We investigated continuous cultures of four strains from distinct phylotypes (A1, A13, A2, and B1) that can be characterized by differential thermal tolerances. We hypothesized that strains with high thermal tolerance have higher concentrations of DMSP and DMS in comparison to strains with low thermal tolerance. DMSP selleck screening library concentrations were strain-specific with highest concentrations

occurring in A1 (225 ± 3.5 mmol · L−1  cell volume [CV]) and lowest in A2 (158 ± 3.8 mmol · L−1 CV). Both strains have high thermal tolerance. Strains with low thermal tolerance (A13 and B1) showed DMSP concentrations in between these extremes (194 ± 19.0 and 160 ± 6.1 mmol · L−1  CV, respectively). DMS data further confirmed this general pattern with high DMS concentrations in A1 and A13 (4.1 ± 1.22 and 2.1 ± 0.37 mmol · L−1 CV, respectively) and low DMS concentrations in A2 and B1 (0.3 ± 0.06 and 0.5 ± 0.22 mmol · L−1 CV, respectively). Hence, the strain-specific differences in DMSP and DMS concentrations did not match the different abilities of the four phylotypes to withstand thermal stress. Future work should quantify the possible dynamics in DMSP and DMS concentrations during periods of high oxidative stress in Symbiodinium sp. and address

the role of these antioxidants in zooxanthellate selleck chemical cnidarians. “
“The PSII photochemical activity in a terrestrial cyanobacterium Nostoc

commune Vaucher ex Bornet et Flahault during rewetting was undetectable in the dark but was immediately recognized in the light. The maximum quantum yield of PSII (Fv/Fm) during rewetting in the light rose to 85% of the maximum within ∼30 min and medchemexpress slowly reached the maximum within 6 h, while with rewetting in the darkness for 6 h and then exposure to light the recovery of Fv/Fm required only ∼3 min. These results suggested that recovery of photochemical activity might depend on two processes, light dependence and light independence, and the activation of photosynthetic recovery in the initial phase was severely light dependent. The inhibitor experiments showed that the recovery of Fv/Fm was not affected by chloramphenicol (CMP), but severely inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) in the light, suggesting that the light-dependent recovery of photochemical activity did not require de novo protein synthesis but required activation of PSII associated with electron flow to plastoquinone. Furthermore, the test indicated that the lower light intensity and the red light were of benefit to its activation of photochemical activity. In an outdoor experiment of diurnal changes of photochemical activity, our results showed that PSII photochemical activity was sensitive to light fluctuation, and the nonphotochemical quenching (NPQ) was rapidly enhanced at noon.

The discrepancy between ConA- and CCl4-induced liver damage in STAT3mye−/− mice could be attributable to the different T helper type 1 (Th1) cytokine (IFN-γ) responses in these two models. In STAT3mye−/− mice, ConA treatment elevated serum IFN-γ levels to more than 2500 pg/mL, whereas CCl4 treatment only elevated IFN-γ levels to 15 pg/mL. Such high levels of IFN-γ in the ConA model not only directly induce liver damage but also inhibit the hepatoprotective STAT3 signal in the liver, further promoting liver injury.3 In addition, ethanol consumption significantly inhibited STAT3 activation in STAT3mye−/− mice. Thus, the protective role of STAT3 is inhibited

in both models of ConA and ethanol treatment. These data suggest that the etiology of liver disease plays a critical role in determining LBH589 concentration the interplay between inflammation and hepatocellular damage. In general, the ratio between proinflammatory and anti-inflammatory factors controls the inflammatory level during liver damage; however, the fate of hepatocytes is determined by the balance between the survival and detrimental factors present within the damaged liver. For example, compared to wild-type mice, STAT3mye−/− mice had increased pro-inflammatory cytokines, eg, IL-6, IL-1, IFN-γ, and chemokines in both the liver and serum.1 However,

proinflammatory factors do not always kill hepatocytes and some of them such as IL-6 protect Pirfenidone rather than kill hepatocytes via activation of survival signal STAT3 in hepatocytes. Thus, inflammation is not always a direct killer of hepatocytes. Besides the dogma that inflammation leads to hepatocyte death, inflammation is also thought as the critical driver for liver fibrogenesis.

However, many studies have demonstrated that inflammation does not always correlate with liver fibrosis in patients with chronic liver disease.4 On the other hand, it is well recognized that degradation of fibrosis needs inflammation.5 Thus, whether inflammation is a friend or a foe is not a simple question. Here, we have three questions for the authors: First, in patients with acute liver failure, inflammatory cells, especially monocytes and macrophages, are central to systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and compensation anti-inflammatory response syndrome (CARS).6 Compared with SIRS 上海皓元医药股份有限公司 patients, patients with MODS have similar levels of proinflammatory cytokines, but higher levels of anti-inflammatory cytokines that suppressed the functions of peripheral and hepatic inflammatory cells. Similarly, in STAT3mye−/− mice, CCl4 treatment resulted in early elevation of proinflammatory cytokines (at 12 hours after treatment), which remained at the same levels or was decreased at later time points (24 hours). In contrast, the levels of the anti-inflammatory cytokine IL-10 were higher at later time (24 hours) than earlier time (12 hours) points.

These results

demonstrated that the interaction of substrate (N-availability) and energy gradients influenced C-allocation, and that general patterns of biochemical responses may be conserved among phytoplankton; they provided a framework for predicting phytoplankton biochemical composition in ecological, biogeochemical, or biotechnological applications. “
“The structure of intertidal benthic diatoms assemblages in the Tagus estuary was investigated during a 2-year survey, carried out in six stations with different NVP-BEZ235 supplier sediment texture. Nonparametric multivariate analyses were used to characterize spatial and temporal patterns of the assemblages and to link them to the measured environmental variables. In addition, diversity and other features related to community physiognomy, such as size-class or life-form distributions, were used to describe the diatom assemblages. A total of 183 diatom taxa were identified during cell counts and their biovolume was determined. Differences between stations (analysis of similarity (ANOSIM), R = 0.932) were more evident than temporal patterns (R = 0.308) and mud content alone was the environmental variable most correlated to the biotic GSK1120212 cost data (BEST, ρ = 0.863). Mudflat stations were typically colonized by low diversity diatom assemblages (H′ ~ 1.9), mainly composed of medium-sized motile epipelic species (250–1,000 μm3),

that showed species-specific seasonal blooms (e.g., Navicula gregaria Donkin). Sandy stations had more complex and diverse diatom assemblages (H′ ~ 3.2). They were mostly composed by a large set medchemexpress of minute epipsammic species (<250 μm3) that, generally, did not show temporal patterns. The structure of intertidal diatom assemblages was largely defined by the interplay between epipelon and epipsammon, and its diversity was explained within the framework of the Intermediate Disturbance Hypothesis. However, the spatial distribution of epipelic and epipsammic life-forms showed that the

definition of both functional groups should not be over-simplified. “
“Characeae (Charophyceae, Charophyta) contains two tribes with six genera: tribe Chareae with four genera and tribe Nitelleae, which includes Tolypella and Nitella. This paper uses molecular and morphological data to elucidate the phylogeny of Tolypella species in North America. In the most comprehensive taxonomic treatment of Characeae, 16 Tolypella species worldwide were subsumed into two species, T. intricata and T. nidifica, in two sections, Rothia and Tolypella respectively. It was further suggested that Tolypella might be a derived group within Nitella. In this investigation into species diversity and relationships in North American Tolypella, sequence data from the plastid genes atpB, psbC, and rbcL were assembled for a broad range of charophycean and land plant taxa. Molecular data were used in conjunction with morphology to test monophyly of the genus and species within it.

Lok – Advisory Committees or Review Panels: Gilead, Immune Targeting System, MedImmune, Arrowhead, Bayer, GSK, Janssen, Novartis, ISIS, Tekmira; Grant/Research Support: Abbott, BMS, Gilead, Merck, Roche, Boehringer The following people have nothing to disclose: Jocelyn Woog, Ajitha Manna-lithara Background Flares during NA therapy are usually associated with antiviral resistance or cessation of therapy. Since ETV resistance is rare and therapy is rarely stopped, we

investigated the frequency and outcome of flares during ETV therapy in CHB. Methods All HBV monoinfected patients treated with ETV from

11 large European centers (VIRGIL Study Group) were studied. Flares were defined as an ALT level Lorlatinib mouse >3× compared to baseline with an absolute ALT level > 3×ULN. Results 733 patients were treated for a median of 168 (IQR 84-213) weeks with ETV monotherapy. Nineteen patients (3%) developed a flare after a median of 26 (10-83) weeks. None of the patients developed genotypic c-Met inhibitor resistance and in only one case non-compliance was documented. Flares were relatively mild with a median ALT peak of 7.3×ULN (IQR 4.5-10-1). Among patients with flares, one developed HBeAg seroconversion, and one lost HBeAg. Baseline HBeAg status (HR 2.91, 95%CI 1.17-7.23, p=0.02), HBV DNA (HR 1.31, 95%CI 1.06-1.63, p=0.01), platelet count (HR 1.0, 95%CI 0.98-1.00, p=0.04) and albumin (HR 0.91, 95%CI 0.84-0.99, p=0.03) were associated with development of a flare. Nine patients (47%) had a flare during decline of HBV 上海皓元 DNA, three

patients (16%) with a stable HBV DNA and seven (37%) with an increase of HBV DNA. Flares during a decline of HBV DNA occurred after a median of 10 weeks (IQR 4-21), which was significantly earlier compared to flares during a stable or increase in HBV DNA (76 weeks, IQR 29-149) (p<0.001). Conclusion Flares during ETV are rare. Flares in patients occurring before week 26 of therapy were almost exclusively present during continued decline of HBV DNA. In these patients ETV can be continued under strict monitoring as the majority have a good biochemical- and virologic outcome. Disclosures: Ivana Carey – Grant/Research Support: Gilead, BMS, Roche; Speaking and Teaching: BMS Ashley S.

We therefore used ≥25 m as the final water depth category. Flow tides indicated tidal condition before high tides and ebb tides after high tides. The Moreton Bay dugongs made

frequent excursions between two very different habitats: shallow seagrass meadows on the Eastern Banks and deeper offshore waters, east of Moreton and North Stradbroke Islands (Fig. 1; Phinn et al. 2008, Lyons et al. 2012). We expected diving patterns in these habitats to be different, because feeding individuals spend more time submerged to excavate or crop seagrasses than when offshore and not feeding (Marsh et al. 2011). We therefore compared the dugong’s availability for detection in each of these habitat types for the Moreton Bay dugongs only. We used logistic regression via generalized linear mixed models (GLMMs). The response LEE011 in vivo variable was binary, and this statistical method can accommodate random components from individual dugongs (Breslow and Clayton 1993). We used Gaussian Hermite Quadrature (GHQ) estimation with lme4 (Bates et al. 2012). The GHQ is based on a restricted maximum likelihood. The GHQ provides estimations that are more accurate than alternative methods, such as Penalized Quasi-likelihood or Laplace approximation (Agresti et al. 2000, Bolker et al. 2009). To compare Midostaurin models, we used Akaike Information Criterion (AIC) and Chi-square tests. Diagnostic plots were used to check the performance

of individual models. Dive data comprised a time-series of depth records separated by 1 or 2 s and were strongly autocorrelated. Visual inspection of dive profiles indicated that successive dives tended to be similar. To ensure independent samples, we treated 10 min as a sampling unit (the subsampled period around a GPS or QFP fix). The 10 min interval ensured that at least one complete dive was included in a sample. Longer intervals were not appropriate because the location

of the dugong could change and the estimated water depth needed to remain constant during a sampling unit. A saturated model was first examined using individual dugong as a random factor and water depth, tidal condition, MCE and habitat types as categorical fixed factors. The model was reduced by removing the tidal variable because some water depth and tide combinations had few observations, and because no tidal effects were identified during exploratory data analysis. We estimated the probabilities of dugongs being in the detection zones using GLMM linear predictor estimates. The 95% confidence intervals for the predicted values were also calculated based on fixed factors. Data manipulations and statistical analyses were executed using SPlus version 8 (TIBCO Software 2007) and R 2.15.1 (R Development Core Team 2011). We estimated and compared the number of dugongs that were not detected during previous aerial surveys of Hervey Bay conducted in 2001, 2005, and 2011 (Lawler 2002, Marsh and Lawler 2006, Sobtzick et al.

We therefore used ≥25 m as the final water depth category. Flow tides indicated tidal condition before high tides and ebb tides after high tides. The Moreton Bay dugongs made

frequent excursions between two very different habitats: shallow seagrass meadows on the Eastern Banks and deeper offshore waters, east of Moreton and North Stradbroke Islands (Fig. 1; Phinn et al. 2008, Lyons et al. 2012). We expected diving patterns in these habitats to be different, because feeding individuals spend more time submerged to excavate or crop seagrasses than when offshore and not feeding (Marsh et al. 2011). We therefore compared the dugong’s availability for detection in each of these habitat types for the Moreton Bay dugongs only. We used logistic regression via generalized linear mixed models (GLMMs). The response Selleck FK506 variable was binary, and this statistical method can accommodate random components from individual dugongs (Breslow and Clayton 1993). We used Gaussian Hermite Quadrature (GHQ) estimation with lme4 (Bates et al. 2012). The GHQ is based on a restricted maximum likelihood. The GHQ provides estimations that are more accurate than alternative methods, such as Penalized Quasi-likelihood or Laplace approximation (Agresti et al. 2000, Bolker et al. 2009). To compare click here models, we used Akaike Information Criterion (AIC) and Chi-square tests. Diagnostic plots were used to check the performance

of individual models. Dive data comprised a time-series of depth records separated by 1 or 2 s and were strongly autocorrelated. Visual inspection of dive profiles indicated that successive dives tended to be similar. To ensure independent samples, we treated 10 min as a sampling unit (the subsampled period around a GPS or QFP fix). The 10 min interval ensured that at least one complete dive was included in a sample. Longer intervals were not appropriate because the location

of the dugong could change and the estimated water depth needed to remain constant during a sampling unit. A saturated model was first examined using individual dugong as a random factor and water depth, tidal condition, MCE and habitat types as categorical fixed factors. The model was reduced by removing the tidal variable because some water depth and tide combinations had few observations, and because no tidal effects were identified during exploratory data analysis. We estimated the probabilities of dugongs being in the detection zones using GLMM linear predictor estimates. The 95% confidence intervals for the predicted values were also calculated based on fixed factors. Data manipulations and statistical analyses were executed using SPlus version 8 (TIBCO Software 2007) and R 2.15.1 (R Development Core Team 2011). We estimated and compared the number of dugongs that were not detected during previous aerial surveys of Hervey Bay conducted in 2001, 2005, and 2011 (Lawler 2002, Marsh and Lawler 2006, Sobtzick et al.

Trough levels were maintained above 5% after 7 days when rIX-FP was administered at 25 IU/kg and after 14 days when given at 50 IU kg−1, suggesting that schedules involving weekly dosing or dosing every 2 weeks are feasible [23]. Native FVIII in the circulation is a heterodimer composed of the heavy and light chain held together by a labile metal-ion bridge, which makes the FVIII molecule relatively unstable. CSL Behring has designed a B-domain deleted rFVIII with a covalent bond

between the heavy and the light chain of FVIII, circulating as a single-chain FVIII molecule buy Metformin [22]. A further modification in the rFVIII results in a significantly increased binding to von Willebrand factor (VWF). Free FVIII has only a half-life of 1 h compared to about 12 h when 95% of FVIII Sirolimus is bound to VWF. Therefore, an increased proportion of VWF bound FVIII translates into an extension of

the FVIII half-life, which for the rFVIII-SC is about 1.5-fold [24]. Although clinical studies phase 1–3 have been started, so far only preclinical data are published. In all animal species systemic availability, mean residence time and terminal half life were increased between 1.6- and 2-fold [25]. Chugai (Chugai Pharmaceutical Co., Ltd., Tokyo, Japan) generated a novel bispecific antibody against FIXa and FX, ACE910, which mimics the cofactor function of FVIII to exert in vivo haemostatic activity [26, 27], and started a phase I clinical study on healthy and haemophilic Japanese individuals in 2012. As ACE910 possesses a different antigenicity from FVIII, it can MCE improve the intrinsic pathway coagulation even in the presence of an inhibitor. Therefore, ACE910 will be used for haemophilia A patients without but also with inhibitors. ACE910 can be administered as subcutaneous infusion and long-acting over 1–2 weeks can be expected. Preclinical studies and ex vivo studies on patient samples suggest that the haemostatic potency of a single bolus of ACE910 1 or 3 mg kg−1 could exert haemostatic effect for haemophilia A patients regardless of the presence of inhibitor [28].

Tissue factor mediates thrombin generation by binding VIIa to the subendothelial cell membrane promoting activation of FX in an FVIII independent manner. This FXa generation is limited by a feedback mechanism controlled by the TFPI. Novo Nordisk has developed a monoclonal antibody (mAb 2012) that is blocking the interaction between FXa and TFPI [29]. In a clinical phase I study in healthy subjects mAb 2021 was found to be safe after i.v. and s.c. administration. A mAb 2021 concentration-dependent effect was observed on plasma TFPI functionality and levels [30]. The clinical study has been set on hold due to late preclinical observation that was obtained while the clinical study was started. The preclinical data are currently awaiting further evaluation.

Methods: We included consecutive HIV mono-infected patients. Hepatic steatosis was diagnosed by hepatic steatosis index (HSI)>36. Significant liver fibrosis was diagnosed by AST-to-platelet ratio index (APRI)>1.5 and/or Fib-4>3.25. Advanced fibrosis was diagnosed by nonalcoholic fatty liver disease (NAFLD) fibrosis score>0.676. We used Cox proportional hazards models adjusted for age, sex, ethnicity, hypertension, HIV infection duration, CD4 count, albumin and glycemia. Results: PS-341 mw 1,291 HIV mono-infected patients (median age 43 years, 70% male) were included in 2007-2013. During a median follow-up of 4.4 (IQR, 1.6-6.3)

years, 24% developed hepatic steatosis, 4% significant liver fibrosis and 2% advanced fibrosis. Variables associated with progression to hepatic steatosis were black ethnicity (HR=2.14; 95% CI 1.55-2.95) and low albumin (HR=0.94; 0.91-0.96). Variables associated with progression to significant liver fibrosis were low CD4 count (HR=0.83; 0.70-0.98), low albumin (HR=0.89; 0.85-0.94) and high glucose (HR=1.16; 1.09-1.24). Variables associated with progression to advanced fibrosis were low CD4 count (HR=0.65; 0.47-0.89) and longer

click here HIV duration (HR=1.64; 1.05-2.56). Figure 1 depicts survival curve of progression to steatosis by ethnicity category. Conclusions: Progression to hepatic steatosis is frequent in HIV mono-infected patients, particularly in those of black ethnicity. This population can also progress to significant and advanced liver fibrosis. Identification of patients at risk for progression can help early initiation of interventions, such as optimization of HIV infection control and targeting euglycemia. Survival curves of progression to hepatic steatosis by ethnicity category Disclosures: Giada Sebastiani – Advisory Committees or Review Panels: Boheringer Ingelheim, Roche, Novartis;

Grant/Research Support: ViiV, Vertex; Speaking and Teaching: Merck, Gilead, Echosens Richard Lalonde – Grant/Research Support: BMS, BI Marina B. Klein – Advisory Committees or Review Panels: viiv, Merck, Gilead, NIH, CIHR, 上海皓元医药股份有限公司 FRQS; Consulting: Merck, viiv; Grant/Research Support: viiv, Merck; Speaking and Teaching: Merck The following people have nothing to disclose: Kathleen C. Rollet-Kurhajec, Nor-bert Gilmore, Costas Pexos BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with varying degrees of fasting glycemia ranging from normal nondiabetic, pre-diabetes mellitus (pre-DM) to diabetes mellitus (DM). NAFLD also increases atherogenic risk profile with increased triglycerides and small density LDL (sdLDL). It is not known if all subjects with NAFLD have a monomorphic atherogenic risk profile and what factors drive inter-subject variability. Specifically, the interactions between glycemic status and liver histology in driving the atherogenic risk profile are unknown.

The size and incidence of subcutaneous tumors were recorded every week. These procedures were approved by The Animal Care and

Use Committee of Fudan University. The cutoff value used in prognosis was estimated using X-tile 3.6.1 software (Yale University, New Haven, CT).21 The results indicated that in blood, a threshold CTC7.5 value of 2 showed the most significant power BI 2536 solubility dmso to predict patient outcome (Supporting Fig. 1); therefore, it was used in all further analyses. Receiver operating characteristic (ROC) analysis confirmed that this level was the optimal cutoff. Statistical analyses were performed with SPSS version 19.0 for Windows (IBM). Data are presented as the mean ± SEM. A chi-squared test, Fisher’s exact test, and Student t test were used for comparison between groups where appropriate.

The relationship between the TTR and CTC counts was analyzed using Kaplan-Meier survival curves and a Wnt antagonist log-rank test. Univariate and multivariate analyses were based on the Cox proportional hazard regression model. P < 0.05 was considered statistically significant. ROC curve analysis was used to determine the predictive value of the parameters, and the differences in the area under the curve (AUC) were detected using Stata version 10 (StataCorp, College Station, TX). The mRNA levels of four putative hepatic CSC biomarkers (EpCAM, CD133, CD90, and ABCG2) were determined via qRT-PCR analysis in CD45-depleted peripheral blood mononuclear cells of 30 HCC patients and 20 healthy volunteers. The expression of EpCAM was significantly higher in cells of HCC patients versus healthy controls (P < 0.05), whereas there was no significant difference in the expression of CD133, CD90, or ABCG2 between the groups (P > 0.05) (Fig. 1A). These data suggested that EpCAM might be a reliable biomarker to identify circulating CSCs in HCC. Because the mRNA level of EpCAM was highly expressed medchemexpress in CD45-depleted peripheral blood mononuclear cells of HCC patients, we investigated the prevalence of EpCAM+ CTCs in HCC patients

using the CellSearch system. CTCs detected with the CellSearch system were defined as nucleated intact cells that were positive for cytokeratins and negative for CD45 (Fig. 1B).8 Apoptotic CTCs, defined as CTCs with fragmented, condensed 4′,6-diamidino-2-phenylindole (DAPI)-stained nuclear,22 were also enumerated and examples were shown in Fig. 1B. The apoptotic cells were excluded from the CTC counts and recorded separately. Preoperatively, EpCAM+ CTCs were detected in 82 of 123 HCC patients at CTC7.5 levels within a range of 1-34, and 51 patients had counts of ≥2. No CTCs were detected in 41 HCC patients or in any of the blood samples derived from healthy volunteers or patients with benign liver disease.

The size and incidence of subcutaneous tumors were recorded every week. These procedures were approved by The Animal Care and

Use Committee of Fudan University. The cutoff value used in prognosis was estimated using X-tile 3.6.1 software (Yale University, New Haven, CT).21 The results indicated that in blood, a threshold CTC7.5 value of 2 showed the most significant power KU-60019 cost to predict patient outcome (Supporting Fig. 1); therefore, it was used in all further analyses. Receiver operating characteristic (ROC) analysis confirmed that this level was the optimal cutoff. Statistical analyses were performed with SPSS version 19.0 for Windows (IBM). Data are presented as the mean ± SEM. A chi-squared test, Fisher’s exact test, and Student t test were used for comparison between groups where appropriate.

The relationship between the TTR and CTC counts was analyzed using Kaplan-Meier survival curves and a Cysteine Protease inhibitor log-rank test. Univariate and multivariate analyses were based on the Cox proportional hazard regression model. P < 0.05 was considered statistically significant. ROC curve analysis was used to determine the predictive value of the parameters, and the differences in the area under the curve (AUC) were detected using Stata version 10 (StataCorp, College Station, TX). The mRNA levels of four putative hepatic CSC biomarkers (EpCAM, CD133, CD90, and ABCG2) were determined via qRT-PCR analysis in CD45-depleted peripheral blood mononuclear cells of 30 HCC patients and 20 healthy volunteers. The expression of EpCAM was significantly higher in cells of HCC patients versus healthy controls (P < 0.05), whereas there was no significant difference in the expression of CD133, CD90, or ABCG2 between the groups (P > 0.05) (Fig. 1A). These data suggested that EpCAM might be a reliable biomarker to identify circulating CSCs in HCC. Because the mRNA level of EpCAM was highly expressed 上海皓元医药股份有限公司 in CD45-depleted peripheral blood mononuclear cells of HCC patients, we investigated the prevalence of EpCAM+ CTCs in HCC patients

using the CellSearch system. CTCs detected with the CellSearch system were defined as nucleated intact cells that were positive for cytokeratins and negative for CD45 (Fig. 1B).8 Apoptotic CTCs, defined as CTCs with fragmented, condensed 4′,6-diamidino-2-phenylindole (DAPI)-stained nuclear,22 were also enumerated and examples were shown in Fig. 1B. The apoptotic cells were excluded from the CTC counts and recorded separately. Preoperatively, EpCAM+ CTCs were detected in 82 of 123 HCC patients at CTC7.5 levels within a range of 1-34, and 51 patients had counts of ≥2. No CTCs were detected in 41 HCC patients or in any of the blood samples derived from healthy volunteers or patients with benign liver disease.