3). The intensity of the band corresponding to Prx III-SO2 was also increased slightly in ethanol-fed Srx−/− mice compared with those in the other three groups. Prx IV-SO2 was not detected in any of the four groups of mice. Neither ablation of Srx nor ethanol feeding substantially

affected the levels of 2-Cys Prxs (Prx I to IV) in the liver (Fig. 3). The extent of Prx hyperoxidation was evaluated further by two-dimensional (2D) PAGE followed by immunoblot analysis (Supporting Information Fig. 5). 2D-PAGE separates not only Prx I and II but also their covalently modified forms. Hyperoxidation of a cysteine residue induces an acidic (leftward) shift in the position of proteins on 2D gels. 2D-PAGE and subsequent immunoblot analysis with antibodies to Prx I revealed two major spots of Prx I for Srx+/+ mice fed the ethanol-containing or control diets as well as for Srx−/− mice fed the control Ipilimumab supplier diet, whereas three major spots were detected for ethanol-fed Srx−/− mice (Supporting Information Fig. 5A). Alignment with the Prx I-SO2 spot of H2O2-treated NIH 3T3 cells revealed that only the leftmost spot for ethanol-fed Srx−/− mice corresponded to hyperoxidized Prx I. The

middle spot that was observed in all four groups of mice appeared to be due to another type of modification, with 2-Cys Prx proteins being known to undergo phosphorylation, acetylation, and COOH-terminal medchemexpress truncation.19-22 The intensities of the three spots suggested that 30% to

50% of Prx selleck chemicals llc I was hyperoxidized in the liver of ethanol-fed Srx−/− mice. A faint spot of Prx I-SO2 at the position corresponding to the leftmost Prx I spot of ethanol-fed Srx−/− mice was also apparent for Srx+/+ mice fed the ethanol-containing diet. These results thus indicated that ethanol feeding results in a slight accumulation of Prx I-SO2 in the liver of Srx+/+ mice and that Srx ablation markedly potentiates this effect. Prx II appeared as a single spot in the liver of all four groups of mice, with no spot corresponding to that of Prx II-SO2 in H2O2-treated NIH 3T3 cells being detected (Supporting Information Fig. 5B), suggesting that Prx II was not susceptible to hyperoxidation by ethanol-induced ROS. Prx III appeared as one major and two minor spots, of which the leftmost spot could not be seen in some samples (Supporting Information Fig. 5C). The immunoblot of H2O2-treated NIH 3T3 cells with antibodies specific for Prx-SO2 indicated that Prx III-SO2 can be found in the positions of both minor spots. A faint spot of Prx III-SO2 was detected only in the liver of ethanol-fed Srx−/− mice, suggesting that Prx III is vulnerable to hyperoxidation by ethanol-induced ROS but that Prx III-SO2 accumulates only in the absence of Srx.

Another study, which was hospital-based, enrolled 54 325 Taiwanese subjects who underwent a health-screening program, and these individuals were classified into eight groups according to their UA level and gout status (≤ 4.9, 5.0–6.9, 7.0–8.9, and ≥ 9.0 mg/dL, with and without gout) to examine the association between gout and NAFLD.[19] The prevalence of NAFLD was significantly higher in subjects with gout (23.1%, n = 445) than in those without gout (10.9%, n = 5724, P < 0.001).

Gout remained associated with an increased risk for NAFLD (OR 1.42; 95% CI 1.25–1.60; P < 0.001) after adjusting for age, gender, presence of metabolic syndrome, and low eGFR. The results showed an independent association between gout and the risk of NAFLD and a dose–response relationship between UA levels and the presence of NAFLD in subjects with and without gout, with UA ≤ 4.9 mg/dL SB203580 purchase in the absence of gout as a reference: OR (95% CI) 2.16 (1.94–2.41)–5.99 (5.19–6.90) without gout and 2.61 (1.39–4.91)–6.31 (5.12–7.77) with gout (Table 1). An investigation was conducted to examine whether elevated levels of serum UA play a causal role in NAFLD. This investigation was a population-based

prospective study among the employees of a Chinese company.[26] The study investigators followed a total of Daporinad in vivo 6890 initially NAFLD-free subjects for 3 years and showed that UA levels were independently and positively associated with a risk for the onset of NAFLD through the use of Cox proportional hazards regression analyses; the age-, gender-, and metabolic MCE公司 syndrome-adjusted HR

(95% CI) for the subjects in quintiles 2, 3, 4, and 5 versus quintile 1 were 1.18 (0.91–1.54), 1.32 (1.03–1.70), 1.39 (1.09–1.78), and 1.50 (1.18–1.92), respectively (Table 2). Another study examined the incidence of NAFLD in 4954 apparently healthy subjects who participated in a health-screening program. The incidence of NAFLD over a 5-year period was assessed according to the individuals’ baseline UA levels, categorized into quartiles.[27] Multiple logistic regression analysis showed that hyperuricemia was associated with the development of NAFLD. When compared with subjects in quartile 1, the ORs for the incidence of NAFLD in subjects in quartiles 2, 3, and 4 were 1.53 (95% CI 1.09–2.16; P = 0.014), 1.69 (95% CI 1.17–2.44; P = 0.005), and 1.84 (95% CI 1.25–2.71; P = 0.002), respectively (Table 2). On the basis of the findings from many of these large studies, more attention should be paid to UA levels than was previously appreciated. Further studies examining the mechanism of this association are desired. Subjects with metabolic syndrome often develop NAFLD, and this has led to an examination into the influence of metabolic syndrome on the onset of NAFLD.

The median time to loss of resistant selleck variants was 13 months overall (Table 2) (13, 15, and 9 months for prior null and partial responders, and relapsers, respectively). The median time to loss of the common genotype 1b variants (position 54 and 156; 3-4 months) was generally less than that of the common genotype 1a variants (position 36, 155, and 36+155; 13-15 months). This subanalysis of peginterferon/ribavirin treatment-experienced patients treated with the HCV protease inhibitor telaprevir in the REALIZE trial explored the effect of peginterferon/ribavirin lead-in, prior peginterferon/ribavirin treatment response,

genotype subtype, and baseline variants on treatment outcome, and further characterized the emergence of resistance in patients who did not achieve an SVR. No new telaprevir-resistant variants were detected and the pattern of resistance pathways Gefitinib cost was consistent with

that seen in treatment-naïve patients.19 Importantly, this analysis also showed that resistant variants could no longer be detected by population sequencing in the majority of patients after a median follow-up time of 11 months. Prior to treatment in the REALIZE trial, predominant variants resistant to protease inhibitors were generally detectable by population sequencing in only a very small percentage (typically <3%) of patients, which is in agreement with other studies including those in the treatment-naïve setting.19-21 Also in line with other studies,20, 22, 23 the presence of resistant variants at baseline does not necessarily preclude successful treatment (i.e., SVR) in all patient groups,

especially in prior relapsers. However, there might have been an effect in prior null responders. Regarding the use of a 4-week peginterferon/ribavirin lead-in phase before the initiation of telaprevir, no differences in the rates of on-treatment virologic failure or relapse were observed between the concurrent and delayed initiation of telaprevir. Further, the use (or not) of a peginterferon/ribavirin 上海皓元 lead-in had no significant effect on the number of patients who had emergent telaprevir-resistant variants, or on the type of variants observed following virologic failure. The data from this virologic analysis are in agreement with results from the primary analysis of the REALIZE trial,4 in which SVR rates were similar between the telaprevir-based treatment arms with and without a lead-in. Therefore, our findings confirm that a peginterferon/ribavirin lead-in is not required with telaprevir. In contrast, a Phase 2 study of boceprevir previously suggested that lowering HCV RNA levels with a 4-week peginterferon/ribavirin pretreatment may reduce the emergence of protease-resistant variants, decrease viral breakthrough rates during treatment, and increase SVR rates.

[15] In these studies, groups of PPAR-α-expressing WD-fed hApoE2 KI mice were included for comparison. Treatment of PPAR-α-expressing

hApoE2 KI mice with GFT505 significantly reduced plasma total cholesterol, triglycerides (TGs), and free fatty acids (FFAs) and strongly increased high-density lipoprotein (HDL) cholesterol levels (Fig. 1A-D). In hApoE2 KI/PPAR-α KO mice, GFT505 failed to influence plasma TGs (Fig. 1A). However, in this strain of mice, GFT505 still decreased plasma FFAs and total cholesterol and increased HDL cholesterol, albeit to a lesser extent (Fig. 1B-D). These data suggest that GFT505 VX-765 concentration may have favorable effects on plasma lipids that are independent of activation of PPAR-α. In contrast, in a similar study, the PPAR-α reference agonist, fenofibrate (100 mg/kg/day), did not show any lipid-modulating effects in hApoE2 KI/PPAR-α KO mice (Supporting Fig. 2A-D). As expected in rodents exposed to a PPAR-α agonist,[11] GFT505 significantly

increased liver weight in hApoE2 KI mice, but not in hApoE2 KI/PPAR-α KO mice (Fig. Inhibitor Library cell line 1E), illustrating the hyperresponsiveness of rodents to PPAR-α-induced peroxisomal proliferation and hepatomegaly. Similar findings were observed with fenofibrate (data not shown). Microscopic examination of livers revealed both macro- and microsteatosis in WD-fed hApoE2 KI/PPAR-α KO mice, whereas PPAR-α-expressing hApoE2 KI mice were relatively resistant to WD-induced steatosis (Fig. 2A-C). In hApoE2 KI/PPAR-α KO mice, GFT505 administration reduced both diet-induced macro- and microsteatosis MCE公司 (Fig. 2A-C) and significantly reduced circulating

levels of the liver dysfunction markers, aspartate aminotransferase (AST) and ALT (data not shown). Interestingly, GFT505 reduced WD-induced increased cellularity in sinusoids (KCs) in both hApoE2 KI and hApoE2 KI/PPAR-α KO mice (Fig. 2D). In contrast, fenofibrate had no effect on cellularity of sinusoids in ApoE2 KI/PPAR-α KO mice (Supporting Fig. 2E,F). These results suggested that GFT505 has liver-protective effects through combined PPAR-α-dependent and -independent mechanisms. In hApoE2 KI mice, GFT505 provoked a significant reduction in hepatic expression of proinflammatory genes, such as interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), the macrophage marker, F4/80, and the fibrosis genes, transforming growth factor beta (TGF-β) and tissue inhibitor of metalloproteinase (TIMP)−2 (Supporting Table 2). In hApoE2 KI/PPAR-α KO mice, these genes were also reduced by GFT505, with significant down-regulation of additional profibrosis markers, such as collagens (Supporting Table 2). In contrast, fenofibrate significantly reduced the expression of proinflammatory and profibrotic genes in hApoE2 KI mice, but had little effect in hApoE2 KI/PPAR-α KO mice. In keeping with PPAR-α agonist-induced hepatomegaly in rodents (Fig.

hispanica than in P. bocagei. Statistically significant find more results were obtained for head-shape asymmetry, supporting the second and the fourth hypotheses. With an overall meristic asymmetry index, none of the hypotheses were corroborated, whereas for certain independent meristic traits, the first, the third and the fourth hypotheses were partially supported. Both head shape and meristic traits constitute precise measures of FA, but FA is more convincingly expressed in head shape and in single meristic traits than in overall meristic traits asymmetry. We conclude that FA reflects population isolation and may be a good indicator of developmental instability.

It seems worthwhile to test for FA in a landlocked system under environmental and genetic stress, for the purpose of conservation biological assessments. “
“Since the mid-1970s, most investigators have agreed that the ‘bizarre’ structures (here referred to as ‘exaggerated’ structures) of dinosaurs – for example, the horns and frills of ceratopsids, the crests of lambeosaurine hadrosaurids, the domes of pachycephalosaurs – functioned first and foremost as signalling and combat structures used CB-839 nmr in mate

competition (Farlow & Dodson, 1975; Hopson, 1975; Molnar, 1977; Spassov, 1979; Ostrom & Wellnhoffer, 1986;Sampson, 1997, 2001; Dodson, Forster & Sampson, 2004). Padian & Horner (2010) argue that the mate competition hypothesis is not supported by available evidence, citing in particular the lack of data documenting sexual dimorphism

within dinosaur species. In place of the mate competition model, they present a challenging and novel alternative, suggesting these traits functioned as species recognition features for identifying conspecifics, thereby facilitating social interactions such 上海皓元医药股份有限公司 as herding, mating and parental care. Padian & Horner offer a pair of tests for distinguishing paleontological examples of exaggerated traits evolving under the influence of species recognition from those resulting primarily from sexual selection. The first test relates to the patterns of diversification of exaggerated structures, predicted to be random under the influence of species recognition and directional if driven by sexual selection. The second test invokes evidence of geographic overlap of closely related, contemporaneous species, thought to be a necessary condition for the evolution of exaggerated structures under the influence of species recognition (in part so as to avoid unwanted matings). These authors argue that known examples of exaggerated structures among dinosaurs pass both of these tests, indicating that species recognition is the preferred (though not necessarily sole) explanation. Padian & Horner highlight a major problem common to most previous studies addressing the function of dinosaurian exaggerated structures – lack of phylogenetic context.

hispanica than in P. bocagei. Statistically significant Selleckchem MLN8237 results were obtained for head-shape asymmetry, supporting the second and the fourth hypotheses. With an overall meristic asymmetry index, none of the hypotheses were corroborated, whereas for certain independent meristic traits, the first, the third and the fourth hypotheses were partially supported. Both head shape and meristic traits constitute precise measures of FA, but FA is more convincingly expressed in head shape and in single meristic traits than in overall meristic traits asymmetry. We conclude that FA reflects population isolation and may be a good indicator of developmental instability.

It seems worthwhile to test for FA in a landlocked system under environmental and genetic stress, for the purpose of conservation biological assessments. “
“Since the mid-1970s, most investigators have agreed that the ‘bizarre’ structures (here referred to as ‘exaggerated’ structures) of dinosaurs – for example, the horns and frills of ceratopsids, the crests of lambeosaurine hadrosaurids, the domes of pachycephalosaurs – functioned first and foremost as signalling and combat structures used OSI 906 in mate

competition (Farlow & Dodson, 1975; Hopson, 1975; Molnar, 1977; Spassov, 1979; Ostrom & Wellnhoffer, 1986;Sampson, 1997, 2001; Dodson, Forster & Sampson, 2004). Padian & Horner (2010) argue that the mate competition hypothesis is not supported by available evidence, citing in particular the lack of data documenting sexual dimorphism

within dinosaur species. In place of the mate competition model, they present a challenging and novel alternative, suggesting these traits functioned as species recognition features for identifying conspecifics, thereby facilitating social interactions such MCE as herding, mating and parental care. Padian & Horner offer a pair of tests for distinguishing paleontological examples of exaggerated traits evolving under the influence of species recognition from those resulting primarily from sexual selection. The first test relates to the patterns of diversification of exaggerated structures, predicted to be random under the influence of species recognition and directional if driven by sexual selection. The second test invokes evidence of geographic overlap of closely related, contemporaneous species, thought to be a necessary condition for the evolution of exaggerated structures under the influence of species recognition (in part so as to avoid unwanted matings). These authors argue that known examples of exaggerated structures among dinosaurs pass both of these tests, indicating that species recognition is the preferred (though not necessarily sole) explanation. Padian & Horner highlight a major problem common to most previous studies addressing the function of dinosaurian exaggerated structures – lack of phylogenetic context.

An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489:57-74. (Reprinted

with permission.) The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Ku-0059436 mw Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. As the world debates the wisdom of excess regulation in other aspects of life, it is becoming increasingly clear that the genome is under highly complex regulatory control. The Human Genome Project (HGP) not only characterized the protein-coding genes of the genome, but also ushered in an era of

personalized medicine, where patients are beginning to receive targeted therapies based on genomic sequence. An immediate example in hepatology is the use of IL28B genotyping in hepatitis C therapy.1 However, expectations selleck chemicals llc of

advances in the pathobiology and treatment of complex diseases have not been fulfilled, since the majority of the genome remains a mystery—nonprotein coding and labeled as “junk DNA.” The aim of the ENCODE project (Fig. 1) was to address this gap in 上海皓元 knowledge. The approach to apply the wealth of genetic information from the HGP to determining susceptibility for complex diseases has thus far been through the use of genome-wide association studies (GWAS). Over 1,500 GWAS studies have been conducted since the first GWAS study was reported in 2005 (www.genome.gov/gwastudies/), and several hundred disease-associated genetic variants have been found.2 However, disappointingly, the majority of these are single nucleotide polymorphisms (SNPs) with only a small effect on the trait or disease being studied. The implication is that a large part of the heritability of these complex diseases remains unexplained. It appears that there are two reasons for the lower “hit rate” from GWAS studies for biological targets than expected. First, the GWAS targets are occasionally in linkage disequilibrium with the specific causative locus, thereby obscuring the true causative gene product.2 However, more commonly, the locus associated with the disease phenotype is not related to a coding region of genomic DNA.

The relationship of H. pylori and GERD is controversial. This study was performed to understand the role of H. pylori virulent genes in GERD

in North India. Methods: This study was conducted among 405 patients who visited the OPD of Yashoda Super Specialty Hospital and agreed to participate in the study. The subjects included patients (n = 342) and controls (n = 63), (those who undergoing endoscopy for reasons other than GERD). The genotyping of the cagA and vacA gene was done by PCR in 63 patients (including GERD (n = 21), NERD (n = 27), antral gastritis (n = 4), Peptic Ulcer (n = 2), Fungal esophagitis (n = 1), Non-ulcer dyspepsia (n = 3) and control patients (n = 5). GERD was diagnosed by FSSG questionnaire Atezolizumab research buy (Score >7) and endoscopic evidence of esophagitis; NERD was diagnosed

if FSSG score >7 and normal endoscopy. Results: H. pylori was cultured from 63 (15.6%) patients. The MAPK Inhibitor Library cell line average age of 63 patients included in the study was 44.9 yr. + 16.6 yr and the M : F ratio was 1:0.615. Of the 63 H. pylori strains, 27 (42.9%) strains were cagA positive while 36 (57.1%) strains were cagA negative. Correlation of the disease status with the genotype. It was observed that cag A positive strains of H. pylori were less prevalent in Reflux esophagitis (8/21; 38.1 %) and Nonerosive reflux esophagitis groups (12/27; 44.4%) than cag negative in Reflux esophagitis (13/21; 61.90 %) strains(Table 1). However, these differences did not achieve significance value (p > 0.05). Further, it was found that the cag negative strains were significantly more (p < 0.05) associated with less severe Reflux esophagitis [(Grade A/B); 13/13 100%] while cag positive strains caused more severe esophagitis [(Grade C/D); 3/8 37.5] CHI SQAURE TEST VALUE = 5.69, p value = .017 (p < 0.05), significant. Conclusion: cag A positive strains of Helicobacter pylori may be causative for severe GERD. Key Word(s): 1. cagA; 2. Helicobacter pylori;

3. Reflux esophagitis; 4. India; Table 1: Relationship between Disease Status and Genotype DISEASE STATUS TOTAL NO. OF PATIENTS NO. OF PATIENTS cagA negative/cagA positive Reflux oesophagitis 21 13 (61.90%)/8 (38.09%) (LA grade A/B/C/D)     NERD 27 15 (55.55%)/12 (44.44%) NUD 3 1 (33.33%)/2 (66.66%) Peptic – DU/GU 2 0/2 (100%) Antral 上海皓元医药股份有限公司 gastritis 4 4 (100%)/0 Fungal Esophagitis 1 1 (100%)/0 Control 5 2 (40%)/3 (60%) Presenting Author: GAILING WU Additional Authors: YU LAN Corresponding Author: GAILING WU Affiliations: gastroenterology; gastroentrology Objective: It is difficult to select the therapy scheme for Helicobacter pylori (H. pylori) infected patients with penicillin allergy. Since the tetracycline is seldom to be obtained, the furazolidone’s adverse effect is high, the antibiotics that used for treating the H. pylori infected patients are clarithromycin, tinidazole, levofloxacin and so forth.

The fossil record provides only a limited amount of certain kinds of evidence (primarily hard tissues such as skeletons and shells, and ichnites such as tracks), limiting the power of interpretations of behaviour. Palaeontologists have only a tiny amount of the data that would be available to an ethologist

studying an extant organism. Some kinds of palaeontological data are readily available, but costly or time consuming to acquire or may damage the specimens (e.g. histological thin sections of bone, or synchotron scanning of fossils). Furthermore, AG-014699 ic50 all fossils specimens are subject to the filter of taphonomy that can potentially profoundly alter the available data, presenting misleading pictures of the evidence (e.g. lamellibranch shells having suffered drilling from predators transport further than do intact ones, Lever et al., 1961). Detailed studies or exceptional specimens can potentially reveal much information (e.g. the potential to separate out at what time various tracks

were laid down relative to one another – Milner, 2005, evidence for transport of material – Voorhies, 1969, and to distinguish between trample marks or bite marks – Fiorillo, 1984) and support for a conjecture. However, these must be put in the context of the specimens, a correct understanding and appreciation of behaviour, and framed as a specific hypothesis. They Staurosporine chemical structure must also be formulated in an appropriate manner that does not immediately lead to a false premise being created. Given the limitations of palaeontological data, we would advocate that formulated hypotheses need not be testable in the present based on the then available data, but at least have the capacity to be tested on the basis of future finds or analyses. Here we outline some previous problems affecting hypotheses about palaeobehaviours. We do not intend to overtly criticize the studies cited as examples, but rather draw attention to potential pitfalls

that may have been previously overlooked. Note that not all of these examples may ultimately be incorrect; however, they are not supported by the data as suggested: (1)  False dichotomy or premise. Mutually exclusive hypotheses are useful as they allow 上海皓元 the evidence for only a single concept to be used to infer the state of another. However, such relationships must truly be antagonistic, or a false dichotomy is created and evidence for one hypothesis incorrectly used as evidence against another. For example, Taylor et al. (2010) showed that Senter’s (2007) claim of a dichotomy between sexual selection and feeding envelope increase in sauropod dinosaur necks was false. Thus Senter’s arguments in favour of sexual selection did not rule out a functional role.

7). Finally, our results show the importance of the Mdm2-NEDD8 network in this website HuR overexpression during malignant transformation, supporting the role of HuR in tumorigenesis. The potential of antitumor activity for the NEDD8-activating enzyme inhibitor, MLN4924, has been shown in human colon and lung tumor xenograft models in immunocompromised mice.34 Taken together, HuR is a new target for NEDDylation, and NEDD-dependent regulation plays a crucial role as a principal conductor of a new regulatory mechanism. Our findings might represent a useful tool to uncover new therapeutic strategies for HCC and

colon cancer. In closing, our results show that NEDDylation is a novel mechanism for HuR regulation, which broadly reveals its influence on the cellular post-transcriptional regulatory machinery. The authors particularly acknowledge the patients enrolled in this study for their participation

and the Basque Biobank for Research-OEHUN for its collaboration in providing the human samples and the clinical information used in this project with appropriate ethics approval. The authors are grateful to Dr. Juan Burgos Raf inhibitor for selection of the human samples and Dr. Félix Royo for helping with statistical analysis. Additional Supporting Information may be found in the online version of this article. “
“As the result of an increasing incidence and a prevalent therapy resistance medchemexpress of hepatocellular carcinoma (HCC), there is a strong need for novel strategies to enhance treatment responses in HCC. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has been proposed as a promising anticancer drug because it can selectively induce apoptosis in cancer cells, but not in healthy cells. Nevertheless, most tumor cells show TRAIL resistance, emphasizing the requirement for apoptosis-sensitizing agents and TRAIL molecules with improved tumor specificity. In this study, we employed a recombinant TRAIL molecule, in which three TRAIL protomers were expressed as a single polypeptide chain (scTRAIL), and a novel TRAIL variant, in which scTRAIL was additionally fused to an antibody fragment recognizing epidermal growth

factor receptor (EGFR) to improve its HCC-targeting properties. We analyzed the proapoptotic effects of both TRAIL versions in combination with the proteasome inhibitor bortezomib (BZB) in hepatoma cells and primary human hepatocytes as well as in intact explants from HCC and healthy liver tissue. We demonstrate that EGFR-targeted TRAIL in combination with BZB induced significantly higher caspase activation and cell death in hepatoma cells, but not in primary hepatocytes. Importantly, when incubated with fresh liver explants, the combination of EGFR-targeted TRAIL and BZB displayed selective cytotoxicity for HCC, but not for tumor-free liver tissue, which could even be verified in liver explants from the same individuals.