[114] Addressing these factors is essential for appropriate management of the orofacial pain, as treatment outcome has been shown to be related to psychological comorbidity.[49] Affective as well as interpretative and cognitive factors play an important role in the patient’s perception of pain. One small qualitative study found that their patients perceived their orofacial pain to “have no limits and to repressively permeate all aspects of their existence:

social, practical, and emotional.”[105] This illustrates the LY2109761 cell line significant impact that orofacial pain can have on quality of life, and provides a focal point for assessment of pain management outcomes. Patients need to know that although the sensation of pain may not be completely alleviated by treatment, the impact of pain upon their Small molecule library daily life can certainly be modulated. Chronic pain management should be holistic in nature and approach, and involves addressing all the factors that modulate the pain experience.[7] Addressing unrealistic patient expectations is important for setting achievable treatment goals. There remains a common perception that pain should always be curable, as demonstrated in this

quote from a patient: “Many don’t understand the pain I feel. They think I should be over this pain by now. Others feel I should seek other doctors. They feel there should be something to relieve this terrible pain and ask me why I’m not trying to find it, if it is so bad. Pain as defined by International Association for the Study of Pain is both a “sensory and emotional experience,” and it should be managed as such. A recent study has shown that chronic musculoskeletal pain can be experienced

as a “constant adversarial struggle,” and the researchers suggest that patient and clinician expectations of a diagnosis unless and cure need to be challenged.[115] Beliefs, coping strategies, and catastrophizing predict functioning in patients with chronic pain, and this should be considered when individualizing pain management programs.[116] This extends to patients’ beliefs about medication as these will influence adherence.[117] Successful pain management is also related to the patient’s self-efficacy beliefs and ability to learn and use positive coping strategies.[118] Recognition of the contribution of social, psychological, and lifestyle factors to the pain experience, as expressed in the patient quote earlier, is essential for taking the next steps in chronic pain management and achieving a reduction in the impact of pain on quality of life. The provision of support for these next steps is a fundamental part of multidisciplinary pain management. Pain management programs delivered in group settings normalizes the pain experience, and the concept of an improved pain experience because of observation of others with a similar complaint is also expressed by the patient quoted earlier.

“
“Aim:  To determine whether donor immature dendritic cells (imDCs) combined with a short postoperative course of rapamycin (Rapa) has the ability to expand the CD4+CD25+Foxp3+ regulatory T (Treg) cells and prolong liver allograft survival. Methods:  Orthotopic liver transplantation (OLT) was performed from Lewis rats to Brown Norway recipients. Three selleck screening library days before transplantation, animals were injected intravenously with 2 × 106 donor bone marrow-derived imDCs. Recipient

rats (the combined treated group) also received Rapa for 7 d after liver transplantation. Additional groups received either imDCs alone, Rapa alone, or saline alone. Every six recipients from each group were killed at 14 days, 28 days after OLT. The changes of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen,

histological changes of liver grafts, and serum cytokine levels Temsirolimus were investigated. The other six recipients were left in each group to observe the animal survival. Results:  Donor imDCs followed by a short postoperative course of Rapa induced long-term allograft survival. The percentage of CD4+CD25+Foxp3+ Treg cells in CD4+ T cells in the combination treatment group were significantly higher compared with the acute rejection group. Moreover, within the CD4+CD25+ T cell population the combination treatment recipients maintained a higher incidence of Foxp3+ T cells compared with the other groups. Despite the lower serum levels of interleukin (IL)-2, IL-12, and interferon-γ in the combined treated group, the cytokine levels in the combined treated group at 7 days after OLT was nearly twice that at 3 days after OLT but decreased significantly compared with the other groups at 28 days after OLT. Serum IL-10 level in the combined treated group was higher than the other groups. Conclusions:  A single imDC infusion followed by a short postoperative

course of Rapa prolongs liver allograft survival and enhances the expansion of Treg cells. This optimal protocol may be a promising administration protocol for the peritransplant tolerance induction. “
“See article in J. Gastroenterol. Hepatol. 2011; 26: 1626–1629. Gastric cancer is a common disease and the fourth most common cancer worldwide, but it is Arachidonate 15-lipoxygenase an uncommon condition at younger age. Although the overall incidence of gastric cancer declines worldwide, recent reports from the USA have remarkably suggested that the incidence in Caucasian patients aged younger than 40 years has increased.1 This in particularly pertaining to gastric cancer localized in the corpus. Helicobacter pylori is considered the most important risk factor for the development of gastric cancer, and its prevalence has declined over the past decades following a birth cohort phenomenon.2 This implicates that the prevalence of H. pylori tends to decrease in subsequent birth cohorts.

In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding

of pain neurobiology. Methods.— C57BL/6 mice received either an injection of 0.9% saline solution or complete Freund’s adjuvant into the right masseter muscle. Animals were video-recorded and then analyzed by an observer Alvelestat mouse blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hours, mice were euthanized and perfused, and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate to determine the nociceptive-specific nature of their behaviors. Results.— We characterized and quantified 3 distinct patterns of acute grooming behaviors: forepaw

NVP-AUY922 order rubbing, lower lip skin/cheek rubbing against enclosure floor, and hindpaw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. Complete Freund’s adjuvant-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after 2 hours. Conclusions.— These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this

common and challenging condition. “
“(Headache 2010;50:1587-1596) Objective.— The aim of the present study was to evaluate a possible Ixazomib nmr involvement of 2 polymorphisms of the serotonin 5HT2A receptor gene (A-1438G and C516T) as risk factors for medication overuse headache (MOH) and whether the presence of these polymorphic variants might determine differences within MOH patients in monthly drug consumption. Background.— Despite a growing scientific interest in the mechanisms underlying the pathophysiology of MOH, few studies have focused on the role of genetics in the development of the disease, as well as on the genetic determinants of the inter-individual variability in the number of drug doses taken per month. Methods.— Our study was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism on genomic DNA extracted from peripheral blood of 227 MOH patients and 312 control subjects.

Secondly, we examined variations of these four variables throughout the depth Crizotinib mw range experienced during transits. This enabled us to investigate

how penguins may anticipate the nature of the dive they are going to undertake in terms of transit rates. The study was carried out on Possession Island, Crozet Archipelago (46.4°S, 51.8°E) from December 2003 to March 2004. Birds used in the study were king penguins breeding at La Baie du Marin, a colony of approximately 16 000 pairs (Delord, Barbraud & Weimerskirch, 2004). The procedures received the approval of the ethics committee of the French Polar Institute (IPEV) and of the French Ministry of the Environment. Detailed description of the general surgical and handling procedure are given in Froget et al. (2004). Six breeding male king penguins were captured while brooding an egg and immediately subjected Paclitaxel mw to isoflurane-anaesthesia, during which they were fitted with data loggers. SMAD data loggers (DEPE-IPHC, Strasbourg, France; 80 × 25 × 10 mm, 54 g) were externally attached to the lower-back feathers of each animal to diminish hydrodynamic drag (Bannasch, Wilson & Culik, 1994) and recorded depth every 2 s. SMAD were also programmed to measure tail-to-head (surge) and ventral-to-dorsal (heave) accelerations during two 1-h high-frequency sessions per day when penguins performed deep dives, and stored these measurements 32 times

per second. Cross-sectional area (CSA) of the external logger (2.5 cm2) represented less than 1% of the smallest bird’s CSA. Modified Mk7 data loggers (Wildlife Computers, Redmond, WA, USA) were also implanted subcutaneously for a study

of peripheral temperatures; these results have been described previously in Schmidt (2006). Together, the mass of both loggers (87 g) represented less than 0.8% of the smallest bird’s mass. The penguins undertook a foraging trip at sea 15–18 days later, after being relieved by their partners. After their return to the colony, the birds were recaptured and anaesthetized using the same procedure, and the loggers click here were removed. All the loggers were recovered, of which five had recorded usable data. Data from these loggers were extracted, prepared and analysed using purpose-written computer programs in Matlab 6.0 (The MathsWorks, Natick, MA, USA). Dives >50 m, hereafter called ‘deep dives’, were used for analysis as they represent the majority of the foraging dives of king penguins (Charrassin et al., 1998). For each dive analysed, the following parameters were calculated: maximum dive depth (m), dive duration (s), subsequent surface interval duration until the next dive of any depth (s), subsequent time interval until the next deep dive (s), rank of the dive in a bout (i.e. sequence of successive dives), number of wiggles during the bottom phase or the entire dive. Wiggles are a particular, undulation-like pattern in the dive profile over time.

38 Maintenance of a pool of reduced GSH is especially important during periods of oxidative stress. Extracellular GSH and its oxidized form, GSH disulfide, are broken down to their constituent amino acids by GGT and then transported back into cells for resynthesis of GSH. As the only enzyme of the γ-glutamyl cycle located on the outer surface of the plasma membrane, GGT plays a key Selleck PD98059 role in GSH homeostasis by providing cysteine, the rate-limiting substrate, for intracellular synthesis of GSH.39

It has been suggested that catabolism of GSH by GGT results in prooxidant metabolites.40 As an adaptive response to exposure to oxidants, the expression of GGT increases, although the mechanisms for induction are uncertain.41, 42 At the population level, GGT activity has been positively associated with C-reactive protein, a general marker for increased oxidative stress.43 It is interesting that GGT activity was associated with fibrosis stage and cirrhosis at baseline and predicted fibrosis progression, but a change in fibrosis score was not associated with change in GGT. Nor

was a change in GGT activity correlated with Gefitinib changes in platelet count or AST/ALT, which are markers of development of cirrhosis. These findings suggest that GGT is a marker of disease activity, and not merely a reflection of disease severity, such as platelet count, which declines as cirrhosis and portal hypertension develop. This finding provides additional, albeit indirect evidence that GGT reflects a state of oxidative

stress in chronic HCV. It is also interesting that ALT was not independently associated with treatment response or with disease progression and that AST was associated with week 20 virological response but not disease progression. Thus, in the setting of HCV associated advanced liver disease, GGT has greater prognostic significance than ALT or AST. Given the prognostic significance of GGT, we examined other patient characteristics with which GGT was associated, a few of which are stressed here. The mechanisms whereby hepatic steatosis and elevated Protein tyrosine phosphatase GGT are associated are not entirely clear, but several have been proposed.44 For example, fatty liver could cause hepatocellular damage that would simulate the synthesis of GGT. Alternatively, excess fat in the liver could enhance oxidative stress, leading to overconsumption of GSH with a compensatory increase in GGT synthesis. Finally, a higher GGT production could be secondary to a low-grade hepatic inflammation induced by hepatic steatosis. PNPLA3 genotype was strongly related to steatosis and steatosis strongly related to GGT, but there was not an association of PNLP3 with GGT activity, which was also the case in at least one other study.22 Thus, it appears that the mechanism for the relationship of PNPLA3 with steatosis is likely different from that of steatosis with GGT activity.

However, the weight of evidence now suggests they increase the rate of myocardial infarction during prolonged use. Whether this risk is greater than with nonselective NSAIDs is currently under intensive investigation. “
“DURING THE PAST quarter of a century, various procedures were developed as local therapy for hepatocellular carcinoma. In 1979, Yamada et al. developed transcatheter arterial embolization (TAE), and this can be regarded as the first treatment approach

that clarified the efficacy of local therapy for hepatocellular carcinoma. Next, with the spread and progress of abdominal ultrasound diagnostic devices, Sugiura et al. created percutaneous ethanol www.selleckchem.com/products/AG-014699.html injection therapy

(PEIT) in 1983. PEIT may be the prototype of various subsequently devised local therapies that are conducted under ultrasonographic imaging. Because this procedure requires only a simple technique, and local injection needles and ethanol are inexpensive, it has quickly spread not only in Japan but also worldwide and is highly valued Palbociclib price for its primary role in hepatocellular carcinoma treatment. Nonetheless, because PEIT is a treatment involving the infusion of a solution, “ethanol”, and because ethanol does not uniformly diffuse in a tumor and pass through the septum or the capsule, problems of residual tumors and local recurrence remain. In order to overcome these disadvantages of PEIT, treatments aimed at thermo-coagulation of tumors by emitting microwaves or radiofrequency waves from the inserted needle were developed. In 1994, Seki et al. presented percutaneous microwave coagulation therapy (PMCT) developed by percutaneous microwave application that had been used in the surgical field. In 1993, Rossi et al. performed percutaneous radiofrequency ablation (RFA) in patients with small hepatocellular carcinoma and reported good therapeutic

efficacy; treatment with radiofrequency waves for hepatocellular carcinoma quickly gained Cediranib (AZD2171) attention. In Japan, it has been conducted at many institutions since 1999. Because the range of necrosis achieved by one session is wider for RFA than for PMCT, RFA has been far more widely adopted than PMCT. In April 2004, RFA was finally covered by the National Health Insurance. Around the time when the 2005 Clinical Practice Guidelines for Hepatocellular Carcinoma were published, RCT comparing PEIT and RFA were presented in Japan and foreign countries. Their results all showed that RFA prolonged life expectancy more than PEIT. Based on such evidence, RFA has become the current standard treatment among local ablation therapies. In this section, we organized evidence on PEIT, PMCT and RFA available as of June 2007.

Bhadoria, Chhagan Bihari, Amna S. Butt, Chan Albert, Yogesh K. Chawla, Abdulkadir Dokmeci, Hasmik Ghazinyan, Saeed S. Hamid, Cho Mong, Guan Huei Lee, Laurentius A. Les-mana, Mamun A. Mahtab, Viniyendra Pamecha, Archana Rastogi, Salimur Rahman, Mohamed Rela, Amrish Sahney, Vivek A. Saraswat, Samir R. Shah, Gamal Shiha, Barjesh C. Sharma, Manoj Kumar, Chitranshu Vashishtha, Ashok Choudhary, Man Fung Yuen Background: Excessive TLR4-mediated innate inflammatory gene induction by lipopolysaccharide (LPS) may result in collateral tissue damage (i.e., immunopathology). To limit this phenomenon, TLR4 induces LDK378 mechanisms such as tolerance aiming to control the inflammatory response. After a first LPS stimulation, innate immune

cells are tolerant to a second LPS challenge. Tolerant cells are characterized by two categories of genes: “tolerizable” genes that are transiently silenced and “non tolerizable” genes that remain inducible at the same or to a greater level. “Tolerizable” and “non tolerizable” are differentially regulated SCH727965 through gene-specific epigenetic

mechanisms. In patients with cirrhosis the innate immune response to a first LPS challenge is known to be altered but the response to a second challenge has not yet been studied. This work aims to study the LPS tolerance in peripheral blood mononuclear cells (PBMCs) from patients with advanced alcoholic cirrhosis. Patients and Methods: PBMCs from 9 patients (median MELD score 17 [7.1-29.4]) and 10 healthy subjects have been isolated and cultured for 24 hours with LPS or medium. After 24 hours, PBMCs have been washed and then received or not a second LPS challenge during 4 hours. RNA was extracted and Plasmin the expression of 32 genes known to be involved

in the innate immune response has been studied by RT-qPCR. Results: After the second LPS stimulation in healthy PBMCs, “tolerizable” genes included proinflammatory genes (e.g., TNF), anti-inflammatory mediators (e.g., IL10, TNFAIP3, IL1RN, NFKBIA) and interferon stimulated genes (ISGs, e.g., MX2, OAS2, IFIT1, MOV10); “non tolerizable” genes included proinflammatory genes (e.g., IL8, CXCL1, CXCL5) and antimicrobial peptide (e.g., LCN2). “Cirrhotic” cells exhibited an enhanced tolerance phenomenon: the expression of IL10, TNFAIP3 and LCN2 was 2.5 (p<0.01), 1.5 (p=0.04) and 2 times (p=0.01) lower as compared to “healthy” cells; the expression of ISGs was also lower (1.6-6.4 times lower, each p<0.05). Furthermore, the second stimulation led to a 3 times stronger down-regulation of IL10 (p<0.01) and an 11 times more pronounced up-regulation of CXCL5 (p=0.02) in cirrhotic cells. Finally, while LCN2 was a “non tolerizable” gene in healthy PBMCs, it was “tolerizable” in cirrhotic PBMCs (p=0.02). Conclusions: Immune cells from patients with advanced alcoholic cirrhosis exhibit alterations of the gene-specific control of inflammation and antimicrobial response during LPS tolerance phenomenon.

In 2002, Imperiale and collaborators reported that adenomas and advanced adenomas presented in 8.5% and 3.5%, respectively, among persons 40 to 49 years of age. At this moment no recommendations for CRC screening in this population have

been Cetuximab made. Aim: To estimate the prevalence of polyps, adenomas, advanced lesions and adenocarcinoma in 45 to 49 year- old patients. Methods: We included consecutive adults between the ages 45 and 49 years who performed colonoscopy because of gastrointestinal signs or symptoms. We excluded patients at high risk for CRC, incomplete procedures and/ or evidence of colonic tumor diagnosed by other methods. The study was conducted in a gastroenterology and endoscopy ambulatory center in Buenos Aires, Argentina, between September 2010 and October 2011. Design: Descriptive, prospective and cross sectional study. Polyethylene glycol (PEG) lavage solution or phosphates, with or without bisacodyl were used for bowel preparation. Colonoscopies were performed under sedation with Olympus 160/180 series equipment. Biopsies were evaluated by pathologists specialized in gastroenterology. Indication for colonoscopy

was registered. The protocol was approved by local IRB. Statistical analysis: VCCstat 2.0. 95% CI were estimated. Results: 814 patients were evaluated. 764 were included. 57% (440/764) were women; average age was 47 years. 1. a) The global prevalence of polyps was 160/764 (20%; 95 CI 18–24); 71/440 (16%; 95 CI 13–20) in women and 89/324 (27%; 95 CI 22–32) in men. 1. b) The global prevalence of adenomas was 107/764 (14%; 95 CI 11–16%), 59/324 (18%; 95 CI 14–22) Protein Tyrosine Kinase inhibitor in men and 48/440 (11%; 95 CI 8–14) in women; 1. c) The global prevalence of advanced adenomas was 39/764 (5%; 95 CI 4–7) and of adenocarcinoma was 2/764 (0.1%; 95 CI 0–0, 7). The most common indications for colonoscopy were proctorrhagia, abdominal pain and altered bowel habits. Conclusion: The prevalence of lesions in this population is lower than average risk population and it is similar to the information

reported internationally. At the moment we do understand that there is no evidence to indicate CRC screening in 45 to 49 individuals. Research on metabolic and epidemiological factors are needed GPX6 to evaluate the biological behavior of CRC in young individuals. Key Word(s): 1. adenomas; 2. advanced lesions; 3. adenocarcinoma; 4. screening; Presenting Author: LUIS CARO Additional Authors: MARIBEL BRANER, SANDRA CANSECO, MICHELE PILOTTO, LEANDRO MANZOTTI, MARÍA CAROLINA BOLINO, MARCELO D ′ALESSANDRO, CECILIO CERISOLI Corresponding Author: MARÍA CAROLINA BOLINO Affiliations: GEDYT Objective: Colorectal cancer (CRC) is a major cause of death from cancer in western world and rectal bleeding is a clinical presentation. In the young population with no risk factors for CRC, its prevalence is lower and the etiology of rectal bleeding is often benign.

A child over 5 years of age with ALF accompanied by a Coombs-negative hemolytic anemia and low or normal serum alkaline phosphatase should heighten the suspicion for WD. WD presenting with an acute hemolytic crisis carries a poor prognosis; short-term clinical and biochemical improvement following plasma exchange coupled with chelation therapy is noted, but outcomes are variable.[168] The AASLD produced joint adult and pediatric guidelines that include recommendations for liver transplant evaluation.[167] Pediatric acute liver failure (PALF) is a rapidly evolving condition that differs from adults with ALF in areas of etiology, management, and learn more outcomes.[169,

170] Efforts to define PALF remain challenging, but entry criteria established for the PALF longitudinal

SP600125 supplier research study serve to identify children who require focused diagnostic and management strategies. Those entry criteria include: 1) absence of a known, chronic liver disease; 2) liver-based coagulopathy that is not responsive to parenteral vitamin K; 3) International Normalized Ratio (INR) between 1.5 and 1.9 with clinical evidence of encephalopathy or 2.0 and higher regardless of the presence of clinical encephalopathy. Children with PALF may experience rapid clinical progression to irreversible brain injury or death.[3, 171] Diagnoses differ between infants, children, and adolescents with some that are potentially treatable, such as herpes simplex,[172] gestational alloimmune liver disease,[173] autoimmune hepatitis,[174] acute acetaminophen toxicity,[175] and Wilson’s disease.[168, 176] As clinical deterioration can occur rapidly and unexpectedly, coordinated management at a pediatric liver transplant center involving a pediatric gastroenterologist

with expertise in liver disease, intensive care specialist, and liver transplant surgeon, along with other Flavopiridol (Alvocidib) supportive personnel will optimize patient outcome. Outcomes vary among and between etiologies, patient age groups, and disease severity.[169] However, children with an indeterminate diagnosis are more likely to receive a liver transplant.[177] Decisions to proceed to liver transplant in PALF are complicated by difficulties in predicting outcome. Unfortunately, disease severity scores fall short in predicting the likelihood of death for an individual patient, raising the possibility that some children may have survived without a liver transplant.[178, 179] Equally problematic is the absence of tools or clinical paradigms to predict irreversible brain injury. Contraindications to LT in PALF include severe multisystem mitochondrial disease, particularly those associated with valproic acid toxicity,[180] uncontrolled sepsis, and irreversible cerebral edema with uncal herniation. Children presenting with ALF due to hemophagocytic lymphohistiocytosis are candidates for nonliver transplant therapies which include immunosuppressive therapy or bone marrow transplantation.[181] 40.

2C), which was consistent with our previous observation. In contrast, cell apoptosis dramatically decreased in the xenografts derived from 7404/EphrinA2 cells, as suggested by the reduced level of cleaved poly(adenosine diphosphate-ribose) polymerase (PARP), a sensitive marker of apoptosis,

whereas knockdown of the exogenous EphrinA2 effectively rescued the expression of cleaved PARP (Fig. 3A). The classic terminal deoxynucleotidyl transferase-mediated Dabrafenib 2′-deoxyuridine 5′-triphosphate nick-end labeling (TUNEL) assay also showed that the apoptosis DNA fragments were dramatically decreased in EphrinA2 overexpressing xenografts (Fig. 3B). These results suggested that the tumor-promoting effect of EphrinA2 was mainly attributed to its suppression of apoptosis in HCC cells. HCC is usually associated with chronic inflammation induced by hepatitis

virus infection, which often leads to elevated level of tumor necrosis factor alpha (TNF-α).22 TNF-α is closely involved in the induction of apoptosis and in triggering destruction of liver.23 To test whether EphrinA2 exerts a similar resistant effect in this cytokine-induced apoptosis, we performed TNF-α treatment on both control and EphrinA2-overexpressing cells. As shown in Fig. 4A, 7404/EphrinA2 cells exhibited stronger resistance to TNF-α–induced apoptosis compared with control cells, whereas this resistance was attenuated after EphrinA2 knockdown. RO4929097 With Amino acid similar effects of overexpression of EphrinA2, exogenous purified EphrinA2-Fc protein also could increase the resistance to TNF-α in 7404 cells (Fig. 4B). Conversely, down-regulation of endogenous EphrinA2 in HepG2 cells, which showed relatively high levels of EphrinA2 (Fig. 1A), also resulted in hypersensitivity to TNF-α treatment (Fig. 4C), which was consistent with our observation in 7404/EphrinA2 cells. In the presence of TNF-α, the apoptotic marker cleaved

PARP was down-regulated dramatically in the EphrinA2 overexpressing 7404 cell, as well as in the EphrinA2-Fc protein-treated 7404 cells. In contrast, its level was increased in the EphrinA2-deficient cells (Fig. 4D). 5-Fluorouracil is another drug commonly used in chemotherapy, and we also found that the expression level of EphrinA2 in HCC cells negatively correlated with the cell sensitivity to 5-fluorouracil–induced apoptosis (Supporting Fig. 3), suggesting that EphrinA2 may participate in the regulation of apoptosis induced by a variety of chemotherapeutic agents in HCC. The PI3K/Akt is a crucial pathway that can deliver anti-apoptotic signals and block induction of apoptosis. Up-regulation of this pathway through the phosphorylation of Akt has been documented as a frequent occurrence in several human cancers24; therefore we examined whether this alteration also occurred in HCC. The level of phosphorylated Akt was significantly elevated in 7404/EphrinA2 cells (Fig.