Deficiency of inflammasome components NLRP3, ASC or Caspase-1, or lack of IL-1 signaling prevented alcohol-induced liver inflammation suggesting that IL-1 determines PKC412 concentration the onset of inflammation in AH. Next we evaluated whether IL-1 also drives the persistence of liver inflammation in AH. We observed that liver

inflammation and increased IL-1 were sustained for at least three days after cessation of alcohol, followed by delayed apoptosis of inflammatory cells in the liver and limited degree of hepatocyte regeneration. We discovered that inhibition of IL-1 signaling using a single dose of IL-1Ra at cessation of alcohol increased apoptosis of liver immune cells, facilitated regeneration of hepatocytes, and resulted in increased rate of recovery from liver injury in AH. These findings were consistent with in vitro studies showing that IL-1 administration check details promotes cytotoxicity of primary hepatocytes while it provides pro-survival benefit for BM-derived immune cells Conclusions: Our novel findings demonstrate that IL-1 drives sustained liver inflammation

and impaired hepatocyte regeneration even after cessation of ethanol exposure in AH. Therapeutic inhibition of IL-1 improves hepatocyte survival and promotes death of activated harmful immune cells in a preclin-ical model of AH. Disclosures: Gyongyi Szabo – Consulting: Idenix; Grant/Research Support: BMS, GSK, Cona-tus, Idera, Johnson&Johnson, Novartis, Ocera, Roche, Shering – Plough, Wyeth, Integrated click here Therapeutics, Idera The following people have nothing to disclose: Jan Petrasek, Arvin Irache-ta-Vellve, Shashi Bala, Timea Csak, Karen Kodys, Evelyn A. Kurt-Jones Background: Epidemiological studies revealed that nearly 80% of heavy drinkers with alcoholic liver disease (ALD) also smoke tobacco. This finding suggests that tobacco and possibly its toxins have cofactor roles in ALD pathogenesis. Our research focused on the potential role of NNK as a mediator

of hepa-tocellular injury in ALD because previous efforts showed that other nitrosamines can cause hepatic steatosis or steatohep-atitis with insulin resistance, inflammation, oxidative and ER stress, and lipotoxicity. Moreover, toxic lipids, particularly ceramides, can promote the same effects. Due to the inability to detect significant molecular profiles by routine histological studies, we explored the potential use of matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry as a diagnostic aid for characterizing the nature and possibly etiology of steatohepatitis. Hypothesis: IMS can be used to generate biochemical signatures of steatohepatitis caused by different agents.

The proband had prolonged PT (60.0 s) and APTT (104.4 s), and inhibitor screening was negative. The levels of other routine coagulation parameters were normal (data not shown). The levels of FX:C based on

the PT and APTT determinations, and amidolytic activity based on the RVV assays were 0.22%, 0.24% and 1.71% of normal levels, respectively, whereas FX:Ag level was 53.36% of normal. The proband was diagnosed with severe FX deficiency characterized by type II deficiency. All results of the FX assays in the pedigree are summarized in Fig. 1b. DNA sequence analysis revealed that there were two novel heterozygous mutations of the F10 gene in the proband: one was a consensus donor splice sequence in intron 5 (IVS5+1G>A), and the other was a 3-bp (GAC) deletion at position 28091-3delGAC, resulting in the deletion of aspartic acid 409 (Asp409del). Pedigree analysis showed that both parents of the proband had previously passed away. However, Selleckchem CHIR 99021 his maternal aunt (I-1) had the heterozygous Asp409del mutation, and his daughter (III-1) only inherited the heterozygous mutation of IVS5+1G>A, suggesting that these two mutations are located in different alleles of the proband. The genetic defects of the pedigree members are shown in Fig. 1. Ectopic transcripts of the proband and one healthy control were analysed using RT-PCR.

Electrophoresis of the PCR products showed that only one normal-sized band (489 bp) was present on the agarose gel of the proband. Moreover, sequencing of the fragment confirmed this website that it was a normal transcript (Fig. 2a and RAD001 b), suggesting that the abnormal transcript derived from the allele with the IVS5+1G>A mutation was not present. To verify this result, the heterozygous deletion (Asp409del) in exon 8 of the other allele was used as an informative marker. The ectopic transcripts of the region from exon 7 to exon 8

were cloned into the pMD18-T vector, and only sequences with the deletion were identified after the sequencing of 30 clones, confirming that the transcript from the IVS5+1G>A mutated allele was absent (Fig. 2c and d). Transient expression results showed that the FX:C levels of the Asp409del mutant in conditioned media were 0.16% ± 0.02% (PT-based), 0.13% ± 0.01% (APTT-based) and 0.08% ± 0.01% (chromogenic assay) of wild-type FX level respectively. Taken together, these results show that the enzymatic activity of the mutant was dramatically impaired. FX:Ag levels of the Asp409del variant expressed in conditioned media and cell lysates were 82.35% ± 3.58% and 103.41% ± 5.69% of wild-type level respectively. The three-dimensional structure of FXa (PDB ID 2BOK) suggests that the sodium ion (Na+)-binding site is proximal to both the catalytic pocket of the enzyme and the FVa-binding helix at residues 163–170 (Fig. 3a). Asp409 is given as Asp185a in chymotrypsin numbering and is located in the Na+-binding loop region of FXa (residues 185–189).

The proband had prolonged PT (60.0 s) and APTT (104.4 s), and inhibitor screening was negative. The levels of other routine coagulation parameters were normal (data not shown). The levels of FX:C based on

the PT and APTT determinations, and amidolytic activity based on the RVV assays were 0.22%, 0.24% and 1.71% of normal levels, respectively, whereas FX:Ag level was 53.36% of normal. The proband was diagnosed with severe FX deficiency characterized by type II deficiency. All results of the FX assays in the pedigree are summarized in Fig. 1b. DNA sequence analysis revealed that there were two novel heterozygous mutations of the F10 gene in the proband: one was a consensus donor splice sequence in intron 5 (IVS5+1G>A), and the other was a 3-bp (GAC) deletion at position 28091-3delGAC, resulting in the deletion of aspartic acid 409 (Asp409del). Pedigree analysis showed that both parents of the proband had previously passed away. However, find more his maternal aunt (I-1) had the heterozygous Asp409del mutation, and his daughter (III-1) only inherited the heterozygous mutation of IVS5+1G>A, suggesting that these two mutations are located in different alleles of the proband. The genetic defects of the pedigree members are shown in Fig. 1. Ectopic transcripts of the proband and one healthy control were analysed using RT-PCR.

Electrophoresis of the PCR products showed that only one normal-sized band (489 bp) was present on the agarose gel of the proband. Moreover, sequencing of the fragment confirmed selleck inhibitor that it was a normal transcript (Fig. 2a and CH5424802 manufacturer b), suggesting that the abnormal transcript derived from the allele with the IVS5+1G>A mutation was not present. To verify this result, the heterozygous deletion (Asp409del) in exon 8 of the other allele was used as an informative marker. The ectopic transcripts of the region from exon 7 to exon 8

were cloned into the pMD18-T vector, and only sequences with the deletion were identified after the sequencing of 30 clones, confirming that the transcript from the IVS5+1G>A mutated allele was absent (Fig. 2c and d). Transient expression results showed that the FX:C levels of the Asp409del mutant in conditioned media were 0.16% ± 0.02% (PT-based), 0.13% ± 0.01% (APTT-based) and 0.08% ± 0.01% (chromogenic assay) of wild-type FX level respectively. Taken together, these results show that the enzymatic activity of the mutant was dramatically impaired. FX:Ag levels of the Asp409del variant expressed in conditioned media and cell lysates were 82.35% ± 3.58% and 103.41% ± 5.69% of wild-type level respectively. The three-dimensional structure of FXa (PDB ID 2BOK) suggests that the sodium ion (Na+)-binding site is proximal to both the catalytic pocket of the enzyme and the FVa-binding helix at residues 163–170 (Fig. 3a). Asp409 is given as Asp185a in chymotrypsin numbering and is located in the Na+-binding loop region of FXa (residues 185–189).

The proband had prolonged PT (60.0 s) and APTT (104.4 s), and inhibitor screening was negative. The levels of other routine coagulation parameters were normal (data not shown). The levels of FX:C based on

the PT and APTT determinations, and amidolytic activity based on the RVV assays were 0.22%, 0.24% and 1.71% of normal levels, respectively, whereas FX:Ag level was 53.36% of normal. The proband was diagnosed with severe FX deficiency characterized by type II deficiency. All results of the FX assays in the pedigree are summarized in Fig. 1b. DNA sequence analysis revealed that there were two novel heterozygous mutations of the F10 gene in the proband: one was a consensus donor splice sequence in intron 5 (IVS5+1G>A), and the other was a 3-bp (GAC) deletion at position 28091-3delGAC, resulting in the deletion of aspartic acid 409 (Asp409del). Pedigree analysis showed that both parents of the proband had previously passed away. However, Ulixertinib chemical structure his maternal aunt (I-1) had the heterozygous Asp409del mutation, and his daughter (III-1) only inherited the heterozygous mutation of IVS5+1G>A, suggesting that these two mutations are located in different alleles of the proband. The genetic defects of the pedigree members are shown in Fig. 1. Ectopic transcripts of the proband and one healthy control were analysed using RT-PCR.

Electrophoresis of the PCR products showed that only one normal-sized band (489 bp) was present on the agarose gel of the proband. Moreover, sequencing of the fragment confirmed selleck chemical that it was a normal transcript (Fig. 2a and learn more b), suggesting that the abnormal transcript derived from the allele with the IVS5+1G>A mutation was not present. To verify this result, the heterozygous deletion (Asp409del) in exon 8 of the other allele was used as an informative marker. The ectopic transcripts of the region from exon 7 to exon 8

were cloned into the pMD18-T vector, and only sequences with the deletion were identified after the sequencing of 30 clones, confirming that the transcript from the IVS5+1G>A mutated allele was absent (Fig. 2c and d). Transient expression results showed that the FX:C levels of the Asp409del mutant in conditioned media were 0.16% ± 0.02% (PT-based), 0.13% ± 0.01% (APTT-based) and 0.08% ± 0.01% (chromogenic assay) of wild-type FX level respectively. Taken together, these results show that the enzymatic activity of the mutant was dramatically impaired. FX:Ag levels of the Asp409del variant expressed in conditioned media and cell lysates were 82.35% ± 3.58% and 103.41% ± 5.69% of wild-type level respectively. The three-dimensional structure of FXa (PDB ID 2BOK) suggests that the sodium ion (Na+)-binding site is proximal to both the catalytic pocket of the enzyme and the FVa-binding helix at residues 163–170 (Fig. 3a). Asp409 is given as Asp185a in chymotrypsin numbering and is located in the Na+-binding loop region of FXa (residues 185–189).

Baseline HBsAg levels significantly varied across HBV genotype, baseline levels were 4.59, 4.23, 3.91, and 4.53 log IU/mL for patients with genotypes A, B, C, and D (P < 0.001 by analysis of variance [ANOVA]). Mean HBsAg decline at 6 months posttherapy was 0.73 log IU/mL. MG-132 nmr HBsAg decline during treatment varied significantly by therapy regimen; patients treated with combination therapy (n = 338) achieved an end of treatment decline

of 1.37 log IU/mL, compared to 0.92 in patients treated with PEG-IFN monotherapy (P < 0.001). However, HBsAg declines at 6 months posttreatment did not differ: declines were 0.68 and 0.80 log IU/mL for patients treated with PEG-IFN alone versus PEG-IFN with LAM (P = 0.293). HBsAg decline during

treatment also varied across the HBV genotypes (Fig. 1). At 6 months posttreatment, mean declines were 1.60 and 0.96 log IU/mL for patients with genotypes A or B, versus 0.46 and 0.39 log IU/mL for patients infected with genotypes C or D (P < 0.001). A decline of HBsAg check details levels was most pronounced in patients who achieved a response (Fig. 2A). HBsAg declines at end of treatment and at 6 months posttreatment were 2.39 and 1.98 log IU/mL in responders, compared to 0.73 and 0.34 log IU/mL in nonresponders (P < 0.001 for responders versus nonresponders). Similar patterns were observed across the HBV genotypes (Fig. 2B-E). Responders achieved more HBsAg decline by 6 months posttreatment than nonresponders,

also when adjusting for combination therapy and HBV genotype: 2.05 versus 0.50 log IU/mL (P < 0.001). Of the 803 enrolled patients, 779 (97%) had available HBsAg levels at week 12, and 788 (98%) had HBsAg levels at week 24. Analysis of the association between HBsAg levels and declines find more at weeks 12 and 24 and response to treatment showed that the previously identified cutoffs from the respective studies (<1,500 for identification of patients with a high likelihood of response, >20,000 IU/mL or absence of a decline for identification of nonresponders) were superior also in the pooled dataset (Supporting Fig. 1A-D). At week 12, patients with HBsAg levels <1500 IU/mL had a probability of response of 45%, compared to 6% in patients with HBsAg >20,000 IU/mL (NPV: 94%, P < 0.001, Fig. 3A). The probability of HBsAg loss was 15% for patients with an HBsAg level <1,500 IU/mL at weeks 12 or 24. However, six patients with HBsAg >20,000 IU/mL at week 12 achieved HBsAg loss by 6 months posttreatment (6 out of 38 with HBsAg loss, or 16%). At week 24, only 4 of 162 patients with HBsAg >20,000 IU/mL achieved a response, and none cleared HBsAg (NPVs 98% and 100%, Fig. 3B). Of patients who did not achieve a decline in HBsAg levels from baseline to week 12, 14% achieved a response (NPV 86%, P = 0.001, Fig. 3C) and two cleared HBsAg (5% of all patients with HBsAg loss). Similar observations were made when decline was assessed at week 24 (Fig. 3D).

Here we show that an unusual phosphatidyl-choline species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine

(DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose Selleckchem Fostamatinib homeostasis. The orphan nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) is regarded as a central regulator of bile salt biosynthesis and bile salts are increasingly recognized as modulators

of glucose and lipid metabolism in mice and men. In their remarkable study, Lee et al.1 identified a ligand for LRH-1, dilauroyl phosphatidylcholine (DLPC), a C12:0/C12:0 phospholipid, which had potent effects on glucose, Selleckchem Compound Library lipid, and bile salt homeostasis in vivo. In a cell-free system, Lee et al. demonstrated by mass spectrometry that DLPC specifically binds to a recombinant LRH-1 ligand-binding domain. Agonism for LRH-1 could be confirmed in an elegant mammalian two-hybrid assay for DLPC and its sister-molecule diundecanoyl phosphatidylcholine (DUPC; C11:0/C11:0). On functional level, DLPC and even more DUPC were strong activators of both human and mouse LRH-1, whereas other nuclear receptors including FXR, CAR, PXR, PPARα and PPARγ were all unaffected in cell culture. DLPC and

DUPC induced transactivation of the native mouse Shp and Oct4 promoters, in line with previous studies on Lrh-1.2, 3 In the human hepatoma cell line HepG2, DLPC induced the expression of CYP8B1. When orally applied to wildtype mice, DLPC and DUPC induced the expression of hepatic Cyp7a1, Cyp8b1, and Sr-b1 but repressed Shp, leading to a modest increase in serum bile salts and total bile salt pool. These findings were consistent with previous observations in selleck inhibitor liver-specific Lrh-1 knockouts.4 More strikingly, DUPC- and DLPC-treated mice showed significantly decreased serum glucose, serum nonesterified fatty acids (NEFAs), and hepatic triglycerides. The effects of DLPC were lost in LRH-1 floxed (Lrh-1f/f) mice after administration of adenoviral Cre (Ad-Cre) vector, deleting LRH-1. Comparative oral administration of cholate (100 mg/kg body weight twice daily) improved serum NEFAs and hepatic triglycerides to a similar degree, but did not affect serum glucose. The surprising effects of DLPC on glucose metabolism were further investigated in a diabetic model, utilizing insulin-resistant leptin receptor deficient db/db mice. DLPC improved glucose homeostasis, as assessed by serum insulin, glucose tolerance test (GTT), and insulin tolerance test (ITT).

Here we show that an unusual phosphatidyl-choline species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine

(DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose Poziotinib mouse homeostasis. The orphan nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) is regarded as a central regulator of bile salt biosynthesis and bile salts are increasingly recognized as modulators

of glucose and lipid metabolism in mice and men. In their remarkable study, Lee et al.1 identified a ligand for LRH-1, dilauroyl phosphatidylcholine (DLPC), a C12:0/C12:0 phospholipid, which had potent effects on glucose, Smad inhibitor lipid, and bile salt homeostasis in vivo. In a cell-free system, Lee et al. demonstrated by mass spectrometry that DLPC specifically binds to a recombinant LRH-1 ligand-binding domain. Agonism for LRH-1 could be confirmed in an elegant mammalian two-hybrid assay for DLPC and its sister-molecule diundecanoyl phosphatidylcholine (DUPC; C11:0/C11:0). On functional level, DLPC and even more DUPC were strong activators of both human and mouse LRH-1, whereas other nuclear receptors including FXR, CAR, PXR, PPARα and PPARγ were all unaffected in cell culture. DLPC and

DUPC induced transactivation of the native mouse Shp and Oct4 promoters, in line with previous studies on Lrh-1.2, 3 In the human hepatoma cell line HepG2, DLPC induced the expression of CYP8B1. When orally applied to wildtype mice, DLPC and DUPC induced the expression of hepatic Cyp7a1, Cyp8b1, and Sr-b1 but repressed Shp, leading to a modest increase in serum bile salts and total bile salt pool. These findings were consistent with previous observations in selleck screening library liver-specific Lrh-1 knockouts.4 More strikingly, DUPC- and DLPC-treated mice showed significantly decreased serum glucose, serum nonesterified fatty acids (NEFAs), and hepatic triglycerides. The effects of DLPC were lost in LRH-1 floxed (Lrh-1f/f) mice after administration of adenoviral Cre (Ad-Cre) vector, deleting LRH-1. Comparative oral administration of cholate (100 mg/kg body weight twice daily) improved serum NEFAs and hepatic triglycerides to a similar degree, but did not affect serum glucose. The surprising effects of DLPC on glucose metabolism were further investigated in a diabetic model, utilizing insulin-resistant leptin receptor deficient db/db mice. DLPC improved glucose homeostasis, as assessed by serum insulin, glucose tolerance test (GTT), and insulin tolerance test (ITT).

APRI, AST/Platelet ratio index; AST, aspartate aminotransferase; BMI, body mass index; GGT, γ-glutamyl transferase; GSH, glutathione; INCB024360 HALT-C, Hepatitis C Anti-viral Treatment Against Cirrhosis Trial; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IFN, interferon; SVR, sustained virological response. HALT-C had two major treatment phases (clinical

trials.gov identifier NCT00006164) and an observational phase.5-7 A lead-in phase used full-dose pegylated interferon alpha 2a (Pegasys, Roche) and ribavirin to attempt to achieve sustained virological response (SVR) among patients with advanced liver disease (Ishak fibrosis score of 3 or greater on liver biopsy) who had previously been treated with standard interferon (IFN) with or without ribavirin. Patients who did not achieve SVR were eligible for the randomized phase, a controlled clinical trial of pegylated interferon alfa-2a at a dosage of 90 μg per week for 3.5 years, as

compared with no treatment. The primary endpoint was progression of liver disease, as indicated by death, hepatocellular carcinoma (HCC), hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Most patients entered the randomized trial through the lead-in phase as nonresponders after 20 weeks ABT-199 cell line of therapy (based on detectable hepatitis C virus (HCV) RNA by Roche Cobas Amplicor assay) or after subsequent breakthrough or relapse. Other patients entered the randomized phase as “express” patients by having failed to clear virus outside of the HALT-C lead-in. All patients also had liver biopsies scheduled at 18 months after randomization and

at the end of treatment 42 months after randomization. Patients continued to be followed in the observational phase for clinical outcomes off therapy for as long as 5 additional years. The median duration of participation in the trial (time from randomization to first outcome or last time known to be outcome-free) was 6.0 years (range, 0-8.7 years). Informed consent in writing was obtained from each patient, and the study protocol was approved by the Institutional Review Committee learn more of each of the participating centers. GGT activity was measured under code on stored frozen samples (−80°C) by Wako Pharmaceuticals (Richmond, VA) under a clinical trial agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. The normal range was reported as 12-64 IU/L for men and 9-36 IU/L for women. Of the 1,319 patients with GGT measurements, 770 participated in both the lead-in and randomized phases of the trial (blood sample drawn shortly before lead-in), 320 only in the lead-in phase (blood sample drawn shortly before lead-in), and 229 only in the randomized phase (blood sample drawn shortly before randomization). GGT results were available on 95.2% of lead-in patients and 95.

5% or 5.0% of AP for the rest of 14 weeks after the administration of DSS. Sixteen weeks after AOM injection, all groups were sacrificed for histopathology analysis and the colon tumor assay. Key molecules of inflammation and proliferation pathway, such as BKM120 nmr IL-1β, IL-6, TNF-α, cyclooxygenase-2 (COX-2), myeloperoxidase (MPO)

and proliferating cell nuclear antigen (PCNA) were assessed by ELISA and Western blot from mice colonic mucosa. Results: Eight (100%), 6 (75%) and 4 (50%) mice in each AOM-treated group (G4-G6) developed cancers (P trend = 0.024). Among AOM-treated mice, significant reduction in tumor multiplicity and tumor size were observed in both groups fed with AP compared to the standard diet group (multiplicity: 10.1 ± 2.3 vs. 2.8 ± 0.9 and 2.6 ± 0.8 P = 0.025, P = 0.023; size: 5.8 ± 0.8 vs. 2.5 ± 0.8 and 2.4 ± 1.0, P = 0.025, P = 0.016). Also, significant reduction in COX-2 expression in the AOM-treated group with 5% AP and inhibition of IL-1β, IL-6, TNF-α, MPO and PCNA expressions in the AOM-treated groups with AP in a dose-dependent manner (all P < 0.05). Conclusion: Açaí reduced the incidence, multiplicity and size of AOM/DSS-induced see more tumor in

mice. Açaí may have a potential to prevent colon carcinogenesis via anti-inflammatory and anti-proliferative properties. Key Word(s): 1. açaí; 2. colon cancer; 3. azoxymethane; 4. dextran Presenting Author: HYUN HO CHOI Additional Authors: CHUL HYUN LIM, MYUNG GUEN CHA, WON KYUNG KANG, JIN SU KIM, YU KYUNG CHO, JAE MYUNG PARK, BO INN LEE, IN SEOK LEE, SANG WOO KIM, MYUNG GYU CHOI Corresponding Author: HYUN HO CHOI Affiliations: The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of

Korea, The Catholic University of Korea, The Catholic University of Korea Objective: In immunoglobulin G4(IgG4)-related disease is a relatively new disease entity characterized by elevated serum IgG4 levels and marked infiltration find more of IgG4-positive plasma cells in mass lesions. Organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs. IgG4-related disease has an older male predominance, with most patients in the 6th decade of life. We report a young female patient with an inflammatory pseudotumor of the low rectum, which was histopathologically confirmed to be IgG4-related disease. Methods: We retrospectively reviewed the medical records of a patient with IgG4-related disease of the low rectum. Results: The patient was a 28-year-young woman who presented with constipation for approximately 3 months.

5% or 5.0% of AP for the rest of 14 weeks after the administration of DSS. Sixteen weeks after AOM injection, all groups were sacrificed for histopathology analysis and the colon tumor assay. Key molecules of inflammation and proliferation pathway, such as check details IL-1β, IL-6, TNF-α, cyclooxygenase-2 (COX-2), myeloperoxidase (MPO)

and proliferating cell nuclear antigen (PCNA) were assessed by ELISA and Western blot from mice colonic mucosa. Results: Eight (100%), 6 (75%) and 4 (50%) mice in each AOM-treated group (G4-G6) developed cancers (P trend = 0.024). Among AOM-treated mice, significant reduction in tumor multiplicity and tumor size were observed in both groups fed with AP compared to the standard diet group (multiplicity: 10.1 ± 2.3 vs. 2.8 ± 0.9 and 2.6 ± 0.8 P = 0.025, P = 0.023; size: 5.8 ± 0.8 vs. 2.5 ± 0.8 and 2.4 ± 1.0, P = 0.025, P = 0.016). Also, significant reduction in COX-2 expression in the AOM-treated group with 5% AP and inhibition of IL-1β, IL-6, TNF-α, MPO and PCNA expressions in the AOM-treated groups with AP in a dose-dependent manner (all P < 0.05). Conclusion: Açaí reduced the incidence, multiplicity and size of AOM/DSS-induced Adriamycin mouse tumor in

mice. Açaí may have a potential to prevent colon carcinogenesis via anti-inflammatory and anti-proliferative properties. Key Word(s): 1. açaí; 2. colon cancer; 3. azoxymethane; 4. dextran Presenting Author: HYUN HO CHOI Additional Authors: CHUL HYUN LIM, MYUNG GUEN CHA, WON KYUNG KANG, JIN SU KIM, YU KYUNG CHO, JAE MYUNG PARK, BO INN LEE, IN SEOK LEE, SANG WOO KIM, MYUNG GYU CHOI Corresponding Author: HYUN HO CHOI Affiliations: The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of Korea, The Catholic University of

Korea, The Catholic University of Korea, The Catholic University of Korea Objective: In immunoglobulin G4(IgG4)-related disease is a relatively new disease entity characterized by elevated serum IgG4 levels and marked infiltration find more of IgG4-positive plasma cells in mass lesions. Organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs. IgG4-related disease has an older male predominance, with most patients in the 6th decade of life. We report a young female patient with an inflammatory pseudotumor of the low rectum, which was histopathologically confirmed to be IgG4-related disease. Methods: We retrospectively reviewed the medical records of a patient with IgG4-related disease of the low rectum. Results: The patient was a 28-year-young woman who presented with constipation for approximately 3 months.