However, correlation of the TGA parameters with in vivo clinical response needs to be further established if we believe that this assay may represent

a surrogate marker for monitoring bypassing therapies in life or limb-threatening as well as in surgical situations. Finally, one should emphasize the critical importance of sampling conditions and manipulation of plasma samples as well as the use of a standardized protocol to obtain selleck compound reproducible and meaningful results. “
“The dawning era of novel recombinant factor VIII and factor IX concentrates, many of which have been bioengineered to achieve prolonged activity, brings with it the need to consider the most appropriate clinical laboratory approaches for potency assignment, as well as the

measurement of postinfusion levels. This session will highlight the learn more known limitations and inconsistencies between existing assay methodologies with respect to currently available products, and discuss some of the early data with respect to the novel agents. The most commonly performed assays for FVIII:C and FIX:C worldwide for many years have been one-stage assays [1, 2]. A minority of centres utilize chromogenic FVIII assays. There are several different chromogenic assay methods [3, 4] and there are important differences in the composition of the reagents which means that results obtained using different assays are not always interchangeable. Some chromogenic FVIII assays include added thrombin to fully activate FVIII whereas in others,

including the original system, thrombin is not added, and must be generated in the first stage for FVIII:C activation. For some chromogenic FVIII assays, Pregnenolone the second stage includes a thrombin inhibitor to prevent cleavage of the chromogenic substrate by any thrombin that might be present. The chromogenic assay is currently recommended by the European Pharmacopoeia [5] and in the past by the FVIII and FIX sub-committee of the Scientific and Standardisation Committees (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) for assignment of potency to FVIII:C concentrates [6]. A recent SSC update on recommendations for potency labelling [7] is discussed below in relation to new long-acting products for haemophilia treatment. Recently, two different chromogenic FIX assays became commercially available, and SSC recommends that manufacturers evaluate chromogenic FIX assays for each individual product [7]. There are a number of sources of variability in relation to FVIII and IX assays. All assays require a reference or standard plasma of known factor concentration that is used to construct a calibration curve relating potency to response. The use of stored calibration curves on analysers is in common use and it is possible to obtain acceptable FVIII assay precision by using a stored calibration curve [8, 9].

1 CHOICE OF FACTOR REPLACEMENT THERAPY PROTOCOLS 44 REFERENCES 44 Tables 1-1 RELATIONSHIP OF BLEEDING SEVERITY WITH CLOTTING FACTOR LEVEL 5 1-2 SITES OF BLEEDING IN HEMOPHILIA 5 1-3 APPROXIMATE FREQUENCY OF BLEEDING AT DIFFERENT SITES 5 1-4 DEFINITIONS OF FACTOR REPLACEMENT THERAPY PROTOCOLS

8 1-5 STRATEGIES FOR PAIN MANAGEMENT IN PATIENTS WITH HEMOPHILIA 11 1-6 DEFINITION OF ADEQUACY OF HEMOSTASIS FOR SURGICAL PROCEDURES 11 3-1 INTERPRETATION OF SCREENING TESTS 20 5-1 DEFINITION OF RESPONSE TO TREATMENT OF ACUTE HEMARTHROSIS 30 7-1 SUGGESTED PLASMA FACTOR PEAK LEVEL AND DURATION OF ADMINISTRATION (WHEN THERE IS NO SIGNIFICANT

AZD0530 RESOURCE CONSTRAINT) 45 7-2 SUGGESTED PLASMA FACTOR PEAK LEVEL AND DURATION OF ADMINISTRATION (WHEN THERE IS SIGNIFICANT RESOURCE CONSTRAINT) 45 The first edition Liproxstatin-1 mouse of these guidelines, published in 2005 by the World Federation of Hemophilia (WFH), served its purpose of being a useful document for those looking for basic information on the comprehensive management of hemophilia. The need for revision has arisen for several reasons. The most significant of these was to incorporate the best existing evidence on which recommendations were based. There are recent high-quality data from randomized controlled trials establishing the efficacy and superiority of prophylactic factor replacement over episodic treatment – although the optimal dose and schedule for prophylaxis continue to be subjects of further research. There is also greater recognition of the need for better assessment

of outcomes of hemophilia TCL care using newly developed, validated, disease-specific clinimetric instruments. This revised version addresses these issues in addition to updating all sections. These guidelines contain several recommendations regarding the clinical management of people with hemophilia (practice statements, in bold). All such statements are supported by the best available evidence in the literature, which were graded as per the 2011 Oxford Centre for Evidence-Based Medicine (Appendix I). Where possible, references for recommendations that fell outside the selection for practice statements were also included. These references have not been graded. A question often raised when developing a guideline document such as this is its universal applicability, given the diversity of health services and economic systems around the world. Our strongly held view is that the principles of management of hemophilia are the same all over the world.

There were also different specific AP characteristics among the three test species under severe P-stressed conditions. In P. donghaiense, AP covered most of the cell, and the AP production sites were mainly on the cell surface, although some could be observed inside cells. AP also covered the whole cell of A. catenella, but the AP sites were mainly inside the cell with only some on the cell surface. Only one or two AP sites could be detected in S. costatum, and they were all on the cell surface. “
“Macroalgae are a diverse group of marine organisms that have developed complex and unique metabolic pathways to ensure survival in highly competitive marine environments. As a result, these

organisms have been targeted for mining of natural biologically active components. The exploration of marine organisms has revealed numerous bioactive compounds JNK inhibitor that are proteinaceous in nature. These include proteins, linear peptides, cyclic peptides and depsipeptides, peptide derivatives, amino acids, and amino acid–like components. Furthermore, some species of macroalgae have been shown to contain significant levels of protein. While some protein-derived bioactive peptides have been characterized from macroalgae, macroalgal proteins currently still represent good candidate raw

materials for biofunctional peptide mining. This review will provide an overview of the important bioactive amino-acid-containing compounds that have been identified ICG-001 in macroalgae. Moreover, the potential of macroalgal proteins as substrates for the generation of biofunctional peptides for utilization as functional foods to provide specific health benefits will be discussed. “
“The

genus Pseudo-nitzschia contains potentially toxic species of problematic taxonomy, making it one of the most intensively studied diatom genera. The study of 35 clonal strains isolated from the Bilbao estuary, an area that experiences recurrent blooms of Pseudo-nitzschia, revealed the presence of two new species, P. abrensis and P. plurisecta, differing from their congeners in both morphology and gene sequence. The morphological features were analyzed by LM and EM, whereas molecular analyses OSBPL9 were based on the internal transcribed spacer (ITS) and large subunit (LSU) regions of the rDNA. P. plurisecta appears closely related to P. cuspidata/P. pseudodelicatissima in the phylogenetic tree, whereas P. abrensis forms a moderately supported clade with P. heimii/P. subpacifica and P. caciantha/P. circumpora. Comparison of the secondary structure of ITS2 regions reveals marked differences in the most highly conserved regions among related taxa. Morphologically, the new species differ from their closest congeners in the arrangement of the poroid sectors and the density of valve striae and fibulae. The two species share similar pigment composition, and belong to the group of Pseudo-nitzschia species containing only chlorophyll c2 and c3.

Among the 44 HCV-infected patients, 23 patients were not current or former alcohol users (group A). Thirteen individuals in group A were male (group A1). Twenty-one

of 44 HCV-infected patients were either current or former alcohol drinkers and they were all male (group B). Group A1 and B were matched for sex, age, and body mass index (BMI) (Table 1). Fifteen Pexidartinib order liver specimens obtained from the donors at the Liver Transplant Program at the University of Kansas Hospital were used as normal controls (group C). Groups A and C were matched for age, sex, and BMI. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBILI), alkaline phosphatase (ALP), total cholesterol INCB024360 (CHOL), triglyceride (TRIG), and fasting plasma glucose were obtained from patients’ charts and all the tests were performed within 3 months of liver biopsy. The HCV genotype was determined by sequencing using the

TRUGENE HCV 5′NC Genotyping Kit. Hematoxylin and eosin–stained as well as Masson’s trichrome-stained liver sections were used for diagnosis by the pathologists. The degrees of inflammation and fibrosis were evaluated according to the criteria proposed by Ishak et al.21 Steatosis was graded based on percentage of hepatocytes involved: none (<5%), mild (5%-33%), moderate (≥33%-66%), or severe (≥66%). Hepatic RNA was extracted for study of gene expression by real-time polymerase chain reaction (PCR). The studied genes are listed in Supporting Table 1. Data were normalized to glyceraldehyde Nitroxoline 3-phosphate dehydrogenase (GAPDH) messenger RNA (mRNA) level. Student t test was used for gene expression comparisons between two groups. For the correlation analysis, comparative cycle threshold (Δ Ct) values were used. Pearson correlation analysis was used to study the correlation between gene expression and hepatic HCV RNA. (According

to the Kolmogorov–Smirnov Z test, the Δ Ct data are within normal distribution.) Multivariate linear regression analysis was used to identify the independent correlations for genes that had significant correlation as identified by bivariate correlation analysis. P < 0.05 was considered statistically significant. Demographic information and clinical data of the 44 studied patients and 15 liver donors are summarized in Table 1. Except for fasting plasma glucose level, which was reduced in patients with a drinking history, other parameters were not different between Group A1 and B or between Group C and A. Most patients in Group B had a heavy drinking history and were binge drinkers. Only 28.6% patients reported that they were current drinkers (Table 2).

37 By contrast, our method of using a combination of SDC and PLA2 delipidated the tissue rapidly

and gently. At least 29 types of collagens (I-XXIX) have been identified with functional roles in cell adhesion, differentiation, growth, tissue development, and structural integrity.38, 39 The major structural component in the matrix, collagens, are known to remain insoluble in high salt concentrations and at neutral pH,28, 40-42 a finding that is the basis of our strategy in preparation of biomatrix scaffolds. The strategy has added advantages that collagens enable preservation of matrix components bound to them, such as laminins and fibronectins (FNs), small leucine-rich proteoglycans (PGs), and GAGs that in turn preserve cytokines, growth see more factors, or cell surface receptors bound to them. Biomatrix this website scaffolds are unique in their profound ability to induce rapid and consistent differentiation of stem/progenitor cells, such as hHpSCs, to adult fates and to maintain those lineage-restricted cells, or to maintain adult cells plated onto the scaffolds, as viable and fully functional

cells for many weeks (>8 weeks). Differentiation of stem cells, such as embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, or varying forms of mesenchymal stem cells (MSCs) into fully mature liver cell types requires multiple sets of signals (soluble and matrix) presented in stages, with induction by one set requiring priming to respond to a different set, and takes many weeks,

up to 6 weeks of culture, to generate cells having the adult liver fate.43 Moreover, lineage restriction of MSCs to liver fates gives inconsistent STK38 results with adult cells having mixed hepatocyte and MSC phenotypes.3, 44, 45 The hepatocyte-like cells from any of these precursors express some, but never all, of the major liver-specific genes, with variability in which genes are observed, and with the protein levels for hepatic genes being usually low46 or high for one hepatic gene and negligible for others.3, 47, 48 For reasons unknown, the results are different from preparation to preparation. In contrast, differentiation of hHpSCs on biomatrix scaffolds resulted in essentially all cells expressing a classic adult phenotype with urea, albumin, and CYP450 activities at near normal levels within 1 to 2 weeks in culture and with stability of that phenotype for many weeks. We assume that the biomatrix scaffolds can greatly facilitate differentiation of other stem cell populations, such as ES, iPS, and MSCs to an adult liver phenotype, a hypothesis now being tested.

In the immunohistochemical staining after an endoscopic biopsy, the tumor cells were oval to spindle shaped with hyperchromatic nuclei and acidophilic cytoplasm and stained strongly positive for SMA, but Rapamycin in vitro negative for KIT, CD34. The diagnosis of leiomyosarcoma was confirmed. Chemotherapy was then initiated, but the cancer progressed and the patient died after 1 year. Our experience suggests that leiomyosarcoma can manifest aggressive biological behavior in its early stage with only vague symptoms. Therefore, although the size of leiomyosarcoma is small, the possibility of metastasis must be taken into

consideration. Key Word(s): 1. leiomyosarcoma; 2. stomach; 3. gastrointestinal Presenting Author: TOMOKO KITAICHI Additional Authors: ASTUSHI MAJIMA, YURIKO ONOZAWA, YUSUKE HORII, AKIRA TOMIE, KENTARO SUZUKI, OSAMU DOHI, KAZUHIRO KAMADA, NOBUAKI YAGI, YUJI NAITO, YOSHITO ITOH,

YASUKO FUJITA, MITSUO KISHIMOTO, AKIO YANAGISAWA Corresponding Author: TOMOKO KITAICHI Affiliations: Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Murakami Memorial Hospital Asahi University, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto Prefectural Apitolisib chemical structure University of Medicine Objective: Adenocarcinoma of the stomach is classified into gastric-type, intestinal-type and mixed gastric- and intestinal-type, according to the histopathologic phenotype. It is often difficult to make clinical and

pathologic diagnosis of gastric-type differentiated adenocarcinoma, because of its mild cellular and structural atypia. Methods: Among 582 early gastric cancers (475 patients) treated by endoscopic submucosal dissection (ESD) between April 2010 and June 2014 at our institution, we performed a retrospective clinicopathologic analysis of 16 gastric-type differentiated adenocarcinomas (15 patients). Using a hematoxylin-eosin staining Etomidate and immunohistochemical approach, we defined gastric-type differentiated adenocarcinoma as the gastric cancer with differentiation into proper gastric gland or foveolar epithelium, and glandular cavity formation. The mean age of the patients was 73 years (range, 58—84 years), and 11 (68.8%) patients were men. Results: The mean diameter of the lesions was 20 ± 14 mm. 12 lesions (75%) were limited in the mucosal layer, and four lesions (25%) had invaded into the submucosal layer. The colors of lesions were reddish in 11 cases (68.8%) and whitish in five cases (31.2%). Ten tumors (62.5%) were elevated type, two of them (12.5%) were flat type, four (25%) were depressed type. Histopathologic findings from initial forceps biopsy were: 10 adenocarcinomas (62.5%), two adenomas (12.

Dynamic MRI was performed with a three-dimensional volumetric interpolated breath-hold examination sequence in an axial plane using the following parameters: 4.7/2.3 TR/TE,

320 × 157 matrix, 10° flip angle, 3-mm slice thickness. Gadolinium (Gadobenate Dimeglutamine [0.5 mmol/L]; Multihance, Bracco, Milan, Italy) was injected at a dose of 0.2 mL/kg at a rate of 2 mL/second. Arterial phase, portal venous, and delayed venous phase images were acquired approximately 30, 80, and 180 seconds from the start of contrast injection, respectively. A breath-hold T1-weighted two-dimensional gradient echo with fat suppression MRI (4.7/2.3 TR/TE, 256 × 157 matrix) and three-dimensional volumetric interpolated breath-hold examination sequences were performed 2 hours after contrast injection (hepatocyte phase). CT was performed with a 64-detector CT scanner (Definition AZD1208 research buy Siemens, Erlangen, XL765 Germany) at 2.5-mm slice thickness and a rotation time of 0.5 seconds. A total of 1.5 mg/kg iodinated contrast medium (Iomeron 400; Bracco, Milan, Italy) was injected with a 4.0 mL/second flow. In all patients, the acquisition time from the start of contrast injection and the start of acquisition sequences was 40 seconds for the arterial phase, 80 seconds for the portal venous

phase, and 180 seconds for the delayed phase. Patients with an unsatisfactory acquisition of arterial phase were to repeat the examination using a bolus tracking technique. Adenosine triphosphate US studies were performed

with a Philips iU22 system (Philips Ultrasound, Bothell, WA), using a multifrequency (5-2 MHz) convex transducer (C5-2). A preliminary gray-scale US examination of the upper abdomen was performed. On identifying the nodule, CE-US was performed with up to two bolus injections of 2.4 mL of a second-generation contrast agent (SonoVue; Bracco, Milan, Italy), having 8-μm microbubbles and stability for 6-8 minutes. The bolus was followed by a 10-mL saline flush. Low mechanical index (<0.1) was set for CE-US examination. Enhancement patterns were studied during the vascular phase for up to 3 minutes, including the arterial phase (0-35 seconds), portal phase (35-120 seconds), and late phase (120-180 seconds). All examinations were obtained and evaluated in real time by two expert echographists (M. F. and S. M.) and digitally stored and documented by a commercially available system or videotapes. Patients with a discrepant result were re-evaluated in a dedicated reading session by the two echographists, who were unaware of the liver biopsy results. The baseline characteristics of the patients are expressed as the median and range or count and proportion. Comparisons between the vascular pattern and tumor cell differentiation of the nodules were performed using a Student t test or Mann-Whitney test for continuous variables and Fisher’s exact test for categorical variables. A conventional P value < 0.05 was considered statistically significant.

The diagnostic capability of the cytopathologist is greatly dependent on the www.selleckchem.com/products/Cisplatin.html integrity of the cellular material provided for analysis. Aims: To compare concurrently the diagnostic efficacy (% of specimens considered adequate for

diagnosis by the cytopathologist) and diagnostic accuracy (compared to the final clinical diagnosis) of EUS-FNA specimens obtained from pancreatic solid tumors and GIST lesions using a liquid-based preparation, SurePath® (SP), and conventional smears with cell-block preparations (CSCB). Methods: Patients with a suspected solid pancreatic mass or GIST lesion referred for EUS and FNA were randomized to SP or CSCB for the first and third pass of the cytology needle. The alternate method was used for the second and fourth passes. The cytologist was not present during the biopsy and CSCB and SP specimens were sent to different laboratories. Results: Twenty seven patients were included in the pilot study. The cohort had a mean age of 68.6; 12 (44%) were female. Diagnosis of malignancy was made in 23/27 (85%) in the CSCB group, and 23/27 (85%) in the SP group. Malignancy was diagnosed on the 1st & 3rd passes alone in

0/27 (0%) patients, on 2nd & 4th pass alone in 4/27 (15%) patients, on both passes in 21/27 (78%) patients and on none of the passes in 2/27 (7%). Six patients had surgery: 5 had malignancy which NVP-LDE225 mw were diagnosed by both SP and CSCB. Conclusion: In this pilot study, SP appears Vasopressin Receptor comparable to CSCB in the diagnosis of solid pancreatic mass and GIST lesions but SP has several distinct advantages:- 1) ease of use and storage of samples, 2) no requirement for cytology technician, 3) a large pellet of cells to assist diagnosis and 4), the ability to use immunochemistry to diagnose specific tumors (e.g, NET). A larger study is necessary to determine which technique has a higher diagnostic accuracy. E JOHNS,1 P WALSH1,2 1Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane,

2Digestive Diseases Queensland, Holy Spirit Northside, Brisbane Introduction: Leaks complicate up to 5% of bariatric surgical operations and are a major cause of morbidity and mortality. Management is problematic with covered stents, clips and newer closure devices producing mixed results. These methods aim to exclude or close the defect to produce healing. 85% of leaks post sleeve gastrectomy occur in the proximal third of the stomach near the gastroesophageal junction. The aetiology is thought to be the elevated intraluminal pressure in this area caused by the reduced distensibility of the distal sleeve. This phenomenon may be a factor in roux-en-y pouch leaks due to narrowing of the gastrojejunostomy in the post-surgical period.

Anti-HCV antibody was assayed by a commercial kit (Abbott HCV EIA 2.0®; Abbott Laboratories, Abbott Park, IL, USA). HCV genotyping was performed at baseline by a reverse hybridization technique (Inno-LiPA HCV II®; Innogenetics). Serum HCV viral load was evaluated quantitatively by RT-PCR analysis (CobasTaqMan HCV Test®, version 2.0; Roche Diagnostics; limit of detection,

25 IU/mL) at baseline, on-treatment (week 4, week 12, the end of treatment), and 24 weeks after the end of treatment. Rapid virologic response (RVR) was defined as seronegativity of HCV RNA at on-treatment week 4. Early virologic response (EVR) was defined as seronegative or at least a 2-log10 decrease from baseline of serum HCV RNA at 12 weeks of treatment. A complete EVR (cEVR) was defined Crizotinib price as HCV RNA seropositivity Paclitaxel at treatment week 4, but seronegativity

at treatment week 12. Partial EVR (pEVR) was defined as HCV RNA seropositivity at week 4 and 12 of treatment but at least a 2-log10 decrease from baseline of serum HCV RNA at 12 weeks of treatment. End-of-treatment virologic response (EOT-VR) was defined as seronegativity of HCV RNA at the end of treatment. The end point of the study was achievement of an SVR, defined as seronegativity of HCV RNA throughout 24 weeks of posttreatment follow-up period. Relapse was defined as HCV RNA reappearance during the follow-up period in patients who achieved an EOT-VR. Genomic DNA was extracted from peripheral blood mononuclear cells by using the QIAamp kits

(Qiagen, Inc., Valencia, CA, USA). Genotyping was performed using ABI TaqMan allelic discrimination kit and the ABI7900HT Sequence Detection System (Applied Biosystems, Foster city, CA, USA). An SNP located around IL28B loci (rs8099917) was genotyped. Mean and standard deviation were calculated for continuous variables. Percentage was used for categorical variables. The baseline characteristics of treatment groups were compared using the chi-square test, Fisher’s exact test, or Student’s t-test, when appropriate. Those not achieving pEVR or cEVR and discontinuing therapy prematurely were counted as treatment failure. Treatment responses were compared by click here using Fisher’s exact test. Univariate and multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) were derived for each factor using logistic regression. In multivariable logistic regression analysis, SVR was the dependent variable. All of the tests of significance were two-tailed, and a P value of less than 0.05 was considered significant. Data were collected in a Microsoft Excel database (Microsoft Excel 2001; Microsoft Corporation, Seattle, WA, USA) and analyzed with Stata statistics software (version 9.2; Stata Corp, College Station, TX, USA). Seventy-five relapsers with HCV genotype 1 infection were enrolled (Fig. 1).

Using this mouse model,

selleck monoclonal antibody erlotinib pre-treatment (5 days before infection) markedly reduced HCV-RNA (genotype 2a) levels by 90%. However, once treatment was discontinued, viral loads rebounded to those of the control-treated mice. These in vivo results hold much promise to potentially treat acute HCV infection in the setting of accidental exposure to HCV (i.e., needle-stick injury). The blocking of HCV entry in this scenario could prove invaluable to prevent the development of a chronic infection. Entry inhibitors may also prove useful for HCV-infected individuals undergoing liver transplantation, where reinfection of the donor tissue is inevitable and is associated with graft loss. In this setting, the use of RTK inhibitors and other entry inhibitors could potentially be used to prevent reinfection of the donor tissue. Though the in vivo studies by Lupberger et al. only assessed the efficacy of erlotinib on genotype 2a, in vitro the investigators demonstrated that siRNA knockdown of EGFR blocked HCV entry by multiple genotypes, including the most common genotype 1a, indicating that EGFR antagonism would block entry for all other HCV genotypes. Using the aforementioned murine

GSK3 inhibitor model system, it will be interesting to evaluate, in other studies, the use of PKIs in combination with the current standard of care for HCV, PEG-IFN-α/ribavirin combination therapy, and the recently approved NS3/4A serine protease inhibitors, Fenbendazole boceprevir and telaprevir. EGFR has also been implicated in the life cycle of a number of other viruses. Most recently, it has been shown that when influenza A virus (IAV) binds to the plasma membrane surface, it causes the aggregation of lipid rafts, which, in turn, induces the clustering of RTKs (including EGFR).11 As a result of this clustering, activation of EGFR occurs, which is then thought to promote the

uptake of IAV via endocytosis.11 A number of oncogenic viruses (e.g., HBV, EBV, and AEV) have also been shown to hijack EGFR signaling and expression. This process is thought to be one of the mechanisms by which these oncogenic viruses induce cellular transformation.12 Although HCV does not appear to directly engage EGFR, the work of Lupberger et al. shows that EGFR signaling promotes HCV entry by the enhancement of both CD81/CLDN1 heterodimerization and fusion of the viral envelope with endosomal membranes without significantly perturbing hepatocyte polarity or tight junction integrity. Interestingly, recent studies have also indicated an interplay between EGFR signaling and HCV at other stages of the viral life cycle. In this context, the HCV NS5A protein has been shown to alter the distribution of EGFR and attenuate EGFR signaling.