Next we tested whether selenium levels modulate AP-1 activity, VEGF, and IL-8 also in the animal organism and affect growth of early tumor stages. Because the IL-8 gene is not conserved in rats, its analog CXCL1 was investigated. The Solt-Farber model of rat hepatocarcinogenesis was used with and without selenium supplementation. Selenium supplementation increased serum selenium levels (Table 1). In the promotion phase, cell proliferation as well as volume of preneoplastic liver nodules were reduced from 38% to 14% volume fraction in the selenium-supplemented rats.25 Hepatic mRNA expression of VEGF and c-fos was reduced in the

promotion but not in the progression phase (Table 1). Nuclear translocation of selleck chemical c-jun and expression of CXCL1 were not influenced by selenium (Table 1). Serum VEGF and CXCL1 proteins were below the detection limit of commercially available ELISAs. Thus, in this rat model selenium supplementation decreases VEGF and c-fos expression as shown above in vitro; this effect is associated with a dramatic reduction of nodule growth.

Finally, we analyzed the effects of selenium and LOOH on growth factors and tumor GW-572016 ic50 size in patients with HCC. LOOH-Ab in blood plasma were determined similar to work published previously.33-35 Interestingly, LOOH-Ab levels were significantly higher in HCC patients than in healthy controls (Fig. 上海皓元 5A), suggesting higher amounts of circulating LOOH. Selenium levels inversely correlated with VEGF and IL-8

and also with tumor size in HCC patients, the latter only in those with tumors diameters up to 3 cm (Table 2; Fig. 5B). LOOH-Ab levels correlated positively with VEGF (only in patients with HCC <3 cm) and IL-8 and also with nuclear localization of c-jun indicating AP-1 activation (Table 2; Fig. 5C,D). These correlations in HCC patients are consistent with the above finding that LOOH enhances VEGF and IL-8 expression and AP-1 activation in cultured HCC cells, and that selenium antagonizes these effects. Finally, we reevaluated published gene expression data from HCC tissue of 60 patients.24 GPx4 but not GPx2 inversely correlated with VEGF and c-fos expression. GPx correlations with IL-8 and c-jun expression were not statistically significant, but VEGF positively correlated with IL-8 (Supporting Table 5). These data agree with the inhibitory role of the selenium-inducible GPx4 on VEGF expression in HCC cells found in vitro (see above). Inflammation and associated formation of ROS are widely accepted risk factors in hepatocarcinogenesis but important mechanistic details are still unknown. Here we report that peroxides of linoleic acid (LOOH) can activate the transcription factor AP-1, a sensor of oxidative stress36-38 and important promoter of hepatocarcinogenesis.

Mark Skinner is a former president of the WFH and Elizabeth Myles is the WFH Chief Operating Officer. “
“Haemophilia has been associated with low bone mineral density (BMD). However, prior clinical studies of this population have neither clearly elucidated risk factors for development of low BMD nor identified C646 who may warrant screening for osteoporosis. The aim of the study was to evaluate the relationship between BMD and haemophilic arthropathy and other demographic and clinical variables. We undertook a cross-sectional study of BMD in adult men with haemophilia. Measures of predictor variables were collected by radiographic

studies, physical examination, patient questionnaires and review of medical records. Among 88 enrolled subjects, the median age was 41 years (IQR: 20); median femoral neck BMD (n = 87) was 0.90 g cm−2 (IQR: 0.24); and median radiographic joint score was 7.5 (IQR: 18). Among subjects <50 years (n = 62), after controlling for BMI, alcohol, HIV and White race, BMD decreased as radiographic joint score increased (est. β = −0.006 mg cm−2; 95% CI −0.009, −0.003; partial R2 = 0.23). Among subjects ≥50 years (n = 26), 38% had osteoporosis (T score less than or equal to −2.5) and there was no association between

BMD and arthropathy. Risk factors for low BMD in men with BGB324 solubility dmso haemophilia <50 years include haemophilic arthropathy, low or normal BMI and HIV. Men with haemophilia over age 50 years should have routine screening for detection of osteoporosis. "
“Summary.  上海皓元 Nonafact®, an ultrapure, monoclonal antibody-purified factor IX concentrate (FIX) was developed to minimize risk of thrombotic complications

and viral transmission. To investigate the pharmacokinetics, efficacy and safety, phase III/IV studies were performed in the Netherlands and Poland from 1996 to 2007. The mean half-life, in vivo response and recovery of Nonafact® were 18.7 (SD 2.0) h, 1.1 (SD 0.2) IU dL−1 per IU kg−1 b.w. of FIX infused and 49% (SD 10%), respectively. Eleven surgical procedures were performed in eight patients. During two surgeries, both high-risk, blood loss was observed. No postoperative bleeding occurred. The in vivo recovery of FIX was higher than expected. In the phase III follow-up study, 26 previously treated patients (PTP) were included with a median follow-up of 1130 days. From the 1617 minor bleedings, 80.5% was stopped after a single infusion. In the phase IV study thirteen patients were treated for a median study period of 737 days. In the two follow-up studies the investigators rated the effect of Nonafact® as excellent/good in 95% of major bleedings. Surgeries for which Nonafact® was given prophylactically were without bleeding problems. In total more than 10 million units of Nonafact® were used during almost 120 person-years. Only one minor adverse event was reported. No inhibitors, viral transmissions and thrombogenic events occurred.

Subsequently pharmacokinetic data on INCB024360 FVIII from 147 individuals with haemophilia A (48 children ages 1–6 years

of age and 99 individuals ages 10–65 years of age) were used for simulations of commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis [30]. The results of the simulations demonstrated that individual half-life of infused FVIII and frequency of dosing have a much larger effect on FVIII trough levels and time per week with FVIII levels <1% than recovery and infused dose. Given the significant variation of individual patients’ FVIII and FIX pharmacokinetic profiles, attention to frequency of infusions should allow a more cost-effective use of FVIII and FIX in prophylaxis regimens. The concept that pharmacokinetically tailored dosing of FVIII and FIX could result in considerable savings of factor concentrates compared to standard

(‘fixed’) prophylaxis protocols is supported by publications of Carlsson, Björkman, Berntorp and co-workers [30–33]. A challenge to PK directed therapy that would allow easy alteration in prophylaxis regimens to achieve, for example, higher threshold (‘trough’) FVIII or FIX levels, is the perceived need to perform very demanding conventional PK studies on individual patients. This problem can be overcome buy Trametinib by using Bayesian PK analysis, utilizing a population pharmacokinetic model that allows a sparse blood sampling protocol [34]. Use of prophylaxis in the late adolescent/adult haemophilia population is increasing particularly in countries with unrestricted access to safe FVIII and FIX concentrates [35,36]. As an

example in a recent survey of 2663 persons with haemophilia A or B followed in Canadian 上海皓元 Comprehensive Care Hemophilia Treatment Centres, 53% of individuals with severe haemophilia A and 20% with severe haemophilia B >18 years of age were identified to be receiving prophylaxis defined as the infusion of FVIII or FIX at least once weekly for >45 weeks during the year 2006 [37]. An important question, in the context of prophylaxis use in the adult haemophilia population, is whether prophylaxis can be safely discontinued in individuals who have been receiving intermediate or full-dose prophylaxis from an early age of life. Data reported from Denmark and the Netherlands are instructive in this regard. In Denmark, patients with severe haemophilia are treated using the high-dose Swedish prophylaxis protocol, whereas the Dutch patients, as described earlier in this review, receive an intermediate-dose prophylaxis regimen. Of a total 49 Dutch patients who received intermediate-dose prophylaxis from an early age in life, 11 (22%) were able to permanently discontinue prophylaxis [38]. The median age of the cohort was 23.4 years at the time of analysis, and the median follow-up off prophylaxis was 3.2 years.

Subsequently pharmacokinetic data on Metformin FVIII from 147 individuals with haemophilia A (48 children ages 1–6 years

of age and 99 individuals ages 10–65 years of age) were used for simulations of commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis [30]. The results of the simulations demonstrated that individual half-life of infused FVIII and frequency of dosing have a much larger effect on FVIII trough levels and time per week with FVIII levels <1% than recovery and infused dose. Given the significant variation of individual patients’ FVIII and FIX pharmacokinetic profiles, attention to frequency of infusions should allow a more cost-effective use of FVIII and FIX in prophylaxis regimens. The concept that pharmacokinetically tailored dosing of FVIII and FIX could result in considerable savings of factor concentrates compared to standard

(‘fixed’) prophylaxis protocols is supported by publications of Carlsson, Björkman, Berntorp and co-workers [30–33]. A challenge to PK directed therapy that would allow easy alteration in prophylaxis regimens to achieve, for example, higher threshold (‘trough’) FVIII or FIX levels, is the perceived need to perform very demanding conventional PK studies on individual patients. This problem can be overcome Regorafenib supplier by using Bayesian PK analysis, utilizing a population pharmacokinetic model that allows a sparse blood sampling protocol [34]. Use of prophylaxis in the late adolescent/adult haemophilia population is increasing particularly in countries with unrestricted access to safe FVIII and FIX concentrates [35,36]. As an

example in a recent survey of 2663 persons with haemophilia A or B followed in Canadian MCE公司 Comprehensive Care Hemophilia Treatment Centres, 53% of individuals with severe haemophilia A and 20% with severe haemophilia B >18 years of age were identified to be receiving prophylaxis defined as the infusion of FVIII or FIX at least once weekly for >45 weeks during the year 2006 [37]. An important question, in the context of prophylaxis use in the adult haemophilia population, is whether prophylaxis can be safely discontinued in individuals who have been receiving intermediate or full-dose prophylaxis from an early age of life. Data reported from Denmark and the Netherlands are instructive in this regard. In Denmark, patients with severe haemophilia are treated using the high-dose Swedish prophylaxis protocol, whereas the Dutch patients, as described earlier in this review, receive an intermediate-dose prophylaxis regimen. Of a total 49 Dutch patients who received intermediate-dose prophylaxis from an early age in life, 11 (22%) were able to permanently discontinue prophylaxis [38]. The median age of the cohort was 23.4 years at the time of analysis, and the median follow-up off prophylaxis was 3.2 years.

Some of the best evidence of the effects of resource competition on females comes from studies of the effects of increasing group size, which commonly depress fecundity and increase mortality of females and their offspring (Clutton-Brock, Albon & Guinness, 1982, van Schaik et al., 1983; Clutton-Brock, 2009b, 2009b, Silk, 2007a; Clutton-Brock, Hodge & Flower, 2008). Very similar patterns of resource competition occur in males, where breeding activity can also have high energetic

costs (Lane et al., 2010), and individuals compete both for direct access to resources Akt molecular weight and for access to feeding territories (Clutton-Brock, 2007), and survival is often sensitive to food shortages (Clutton-Brock, Major & Guinness, 1985). As well as competing for access to resources, females, like males, often compete to breed and, as in males, the structure of social groups intensifies conflicts of interest between group members (West-Eberhard, 1983, 1984). In some mammals, females compete to become sexually mature and, in extreme cases, one female suppresses the sexual development of all other females, evicting individuals that attempt see more to breed (Creel & Creel, 2002; Clutton-Brock et al., 2006; Clutton-Brock, 2009b).

In others, females compete for access to mates, even though operational sex ratios (the ratio of males to females that are ready to mate at a given time) are biased towards males. For example, in some ungulates where males defend groups of females during a well-defined mating season, there is often more than one receptive female in a male’s harem on the same day, and females commonly compete for the attentions 上海皓元 of males (Bro-Jørgensen, 2002, 2011). Female competition may help females to ensure that they are mated by one or more males

within the time frame of their reproductive cycles (Parker & Ball, 2005), for the sperm supplies of successful males can become depleted (Dewsbury, 1982; Preston et al., 2001, Wedell, Gage & Parker 2002) or popular males may strategically conserve sperm for subsequent mating opportunities (Parker et al., 1996, Wedell et al., 2002). As would be expected, the frequency of overt female competition for mating partners increases in populations where adult sex ratios are strongly biased towards females (Milner-Gulland et al., 2003, Cheney, Silk & Seyfarth, 2012), where there is a high degree of reproductive synchrony (Emlen & Oring, 1977; Stockley & Bro-Jorgensen, 2011), or where females mate with multiple partners (Charlat et al., 2007).

in this study. Furthermore, nonphosphorus lipids, PF-02341066 concentration phospholipid substitutions, are recently suggested as fundamental biochemical mechanisms to maintain phytoplankton growth in response to P limitation (Van Mooy et al. 2009). Van Mooy et al. (2009) found that marine phytoplankton showed different ability to substitute the nonphosphorus membrane

lipids for the phospholipids. Thus, further studies concerning the regulation of phospholipids and phospholipid substitutions are highly recommended to explore the interspecific effect of P deficiency on PUFAs in phytoplankton. The results discussed above suggest that the association of PUFAs with different types of lipids, e.g., TAGs, phospholipids, and phospholipid substitutions, should be considered

in further studies on Alectinib purchase lipid biosynthesis under different nutrient supply. Moreover, advanced analytical techniques, e.g., HPLC/electrospray ionization–mass spectrometry (ESI-MS), have been recently used to improve the identification of different types of lipids in the ocean (Van Mooy et al. 2006, 2009, Van Mooy and Fredricks 2010). In conjunction with the advent of advanced techniques, this study will provide important empirical data for further studies on lipid biosynthesis of phytoplankton in changing oceans. In this study, significant effects of N or P deficiency on FAs in the three species were only observed at lower growth rates (20% or 40% of μmax). It has been suggested that nutrient limitation does not have direct effects on FA synthesis of phytoplankton, but a consequence of a limited growth rate leads to FA changes (Piepho et al. 2012). However, our study showed significant responses of FAs to N or P deficiency at the same growth rate

in all three species, while the effects of N and P deficiency became nonsignificant when growth rate increased. Our previous study demonstrated that high dilution rate (loss rate) could explain the limited flexibility of phytoplankton stoichiometry in natural communities (Bi et al. 2012). Thus, the optimal nutrient uptake ratio of phytoplankton at higher growth rates may explain the optimal N:P biomass 上海皓元 ratios, as well as the relative stability of FA contents, irrespective of N:P supply ratios. It is commonly accepted that total lipid content increases with decreasing growth rate (Borowitzka 1988, Sterner and Hessen 1994). This is probably due to the low requirement for synthesis of protein and instead a steady accumulation of lipid, mainly TAGs, when growth slows down (Siron et al. 1989, Reitan et al. 1994, Guschina and Harwood 2009). FA accumulation at lower growth rates has been found for several algal species in previous studies (e.g. Reitan et al. 1994, Otero and Fábregas 1997, Ferreira et al. 2011, Spijkerman and Wacker 2011). Also, in this study TFAs contents in both Rhodomonas sp. and I. galbana were relatively higher at lower growth rates. The lack of significant TFA response in P.

Initial depletion of Tregs revealed their complex regulatory function during acute infection. Tregs mitigated immunomediated liver damage by down-regulating the antiviral activity of

effector T cells by limiting cytokine production and cytotoxicity, but did not influence development of HBV-specific CD8 T cells or development of memory T cells. Furthermore, Tregs controlled the recruitment of innate immune cells such as macrophages and dendritic cells to the infected liver. As a consequence, Tregs significantly delayed clearance of HBV from blood and infected hepatocytes. Conclusion: Tregs limit immunomediated liver damage early after an acute infection of the liver, thereby contributing to conservation of tissue integrity and organ function at the cost of prolonging virus clearance. (HEPATOLOGY 2012;56:873–883) CAL-101 Hepatitis B is a major global health problem caused by the human hepatitis B virus (HBV). Up to 10% of adults and >90% of neonates infected with this virus develop chronic infection, correlating with T cell dysfunction and hyporesponsiveness.1 Currently, about 350 million people RO4929097 price worldwide are chronic

HBV carriers, and >0.5 million die every year due to HBV-associated liver disease and hepatocellular carcinoma. Our knowledge about the mechanisms resulting in HBV persistence and disease pathogenesis is limited due to the lack of suitable model systems and appropriate patient material for immunological studies. Chronically infected patients are not able to launch strong and polyclonal CD8+ and CD4+ T cell responses, which are essential for clearance of viral infection from the liver.1 Several possible explanations for this lack of antigen-specific cellular immunity against chronic viral infection in the liver have been put forward. Negative selection of HBV-specific T cells, immunological ignorance or anergy—as a result of continuous exposure to high levels of viral antigens—or

medchemexpress impaired activation of innate immunity may result in T cell hyporesponsiveness. Furthermore, the liver provides an inherently tolerizing immunological environment,2 where antigen-presenting cells skew immune responses generated in the liver toward tolerance and limit effector function of T cells by expression of coinhibitory molecules such as B7H1. It remains an open question, however, whether regulatory T cells (Tregs) that have been defined as key cell population in limiting antigen-specific immunity,3 contribute to severity of liver damage and influence the outcome of acute infection. CD4+Foxp3+ Tregs were originally shown to be a specialized T cell subpopulation suppressing autoreactive T cell responses and maintaining immunological tolerance.4 This T cell subset was first characterized by constitutive surface expression of the interleukin-2 receptor alpha (CD25),5, 6 but CD25 is also expressed on activated conventional effector T cells limiting specific depletion.

The genomic deletions were confirmed by internal genomic PCR (Fig. 1B, right panel). The structure of the resultant protein encoded by the Δex2 allele (Cas PI3K Inhibitor Library order Δex2) is shown at the bottom of Fig. 1A. As shown by western blotting (Fig. 1C), a protein of the expected molecular weight (∼90 kDa) was detected in the sample from CasΔex2/Δex2 mice (Cas Δex2), and this indicated correct targeting, the excision of Cas exon 2, and the production of the short Cas protein lacking the corresponding segment. Heterozygous (Cas+/Δex2) mice were apparently normal and were intercrossed to produce homozygous (CasΔex2/Δex2) mutants. No live CasΔex2/Δex2 neonates were obtained, and this indicated that the CasΔex2/Δex2

mice died as embryos. To investigate the date of embryonic lethality, embryos obtained from the intercrossing of Cas+/Δex2 mice were examined at different embryonic stages. As shown in Table 1, CasΔex2/Δex2 embryos were alive until

12.5 dpc, but no live CasΔex2/Δex2 embryos were obtained after 13.5 dpc. To examine the cause of embryonic lethality in CasΔex2/Δex2 mice, wild-type (WT) and CasΔex2/Δex2 embryos at approximately 12.5 dpc were subjected to pathological examination. A remarkable and progressive change was observed in the livers of CasΔex2/Δex2 embryos. At 11.5 dpc, when macroscopic change was not yet apparent (Fig. 2A, left panels), hematoxylin DMXAA cell line and eosin (HE)–stained sections revealed that part of the liver of a CasΔex2/Δex2 embryo began to collapse from the inside (Fig. 2B, second bottom panel). At 12.5 dpc, this change was more pronounced, and the liver capsule of a CasΔex2/Δex2 embryo was macroscopically 上海皓元 enlarged with a mass left inside (Fig. 2A, fourth panel). HE-stained sections showed that most of the hepatocytes were lost, whereas hematopoietic cells were preserved (Fig. 2B, fourth bottom panel). Despite intensive analysis, no pathological abnormalities were found in other organs, including

the brain, heart, lungs, spleen, and kidneys (data not shown). Therefore, we concluded that progressive liver degeneration was the primary cause of death of CasΔex2/Δex2 embryos. The pathological pictures suggested that the progressive hepatocyte reduction in CasΔex2/Δex2 embryos was due to apoptosis. To address this possibility, livers of CasΔex2/Δex2 and WT embryos 12.5 dpc were subjected to the TUNEL assay. As shown in Fig. 2C, no obvious staining was observed in the WT liver (left panels), whereas several round hepatocytes surrounding the central collapsed area were positively stained in the CasΔex2/Δex2 liver (indicated by arrowheads in the right bottom panel); this confirmed the apoptotic reduction of hepatocytes. To investigate the mechanism underlying hepatocyte apoptosis, localization of the Cas protein in the embryonic liver was examined by immunohistochemistry. Normal livers at 11.

7, 21-23 We found significantly increased IL1Ra expressions, at both messenger RNA (mRNA) and protein levels, in ARKO BM-MSCs-transplanted livers, as compared

with those transplanted with WT BM-MSCs (Fig. 2D-j-l), and transplanted BM-MSCs are the major cells secreting IL1Ra (Supporting Fig. 5A,B). However, we detected no significant difference in HGF, VEGFB, and VEGFC expressions (Supporting Fig. 4C-E). Surprisingly, we observed significantly reduced MMP-2 and -9 expressions upon BM-MSC transplantation, and ARKO BM-MSCs showed better reduction than WT BM-MSCs (Supporting Fig. 4F,G), implying that BM-MSCs transplantation inhibited inflammatory response. selleckchem These results are consistent with the clinical observation showing MMP-2 and -9 were elevated in chronic and inflammatory liver disease patients,24, 25 but opposite to the report proposing BM-MSCs INCB018424 in vivo therapeutic effects through elevating MMPs.23 To dissect the potential mechanisms by which knockout of AR in BM-MSCs could lead to better transplantation efficacy through anti-inflammation/anti-fibrosis

signals, we investigated the self-renewal and migration potentials of BM-MSCs that have been shown to improve therapeutic outcomes on myocardial infarction and liver cirrhosis through anti-inflammatory and anti-fibrotic actions.26-28 We found higher self-renewal potential in ARKO BM-MSCs than WT BM-MSCs using the CUF-f 上海皓元医药股份有限公司 assay29 (Fig. 3A-a). Western blotting analysis also showed higher PCNA expression in ARKO BM-MSCs than WT BM-MSCs (Fig. 3A-b). We then dissected the mechanisms by which ARKO BM-MSCs have higher

self-renewal ability, and found that knocking out AR in BM-MSCs led to activation of extracellular signal-related kinase 1 and 2 (Erk1/2) and protein kinase B (Akt) signals and their upstream signal, endothelial growth factor/endothelial growth factor receptor (EGF/EGFR; Fig. 3A-c,d), suggesting that AR in BM-MSCs might be able to promote the self-renewal potential through modulation of EGF-Erk1/2 and EGF-Akt signals. It is interesting to know whether human MSCs (hMSCs) also express AR and whether knockdown of AR in hMSCs results in the similar mechanistic regulation as observed in mouse models. We demonstrated that hMSCs have detectable AR expression (Supporting Fig. 6A). Knockdown of AR in hMSCs enhanced EGFR expression to result in activation of Akt and Erk1/2 (Supporting Fig. 6B,E,F). We then examined AR knockout effect in BM-MSCs on cell migration using Boyden chamber assays, and found that ARKO BM-MSCs have higher migration ability than WT BM-MSCs, as demonstrated by positively stained migrated cells (Fig. 3B-e,f). We then dissected the mechanisms by which the ARKO BM-MSCs have higher migration ability, and found that ARKO BM-MSCs have higher MMP-9 expression than WT BM-MSCs (Fig. 3B-g).

We examined the role of heme-sensing nuclear receptor Rev-erbα, a transcriptional repressor involved in metabolic and circadian regulation

known to promote adipogenesis in preadipocytes, in HSC transdifferentiation. We discovered that Rev-erbα protein was up-regulated in activated HSCs and injured livers; however, transcriptional repressor activity was not affected by fibrogenic treatments. Surprisingly, increased protein expression was accompanied with increased cytoplasmic accumulation of Rev-erbα, which demonstrated distributions similar to myosin, the major cellular motor protein. Cells overexpressing a cytoplasm-localized Rev-erbα exhibited enhanced contractility. Ectopically expressed mTOR inhibitor Rev-erbα responded to both adipogenic ligand and fibrogenic transforming growth factor beta treatment. Rev-erb ligand SR6452 down-regulated cytoplasmic expression of Rev-erbα, decreased expression of fibrogenic markers and the activated phenotype in HSCs, and ameliorated

fibrosis and PH in rodent models. Conclusions: Up-regulation of Rev-erbα is an intrinsic fibrogenic response characterized by cytoplasmic accumulation of the protein in activated HSCs. Cytoplasmic expression of Rev-erbα promotes selleckchem a contractile phenotype. Rev-erbα acts as a bifunctional regulator promoting either anti- or profibrogenic response, depending on milieu. Rev-erb ligand SR6452 functions by a previously undescribed mechanism, targeting both nuclear activity and cytoplasmic expression of Rev-erbα. Our studies identify Rev-erbα as a novel regulator of HSC transdifferentiation and offers exciting new insights on the therapeutic potential of Rev-erb ligands. (Hepatology 2014;59:2383–2396) “
“Sorafenib is the standard systemic therapy for patients with advanced hepatocellular carcinoma (HCC). We aimed to assess the efficacy 上海皓元医药股份有限公司 and safety of sorafenib therapy in very elderly patients aged 80 years and older with advanced HCC. In a retrospective multicenter study in Japan, we reviewed 185 patients (median age, 71 years; 82% male;

95% Child–Pugh class A) with advanced HCC who received sorafenib therapy. Data were compared between 24 (13%) patients aged 80 years and older and 161 (87%) patients aged less than 80 years. We used propensity score matching to adjust for differences between the two groups. Median overall survival was 10.6 months in all patients: 11.7 months in patients aged 80 years and older and 10.5 months in those aged less than 80 years. There were no significant differences in overall survival, tumor response, and frequency and severity of drug-related adverse events between patients aged 80 years and older and those aged less than 80 years in both the entire study cohort and the propensity-matched cohort. Sorafenib may be effective and well tolerated, even in patients with advanced HCC who are aged 80 years and older, as well as those aged less than 80 years.