were detected in seeds of at least eight cultivars, but Fusarium species in seeds of only two barley cultivars (Jimah-54 and Jimah-58). Crown rot and root rot symptoms developed on barley BYL719 ic50 and wheat cultivars following germination of infected seeds in sterilized growing media. Bipolaris sorokiniana was the only pathogen consistently isolated from crowns and roots of the emerging seedlings. In

addition, crown rot and root rot diseases of non-inoculated barley cultivars correlated significantly with B. sorokiniana inoculum in seeds (P = 0.0019), but not with Fusarium or Alternaria (P > 0.05). These results indicate the role of seed-borne inoculum of B. sorokiniana in development of crown rot and root rot diseases. Pathogenicity tests of B. sorokiniana isolates confirmed its role in inducing crown rot and root rot, with two wheat cultivars being more resistant to crown and root rots than most barley

cultivars (P < 0.05). Barley cultivars also exhibited significant differences in resistance to crown rot (P < 0.05). In addition, black point Unoprostone disease symptoms were observed on seeds of three barley cultivars and were found to significantly affect seed germination and growth of some of these cultivars. This study confirms the role of seed-borne inoculum of B. sorokiniana in crown and root rots of wheat and barley and is the first report in Oman of the association of B. sorokiniana with black point disease of barley. “
“The infection of wheat spikelets by Bipolaris sorokiniana, the causal agent of black point on grains and grain shrivelling, was examined by light and electron microscopy. Conidia of the pathogen germinated 6–12 h after inoculation on the surfaces of the different spike tissues. Extracellular sheaths were observed on germ tubes and appressoria attached to the surfaces of lemma, palea and seeds, but were only scarcely detected on the surface of conidia.

In diseased liver specimens, hepatocellular staining was also mem

In diseased liver specimens, hepatocellular staining was also membranous, whereas staining of the intermediate cells of the ductular reactions ranged from cytoplasmic to membranous, depending on the degree of hepatocellular differentiation. We compared staining using all three immunohistochemistry methods, by circulating sequential slides from all three

institutions to each institution. Circulated slides included normal Selleck Kinase Inhibitor Library controls, early stage CHC, and CHB cirrhosis. Neither the institutional staining investigators (R. K., P. H., Y. N. P.) nor the central coordinating pathologist (N. D. T.) noted any differences in staining intensity or pattern of localization, emphasizing the ease and reliability of staining for

this antigen with diverse clones, methods of antigen retrieval, and detection procedures (data not shown). When sequential slides were stained for EpCAM and K19, in all stages of chronic hepatitis, EpCAM(+) hepatocytes were always located in contiguity with K19(+) ductular cells, with the EpCAM(+) cells arrayed around the periphery of ductular reactions (Fig. 1A-D). In 12 cases in which double staining for EpCAM and K19 was accomplished (stages 1-4), all cells of the Everolimus ductular reaction and surrounding hepatocytes with K19 expression were also EpCAM(+) (Fig. 1E,F), and EpCAM(+)/K19(−) cells, particularly hepatocytes, increased with increasing stage of disease (data not shown). Table 3 summarizes the semiquantitative assessment of the extent of EpCAM(+) hepatocyte staining in biopsy specimens according to the stage of chronic hepatitis. Normal livers had no EpCAM hepatocyte staining, or only slight staining (<5%). The extent of EpCAM(+) hepatocytes, overall, increased in parallel with the stage of disease. Only cirrhotic livers had 4+ (>50%) of parenchyma displaying

membranous EpCAM staining. There was no association between hepatocyte EpCAM expression and grade of necroinflammation, nor were there significant differences between livers of comparable stage between those with CHC versus CHB. As expected, p21WAF1/Cip1 and PCNA were expressed in cell nuclei. Labeling indices were calculated for various cell types of normal livers (bile duct lining cells, canal of Hering cells, hepatocytes) and of CHB cirrhotic livers check (bile duct lining cells, hepatobiliary cells of ductular reactions, hepatocytes) (Fig. 2; Supporting Tables 1 and 2), including EpCAM(+) versus EpCAM(−) hepatocytes (Fig. 3). For both antigens, there were statistically significant labeling index differences between CHB cirrhosis and normal controls, concerning all epithelial cell types. In particular, hepatocytes in cirrhosis showed significantly increased p21 expression compared with hepatocytes in normal livers, whereas reactive ductular cells had even more marked difference from the normal canal of Hering cells (Fig. 2A).

Taken together, these studies demonstrate that Hex is essential f

Taken together, these studies demonstrate that Hex is essential for the development of liver from gut endoderm and that it functions downstream of the signaling pathways that regulate the specification of the hepatic lineage. Defining the pathways and transcription factors that regulate lineage commitment in the early embryo is essential for our basic understanding of developmental biology

as well as for establishing strategies for the directed lineage-specific differentiation of ESCs in culture. By translating findings from the embryo to this in vitro model, it has been possible to develop approaches for the efficient and reproducible induction of endoderm and early hepatic and pancreatic cell fates from both mouse and human ESCs.16–18 Although the above selleck chemical studies have established the principal signaling pathways regulating hepatic specification, none has investigated the role of the key transcription factors in this process. In the present report, we have used the ES/EB model to study the role of Hex in hepatocyte development in vitro and demonstrate that as in the early embryo, this transcription factor is

essential for the establishment of hepatocyte lineage. Afp, alpha-fetoprotein; Alb, albumin; BMP-4, bone morphogenetic protein 4; Cps1, carbamoyl phosphate synthetase; Dlk1, Delta-like 1; Dox, doxycycline; Apoptosis inhibitor EB, embryoid body; ECD, E-cadherin; ESC, embryonic stem cell; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; Hex, hematopoietically expressed homeobox; mRNA, messenger RNA; RT-PCR, reverse-transcription polymerase chain reaction; Tcf1, transcription factor 1. The development and characterization of Hex+/+, Hex+/−, and Hex−/− ESC lines,15 the GFP-Bry ESC line,19 and tet-Hex ESCs20 have been described. Bry-Ainv cells were generated by targeting green fluorescent protein to the brachyury locus in the Ainv 18 ESC line19, 21 Sclareol (unpublished data). The Hex-plox targeting plasmid was electroporated into the Bry-Ainv cells, yielding tet-Hex Bry-Ainv ESCs. ESCs were maintained on irradiated

mouse embryo fibroblast feeder cells as described.22 To assess the function of Hex in developmental progression of hepatocytes during ESC differentiation, tet-Hex ESCs, in which Hex expression can be induced by exposure to doxycycline (Dox) at specific time points, were cultured as previously described for ectoderm with some modification.20 For differentiation of endoderm, activin induction was performed using a two-step protocol as described.22 To induce Hex expression, Dox (1–30 μg/mL in Iscove’s modified Dulbecco’s medium with 15% SR and 2 mM glutamine) was added to the cultures at different stages and for varying periods of time. After a total of 10 days of differentiation, EBs were replated on Matrigel-coated 6-well dishes in Iscove’s modified Dulbecco’s medium supplemented with 15% fetal bovine serum (Vitromex, Geilenkirchen, Germany), 2 mM glutamine, and 10−6 M dexamethasone.

A reformulated iso-osmotic version was approved for European use

A reformulated iso-osmotic version was approved for European use in 2007. This study was conducted to evaluate the safety of nonacog alfa in

a usual care setting, and provide clinical trial and postmarketing surveillance data support. This open-label, non-interventional, prospective observational cohort study (registry) comprised 52 sites in nine European countries. Patients with haemophilia B receiving nonacog alfa in either formulation for prevention or treatment were followed on a usual care schedule. A total of 218 patients were enrolled, of whom 66 (30.3%) were <18 years of age. Haemophilia severity was evenly distributed, with baseline FIX activity of <1%, 1–5% and >5% in 33.3%, 36.6% and 30.1% of patients, respectively. find more One hundred thirty-eight patients received the original formulation alone; 80 switched to or received only the new formulation. There was a low incidence of events of special interest (ESIs), with less-than-expected therapeutic effect in five patients (2.2%), inhibitor development in two (0.9%), thrombosis in one (0.5%) and allergic events in eight (3.7%).

These accounted for the majority of the 15 serious AEs reported in six patients. Six patients discontinued because of AEs, primarily related to hypersensitivity. Nonacog alfa was shown to be safe for the treatment of haemophilia B, with a low incidence of serious AEs and ESIs. “
“Immune tolerance induction (ITI) can overcome inhibitory factor VIII (FVIII) antibodies in haemophilia A patients receiving FVIII replacement therapy. The objective was to evaluate the BAY 57-1293 mw use of sucrose-formulated, full-length recombinant FVIII (rFVIII-FS) for ITI therapy. Patients (<8 years at ITI start) with severe haemophilia A and a peak inhibitor titre >5 Bethesda units (BU) who underwent ITI with any Isoconazole rFVIII-FS dose for ≥9 months (or until success) were eligible for this retrospective study. Efficacy analyses included descriptions of ITI treatment regimens and outcomes; ITI success was determined solely

at the discretion of the investigator. Safety analyses included assessment of adverse events. Of 51 enrolled patients, 32 [high dose (≥85 IU kg−1 day−1), n = 21; low dose, n = 11] were eligible for analysis. ITI was successful in 69% (22/32) of patients (high dose, 66.7%; low dose, 72.7%) after a median of 1.4 years (range, 0.1–3.6 years). Influencing factors for ITI success were start of ITI <1 year after inhibitor detection and an inhibitor titre <10 BU at ITI start. All patients successfully tolerized with ITI continued to receive rFVIII-FS prophylaxis as maintenance therapy, with no inhibitor recurrence from the end of ITI until study enrolment. Use of rFVIII-FS for ITI was effective and well tolerated; success rates were similar to those in published studies. "

huxleyi was decreased by 16-fold, whereas cellular volume

huxleyi was decreased by 1.6-fold, whereas cellular volume MLN0128 cost was increased by 1.9-fold. Se limitation also decreased chl a (2.5-fold), maximum relative electron transport rate (1.9-fold), and saturating light intensity (2.8-fold), suggesting that Se plays a role in photosynthesis or

high-light acclimation. Pigment analysis for Antarctic taxa provided an interesting counterpoint to the physiology of E. huxleyi. For all Se-dependent Antarctic diatoms, Se limitation decreased growth rate and chl a content, whereas cellular volume was not affected. Pigment analysis revealed that other pigments were affected under Se deficiency. Photoprotective pigments increased by 1.4-fold, while diadinoxanthin:diatoxanthin PCI 32765 ratios decreased by 1.5- to 4.9-fold under Se limitation, supporting a role for Se in photoprotection. Our results demonstrate an Se growth requirement for polar diatoms and indicate that Se could play a role in the biogeochemical cycles of other nutrients, such as silicic acid in the Southern Ocean. Se measurements made during the austral summer in the Southern Ocean and Se biological requirement were used to discuss possible Se limitation in phytoplankton from contrasting oceanographic regions. “
“Mitochondrial DNA (mtDNA) of the isogamous brown alga Scytosiphon lomentaria (Lyngb.) Link is inherited maternally. We used molecular biological

and morphological analyses to investigate the fate of male mitochondria. Ultrastructural observations showed that the number of 25 mitochondria in a zygote coincided with

the number of mitochondria derived from male and female gametes. This number remained almost constant during the first cell division. Strain-specific PCR in single germlings suggested that mtDNA derived from the female gamete remained in the germling during development, while the male mtDNA gradually and selectively disappeared after the four-cell stage. One week after fertilization, male 3-mercaptopyruvate sulfurtransferase mtDNA had disappeared in sporophytic cells. Using bisulfite DNA modification and methylation mapping assays, we found that the degree of methylation on three analyzed sites of mtDNA was not different between male and female gametes, suggesting that maternal inheritance of mtDNA is not defined by its methylation. This study indicates that the mechanism of selective elimination of male mtDNA is present in each cell of a four-celled sporophyte and that it does not depend on different degrees of DNA methylation between male and female mtDNA. “
“We investigated the relationship between daily growth rates and diel variation of carbon (C) metabolism and C to nitrogen (N) ratio under P- and N-limitation in the green algae Chlorella autotrophica. To do this, continuous cultures of C. autotrophica were maintained in a cyclostat culture system under 14:10 light:dark cycle over a series of P- and N-limited growth rates.

Serum total bilirubin and cholestatic enzymes (ALP, GGT) are impo

Serum total bilirubin and cholestatic enzymes (ALP, GGT) are important

for assessing the activity and progression of PBC. Liver biochemical tests should be done every 3–6 months. In addition, thyroid hormone (every year) and bone mineral density (every 2–4 years) tests are recommended because PBC is likely to be complicated with other autoimmune diseases, such as Sjögren’s syndrome, chronic thyroiditis, and rheumatoid arthritis. Regular upper gastrointestinal endoscopy, depending on stage (1 or 2 times per year), is required because esophageal/gastric varices may develop even in patients without jaundice. Abdominal GSK3235025 ultrasound (US) and serum AFP testing every 6–12 months are necessary in patients with definite or suspected liver cirrhosis. Liver cirrhosis, older age, and male sex are high risk factors for developing hepatocellular carcinoma (HCC). Therefore, testing for tumor markers and imaging studies [US and computed tomography (CT)] are required for early detection of HCC in patients with advanced PBC. Management

for other complicating autoimmune diseases should be done depending on each symptom. Finally, special attention should be paid to pregnancy in PBC and patients who have a desire to bear children. The chance for pregnancy could be the same in the early stage of aPBC as in the normal population; there is no evidence to recommend Ruxolitinib mouse avoidance of pregnancy in patients with aPBC. In sPBC, however, if worsening of icterus either or varices is reported, then avoidance of pregnancy could be justified. The impact of pregnancy on PBC is unclear because both exacerbation and improvement of cholestasis have been reported. Estrogen could potentially worsen cholestasis; pruritus may become severe in pregnancy and could be prolonged even after delivery. Conversely, it should be noted that cholestasis could be symptomatic after pregnancy. After a patient has become pregnant, monitoring for varices is necessary as in other

cirrhotic patients, especially after the second trimester, due to increase in circulating blood volume. The use of β blockers is considered to be safe. It is also advisable to shorten the second trimester of pregnancy, if possible. Recommendations: The blood and other clinical tests should be undertaken regularly to investigate complicating comorbidities, prevent complications, and detect portal hypertension and liver cancer as early as possible. (Table 13) (LE 3, GR B) It is advisable to consult with hepatologists when the diagnosis of PBC is made, or when patients with PBC become symptomatic. In patients with atypical forms of PBC such as PBC–AIH overlapping syndrome, earlier referral is recommended. (Table 14) (LE 6, GR A-B) For patients in the symptomatic stage, there is a likelihood of worsening of pruritus or icterus in the pregnancy, as well as an increased possibility of variceal rupture.

Methods: Chinese subjects aged 50 years and above were recruited

Methods: Chinese subjects aged 50 years and above were recruited from gastroenterology clinics of four major public hospitals in Singapore from 2004–2010. Endoscopy surveillance was offered for a minimum of 5 years. Informed consent was obtained from all subjects and the study was approved by the institutional review boards. The main outcome measurement is the number of

subjects who develop high grade dysplasia or gastric adenocarcinoma. Results: 3033 subjects with mean age 59 ± 7 years were recruited. 51% were male, 16% had family history of gastric cancer and 30% had H. pylori infection history based on their medical records. The prevalence of chronic gastritis, current H. selleck products pylori infection, atrophic gastritis and intestinal metaplasia

at baseline were 81%, 20%, 19% and 44% respectively. The study is in progress, 1,300 have completed 5 years surveillance and the rest will complete by 2015.18 high grade dysplasia or early gastric cancers were detected so far after an average follow up period of 3 years. 12 of those cases were high grade dysplasia or intramucosal carcinoma and 6 were invasive cancers in stage 1A or 1B. The interval between the most recent endoscopy with no abnormal findings and the endoscopy where cancer was diagnosed is 4–25 months. Conclusion: Endoscopic surveillance is effective, and has already selleck chemicals llc detected high grade dysplasia or early gastric cancer in a high risk Singaporean Chinese population. Key Word(s): 1. gastric caner; 2. endoscopy screening; 3. risk stratification; 4. cohort study; Presenting

Author: IOAN CHIRILA Additional Authors: STK38 FLORINDUMITRU PETRARIU, VASILELIVIU DRUG Corresponding Author: IOAN CHIRILA Affiliations: University of Medicine and Pharmacy Grigore T. Popa Iasi, National Institute of Public Health, Iasi, Romania; University of Medicine and Pharmacy “Grigore T. Popa” – Iasi; University of Medicine and Pharmacy Grigore T Popa Iasi Objective: The aim of the study was to determine the presence of gastro-esophageal reflux symptoms and the prevalence of gastro-esophageal reflux disease (GERD) in general urban population and to evaluate the type of diet associated with this pathology. Methods: A randomized sample of subjects (n = 300) from a general urban population from Iasi city selected from the family doctors patient lists was invited for interview in the doctor’s office. Selected subjects were evaluated for recent symptoms using Gastrointestinal Symptom Rating Scale (GSRS), for the diagnosis of GERD using Montreal criteria and for their diet using a food frequency questionnaire. Results: In the last 7 days preceding the survey, were present relevant symptoms for gastro-esophageal reflux in 26.4% of investigated subjects and GERD was diagnosed in 31.1% of subjects. People aged over 50 years experienced an increased prevalence of recent symptoms (36.4%, p < 0.001) and GERD (37.

The number of expected cancer patients in a healthy population ma

The number of expected cancer patients in a healthy population matched for sex and age with the CD

patients in our hospital was then calculated. Selleckchem EPZ 6438 The relative risk, or SIR, was also calculated. The total observation period was 10 552 person-years, during which 19 cases (2.5%) of cancer were discovered in 770 subjects. The cancer cases included nine cases of colorectal cancer (CRC), one case of small bowel cancer, one case of stomach cancer, three cases of acute myeloid leukemia, two cases of endometrial cancer, one case of lung cancer, one case of skin cancer, and one case of thyroid cancer. The SIR for cancers in Japan in 2003 was 0.87 (95% confidence interval [CI] 0.52–1.35) for all cancers, 2.79 (95% CI 1.28–5.29) for CRC, and 6.94 (95% CI 1.43–20.3) for leukemia. Among the cancers in CD patients in our hospital, no significant difference was seen in the risk for all cancers in comparison with the standard population. However, the risks for CRC and leukemia were significantly higher than in the standard population. “
“We shall not cease from exploration And the end of all our exploring Will be to arrive where we started And know

the place for the first Selleckchem AG14699 time T.S. Eliot, Four Quartets Alcoholic liver disease (ALD), either alone or in conjunction with other diseases such as chronic hepatitis C infection,

has become a major indication for liver transplantation in North America and Europe.1 How different were the predictions PRKACG of the watershed National Institutes of Health (NIH) consensus meeting on liver transplantation in 1984 that declared: “Patients who are judged likely to abstain from alcohol and who have established clinical indicators of fatal outcomes may be candidates for transplantation. Only a small proportion of alcoholic patients with liver disease would be expected to meet these rigorous criteria.” The initial reticence centered not only on concern that ALD transplant recipients would relapse to alcohol use, but also that alcoholic patients were less deserving of scarce donor organs because of their complicity in causing liver damage, and that the low esteem in which the public holds alcoholics would translate into donor families declining to donate if the recipient were likely to be an alcoholic.3, 4 ALD, alcoholic liver disease; HCV, hepatitis C virus; MELD, Model for Endstage Liver Disease; UNOS, United Network for Organ Sharing. This orthodoxy was challenged by Dr. Thomas Starzl who, in 1995, reported that alcoholic patients had excellent short-term outcomes after liver transplantation.

Restoration of Bowel Continuity Following Resection of Diseased B

Restoration of Bowel Continuity Following Resection of Diseased Bowel Resection of diseased bowel is performed in the following settings: *  Bowel gangrene secondary to vascular compromise resulting from mesenteric vascular disease, prolonged intestinal obstruction, intussusceptions, or volvulus Bypass of Unresectable Diseased Bowel Bypass of unresectable diseased bowel is performed

in following settings: *  Locally advanced tumor causing luminal obstruction Pediatric Conditions Pediatric conditions for which intestinal anastomosis may be required include the following: *  Congenital anomalies, such as Meckel diverticulum, intestinal atresia, malrotation selleck inhibitor with volvulus leading to gangrene, meconium ileus, duplication cysts, and Hirschsprung disease Adequate exposure and access, gentle handling of the bowel, adequate hemostasis, approximation of well-vascularized bowel, absence of tension at anastomosis, Selleckchem Poziotinib good surgical technique, and avoidance of fecal contamination are tenets of good intestinal anastomosis. Methods: This study was done in 100 casesmay of exploratory laparotomy requiring intestinal anastomoses. In all cases single layer anastomosis was done with non absorbable sutures (3–0 silk sutures). All cases

were of end to end anastomosis and majority of cases were of Ileo-ileal anastomosis. Rest were of Ileo-colic, col0-colic, oesophago-gastric, biliary-enteric anastomoses. Cases were of both emergency and elective type. Posterior layer was done with simple full thickness sutures. Anterior layer was of inverting sutures. Close apposition was ensured. Results: All cases did well post-operatively. Only 3 cases had anastomotic leak which

was minor and was managed conservatively. Re exploration Branched chain aminotransferase was not done in any case. Patients were put to oral diet on 5th Post -operative day starting with liquid diet. No patient reported in the later period with the clinical features of stricture formation or any other complication. Conclusion: Single layer intestinal anastomosis is comfortable procedure. It is less time consuming and cost-effective. Complication rate like anastomotic leakage is almost negligible. Morbidity and mortality is decreased. So this is an advisable procedure in all types of intestinal anastomoses. Key Word(s): 1. intestines; 2. sutures; 3. anastomosis; 4. laparotomy; Presenting Author: KAKA RENALDI Additional Authors: ACHMAD FAUZI Corresponding Author: KAKA RENALDI, ACHMAD FAUZI Affiliations: CiptoMangunkusumo Hospital Objective: Amyloidosis is a condition in which an abnormal protein called amyloid builds up in your tissues and organs. When it does, it affects their shape and how they work. Amyloidosis is a serious health problem that can lead to life-threatening organ failure. Methods: Case: A 50 year old male, came with chronic diarrhea and the condition is very cahectic with hypoalbuminemia.

All isolates had wild-type polymerase gene sequences despite 14 c

All isolates had wild-type polymerase gene sequences despite 14 currently or previously receiving antiviral treatment. The canonical sG145R vaccine-escape variant was detected in the surface antigen of virus from two patients. The exclusive HBV genotype in this ancient population is genotype C4. Whole genome sequencing and clinical follow-up of this cohort are in progress, with the aim of exploring the clinical significance of these findings. “
“Intrahepatic metastasis is the primary cause of the high recurrence

selleck compound and poor prognosis of human hepatocellular carcinoma (HCC). However, neither its molecular mechanisms nor markers for its prediction before hepatectomy have been identified. We recently revealed up-regulation of erythroblastic leukemia viral oncogene homolog 3 (ERBB3) in human HCC. Here we examined the clinical and biological significance of ERBB3 in HCC. Up-regulation Sotrastaurin in vivo of ERBB3 in HCC was strongly associated with male gender (P< 0.001), chronic

hepatitis B (P = 0.002), microscopic vascular invasion (P = 0.034), early recurrence (P = 0.003), and worse prognosis (P = 0.004). Phosphorylated ERBB3 and its ligands [neuregulins (NRGs)] were detected in both HCC tissues and cells. Phosphorylation of ERBB3 could be induced by conditioned media of HCC cells and abolished by the pretreatment of conditioned media with anti-NRG antibodies or by the silencing of the endogenous NRG expression of the donor HCC cells. Human epidermal growth factor receptor 2 was required for ERBB3 phosphorylation. The downstream phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene homolog pathways were primarily elicited by NRG1/ERBB3

signaling, whereas the mitogen-activated protein kinase/extracellular signal-regulated kinase pathways were elicited by both epidermal growth Phosphoglycerate kinase factor/epidermal growth factor receptor and NRG1/ERBB3 signaling. The activation and silencing of ERBB3-dependent signaling had potent effects on both the migration and invasion of HCC cells, but neither had significant effects on the proliferation of HCC cells, tumor formation, or tumor growth in vitro and in vivo. Conclusion: The constitutive activation of ERBB3-dependent signaling via the NRG1/ERBB3 autocrine loop plays a crucial role in the regulation of cell motility and invasion, which contribute to intrahepatic metastasis and early recurrence of HCC. ERBB3 is a marker for the prediction of intrahepatic metastasis and early recurrence. ERBB3-dependent signaling is a candidate target for the treatment of microscopic vascular invasion and for the prevention of HCC recurrence. (HEPATOLOGY 2011;53:504-516) (This article firstt published online on January 18, 2011; the title has since changed; the correct version appears in print. Frequent intrahepatic metastasis is a unique feature of hepatocellular carcinoma (HCC) and the primary cause of high rates of early recurrence after initial curative therapy.