It was shown that HSCs could act as a regulatory bystander, enhancing differentiation and accumulation of Tregs.[9] Activated HSCs can also induce NK cell activation, which results in suppression of liver fibrosis and HCV infection.[5-7, 11] Furthermore, TLR-3 or RIG-I-activated HSCs could produce both type I and type III IFNs that could inhibit HCV replication in hepatocytes.[8, 12, 15] These novel observations, although require further ex vivo and in vivo studies

to confirm, highlight the importance of HSCs in liver immunity against HCV infection. This work was supported by grants (DA12815, DA22177, and DA27550) from the National Institutes of Health. The authors declare that there is no conflict of interest. “
“Wilson disease is a copper metabolism disorder caused by mutations in ATP7B, a copper-transporting adenosine triphosphatase. A molecular diagnosis was performed on 135 Selleckchem Birinapant patients with Wilson disease in Taiwan. We identified 36 different mutations, eight of which were novel: five missense mutations (Ser986Phe, Ile1348Asn, Gly1355Asp, Met1392Lys,

and Ala1445Pro), one deletion (2810delT) in the coding region, and two nucleotide substitutions (−133AC and −215AT) in the promoter region. These mutations were click here not observed in 100 control subjects and reduced the activity of the mutated protein by at least 50% when compared with wild-type ATP7B. In addition to exon 8, our data indicate another mutation hotspot in exon 12 where 9.62% of all mutations occurred. An alternative splice variant of ATP7B lacking exon 12 was observed in one patient who had a homozygous 2810delT mutation and very mild clinical symptoms. Clinical examination and functional characterization of alternative splice variants selleck inhibitor of ATP7B lacking exon 12 showed that they retained 80% of their biological activity. The 2810delT mutation increased the expression of these variants, which may have explained the mild symptoms in the patient with the 2810delT mutation. We also discovered that treating liver cancer cells with a Na+/H+ exchanger inhibitor,

5-(N-ethyl-N-isopropyl)-amiloride, significantly enhanced the expression of the alternative splice variant of ATP7B lacking exon 12. Conclusion: This study suggests a novel therapeutic strategy for patients with mutations in exon 12. (Hepatology 2010;52:1662-1670) Wilson disease (WD) is an autosomal recessive copper metabolism disorder with a prevalence of 1 in 35,000 to 100,000 live births.1-3 It is characterized by impaired biliary excretion and deficient incorporation of copper into ceruloplasmin, leading to toxic accumulation of copper in the liver, brain, cornea, and kidney. The resulting liver cirrhosis and neurological damage are fatal if not treated with copper-chelating agents such as penicillamine. Prompt and appropriate treatment depends on correctly diagnosing WD in the patient and any affected siblings.

It was shown that HSCs could act as a regulatory bystander, enhancing differentiation and accumulation of Tregs.[9] Activated HSCs can also induce NK cell activation, which results in suppression of liver fibrosis and HCV infection.[5-7, 11] Furthermore, TLR-3 or RIG-I-activated HSCs could produce both type I and type III IFNs that could inhibit HCV replication in hepatocytes.[8, 12, 15] These novel observations, although require further ex vivo and in vivo studies

to confirm, highlight the importance of HSCs in liver immunity against HCV infection. This work was supported by grants (DA12815, DA22177, and DA27550) from the National Institutes of Health. The authors declare that there is no conflict of interest. “
“Wilson disease is a copper metabolism disorder caused by mutations in ATP7B, a copper-transporting adenosine triphosphatase. A molecular diagnosis was performed on 135 RAD001 in vivo patients with Wilson disease in Taiwan. We identified 36 different mutations, eight of which were novel: five missense mutations (Ser986Phe, Ile1348Asn, Gly1355Asp, Met1392Lys,

and Ala1445Pro), one deletion (2810delT) in the coding region, and two nucleotide substitutions (−133AC and −215AT) in the promoter region. These mutations were INCB024360 research buy not observed in 100 control subjects and reduced the activity of the mutated protein by at least 50% when compared with wild-type ATP7B. In addition to exon 8, our data indicate another mutation hotspot in exon 12 where 9.62% of all mutations occurred. An alternative splice variant of ATP7B lacking exon 12 was observed in one patient who had a homozygous 2810delT mutation and very mild clinical symptoms. Clinical examination and functional characterization of alternative splice variants click here of ATP7B lacking exon 12 showed that they retained 80% of their biological activity. The 2810delT mutation increased the expression of these variants, which may have explained the mild symptoms in the patient with the 2810delT mutation. We also discovered that treating liver cancer cells with a Na+/H+ exchanger inhibitor,

5-(N-ethyl-N-isopropyl)-amiloride, significantly enhanced the expression of the alternative splice variant of ATP7B lacking exon 12. Conclusion: This study suggests a novel therapeutic strategy for patients with mutations in exon 12. (Hepatology 2010;52:1662-1670) Wilson disease (WD) is an autosomal recessive copper metabolism disorder with a prevalence of 1 in 35,000 to 100,000 live births.1-3 It is characterized by impaired biliary excretion and deficient incorporation of copper into ceruloplasmin, leading to toxic accumulation of copper in the liver, brain, cornea, and kidney. The resulting liver cirrhosis and neurological damage are fatal if not treated with copper-chelating agents such as penicillamine. Prompt and appropriate treatment depends on correctly diagnosing WD in the patient and any affected siblings.

Recently, Hatziapostolou et al.[9] reported that HNF4α can modulate inflammatory signaling to prevent and suppress hepatocellular carcinogenesis through up-regulation of miR-124. We identified here a positive correlation between miR-134 and HNF4α in HCC pathogenesis. We also

show that miR-134 acts as an important functional effector of HNF4α for KRAS suppression and reversion of HCC malignancy. These findings suggest regulating the HNF4α-miRNA cascade could be developed as a strategy for the treatment of HCC. In summary, we have identified a novel mechanism by which HNF4α reverses HCC malignancy through up-regulation of an miRNA cluster in the DLK1-DIO3 region, particularly miR-134. Alisertib cell line Further investigations of the other miRNAs in this cluster are merited. Additional Supporting Information may be found in the online version of this article. “
“Background and Aim:  As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity

in several models, it is important to confirm its application to the diagnosis of non-alcoholic fatty liver disease. Methods:  C57BL/6, KK-Ta and KK-Ay mice were fed a high-fat diet for 8 weeks and serum enzyme markers were examined. Serum OCT and alanine aminotransferase (ALT) were also measured in diabetic obese ob/ob JAK inhibitor and db/db mice fed a normal diet. Liver damage in these mice was evaluated by the hepatic content of tumor necrosis factor-alpha. Results:  Serum levels

of OCT increased in KK-Ay fed a high-fat diet compared with the normal diet-fed group, whereas C57BL/6 and KK-Ta mice were not affected. In ob/ob mice, the relative increase was always greater in OCT than in ALT. In contrast, in db/db mice, the relative increase was always greater in ALT. Hepatic tumor necrosis factor-alpha was significantly elevated in ob/ob mice, but not in db/db mice. Conclusions:  Serum OCT seemed to reflect selleck screening library tumor necrosis factor-alpha-mediated hepatic damage when compared with ALT in diabetic obese mice and could be useful in the application for non-alcoholic fatty liver disease with features of metabolic syndrome, such as obesity and diabetes. “
“Clinical studies of bone marrow (BM) cell therapy for liver cirrhosis are under way but the mechanisms of benefit remain undefined. Cells of the monocyte-macrophage lineage have key roles in the development and resolution of liver fibrosis. Therefore, we tested the therapeutic effects of these cells on murine liver fibrosis. Advanced liver fibrosis was induced in female mice by chronic administration of carbon tetrachloride. Unmanipulated, syngeneic macrophages, their specific BM precursors, or unfractionated BM cells were delivered during liver injury. Mediators of inflammation, fibrosis, and regeneration were measured. Donor cells were tracked by sex-mismatch and green fluorescent protein expression.

Isotope fractionation from mother to pup was validated using paired whisker and blood serum samples with no significant difference between δ13C and δ15N enrichment of +1.27‰ (whiskers) and +1.92‰ (blood serum) from mothers to pups. Isotope ratios from whisker samples representing over 50% of pups born

at three colonies revealed significant intercolony differences in maternal foraging ecotype frequencies. These results are unique in that ecological partitioning over Cytoskeletal Signaling inhibitor such a small spatial scale has not been described in any other otariid species. “
“On 16 June 1979, a herd of 41 sperm whales stranded near the mouth of the Siuslaw River in Florence, Oregon. The stomach contents from 32 whales were collected, identified to the lowest taxonomic level possible, enumerated, and measured. A total of 20,247 cephalopod lower beaks that represented 24 species from 14 different families were recovered. The most numerous species were Histioteuthis hoylei (25.9%), Taonius borealis (12.9%), Galiteuthis phyllura (11.2%), Gonatopsis/Berryteuthis type (10.9%), and Moroteuthis robusta (10.7%). Reconstructed estimates of mass indicated that M. robusta contributed almost 50% of the total mass of cephalopods consumed, followed by H. hoylei (19.3%), FK506 chemical structure and T. borealis (7.0%). The most important species in the diet of stranded whales were M. robusta, H. hoylei, T. borealis, G. phyllura,

Octopoteuthis deletron, and Gonatopsis/Berryteuthis type. There were significant differences in the diet of males and females, but no differences between sperm whales of different age groups. Overall, sperm whales primarily consumed small cephalopods that were likely eaten south of 45ºN in or near the California Current System. This study selleck screening library provides new estimates of the food habits of sperm whales in the northeast Pacific from one of the largest strandings of this species. “
“Fission-fusion dynamics typical of many delphinid populations allow for a variety of social grouping patterns. Identifying these groupings is crucial before conducting a detailed social structure analysis. This study analyzed the structure of a population of Bahamian spotted dolphins, Stenella

frontalis. Through long-term observations and preliminary analysis, three clusters were defined: Northern, Central, and Southern. To quantitatively investigate these delineations, we conducted analysis on 12 yr of sighting data using SOCPROG 2.3. Coefficients of association (CoA) were calculated using the half-weight index, with individuals sighted six or more times per pooled period (3 yr each). Nonmetric multidimensional scaling (MD), hierarchical agglomerative cluster analysis and Mantel tests were conducted to determine if any divisions were present. Mantel tests and MD plots analysis supported the delineations into the three clusters. Cluster analysis showed cluster groupings, but with less clear distinctions between the clusters.

[9] In addition, this multicenter study included patients with CD from 13 hospitals nationwide. Most patients were referred by primary care physicians and were subsequently diagnosed and treated by IBD specialists at each hospital. These factors may attenuate the recruitment bias. Second, the follow-up period of CD patients was relatively short and variable. It may affect the cumulative rate of CD-related surgery, which was presented in Figure 1. Most censorings happened during

the first 10 years and the steep rise of Kaplan–Meier curve occurred after that. However, we did not anticipate that it would greatly influence the results

click here in assessment of predictors for the clinical outcomes because Kaplan–Meier and Cox regression methods measure the proportion of patients over a period of time for each group. Additionally, only patients with a follow-up period of more than 6 months were included in our cohort. Considering a part of CD patients presented with severe disease requiring biologics in the initial course of disease, the inclusion criteria of our study may cause potential bias, which can influence on the results. Finally, because this study was conducted in a retrospective manner, we could not control all confounding factors in the analysis. Especially, variety of confounding factors such as different indication or timing for starting this website immunosuppressants (azathioprine Selleckchem ABT199 or 6-mercaptopurine) or biologics (infliximab)

according to doctors might influence the results when analyzing factors related to use of these agents. Despite these limitations, the strength of this study is that it was a large, multicenter cohort study to identify predictive factors associated with clinical outcomes in the Korean population. In addition, we identified variables associated with three different end-points (first surgery, need of immunosuppressive agents, or biological agents) in one study. In conclusion, the present study identified stricturing, penetrating disease behavior, and smoking habits at the time of diagnosis as independent predictors for a first CD-related surgery. In addition, we also found that younger age (< 40 years), ileal involvement, and perianal disease at diagnosis are associated with the need for immunosuppressive or biological agents. Given the differences in pathophysiology and clinical aspects with different ethnicities, our results may characterize the natural disease course in Korean CD patients and be useful to assess risk, predict the clinical outcomes, and determine optimized treatment plans for these patients.

Favourable efficacy and safety profiles were reported. Routine prophylaxis with 1 or 2 rFIX infusions per week over an average of greater than 6 months of therapy resulted in near complete prevention of spontaneous breakthrough haemorrhages (<1 per year), with most children (77%) having none, including seven patients (32%) who had no bleeding episodes at all. Haemorrhages in joints were less common than those outside joints (27% vs. 73% of haemorrhages). In a patient

population that included children with multiple prior haemarthroses, 68% of children had no joint bleeding. Breakthrough haemorrhages resolved with 1 or 2 infusions in 89% of episodes. The absence of changes in prophylaxis LY2606368 mouse infusion schedules suggests that 1 or 2 rFIX infusion(s) per week were well-tolerated by these young patients, including those with (41%) and without (59%) central venous access devices. Safety was established by the low incidence of treatment-related adverse events. “
“This chapter contains

sections titled: Central nervous system bleeding Intracranial hemorrhage Spinal hematoma Clotting factor replacement: recommendations for the treatment of central nervous system bleeds Non-central nervous system-emergent events Bleeding from organ rupture or hematoma of an abdominal viscus Symptoms of nerve compression or compartment syndrome Ophthalmologic emergencies Rare clinical emergencies Rupture of a pseudotumor Conclusion References selleckchem “
“Previous work has shown that normalized haemostasis only at the time of an injury is not sufficient to promote optimal wound healing in haemophilia B (HB) mice. However, the duration of treatment required for optimal healing has not been established. The goal of these studies was to determine the effect of different durations selleck chemical of replacement or bypassing therapy [factor IX(FIX) or factor VIIa (FVIIa)] on wound healing parameters in a mouse model of HB. A dermal wound was placed on the back of HB mice. Animals were either untreated or pretreated and then subsequently treated for 3 days, 5 days, or 7 days with FIX or FVIIa. Wound area, time to wound healing,

haematoma formation and iron deposition were measured. All treated animals showed shortened time to healing relative to untreated animals. Haematoma formation was prevented by treatment and bleeding into the wounds, measured by iron scores, was reduced by treatment. In addition, there was a progressive improvement in healing with 7 days of treatment more effective than 5 days which was more effective than 3 days. Replacement therapy with FIX had slightly shorter healing times than bypassing therapy with FVIIa. HB mice treated with FIX had slightly smaller wound area than untreated animals; by contrast, FVIIa-treated animals had much smaller wound areas that were close to the wound areas seen in wild-type animals. The data suggest that sustained therapy is required for normal wound healing.

, MD (AASLD Postgraduate Course, Panobinostat order Early Morning Workshops) Consulting: Lumena Grant/Research Support: Intercept, Salix,

Gilead Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Taouli, Bachir, MD (Transplant Surgery Workshop) Nothing to disclose Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Teckman, Jeffrey, MD (Parallel Session) Advisory Committees or Review Panels: The Alpha-1 Project Consulting: Isis Pharmaceuticals, Arrowhead, Agios Grant/Research Support: Alnylam, Alpha-1 Foundation Independent Contractor: Vertex Speaking and Teaching: Alpha-1 Association Terrault, Norah, MD (Early Morning Workshops, HCV Symposium, Plenary Session) Advisory Committees or Review Panels: Eisai, Biotest Consulting: BMS Grant/Research Support: Eisai, Biotest, Vertex, Gilead, AbbVie, Novartis Thuluvath, Paul

J., MD, FRCP (Parallel Session) Advisory Committees or Review Panels: Bayer, Gilead, Vertex Grant/Research Support: Gilead, AZD3965 Abbott, BMS, Boehringer, Salix Speaking and Teaching: Bayer/Onyx, Vertex, Gilead Thursz, Mark R., MD (SIG Program) Advisory Committees or Review Panels: Gilead, BMS, Abbott Laboratories Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Torok, Natalie, MD (Early Morning Workshops, Parallel Session, SIG Program) Nothing to disclose Torres, Dawn M., MD (Early Morning Workshops) Advisory Committees

or Review Panels: Genetech Speaking and Teaching: Merck Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Tran, Tram T., MD (AASLD Postgraduate Course, Early Morning Workshops) Advisory Committees or Review Panels: Gilead, Bristol Myers Squibb, Vertex Consulting: Gilead Grant/Research Support: Bristol Myers Squibb Speaking and Teaching: Bristol Myers Squibb, Gilead, Vertex Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Trautwein, Christian, MD (Parallel learn more Session, SIG Program) Grant/Research Support: BMS, Novartis, BMS, Novartis Speaking and Teaching: Roche, BMS, Roche, BMS Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Trotter, James, MD (AASLD/ILTS Transplant Course, Parallel Session, SIG Program) Speaking and Teaching: Salix, Novartis Content of the presentation does not include discussion of off-label/investigative use of medicine(s), medical devices or procedure(s) Tsukamoto, Hidekazu, DVM, PhD (Early Morning Workshops, Parallel Session) Consulting: Shionogi & Co., S. P. Pharmaceutics Grant/Research Support: The Toray Co.

Fortunately, most of these injuries are classified as mild, resulting in no loss

of consciousness or loss of consciousness less than 30 minutes. Many of these veterans develop headaches as a principle symptom after these injuries. By formal headache classification, click here post-traumatic headache must start within 7 days of these injuries, but in real life war, headache is often noted later. TBI is considered mild when loss of consciousness is less than 30 minutes in duration. About 75% of mild TBI comes from blast injuries, 29% from falls, and 22% from motor vehicle injuries (multiple insults occurring per injury accounts for the overlap). Many veterans experience multiple blast exposures, and these are believed to heighten the risk of headaches 5-Fluoracil in vitro and other symptoms. Headaches sometimes become noticeable weeks after the blast is experienced. What are the symptoms associated with TBI or concussive injury? Although headache is perhaps the most common one, other symptoms that may make the headaches worse are sleep disorders, memory

loss, dizziness, fatigue, sensitivity to loud noises, irritability, anxiety, and inability to pay attention and concentrate. Insomnia occurs in 56% of veterans with mild to moderate TBI, and this interlocks with their headache disorder, such that the insomnia worsens the headaches, and the headaches may keep the individual awake at night. Sleep disturbance contributes to and worsens TBI symptoms (pain, memory, and attention). Insomnia can alter pain processing and interferes with an individual’s natural pain control system. Headache pain may in itself disrupt sleep and cause multiple arousals during the night. Use of typical sleep agents can worsen memory and attention capabilities, as well as depression, and usually these are not recommended. Small studies using

prazosin, a blood pressure medication, have shown promise in quieting the nightmares that can worsen veteran sleep quality. There is a strong link between post-traumatic headache and post-traumatic stress disorder (PTSD) in veterans with TBI. One study showed that 44% of Iraqi veterans who experienced injury with brief loss of consciousness had PTSD. Veterans with PTSD are 4 times more likely to have headaches. What is PTSD? It is a disorder occurring after a life-threatening exposure, such as war, in which the individual experiences find more flashbacks to the traumatic event, intrusive thoughts, sometimes numbness, increased awareness of or attention to perceived danger, sleep disturbance, and heightened anxiety. Linking headaches, TBI, sleep disorder, and PTSD is important, as it suggests that treatment is unlikely to be successful with a single pill or intervention. Research suggests that a coordinated team approach in which symptoms are addressed and treated, with an overseeing clinician advocate making sure that care is not fragmented or contradictory, is the best way forward. Medicines can be helpful.

Variants Ganetespib purchase at positions R155 and D168 are known to cause decreased sensitivity to vaniprevir in vitro17 and have also been reported on previously in studies of other HCV protease inhibitors.23-26 The R155K variants were not observed in patients with genotype 1b infection who exhibited virologic failure in this study or in previous clinical studies.27 This can be partly explained by the fact that the codon-encoding lysine at position 155 in the genotype 1b virus requires two

base-pair (bp) changes from the baseline arginine codon, but only a single bp change in genotype 1a viruses. In conclusion, vaniprevir is a highly potent second-wave HCV protease inhibitor with a predictable resistance and a favorable safety profile that is suitable for QD or BID administration. The rates of RVR described in this study are among the highest reported for HCV protease inhibitor-based triple therapies, and although patients with cirrhosis were excluded from this study and the duration of vaniprevir exposure

was limited to 28 days, the observed safety profile was reassuring. Furthermore, there were only a limited number of treatment failures associated with the appearance of previously described HCV NS3/4A RAVs. However, the number of patients enrolled in this phase II study was limited, and therefore vaniprevir dosing will be extended in future studies BI 6727 molecular weight to further define treatment regimens that yield optimized antiviral effects. These future studies will consider whether vaniprevir-based regimens are comparable or superior to other HCV protease inhibitor-based triple therapies with regard to efficacy, safety, tolerability, or treatment duration. Based on the results of this study, vaniprevir should be further developed for HCV protease inhibitor-based triple therapies. Vaniprevir is also a promising candidate for inclusion within

future all-oral anti-HCV strategies. The External Data Monitoring Committee for this study: Loren Laine, Bruce Bacon, Luis Balart, Gregory Everson, and James Neaton. The authors thank the patients and site staff who made this study possible and Amelia Warner and Karina Bienfait for their assistance with IL28B methods. Medical writing and editorial assistance were provided by Tim Ibbotson, Ph.D., and Santo D’Angelo, Ph.D., M.S., of ApotheCom (Yardley, PA). This assistance was funded by Merck Sharp selleck products & Dohme Corp., a subsidiary of Merck & Co., Inc. (Whitehouse Station, NJ). The MK-7009 Protocol 007 Study Group: Yacov Baruch, M.D. (Liver Unit, Rambam Healthcare Campus, Haifa, Israel); Yves Benhamou, M.D. (Hôpital Pitié-Salpétrière, Paris, France); Matthew Cave, M.D. (University of Louisville Hospital, Louisville, KY); Gary Davis, M.D. (Baylor University Medical Center, Dallas, TX); Shaban Faruqui, M.D. (Gulf Coast Research LLC, Baton Rouge, LA); Michael Fried, M.D. (University of North Carolina at Chapel Hill, Chapel Hill, NC); Eliot Godofsky, M.D. (University Hepatitis Center at Bach and Godofsky, M.D., Sarasota, FL); Michael Gschwantler, M.

This consensus process was not directly sponsored by any commercial companies. The first face-to-face meeting in Kuala Lumpur was sponsored by the Steering Committee of ANMA and the Aloxistatin second face-to-face meeting

in Beijing was sponsored by the Organizing Committee of ANMA 2011 Beijing Congress. No consensus team member has any financial disclosure to declare in relationship with this consensus process. “
“The liver architecture plays an important role in maintaining hemodynamic balance, but the mechanisms that underlie this role are not fully understood. Hepsin, a type II transmembrane serine protease, is predominantly expressed in the liver, but has no known physiological functions. Here, we report that hemodynamic balance in the liver is regulated through hepsin. Deletion of hepsin (hepsin−/−) in mice resulted in enlarged hepatocytes and narrowed liver sinusoids. Using fluorescent microbeads Selleckchem U0126 and antihepsin treatment, we demonstrated that metastatic cancer cells preferentially colonized the hepsin−/− mouse liver as a result of the retention of tumor cells because of narrower sinusoids. The enlarged hepatocytes expressed increased levels of connexin, which

resulted from defective prohepatocyte growth factor (pro-HGF) processing and decreased c-Met phosphorylation in the livers of hepsin−/− mice. Treatment of hepsin−/− mice with recombinant HGF rescued these phenotypes, and treatment of wild-type selleck chemicals llc mice with an HGF antagonist recapitulated the phenotypes observed in hepsin−/− mice. Conclusion: Our findings show that the maintenance of hepatic structural homeostasis occurs through HGF/c-Met/connexin signaling by hepsin, and hepsin-mediated changes in liver architecture significantly enhance tumor metastasis to the liver. (HEPATOLOGY 2012;56:1913–1923) Type II transmembrane serine proteases (TTSPs) have important physiological functions and pathological implications in iron metabolism,1 blood pressure regulation, and metastasis of cancers.2 More than 20 TTSPs exist and they are

divided into four subfamilies. Among these families, the hepsin/enteropeptidase subfamily is recognized structurally by a scavenger receptor cysteine-rich domain linked to a serine protease domain contained within an extracellular stem region. Although hepsin may be involved in the progression of several human cancers,3 its physiological function has not yet been fully characterized. Hepsin is predominantly expressed in the liver.4 Antisense-oligonucleotide blockade of hepsin affects cell growth and enlarges and flattens hepatoma cells.5 Several in vitro studies have identified substrates for hepsin, including coagulation factor VII,6 prohepatocyte growth factor (pro-HGF),7 and prourokinase-type plasminogen activator.8 In addition, hepsin colocalizes with desmoplakin at the sites of desmosomal junctions.9 Previously, Wu et al.