Neither age nor gender had an effect on HCV knowledge. Conclusions: Tattoo parties represent

an illegal and unregulated environment where HCV may be transmitted. Our results demonstrate that younger adults are more likely to engage in tattooing behavior that may place them at higher risk for acquiring HCV. Younger adults who have tattoos also appear to have a lower self-perceived CH5424802 in vivo risk for contracting HCV than older adults. Together these findings suggest that individuals born outside of the 1945 to 1965 birth cohort may benefit from targeted education emphasizing the potential health dangers of tattooing in unregulated settings. Future studies are needed to determine the prevalence of tattoo parties in communities outside of Philadelphia and to assess the risk of acquiring

HCV in this setting. Disclosures: Amy Nunn – Consulting: Mylan; Grant/Research Support: Gilead Stacey B. Trooskin – Advisory Committees PLX3397 or Review Panels: Gilead Sciences; Grant/Research Support: Gilead Sciences The following people have nothing to disclose: Audun Lier, Sophie C. Feller, Caitlin Towey, Joanna Poceta, Hwajin Lee, Gladys L. Thomas Background: The FIBROSpect II (FSII) assay is used as a surrogate to liver biopsy in estimating the severity of liver fibrosis. This retrospective analysis was designed to specifically address the issue of utilizing the FSII assay to define minimal vs significant fibrosis

in African Americans (AA) with chronic hepatitis C (CHC). Methods: AA (n=275) and Caucasian (Cau)(n= 44) seen between 1/1/2008 and 6/30/2013 at the Wayne State University and for whom a FSII result was available regardless of diagnosis were identified using EMR. The FSII assay uses serum levels of hyaluronic acid, TIMP-1 and alpha 2 macro-globulin to calculate an index range from 1 to 99. A cut-off of >41 is used to differentiate mild from advanced fibrosis (METAVIR F0–F1 vs. F2–F4). Demographics, lab results within 6 months of the assay, biopsy results within an average of 4 years ( AA (n= 149) and Cau (n=19)), imaging studies, and EGD results were extracted from the EMR. Results: The patient population was predominately AA (86%), male biased (57%) and had an average age of 58 years. CHC was the primary reason for check details ordering FSII (90% AA, 66% Cau). AA were more likely to have a high FSII index compared to Cau (defined either by average score (60±2 vs 46±4 p<0.005 by Student-t-test or Metavir F2-F4 assessment (AA 182/275= 66% vs Cau 20/44=45% p= 0.01 Chi-square). This was in contrast to biopsy results where AA had less fibrosis than Cau (1.5±0.1 vs 2.1± 0.3 p<0.05 continuous variable; Pierson Chi-Square p<0.005 as a nominal variable). Since these result suggest that the FSII assay may over predict fibrosis for AA with CHC, we used paired biopsy to test the hypothesis.

DNA was purified by one extraction JQ1 price with phenol-chloroform followed by ethanol precipitation and used for quantitative real-time PCR. Anti-trimethylated histone 3 lysine 4 (H3K4), anti-dimethylated H3K4, and anti-monomethylated H3K27 antibodies were purchased from Millipore (Temecula, CA). Anti-monomethylated H3K4, anti-trimethylated H3K9, anti-dimethylated H3K9, anti-monomethylated H3K9, anti-trimethylated H3K27,

anti-trimethylated H3K20, anti-monomethylated H3K20, and anti-JMJD2c antibodies were purchased from Abcam (Cambridge, MA). Anti-JMJD2a and anti-activating signal cointegrator-2 (anti–ASC-2) antibodies were purchased from Bethyl Laboratories (Montgomery, TX), anti-JMJD2b antibody was purchased from Cell Signaling (Danvers, MA), and anti-JMJD2d antibody was purchased from Abgent (San Diego, CA). Sequences of the primers used for ChIP assays are available upon request. All data represent hypoxia-inducible factor pathway at least three independent experiments and are expressed as the mean ± SD. Student t test was used to calculate P values, and P < 0.05 was considered significant. Drug-mediated CAR activation

during development may result in a persistent change of its target gene expression. To test this hypothesis, mice on the third day after birth (neonates) were administered a single intraperitoneal injection of either corn oil or the specific CAR agonist TCPOBOP. At 12 weeks after injection, the mice were sacrificed and the messenger RNA (mRNA) levels of 21 target genes of CAR in liver were examined (Supporting Table 1). Compared with control groups, neonatal exposure selleck compound to the CAR agonist resulted in a 4750-fold induction of Cyp2B10 and a 3.8-fold induction of Cyp2C37 in adult WT mouse livers

(12-week-old). Deletion of the CAR gene (CAR−/−) completely abolished the induction of these genes (Fig. 1). In response to transient activation of CAR on the third day after birth, the up-regulation of Cyp2B10 and Cyp2C37 was also observed in aged (23-month-old) WT but not CAR−/− mouse livers (data not shown). These data indicate that transient activation of CAR by neonatal exposure to TCPOBOP specifically induces the expression of the CAR target genes Cyp2B10 and Cyp2C37 in mouse livers throughout their lives. In addition, the expression levels of these genes in adult mice that were neonatally exposed to TCPOBOP were compared with those in adult mice pretreated with TCPOBOP 3 days before RNA isolation. Twelve-week-old mice were treated with a single dose of TCPOBOP, which dramatically induced the expression of Cyp2B10 and Cyp2C37 in liver. Levels of Cyp2B10 and Cyp2C37 were 8.6-fold and 2.0-fold, respectively, higher than those caused by neonatal exposure to TCPOBOP (Fig. 1). We then asked whether this persistent induction of CAR target genes resulted in a physiological increase in drug clearance. The muscle relaxant zoxazolamine, a substrate of several cytochrome P450 enzymes, is a simple indicator of drug clearance.

At 3-4 weeks after vector injection, either 1 × 106 (Fig. 1C; Fig. 5) or 5 × 106 (Fig. 1A–B,D; Fig. 2; Fig. 3; Fig. 4; Fig. 6) T cells (>90% pure) were injected intravenously in

the tail vein. DCs were enriched from the spleen using the technique of Livingstone,19 with modifications.20 Spleens from C57BL6 mice were digested in HBSS containing 2.4 mg/mL collagenase IV (Sigma Aldrich), and 1 mg/mL deoxyribonuclease (Sigma Aldrich) at 37°C for 30 minutes. Cells were resuspended in 60% Percoll and overlayed with 2 mL HBSS +5% fetal bovine serum. This gradient was spun at 650g for 20 minutes. DCs from the interface were allowed to attach for 90 minutes and nonadherent cells washed away. Adherent cells were incubated overnight with 1 ng/mL granulocyte-macrophage colony-stimulating factor and 1 μM SIINFEKL peptide, and harvested the next day by gentle washing. Opaganib DCs (1 × 106) were given intravenously with the OT-1 cells. Intrahepatic lymphocytes were isolated as described.14 Cells in staining buffer (1% fetal bovine serum in PBS) were first incubated with Fc-block (Pharmingen) for 5 minutes. Antibodies used were anti-CD62L (phycoerythrin [PE]), anti-CD44 (PE and PE-cyanin5 [Cy5]), anti-CD8 (peridinin chlorophyll protein [PCP], allophycocyanin [APC], and PE-Cy7), and anti-CD4 (PCP and Pacific Blue) all from Pharmingen. Pacific Blue–conjugated anti-CD127, anti-PD-1 (PE), anti-CD45.1 (APC and PE-Cy7), anti-CD45.2 (AlexaFluor

Epigenetics inhibitor 700), anti-CD62L (APC-AlexaFluor 750) were from eBioscience. Data were acquired using FACSCalibur or LSRII flow cytometers,21 and analyzed using FlowJo (TreeStar) on an iMac computer. Live lymphocytes were gated based on forward scatter and side scatter (FSC/SSC). Data in the figures represent the mean ± standard error of the mean (SEM). A Student t test was used to analyze the results where applicable, and probability values of P < 0.05 were considered click here significant. To test the capacity of the AAV2-ova vector to activate CD4+ T cells in vivo, mice received an intrahepatic injection of either AAV2-ova, or a control vector AAV2-gfp. After

3 weeks, mice were given CFSE-labeled OT-II transgenic CD4+ T cells, specific for the ISQAVHAAHAEINEAG peptide (ova323-339). These T cells did not respond, similar to OT-II T cells infused into mice that had been given the antigen-negative AAV2-gfp control vector (Fig. 1A, two upper left panels). However, the OT-II cells were competent to proliferate in vivo, revealed by their response to peptide-pulsed splenocytes (marked “pep” in Fig. 1); after this treatment, we observed divided OT-II T cells in the liver,19 spleen (“SPL” in Fig. 1) and PLN.6 To detect T cell activation, we also measured the expression of the lymph node homing receptor CD62L (Fig. 1B). Nondividing OT-II T cells maintained high expression of CD62L, whereas responding T cells expressed less. These results were confirmed using D0.11.

At 3-4 weeks after vector injection, either 1 × 106 (Fig. 1C; Fig. 5) or 5 × 106 (Fig. 1A–B,D; Fig. 2; Fig. 3; Fig. 4; Fig. 6) T cells (>90% pure) were injected intravenously in

the tail vein. DCs were enriched from the spleen using the technique of Livingstone,19 with modifications.20 Spleens from C57BL6 mice were digested in HBSS containing 2.4 mg/mL collagenase IV (Sigma Aldrich), and 1 mg/mL deoxyribonuclease (Sigma Aldrich) at 37°C for 30 minutes. Cells were resuspended in 60% Percoll and overlayed with 2 mL HBSS +5% fetal bovine serum. This gradient was spun at 650g for 20 minutes. DCs from the interface were allowed to attach for 90 minutes and nonadherent cells washed away. Adherent cells were incubated overnight with 1 ng/mL granulocyte-macrophage colony-stimulating factor and 1 μM SIINFEKL peptide, and harvested the next day by gentle washing. Selleckchem MK-3475 DCs (1 × 106) were given intravenously with the OT-1 cells. Intrahepatic lymphocytes were isolated as described.14 Cells in staining buffer (1% fetal bovine serum in PBS) were first incubated with Fc-block (Pharmingen) for 5 minutes. Antibodies used were anti-CD62L (phycoerythrin [PE]), anti-CD44 (PE and PE-cyanin5 [Cy5]), anti-CD8 (peridinin chlorophyll protein [PCP], allophycocyanin [APC], and PE-Cy7), and anti-CD4 (PCP and Pacific Blue) all from Pharmingen. Pacific Blue–conjugated anti-CD127, anti-PD-1 (PE), anti-CD45.1 (APC and PE-Cy7), anti-CD45.2 (AlexaFluor

see more 700), anti-CD62L (APC-AlexaFluor 750) were from eBioscience. Data were acquired using FACSCalibur or LSRII flow cytometers,21 and analyzed using FlowJo (TreeStar) on an iMac computer. Live lymphocytes were gated based on forward scatter and side scatter (FSC/SSC). Data in the figures represent the mean ± standard error of the mean (SEM). A Student t test was used to analyze the results where applicable, and probability values of P < 0.05 were considered selleck compound significant. To test the capacity of the AAV2-ova vector to activate CD4+ T cells in vivo, mice received an intrahepatic injection of either AAV2-ova, or a control vector AAV2-gfp. After

3 weeks, mice were given CFSE-labeled OT-II transgenic CD4+ T cells, specific for the ISQAVHAAHAEINEAG peptide (ova323-339). These T cells did not respond, similar to OT-II T cells infused into mice that had been given the antigen-negative AAV2-gfp control vector (Fig. 1A, two upper left panels). However, the OT-II cells were competent to proliferate in vivo, revealed by their response to peptide-pulsed splenocytes (marked “pep” in Fig. 1); after this treatment, we observed divided OT-II T cells in the liver,19 spleen (“SPL” in Fig. 1) and PLN.6 To detect T cell activation, we also measured the expression of the lymph node homing receptor CD62L (Fig. 1B). Nondividing OT-II T cells maintained high expression of CD62L, whereas responding T cells expressed less. These results were confirmed using D0.11.

14 Given the accumulating evidence that γ-GT is not merely a sensitive marker for liver and bile disorders, but also a risk marker for a multiplicity of other chronic diseases, γ-GT may represent a promising risk marker to identify workers at risk of occupational disability and who may benefit from targeted intervention. A study from Sweden indicated elevated values of γ-GT among middle-aged men before as well as after receiving a disability pension, which was ascribed in this study to overconsumption of alcohol.15 In a previous cohort study from Germany the risk of occupational

Idasanutlin mw disability was found to be significantly increased with elevated γ-GT levels compared to those with γ-GT levels in the normal range.16 However, in that former Deforolimus order analysis, the size and follow-up time of the cohort were too small to assess dose-response patterns or the associations of γ-GT with disability due to different causes in detail. Therefore, we enlarged the cohort and extended follow-up in order to assess dose-response patterns with respect to overall and cause-specific disability. BMI: body mass index; γ-GT: gamma-glutamyltransferase; ICD-9: International Classification of Diseases (9th revision). The study cohort at baseline comprised 19,421 male employees from the German construction

industry, age 25 to 59 years, belonging to one of the following occupations: bricklayers (n = 6,204), painters (n = 2,947), laborers (n = 2,874), plumbers (n = 2,804), carpenters (n = 2,594), and plasterers (n = 1,998). They participated in a routine occupational health examination by the Workmen’s Compensation Board for construction workers in Württemberg (in the south of Germany) between August 1986 and December 1992. This occupational health surveillance is based on legislation on health and safety at work and regular examinations are offered to all construction selleck workers. In the period of recruitment, over 75% of all invited employees

participated in the medical examination and were eligible for follow-up. All participants were members of the statutory pension fund and did not receive a disability pension at baseline examination. They were representative for the underlying population of all construction workers with respect to age, nationality, and type of occupation. All patients gave informed consent regarding analysis of the health data. The retrospective follow-up study was approved by the Ethics Committees of the medical faculties of the University Clinics of Heidelberg and Ulm, by the data protection officer of Baden-Württemberg, and by the Baden-Württemberg State Ministry of Social Affairs.

14 Given the accumulating evidence that γ-GT is not merely a sensitive marker for liver and bile disorders, but also a risk marker for a multiplicity of other chronic diseases, γ-GT may represent a promising risk marker to identify workers at risk of occupational disability and who may benefit from targeted intervention. A study from Sweden indicated elevated values of γ-GT among middle-aged men before as well as after receiving a disability pension, which was ascribed in this study to overconsumption of alcohol.15 In a previous cohort study from Germany the risk of occupational

buy NVP-BGJ398 disability was found to be significantly increased with elevated γ-GT levels compared to those with γ-GT levels in the normal range.16 However, in that former Rapamycin price analysis, the size and follow-up time of the cohort were too small to assess dose-response patterns or the associations of γ-GT with disability due to different causes in detail. Therefore, we enlarged the cohort and extended follow-up in order to assess dose-response patterns with respect to overall and cause-specific disability. BMI: body mass index; γ-GT: gamma-glutamyltransferase; ICD-9: International Classification of Diseases (9th revision). The study cohort at baseline comprised 19,421 male employees from the German construction

industry, age 25 to 59 years, belonging to one of the following occupations: bricklayers (n = 6,204), painters (n = 2,947), laborers (n = 2,874), plumbers (n = 2,804), carpenters (n = 2,594), and plasterers (n = 1,998). They participated in a routine occupational health examination by the Workmen’s Compensation Board for construction workers in Württemberg (in the south of Germany) between August 1986 and December 1992. This occupational health surveillance is based on legislation on health and safety at work and regular examinations are offered to all construction this website workers. In the period of recruitment, over 75% of all invited employees

participated in the medical examination and were eligible for follow-up. All participants were members of the statutory pension fund and did not receive a disability pension at baseline examination. They were representative for the underlying population of all construction workers with respect to age, nationality, and type of occupation. All patients gave informed consent regarding analysis of the health data. The retrospective follow-up study was approved by the Ethics Committees of the medical faculties of the University Clinics of Heidelberg and Ulm, by the data protection officer of Baden-Württemberg, and by the Baden-Württemberg State Ministry of Social Affairs.

039, P = 0.033, P = 0.001). The VMR on 40 and 60 mmHg CRD in 17β-estradiol Torin 1 manufacturer treated group was not significantly different from that in 17β-estradiol plus Ro25-6981 treated group. Whilst, significant differences of VMR were noted between 17β-estradiol treated group and 17β-estradiol plus AP5 treated group on 60, 80 mmHg CRD, respectively.17β-estradiol increased NR2B mRNA in anterior cingulate cortex (0.57 ± 0.41 vs 0.21 ± 0.13, P = 0.048), but not in dorsal root

ganglia (0.35 ± 0.45 vs 0.38 ± 0.31, P = 0.465). Stress-induced visceral hypersensitivity in the hormonally-restored visceral hyper-responsiveness of bilaterally ovariectomized rats was antagonized by AP5 or Ro25-6981. Conclusion: Estrogen may be mediated through NR2B activation to enhance visceral sensitivity in female stressed rats, that probably related with the inceased expression of NR2B mRNA in anterior cingulate cortex. Key Word(s): 1. IBS; 2. Estrogen; 3. Sress; 4. N-methyl-D-aspartate; SCH772984 in vivo Presenting Author: LU XIA Corresponding Author: LU XIA

Affiliations: Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University Objective: Presence of intestinal microbes is considered a prerequisite for the development of ulcerative colitis (UC) including fungal community in the gut. However, there is little knowledge about the mechanisms. In the present study, we investigated the role of C-Type lectin receptor Dectin-1 in the regulation of anti-fungi find more immune responses in ulcerative colitis. Methods: The distribution of Dectin-1 in the gut were detected in biopsy tissues from UC patients and compared with normal controls by immunohistochemistry

and immunofluorescence staining. Dectin-1 expression levels were assessed from tissues in active UC patients, normal controls by RT-PCR and western bloting. We examined prevalence of fungi in human fecal and colonic mucosa, and identified the changes in fungal microbiome by PCR. Pripheral blood monouclear cells (PBMC) from healthy donors were co-cultured with zymosan, then we assessed the dectin-1 expression by flow cytometry and the production of inflammatory cytokines by ELISA. Results: Our results revealed an inverse relationship between dectin-1 expression and disease activity score in active UC patients. We demonstrated that the level of opportunistic pathogen fungus was higher than nonpathogenic fungus. Dectin-1 recognized theβ-glucan of fungal cell wall and bone marrow-derived monocyte responsed toβ-glucan producted inflammatory cytokines. In addition, Dectin-1 could crosstalk with TLRs and activate NF-κB by Myd88, SYK/CARD9 pathway. Finally, β-glucan particles zymosan could stimulate PBMC to express high level of Dectin-1 and produce high level of inflammatory cytokines. Conclusion: These findings suggest thatβ-glucan can interact with dectin-1 and activate NF-κB signaling pathway to regulate the inflammation process.

(HEPATOLOGY 2012;56:1792–1803) Primary liver cancer (PLC) is the second most lethal cancer for men in the world.1 Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of PLC. Although ICC is much less common than hepatocellular carcinoma (HCC), its incidence has increased drastically over the past two find more decades.2,

3 However, the molecular pathogenesis of ICC is largely unknown. Understanding of the tumor biology of HCC and ICC that contributes to tumor heterogeneity is paramount in developing effective therapies to improve patient outcome. The cellular origin of HCC and ICC has been subject to intense debate in recent years. It is thought that HCC is derived from hepatocytes, whereas ICC arises from intrahepatic biliary epithelium. However, a mixed form of HCC and ICC, also known as combined hepatocellular cholangiocarcinoma (CHC), has been described to have distinct clinicopathological features but morphological intermediates

of HCC and ICC, suggesting that HCC and ICC could share the same cellular origin.4-6 Recent studies utilizing high-resolution genomic approaches have shed light on the revelation of cellular origin of HCC and suggest that a subset of HCC contains stem cell-like features.7-10 For example, a subset of tumor cells isolated from HCC patients are tumor-initiating cells with stem cell traits.11-14 Moreover, HCC may share an ICC-like gene expression trait.15 These results are consistent with the cancer buy CYC202 stem cell (CSC) hypothesis, which suggests that most tumor cells are derived from undifferentiated selleck products cells with stem-like capabilities and that both ICC and HCC may share the same cellular origin of hepatic stem/progenitor cells. Global messenger RNA (mRNA) and microRNA profiling approaches have been proven to be effective in identifying genes critical to HCC.8, 9, 16-22 In this study, we used both mRNA and microRNA profiling approaches to determine tumor heterogeneity and molecular characteristics of ICC. We found

that ICC samples consist of at least two main subtypes that share similar molecular activities, with HCC linked to stem cell-like gene expression and patient survival. Integrative genomic analyses revealed that genes and microRNAs involved in epithelial-mesenchymal transition (EMT) are altered in stem-like ICCs. Our results shed light on ICC diagnosis and may open new avenues for therapeutic interventions for targeting poor prognosis ICC patients. CHC, combined hepatocellular cholangiocarcinoma; CSC, cancer stem cell; EMT, epithelial-mesenchymal transition; FNH, focal nodular hyperplasia; GEO, gene expression omnibus; HCC, hepatocellular carcinoma; HpSC-ICC, hepatic stem cell-like ICC; ICC, intrahepatic cholangiocarcinoma; MH-ICC, mature hepatocyte-like ICC; PLC, primary liver cancer; x-HCC; extreme HCC.

(HEPATOLOGY 2012;56:1792–1803) Primary liver cancer (PLC) is the second most lethal cancer for men in the world.1 Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of PLC. Although ICC is much less common than hepatocellular carcinoma (HCC), its incidence has increased drastically over the past two Selleck Quizartinib decades.2,

3 However, the molecular pathogenesis of ICC is largely unknown. Understanding of the tumor biology of HCC and ICC that contributes to tumor heterogeneity is paramount in developing effective therapies to improve patient outcome. The cellular origin of HCC and ICC has been subject to intense debate in recent years. It is thought that HCC is derived from hepatocytes, whereas ICC arises from intrahepatic biliary epithelium. However, a mixed form of HCC and ICC, also known as combined hepatocellular cholangiocarcinoma (CHC), has been described to have distinct clinicopathological features but morphological intermediates

of HCC and ICC, suggesting that HCC and ICC could share the same cellular origin.4-6 Recent studies utilizing high-resolution genomic approaches have shed light on the revelation of cellular origin of HCC and suggest that a subset of HCC contains stem cell-like features.7-10 For example, a subset of tumor cells isolated from HCC patients are tumor-initiating cells with stem cell traits.11-14 Moreover, HCC may share an ICC-like gene expression trait.15 These results are consistent with the cancer buy DAPT stem cell (CSC) hypothesis, which suggests that most tumor cells are derived from undifferentiated selleck products cells with stem-like capabilities and that both ICC and HCC may share the same cellular origin of hepatic stem/progenitor cells. Global messenger RNA (mRNA) and microRNA profiling approaches have been proven to be effective in identifying genes critical to HCC.8, 9, 16-22 In this study, we used both mRNA and microRNA profiling approaches to determine tumor heterogeneity and molecular characteristics of ICC. We found

that ICC samples consist of at least two main subtypes that share similar molecular activities, with HCC linked to stem cell-like gene expression and patient survival. Integrative genomic analyses revealed that genes and microRNAs involved in epithelial-mesenchymal transition (EMT) are altered in stem-like ICCs. Our results shed light on ICC diagnosis and may open new avenues for therapeutic interventions for targeting poor prognosis ICC patients. CHC, combined hepatocellular cholangiocarcinoma; CSC, cancer stem cell; EMT, epithelial-mesenchymal transition; FNH, focal nodular hyperplasia; GEO, gene expression omnibus; HCC, hepatocellular carcinoma; HpSC-ICC, hepatic stem cell-like ICC; ICC, intrahepatic cholangiocarcinoma; MH-ICC, mature hepatocyte-like ICC; PLC, primary liver cancer; x-HCC; extreme HCC.

(HEPATOLOGY 2012;56:1792–1803) Primary liver cancer (PLC) is the second most lethal cancer for men in the world.1 Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of PLC. Although ICC is much less common than hepatocellular carcinoma (HCC), its incidence has increased drastically over the past two selleck decades.2,

3 However, the molecular pathogenesis of ICC is largely unknown. Understanding of the tumor biology of HCC and ICC that contributes to tumor heterogeneity is paramount in developing effective therapies to improve patient outcome. The cellular origin of HCC and ICC has been subject to intense debate in recent years. It is thought that HCC is derived from hepatocytes, whereas ICC arises from intrahepatic biliary epithelium. However, a mixed form of HCC and ICC, also known as combined hepatocellular cholangiocarcinoma (CHC), has been described to have distinct clinicopathological features but morphological intermediates

of HCC and ICC, suggesting that HCC and ICC could share the same cellular origin.4-6 Recent studies utilizing high-resolution genomic approaches have shed light on the revelation of cellular origin of HCC and suggest that a subset of HCC contains stem cell-like features.7-10 For example, a subset of tumor cells isolated from HCC patients are tumor-initiating cells with stem cell traits.11-14 Moreover, HCC may share an ICC-like gene expression trait.15 These results are consistent with the cancer Caspase-dependent apoptosis stem cell (CSC) hypothesis, which suggests that most tumor cells are derived from undifferentiated selleck chemical cells with stem-like capabilities and that both ICC and HCC may share the same cellular origin of hepatic stem/progenitor cells. Global messenger RNA (mRNA) and microRNA profiling approaches have been proven to be effective in identifying genes critical to HCC.8, 9, 16-22 In this study, we used both mRNA and microRNA profiling approaches to determine tumor heterogeneity and molecular characteristics of ICC. We found

that ICC samples consist of at least two main subtypes that share similar molecular activities, with HCC linked to stem cell-like gene expression and patient survival. Integrative genomic analyses revealed that genes and microRNAs involved in epithelial-mesenchymal transition (EMT) are altered in stem-like ICCs. Our results shed light on ICC diagnosis and may open new avenues for therapeutic interventions for targeting poor prognosis ICC patients. CHC, combined hepatocellular cholangiocarcinoma; CSC, cancer stem cell; EMT, epithelial-mesenchymal transition; FNH, focal nodular hyperplasia; GEO, gene expression omnibus; HCC, hepatocellular carcinoma; HpSC-ICC, hepatic stem cell-like ICC; ICC, intrahepatic cholangiocarcinoma; MH-ICC, mature hepatocyte-like ICC; PLC, primary liver cancer; x-HCC; extreme HCC.