[1] According to Japanese annual health check reports, 9–30% of Japanese adults suffer from NAFLD.[2-4] This prevalence of NAFLD is similar to that reported from Western countries due to the westernization of lifestyles and the increasing rates of obesity and diabetes.[5, Copanlisib 6] Non-alcoholic fatty liver disease is characterized by hepatic steatosis in the absence of significant alcohol use or other known liver diseases. NAFLD includes a wide spectrum of liver diseases, ranging from non-alcoholic fatty liver (NAFL), a benign and non-progressive condition, to non-alcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and hepatocellular carcinoma.[7-10] Hepatic steatosis is a common feature

among patients with not only NAFLD but also alcoholic liver disease and those with hepatitis C viral infection. In patients with chronic hepatitis C, coexisting steatosis reportedly accelerates fibrosis progression and reduces the treatment response.[11] As such, the ability to accurately diagnose hepatic steatosis has important

implications for clinical management. Liver biopsy is very useful for establishing diagnosis, activity grade (degree of inflammation and cellular injury) and stage of fibrosis in NAFLD, though it is an invasive method to examine the liver histology, sometimes frequently. Furthermore, there may be risks of interobserver differences and/or sampling errors. The ideal non-invasive test should be simple, reproducible, readily available, less expensive, and able to predict both liver fibrosis stages and grades of steatosis occurring with therapy. Several simple laboratory tests (in isolation or Aprepitant LEE011 purchase in combination), serum markers of fibrogenesis, have been evaluated as a substitute for liver biopsy in NAFLD and had showed varying degrees of accuracy when compared to liver biopsy. So

far, ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) are available for diagnosing fatty infiltration of the liver non-invasively. Recently, a novel attenuation parameter has been developed to detect and quantify steatosis as fat affects ultrasound propagation. This parameter, which is called the controlled attenuation parameter (CAP) because it specifically targets the liver, is based on the ultrasonic properties of the reflected radio frequency signals acquired by the FibroScan probe (Echosens, Paris, France). By employing this method, we have reported that CAP is a promising tool to detect the presence of steatosis, immediately, repeatedly and non-invasively.[12] On the other hand, CT scans have proven to be useful in diagnosing the presence and quantifying the severity of liver fat non-invasively and have been traditionally used. The Hounsfield unit attenuation of liver on CT scans is usually higher than the spleen; when this ratio is reversed, this can be used to diagnose the presence of liver fat.[13] So far, fatty liver has been reported to be defined as less than 0.

They concluded that H. pylori infection along with an elevated TGF-β1 might accelerate hepatic fibrosis through increased TGF-β1-induced pro-inflammatory signaling pathways in hepatic stellate cells. Moreover, they suggest that H. pylori infection would

increase the risk of TGF-β1-mediated tumorigenesis by disturbing the balance between apoptosis and proliferation of hepatocytes. Bacterial infection is accepted as a precipitating check details factor in cholesterol gallstone formation, and recent studies have revealed the presence of Helicobacter species in the hepatobiliary system. Lee et al. utilized PCR to establish the presence of bacterial DNA, including from Helicobacter species, in gallstones, bile juice, and gallbladder mucosa MLN8237 mw from patients with gallstones [24]. At cholecystectomy, 58 gallstones, 48 bile samples, and 46 gallbladder mucosal specimens were obtained and subjected to nested PCR using specific 16S rRNA primers of H. pylori and other bacteria. Bacterial 16S rRNA was detected in 25 of 36 (69.4%) mixed cholesterol gallstones, one of 10 (10%) pure cholesterol gallstones, and 9 of 12 (75%) pigmented stones, and 16S rDNA sequencing identified Escherichia coli, Pseudomonas, Citrobacter, Klebsiella, and Helicobacter species. Helicobacter DNA was detected in 4 of 58 (6.9%) gallstones, 6 of 48 (12.5%) bile samples, and 5 of 46 (10.9%) gallbladder specimens. Direct sequencing of

Helicobacter amplicons confirmed H. pylori strains in all four gallstones, in five of 6 (83.3%) bile samples, and in three of 5 (60%) gallbladder specimens. Although almost all mixed cholesterol gallstones appear to harbor bacterial DNA, predominantly E. coli, H. pylori was also found in the biliary system, suggesting that these bacteria play a role in the gallstone formation. Helicobacter pylori has been suggested to

be involved in pancreatic diseases, namely autoimmune pancreatitis and pancreas cancer. Jesnowski et al. investigated the presence of conserved sequences of Helicobacter in pancreatic tissue and pancreatic juice from patients Rutecarpine with chronic nonautoimmune and autoimmune pancreatitis as well as pancreatic ductal adenocarcinoma [25]. They collected 35 pancreatic juice samples during routine endoscopic retrograde cholangiopancreatography and 30 pancreatic tissue samples and performed a nested PCR to detect H. pylori in the isolated DNA samples. However, they could detect no H. pylori DNA, suggesting that a direct infection of the microbial agent in the pancreas seems unlikely. Dobbs et al. examined the effect of eradicating H. pylori in idiopathic parkinsonism by a randomized, placebo-controlled study [26]. Thirty idiopathic parkinsonism patients infected with H. pylori and taking no anti-parkinsonian medication were enrolled. Stride length improved (73 mm/year; [95% CI: 14–131]; p = .

The differential diagnosis can include drug-induced cholestasis, cardiac failure and various viral and fungal hepatic infections. With Doppler ultrasonography,

findings consistent with sinusoidal obstruction syndrome are retrograde portal venous flow, a reduction in hepatic venous flow and edema of the gallbladder wall. Treatment with defibrotide may be helpful for some patients but the drug has not been tested in a controlled trial. Ursodeoxycholic acid may also be helpful for prophylaxis in higher-risk patients. Although sinusoidal obstruction syndrome can resolve spontaneously, patients with severe disease can progress to multiorgan failure and death. In the setting of myeloablative regimens, mortality rates are often of the order Navitoclax nmr of 15–20%. Contributed by “
“Apoptosis (a crucial physiological form of programmed cell death) of hepatocytes

is a critical prerequisite to preserve liver homeostasis and protect against malignant transformation and carcinogenesis. In a report by Weber et al. in this issue of HEPATOLOGY,1 the authors identify the prosurvival B cell lymphoma-2 (Bcl-2) family member myeloid cell leukemia-1 (Mcl-1) as a critical learn more player in hepatocyte apoptosis. Interestingly, the authors provide data that the increased spontaneous apoptosis observed in hepatocytes lacking Mcl-1 translates into development of malignant hepatocellular carcinoma (HCC)-like lesions in mice starting from 8 months of age. Using a mouse model harboring the loxP-targeted allele of Mcl-1 in addition to Cre recombinase expressed under the albumin promoter, the study provides convincing, genetically precise experimentation and an intriguing finding: increased apoptosis in hepatocytes goes hand in hand with carcinogenesis illustrating an intriguing connection between apoptosis and cancer research. Bcl-2, B cell lymphoma-2; Glycogen branching enzyme BH3, Bcl-2 homology domain 3; Bid, BH3-interacting domain death agonist; HCC, hepatocellular carcinoma; Mcl-1,

myeloid cell leukemia-1. The critical role of the prosurvival Bcl-2 family members Mcl-1 and Bcl-x(L) in guarding apoptosis in hepatocytes has previously been described by the same group and others.2-4 Mice lacking either Mcl-1 or Bcl-x(L) (both constitutively expressed in the liver) specifically in their hepatocytes present with strongly increased spontaneous hepatocyte apoptosis and liver fibrosis. Furthermore, Mcl-1–deficient hepatocytes are more susceptible to Fas-mediated liver damage.2 Mcl-1 and Bcl-x(L) cooperatively regulate hepatocyte integrity to a point where liver-specific deletion of both proteins leads to rapid postnatal death of experimental animals due to hepatic failure.3 The findings on the apoptotic function of Mcl-1 and Bcl-x(L) are interesting, but somewhat expected, especially in the light of their known antiapoptotic function and their expression pattern in the liver.

Effects of dasatinib on cell cycle were assessed using Nim-Dapi staining. Cells were plated evenly in control and experimental wells and allowed to grow to log-phase then treated with 100 nM dasatinib for 24 hours. To perform cell cycle analysis, cells were washed with PBS and trypsin was applied to release cells, which were then centrifuged at 3,000 rpm for 5 minutes. Supernatant was aspirated and cells were then resuspended in 100 μL of Nim-Dapi (NPE Systems, Pembroke Pines, FL) and gently vortexed. Cells were analyzed Selleck Midostaurin with UV using a Cell Lab Quanta SC flow cytometer (Beckman-Coulter). Apoptosis assays were performed using

an Annexin V-FITC apoptosis detection kit (MBL, Woburn, MA) and flow cytometry. Cells were plated and treated as for cell cycle studies and exposed to 100 nM dasatinib for 5 days. After incubation, cells were processed as directed in the kit and analyzed using an FITC signal detector and propidium iodide (PI) detector using a Cell Lab Quanta SC flow cytometer. A one-sided t test was performed measuring significance of the increase in G0/G1 and the decrease in living cells in cell cycle and apoptosis assays, respectively. Lentivirus transduction of a Src short hairpin RNA (shRNA)

was used to knockdown Src expression. HLE and SNU 423 cells were plated in a six-well plate at a density of 2-2.5 × 105 cells/well and incubated overnight at 37°C and 5% CO2 in their respective media. Lentiviral particles containing this website c-SRC shRNA (Santa Cruz Biotechnology) was diluted with transduction media consisting

of serum-free, antibiotic-free media and 5 μg/mL of Polybrene (Santa Cruz Biotechnology) to a multiplicity of infection (MOI) 7 and 13. Cells were washed with PBS and then 1 mL of diluted virus was added. Cells transfected with lentiviral particles containing scramble shRNA were used as a negative control and cop-GFP lentivirus was used as a control for transduction efficiency. After 18 hours, lentiviral shRNA media was removed and replaced with media containing serum and antibiotics. After overnight incubation the cells were trypsinized and placed in T-25 flasks with media containing 5 μg/mL puromycin (Santa Cruz Biotechnology). Cells were detached 72 hours posttransduction and analyzed by flow cytometry for green fluorescence protein why (GFP) expression. All noninfected cells were killed by puromycin, and remaining cells had GFP expression, indicating 90%-100% transduction efficiency. Western blot was performed for total Src and phospho-Src as described above. Growth effects of shRNA were analyzed as described above comparing a vector control with the respective shRNA clone. EGFR, epidermal growth factor receptor; GEO, Gene Expression Omnibus; HB, hepatoblast; HC, hepatocyte; HCC, hepatocellular carcinoma; PI, propidium iodide; SFK, Src-family of tyrosine kinases. A total of 20 human HCC cell lines were used in the study. Available clinical data from the respective repositories are in Table 1.

A. coffeaeformis

had a greater tolerance to higher temperatures than C. sublittoralis, with nonphotochemical quenching (NPQ) activated at temperatures of 45°C and 50°C. C. sublittoralis, however, demonstrated a more rapid rate of recovery at ambient temperatures. Temperatures between 10°C and 20°C were determined to be optimal for photosynthesis for both species. High temperatures and irradiances caused PARP inhibitor a greater decrease in ΔF/Fm’ values. These results suggest that the effects of temperature are species specific and that short-term exposure to adverse temperature slows the recovery process, which subsequently leads to photoinhibition. “
“The charophyte algae are the closest living relatives of land plants. Their life cycles are usually characterized as haploid with zygotic meiosis. This conclusion, however, is based on a small number of observations and on theoretical assumptions about what kinds of life cycle are possible. Little is known about the life cycles of most charophytes, but unusual phenomena have been reported in comparatively well-studied taxa: Spirogyra and Sirogonium are reported to produce diploid gametes with synapsis of homologous RGFP966 supplier chromosomes before fusion of gametic nuclei; Closterium ehrenbergii is reported to undergo chromosome reduction both before and after

syngamy; and zygotes of Coleochaete scutata are reported to replicate their DNA to high levels before a series of reduction for divisions. All of these phenomena require confirmation, as does the conventional account. “
“The effects of different temperatures and light intensities on growth, pigments, sugars, lipids, and proteins, as well as on some antioxidant and proteolytic enzymes of Trachydiscus minutus (Bourr.) H. Ettl, were investigated. The optimum growth temperature and light intensity were 25°C and 2 × 132 μmol photons · m−2 · s−1, respectively. Under these conditions, proteins were the main biomass components (33.45% dry weight [dwt]), with high levels of carbohydrates (29% dwt) and lipids (21.77% dwt). T. minutus tolerated temperatures

between 20°C and 32°C, with only moderate changes in cell growth and biochemical composition. Extremely low (15°C) and high (40°C) temperatures decreased chl and RUBISCO contents and inhibited cell growth. The biochemical response of the alga to both unfavorable conditions was an increase in lipid content (up to 35.19% dwt) and a decrease in carbohydrates (down to 13.64% dwt) with much less of a change in total protein content (in the range of 30.51%–38.13% dwt). At the same time, the defense system of T. minutus was regulated differently in response to heat or cold treatments. Generally, at 40°C, the activities of superoxide dismutase (SOD), catalase (CAT), and proteases were drastically elevated, and three polypeptides were overexpressed, whereas the glutathione reductase (GR) and peroxidase (POD) activities were reduced.

One study observed HBeAg positive patients, 233 treated with IFN and 233 untreated for 6.8 years, with cancers detected in 2% of treated patients and 7%

of untreated controls, showing carcinogenesis significantly reduced in the IFN therapy group (P < 0.025).[90] On the other hand, the other study of HBeAg positive patients, 208 treated with IFN and 203 untreated, found no significant difference in the rate INCB018424 order of carcinogenesis (2.9% vs 0%).[260] Although many other studies have evaluated the relationship between IFN therapy and carcinogenesis,[261-266] they have all been cohort studies and their results do not consistently demonstrate a carcinogenesis suppressor effect for IFN. In these cohort studies, the carcinogenesis rate in the control group (untreated patients) varies greatly from 0% to 30.8%, and the rate including patients with cirrhosis also varies from 0% to 100%, with considerable differences in subject clinical backgrounds. These differences

in the clinical background of applicable cases may be related to the variations in the reported carcinogenesis suppression effect of IFN. check details A number of meta-analyses have examined the relationship between IFN therapy and carcinogenesis. One analysis of 11 studies comprising 1006 patients treated with IFN and 1076 untreated controls found IFN therapy significantly reduced the carcinogenesis risk ratio to 0.59.[267] Another meta-analysis of 8 studies found that, although carcinogenesis was suppressed in IFN treated patients compared to untreated controls BCKDHA (risk difference 5.0%), the carcinogenesis suppression

effect was found in a subgroup of ethnic Asians, where the carcinogenesis rate in the untreated controls was ≥10%, and ≥70% of subjects were HBeAg positive.[268] A third meta-analysis of 7 studies evaluated the therapeutic effect of IFN in patients with cirrhosis, 122 cases of HCC developed in 1505 patients with liver cirrhosis, and a carcinogenesis risk difference of 6.4% in IFN treated patients compared to untreated controls.[269] The authors discussed that, although all 7 studies indicated a tendency for IFN therapy to suppress carcinogenesis, only 3 studies showed a significant difference, of which 2 studies were results from Asia. Then they concluded that the overall significant difference disappeared with elimination of the last 2 Asian studies, and no firm conclusion was made concerning carcinogenesis suppression by IFN therapy. Another meta-analysis of 12 studies examining 1292 IFN treated patients and 1450 untreated controls, IFN therapy significantly reduced the carcinogenesis risk ratio to 0.66.[270] A sub-analysis indicated that carcinogenesis was suppressed by IFN therapy in liver cirrhosis patients (11.6% vs 21.5%, risk ratio 0.53, 95% CI: 0.36–0.78), whereas for non-cirrhosis patients the cancer rate was low, 0.9% in treated patients and 1.1% in untreated controls, showing no significant difference.

Nodular gastritis is also known as nodular hyperplasia, antral nodularity, nodular antritis,

micronodular gastritis, gastric lymphoid hyperplasia, follicular gastritis, lymphofollicular gastritis, goose-flesh- or chicken-skin-appearing gastritis. In a Japanese study, 0.19% of the general population showed nodular gastritis on routine endoscopic examination, click here and all had H. pylori infection.8 It seems that when a new onset of H. pylori infection occurs in adults, some individuals show an immature and aggressive tissue response.9 Some may progress to a diffuse-type nodular gastritis (Fig. 1), but most regress either by atrophic change or H. pylori eradication (Fig. 2). A few may progress to a lymphofollicular malignancy, such as MALT lymphoma, and a few may progress to an https://www.selleckchem.com/products/lgk-974.html undifferentiated adenocarcinoma (Fig. 3). Nodular gastritis can be

improved by H. pylori eradication (Table 2), and disappearance of nodularity on endoscopy is accompanied by a decrease in follicular gastritis score. It has been speculated that inflammatory cytokines or H. pylori-infection-induced prostaglandins might strongly inhibit gastric acid secretion, and these mediators of nodular gastritis can be normalized after successful H. pylori eradication in nodular gastritis.14 Severe inflammation, increased cell proliferation, marked acid inhibition, and active gastritis are known to be linked to H. pylori-associated enlarged-fold gastritis. This special form of H. pylori gastritis can be distinguished from the tumorous condition Astemizole by eradicating H. pylori in patients with gastric giant folds.19 In hypertrophic gastritis, endoscopic ultrasonography demonstrates diffuse thickening of the inner three gastric wall layers (superficial mucosa, muscularis mucosa, and submucosa) without thickening of the outer two layers (muscularis propria and serosa).20 After H. pylori eradication, endoscopic ultrasonography demonstrates concomitant resolution of thickening and normalization of these inner three layers. The prevalence of diffuse-type early gastric cancer can

be increased with increasing gastric-fold width.21 The mutagenicity of gastric juice from the patients with enlarged-fold gastritis was significantly greater than that in H. pylori-negative controls or in H. pylori-positive patients without enlarged folds. Eradication of H. pylori significantly decreased the mutagenicity of gastric juice. Further, 8-Hydroxy-2-deoxy guanosine (8-OHdG) and interleukin-1 beta (IL-1β) levels are increased in the gastric mucosa from patients with enlarged-fold gastritis, and the odds ratio for gastric carcinoma increased up to 35.5 in patients with gastric-fold width ≥ 7 mm. The methylation of E-cadherin in gastric mucosa decreased significantly after H. pylori eradication abolished enlarged-fold gastritis.22 It is also known that such eradication increases acid secretion in H. pylori-associated enlarged-fold gastritis. In one study,23 increases in acid secretion after H.

Change (percentage reduction) in the

number of migraine headache days at each interim visit Cobimetinib order compared to baseline in group A vs group B. Change in the number of migraine attacks at each interim visit (treatment period months 1, 2, and 3) compared to baseline between group A and B. Change in number of subjects with at least a 50% reduction in number of migraine headache days comparing baseline to each visit (treatment period months 1, 2, and 3) in the SumaRT/Nap arm vs the naproxen sodium arm. Change in 2-hour migraine headache relief scores between group A and B. Change in total number of doses of acute medication taken per month comparing baseline to each study visit. Adverse events in the SumaRT/Nap arm vs the naproxen sodium arm. Changes in MIDAS scores at randomization vs 3 months for group A vs group B. Headache history collected by daily diary during the 30-day baseline period between visit 1 and visit 2 for both groups. A migraine day is defined as a day (00:00 to 23:59) R788 with 4 or more hours of headache of at least moderate pain intensity per subject diary, or any day with headache of any duration that has been treated. A migraine attack is defined as a migraine headache lasting at least 4 hours or treated with study medication with a 48-hour pain-free interval between headaches.

Specific quantities of acute medication defined by ICHD-II criteria as medication overuse.[11] Worsening of underlying headache pattern associated with increasing utilization of acute medications and quantities defined by Revised Criteria for MOH.[13] In this study, the determination was made by primary and/or sub-investigators. Data were statistically analyzed for changes between groups and across time via a 2-tailed repeated measures analysis of variance (ANOVA) and t-tests with individual means comparisons compared within

and between group differences on reported number of migraine headache days and attacks per month for the 2 groups. In this analysis, the within-subjects factor consisted of all sample time points, while the between-subjects factor consisted of 2 levels about (Group A and Group B). Data were analyzed from the per-protocol population. An intent-to-treat analysis was considered, but rejected, as the main objective of this study was exploratory in nature and any type of adjusting for missing data would have decreased variability within the small sample size as well. Fifty-nine subjects were screened for this study, satisfying the proposed sample size of 40 subjects. The study population consisted of 39 subjects who randomized per protocol; 3 males and 36 females with a mean age of 39.5 years with a range of 24-57 years with a diagnosis of frequent ICHD-II episodic migraine; 35 were Caucasian, 3 Asian, and 1 Hispanic. Nineteen subjects were randomized to group A (SumaRT/Nap) and 20 to group B (naproxen sodium). Seven subjects did not complete the study; 1 in group A and 6 in group B.

These results indicate that BCHE may be involved in the pathogenesis of HCV-related fibrosis among injection drug users. (HEPATOLOGY 2012) Hepatitis C virus (HCV) affects approximately 170 million people worldwide.1, 2 Nearly 85% of these persons develop chronic infection; the natural history of chronic infection in many cases RG7204 datasheet leads to complications that are the leading reasons for liver transplantation in the United States. Complications usually begin with hepatic fibrosis, lead to cirrhosis, and can ultimately result in hepatocellular carcinoma.3 Progression

to hepatic fibrosis in chronic HCV infection has been previously associated with common downstream mechanisms such as transforming growth factor beta (TGF-β)4, 5 and platelet-derived growth factor (PDGF) signaling pathways6; however, the earliest molecular mechanisms underlying HCV-induced hepatic fibrosis are largely unknown. Therefore, determining how HCV induces hepatic fibrosis is crucial for identifying targetable biological determinants of progressive HCV infection. Progressive hepatic fibrosis is orchestrated by several cellular constituents; however, it is not well understood

how hepatocytes, the sites of HCV replication, contribute to the ensuing fibrosis separately from abundant inflammation and stellate cells that ultimately produce collagen. To understand the direct link between HCV infection and fibrosis, CTLA-4 antibody inhibitor we hypothesized that hepatocyte transcriptomes could be separated from bulk liver tissue and studied. Human liver biopsies deliver only a limited amount of material, and cell separation has

not been attempted to enrich transcriptomes. In addition, the absence of a representative animal model of progressive liver disease has compelled researchers to use in situ methods in studies of HCV pathogenesis. In this context, laser capture ADAMTS5 microdissection (LCM) is an emerging technology that allows isolation of specific cell types while preserving key anatomic relationships of the tissue. The present study was structured into three phases: in the first (discovery) phase, gene expression arrays were used to explore potential markers of fibrosis progression from laser captured hepatocytes and portal tracts. In the second (validation) phase, differential expression of the lead gene, butyrylcholinesterase (BCHE), a critical enzyme in cocaine and heroin metabolism, was confirmed in an expanded cross-sectional cohort of HCV-infected intravenous drug users (IDUs) by measuring a surrogate of BCHE protein expression in archived serum samples. In the third (longitudinal) phase, BCHE expression over time was measured in liver disease progressors and nonprogressors. BCHE, therefore, is a potential pathogenic node that may link drugs of abuse with the development of liver disease in persons with chronic HCV.

All reactions were performed in triplicate using the ABI 7300 real-time PCR system (Life Technologies). The ITGB6, B4 and A3 expression levels were normalized using the average expression levels of the endogenous control genes B2M and TBP. The correlations among the clinicopathological findings and among Fostamatinib order integrins β6, β4 and α3, fibronectin and laminin expression in CoCC, CCC, HCC and classical CHC were assessed by Fisher’s exact test or the

χ2-test and Mann–Whitney U-test. anova was used in the comparison among the ITGB6, B4 and A3 mRNA levels in the hepatic tumors. P < 0.05 was considered significant. IMMUNOHISTOCHEMISTRY DEMONSTRATED THE absence of β6 integrin in normal liver cells and bile duct epithelia but frequent expression on the bile duct epithelium of interlobular and septal ducts with weak positivity on bile ductular epithelium in injured liver tissues, including chronic hepatitis. No positivity for β6 integrin immunostaining was observed in 21 (91%) of 23 CoCC (Table 2, Fig. 1a,b,h) and all HCC (Fig. 1g),

whereas low or highly positive staining for these integrins was demonstrated in 23 (82%) of 28 CCC (Table 2, Fig. 1d–f). The cytoplasmic, cell membrane and basal lamina SAHA HDAC research buy patterns of positive immunostaining were found in CCC (Fig. 1i) and CoCC. The predominant pattern observed in CCC was the cell membrane pattern (61%), whereas the cytoplasmic pattern or basal lamina pattern was predominant in each of two CoCC with focal positivity (Fig. 1c). Positive immunostaining for biliary type integrins many β4 and α3 in normal liver was evident on the biliary epithelium of the interlobular and septal

bile ducts, with faint or no positive staining on the bile ductular epithelium. Positive immunostaining for β4 and α3 on the bile duct epithelium was enhanced in the injured or diseased liver tissues. With regard to hepatic tumors, no or low positive staining for β4 was observed in most (91%) CoCC and all HCC, except one, whereas highly positive staining was evident in most (96%) CCC (Table 2, Fig. 2a–d,j). The predominant pattern of positive staining in CCC was the basal lamina type (Fig. 2d,k). Highly positive immunostaining for α3 was found in 11 (48%) of 23 CoCC and eight (19%) of 42 HCC, but it was more frequently observed in 21 (75%) of 28 CCC (Table 2, Fig. 2f–i,l). The immunoreactivity for α3 was localized to the cytoplasm of the tumor cells, and it was not detected in the cell membrane or basal lamina (Fig. 2f,h,i).