As such, NR-targeted treatment strategies will add to the evolvin

As such, NR-targeted treatment strategies will add to the evolving field of individualized medicine in hepatology. Future drug development should take advantage of the fascinating explosion of new relevant ERK inhibitor and unexpected information that place NR pathways into the heart of liver function in health and disease. Over the next years we may also hope to obtain further insights into the role of genetic NR variants as modifiers of liver disease and additional NR-based therapeutics, expanding our armamentarium to combat both common and orphan liver diseases. Note: The tables and associated text are available as Supporting Material

1. Only the first seven references in the introduction section of this article are available below in print. The remaining

references are available online only with the electronic version of this article as Supporting Material 2. To access the remaining references, visit the online version of Hepatology at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350. this website Additional supporting information may be found in the online version of this article. “
“Human immunodeficiency virus (HIV) co-infection accelerates both hepatitis C (HCV) and hepatitis B (HBV) natural history leading to faster progression to and increased incidence of cirrhosis, hepatocellular carcinoma (HCC) and death. HIV/HCV co-infected patients have twice the risk of developing cirrhosis and a sixfold increased risk of liver failure compared with those with HCV alone. Effective treatment of HBV and HCV in HIV co-infected patients increases survival. Treatment responses to TVR do not differ between HIV/HCV co-infected and HCV mono-infected patients. In patients treated with TVR combination treatment, overall safety and tolerability profile was comparable to that previously observed in chronic genotype 1 HCV mono-infected patients. In HIV/HBV co-infected patients, any treatment decision for hepatitis B should take into account the possible impact on HIV and vice-versa. For HIV/HBV co-infected patients, initiation of ART with active anti-HBV coverage is now recommended at any CD4+ T-cell count to reduce the risk of liver disease

progression. “
“Background MCE and Aim:  We intended to investigate the effects of pre-existing mutations at reverse transcriptase region of hepatitis B virus (HBV) on the occurrence of virological breakthrough (VB) to adefovir dipivoxil (ADV) in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). Methods:  Ninety-seven patients with LAM-resistant CHB were treated with ADV at a dose of 10 mg daily, and were followed for a median period of 13 months. Just before the initiation of ADV therapy, the whole length of reverse transcriptase region of serum HBV-DNA was sequenced using direct sequencing. Results:  All patients had genotype C HBV and mutations in the YMDD motif, specifically, YIDD (65%), YVDD (28%), or both (7%).

Li Conclusion: These results showed we had successfully establis

Li. Conclusion: These results showed we had successfully established a Hyper-IL-6-expressing mouse hepatocellular carcinoma cell clones which would enable us to further study to established a promising tumor model as a new hepatocellular carcinoma vaccine. Key Word(s): 1. Interleukin

6; 2. Hyper-IL-6; 3. tumorigenicity; RAD001 mouse Presenting Author: XIUJING SUN Additional Authors: JIHUIJ. QIU, SHENGTAO ZHU, BANGWEI CAO, LIN SUN, PENG LI, XIYIN WANG, SEN LI, SHUTIAN ZHANG, SHUO DONG Corresponding Author: SHUTIAN ZHANG, SHUO DONG Affiliations: Beijing Friendship Hospital Affiliated to Capital Medical University; Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, USA; Department of Gastroenterology, Saracatinib cost Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China; Department of Oncology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China Objective: Overexpression or mutation of some histone demethylases has been implicated in the course of esophageal squamous cell carcinoma initiation and progression. The aim of this study is to investigate the role of a new histone demethylase, PHF8 in

the caicinogenesis of ESCC. Methods: Three ESCC cell lines (TE-1, TE-2 and TE-8) were analysized in this study and each cell line was divided into three groups: PHF8-shRNA experimental group, Nonsilencing-shRNA negative group and control group. Via lentivirus mediated shRNA method, we knockdown the 上海皓元医药股份有限公司 expression of PHF8 of the studied cell lines. And stable cell lines were constructed using puromycin selection assay. Real-time PCR and Western Blot were used to confirm the silencing of PHF8. Research on the regulatory role of PHF8 on proliferation, colony formation ability, migration and invasion ability, and apoptosis of ESCC cells was carried out by cell viability assay (MTS), plate and soft agar colony formation assay,

in vitro migration and invasion assay, and flow cytometry (FCM). The effect of PHF8 on tumorigenicity of ESCC cells in vivo was performed by xenograft studies of nude mice. Results: Lentivirus mediated shRNA effectively reduced the expression of PHF8 mRNA and protein in ESCC cell lines. Knockdown of PHF8 suppressed the proliferation and colony formation ability, induced the apoptosis, and inhibited the migration and invasion activity of ESCC cells. And it also effectively inhibited the growth of tumor of human esophageal squamous cell carcinoma-bearing nude mouse. Conclusion: PHF8 is involved in the carcinogenesis of esophageal squamous cell carcinoma. Key Word(s): 1. esophageal cancer; 2. epigenetics; 3. histone demethylase; 4. PHD finger protein 8; Presenting Author: WENJI YAN Additional Authors: MINGZHOU GUO, YUNSHENG YANG, KONGMING WU, JAMESG. HERMAN, MALCOLMV.

001) The 3-year overall survival rate was 640% in cohort A and

The 5-year follow-up was not yet finished in cohort C; therefore, only cohort B was compared with cohort A in the analyses of 5-year survival time. The 5-year survival rates with native liver in cohorts A and B were 37.5% and 64.3%, respectively (P = 0.01). The 5-year

jaundice-free survival RG7420 rate with native liver was significantly higher in cohort B than in cohort A (64.3% versus 27.3%; P < 0.001) and the 5-year overall survival rates were 89.3% and 55.7%, respectively (P < 0.001). However, 15 cases in cohort B+C, despite their birth after the launch of the stool card screening program, were not successfully screened using the stool card. In order to clearly demonstrate PD 332991 the effect of the stool card screening program, we further analyzed the outcome by redividing our total cases from 1990 to 2005 into two groups for comparison: one group representing BA children without the screening program or not screened out by the stool card, the other group representing BA children who benefited from stool card screening (Supplement Table 1). The results are similar to the comparisons of cohort A and cohort B+C (Table 1). Logistic regression analyses revealed that patients who underwent Kasai operation before 60 days of age had a higher jaundice-free

rate at 3 months after surgery compared with those who underwent surgery after 60 days of age (odds ratio [OR] 2.62; P = 0.001) (Table 2). Patients born in the stool card screening era (cohort B+C) had a significantly higher jaundice-free rate at 3 months postsurgery than patients born before the screening era (cohort A) (OR 2.90; P < 0.001). The 3-year survival rates with native liver in patients who received Kasai operation before 60 days of age and after 60 days of age were 64.9% and 46.3%, respectively (OR 2.15; 95% confidence interval [CI] 1.19-3.86; P = 0.01). The 5-year survival rates with native liver in

patients who underwent surgery before 60 days old and after 60 days old were 上海皓元 55.0% and 32.1%, respectively (OR 2.58; 95% CI 1.21-5.50; P = 0.01). The 3-year survival rates with native liver in patients who were and were not jaundice-free at 3 months after Kasai operation were 84.9% and 30.6%, respectively (OR 12.79; 95% CI 6.27-26.08; P < 0.001). The 5-year survival rates with native liver in patients who were and were not jaundice-free at 3 months postsurgery were 77.6% and 19.4%, respectively (OR 14.35; 95% CI 5.81-35.43; P < 0.001). Jaundice-free survival with native liver was considered as quality outcome. Cohort B+C had higher rates of 3- and 5-year jaundice-free survival with native liver than cohort A (OR 2.87, P = 0.001, and OR 4.80, P = 0.001, respectively) (Table 3). Patients who received Kasai operation before 60 days of age had better 3- and 5-year jaundice-free survival with native liver than patients who received an operation after 60 days of age (OR 3.25, P < 0.001 and OR 2.63, P = 0.

16 Genotoxic and other stressful stimuli not only induce an accum

16 Genotoxic and other stressful stimuli not only induce an accumulation of p53, but also the phosphorylation of mdm2, thereby enhancing p53′s nuclear localization, ubiquitination and subsequent degradation.17 Of note, mdm2 is overexpressed in many tumors and effectively impairs p53 function by PI3K Inhibitor Library binding

directly to p53; this promotes its ubiquitination and targeting to the 26S proteasome for protein degradation.17 Protein–protein interactions have long been considered challenging targets for therapeutic intervention, because their opposing surfaces are often too large or flat for effective disruption by small molecules. The more successful chemical antagonists take advantage of specific interactions

within well-defined pockets on the surfaces SRT1720 purchase of one or both protein partners.18 The discovery that p53-mdm2 binding was dependent on only three p53 amino acid residues interacting with a discrete mdm2 pocket stimulated efforts to identify potential small molecule inhibitors.19 The first potent and selective antagonists of p53-mdm2 were the Nutlins.20 They represent a class of cis-imidazole analogues that bind to the p53 pocket on the surface of mdm2 in an enantiomer-specific manner. The three reported Nutlins, -1, -2 and -3, show potency against p53-mdm2 binding in the 100–300 nmol range with 150- to 200-fold range in affinity between enantiomers. They inhibit the p53-mdm2 上海皓元 axis by mimicking the interaction of the three critical amino acid residues with the hydrophobic activity of mdm2.20 In addition to their high potency in vitro, they penetrate cell membranes, activate p53 and inhibit cell proliferation at a range of 1–3 µmol. Released from its negative control in the presence of Nutlin (Fig. 1b), p53 is stabilized and accumulates in cells leading to the activation of target genes; for example, p21 and mdm2. This effect, however, is dependent on the presence of wt p53, because cells in

which p53 is deleted or mutated do not respond to Nutlin treatment.20 In addition to parenteral routes, Nutlins can also be given orally, which is highly desirable for their applicability in animal models and in the clinic.20 In this issue of the Journal, Wang et al.21 utilized Nutlin-3 against three human HCC cell lines with wt (HepG2), mutant (Hep3B) and null p53 (Huh7). This selective mdm2 antagonist induced growth arrest in all three cell types in vitro with significant abrogation of the pro-proliferative genes, cyclin D1/cdk4, cyclin E/cdk2 and E2F transcription factor. Cell cycle arrest was mediated by upregulation of p21 only in p53-intact HepG2 cells, whereas p27, another downstream target of p53, was expressed by all three tumor cell lines. Regardless of p53 status, Nutlin-3 treatment triggered increased apoptosis in all tumor cells, as well as increased expression of Bax, Noxa and PUMA.

The target puncture sites on the portal vein branch are either at

The target puncture sites on the portal vein branch are either at the portal vein imaging Palbociclib clinical trial bifurcation or beyond. Conclusion: There is an upper-rear and lower-front spatial relationship between the right hepatic vein and the portal vein, and that the distance between the right hepatic vein opening and portal vein bifurcation is, in the vast majority of cases, equal to or greater than one vertebra, providing guidance to the direction and

distance of the TIPS puncture. The location of the right hepatic vein, the location of the portal vein, and the portal vein branches are not correlated with gender, age and Child classification of the patients, and the safe target for portal vein puncture is at the portal vein imaging bifurcation and beyond. Key Word(s): 1. TIPS; 2. cirrhosis; 3. portal vein; 4. imaging; Presenting Author: YANG SHUYIN Additional Authors: LIU QING, DONG XIAOJUN, ZHOU TINGTING, LI SHUTING, ZENG BO, XIA QIANG, WANG TAILING, LI HAI Corresponding Author: LI HAI Affiliations: Department of Gastroenterology, Renji Hospital Shanghai Jiaotong University

School of Medicine, Shanghai Institute of Digestive Disease; Department of Pathology, China-Japan Friendship Hospital; Liver Transplantation CHIR-99021 nmr Center, Renji Hospital Shanghai Jiaotong University School of Medicine Objective: Studied the pathological features of HBV cirrhotic liver with massive/submassive hepatic necrosis (MHN/SMHN). Methods: Patients with clinically diagnosed HBV related cirrhosis who underwent a liver transplantation from 2008 to 2011 were studied. 2.5 x 2.5 cm liver tissue was sectioned. Necrosis, ductualar regeneration, cholestasis and sepsis parameters were evaluated by hematoxylin and eosin, Masson trichrome stains and immunohistochemical staining for CK7. Results: 174 enrolled patients with chronic HBV related cirrhosis were divided into 2 groups, with 69 patients in MHN/SMHN(+) group and 105 patients in MHN/SMHN(–) group. Microscopically, the characteristic features of MHN/SMHN(+) livers were: 1)Massive/submassive necrosis, found in part of cirrhotic nodules, distributed along terminal hepatic veins. The necrotic area was divided into three levels, including less than 1/3, 1/3-2/3 and over 2/3. The percentages

of patients of each level were 17.4%, 66.7%, and 15.9%, respectively. 2)There were obvious periportal ductular regeneration(CK7 positive) and some degree of hepatocytes MCE公司 diffferenciation(so called intermediate hepatocytes). The percentage of patients with ductular regeneration and intermediate hepatocytes in MHN/SMHN (+) group were 78.2% and 62.3%, respectively while those in MHN/SMHN(–) group were only 3.9% and 1.3%, respectively (p < 0.001). 3)Cholestasis in hepatocytes, bile canaliculus and regenetive ductules, were 81.2%, 87% and 92.8% respectively in MHN/SMHN(+) group while only 7.8%, 9.1% and 7.8% in MHN/SMHN(–) group (p < 0.001 respectively).4)The percentage of patients with cholestasis in ductules of cirrhotic nodules, indicating sepsis, was 6.

Resistance to steroids only becomes apparent when

the ind

Resistance to steroids only becomes apparent when

the individual develops a disease that requires steroid pharmacotherapy.28 Our data therefore Dorsomorphin clinical trial suggests that such intrinsic steroid resistance plays a significant role in the failure to respond to steroid therapy in SAH. This finding is consistent with previous reports in other conditions, such as ulcerative colitis,13, 16, 29 asthma,12 rheumatoid arthritis,15 and a very recent report in AH.11 In this study, early bilirubin change correlated with in vitro steroid sensitivity (Imax). Our study adds to this report by demonstrating that in vitro steroid resistance also correlates with a hard clinical endpoint, namely, death. This was possible in our study as we had more patients (n = 20 versus n = 12) and more deaths (11 versus 4), and we would anticipate that extension of the study of Kendrick et al.11 to a further follow-up and/or a larger cohort would lead to EPZ-6438 similar conclusions. No correlation was seen between measures of baseline disease severity (MdF score, Glasgow score, Lille score) and outcome in response to steroids in this cohort (Fig. 1). Although some previous studies relating baseline disease severity in AH to clinical response have shown a correlation with outcome, these studies have included all grades of disease severity and not specifically correlated outcome in the most severe group treated with steroids.

The lack of correlation with disease severity in our cohort emphasizes that the failure to respond adequately to steroids in some individuals is not simply explained by differences in baseline disease severity and that the role played by intrinsic steroid resistance in determining outcome is independent of disease severity. Consistent with previous reports,1, 25, 30-37 we did observe in our cohort a correlation between fall in bilirubin by day 7 (a measure of early response rather than disease severity) and long-term outcome (Fig. 1). The separation in outcome between individuals determined to be steroid-resistant or steroid-sensitive at baseline was not complete (Fig. 3). Hence, measurement of in vitro steroid sensitivity should not be considered a robust predictive marker for

use in clinical 上海皓元 management. Rather, the present finding provides evidence for an important factor that contributes to outcome, and which might represent a target for pharmacotherapy to improve overall outcomes. In this context, we noted that that addition of basiliximab to in vitro cell cultures, competitively targeting CD25, a key component of the high-affinity IL-2 receptor,38 improved steroid sensitivity in all individuals with low Imax on the DILPA test, consistent with previous reports in ulcerative colitis.16, 29, 39 The mechanisms involved in steroid resistance are unknown but IL-2 may play an important immunological role. Combination of IL-2 and IL-4 has been shown to reduce glucocorticoid receptor-binding affinity and consequent T-cell response to steroids.

Resistance to steroids only becomes apparent when

the ind

Resistance to steroids only becomes apparent when

the individual develops a disease that requires steroid pharmacotherapy.28 Our data therefore STA-9090 clinical trial suggests that such intrinsic steroid resistance plays a significant role in the failure to respond to steroid therapy in SAH. This finding is consistent with previous reports in other conditions, such as ulcerative colitis,13, 16, 29 asthma,12 rheumatoid arthritis,15 and a very recent report in AH.11 In this study, early bilirubin change correlated with in vitro steroid sensitivity (Imax). Our study adds to this report by demonstrating that in vitro steroid resistance also correlates with a hard clinical endpoint, namely, death. This was possible in our study as we had more patients (n = 20 versus n = 12) and more deaths (11 versus 4), and we would anticipate that extension of the study of Kendrick et al.11 to a further follow-up and/or a larger cohort would lead to C646 similar conclusions. No correlation was seen between measures of baseline disease severity (MdF score, Glasgow score, Lille score) and outcome in response to steroids in this cohort (Fig. 1). Although some previous studies relating baseline disease severity in AH to clinical response have shown a correlation with outcome, these studies have included all grades of disease severity and not specifically correlated outcome in the most severe group treated with steroids.

The lack of correlation with disease severity in our cohort emphasizes that the failure to respond adequately to steroids in some individuals is not simply explained by differences in baseline disease severity and that the role played by intrinsic steroid resistance in determining outcome is independent of disease severity. Consistent with previous reports,1, 25, 30-37 we did observe in our cohort a correlation between fall in bilirubin by day 7 (a measure of early response rather than disease severity) and long-term outcome (Fig. 1). The separation in outcome between individuals determined to be steroid-resistant or steroid-sensitive at baseline was not complete (Fig. 3). Hence, measurement of in vitro steroid sensitivity should not be considered a robust predictive marker for

use in clinical 上海皓元医药股份有限公司 management. Rather, the present finding provides evidence for an important factor that contributes to outcome, and which might represent a target for pharmacotherapy to improve overall outcomes. In this context, we noted that that addition of basiliximab to in vitro cell cultures, competitively targeting CD25, a key component of the high-affinity IL-2 receptor,38 improved steroid sensitivity in all individuals with low Imax on the DILPA test, consistent with previous reports in ulcerative colitis.16, 29, 39 The mechanisms involved in steroid resistance are unknown but IL-2 may play an important immunological role. Combination of IL-2 and IL-4 has been shown to reduce glucocorticoid receptor-binding affinity and consequent T-cell response to steroids.


“It has been argued that executive tests should capture ce


“It has been argued that executive tests should capture central aspects of executive functions in everyday life such as initiating and monitoring parallel actions in low-structured environments (so-called multitasking; see Burgess, 2000). We present a cooking task in order to assess

executive function impairments in brain-damaged patients, which focuses on a central feature of multitasking, the interleaving of tasks (Burgess, 2000). Behavioural performance of 21 brain-damaged patients (stroke, traumatic brain injury) and of a group of matched controls was analysed on the basis of a standardized protocol. In comparison to controls, the patients explored less, Ipatasertib clinical trial were less successful in monitoring their actions and corrected errors less efficiently. Interleaving of actions was observed less frequently

in patients, with respect to both cooking itself as well as to subordinate goals (e.g., cleaning up). Interleaving proved efficient, as it was associated with less time to complete PI3K inhibitor the task. Patients’ scores in the cooking task correlated with performance in both the Behavioural Assessment of the Dysexecutive Syndrome (BADS) Zoo Map Test and the BADS Six Elements Test, but not with tests of attention, verbal memory, or figural fluency, thus demonstrating convergent and discriminant validity. In summary, our task demonstrates that cooking can provide a valid testing ground for assessing a central aspect of everyday 上海皓元 multitasking demands, namely, the interleaving of actions. “
“All electrostimulation studies on arithmetic have so far solely reported general errors. Nonetheless, a classification of the errors during stimulation can inform us about underlying arithmetic processes. The present electrostimulation study was performed in a case of left parietal glioma. The patient’s erroneous responses suggested that calculation was mainly applied for addition and a combination of retrieval and calculation was mainly applied for multiplication. The findings of the present single-case study encourage follow

up with further data collection with the same paradigm. “
“We report a case of probable Alzheimer’s disease who presented with the unusual feature of disinhibited rhyming. Core language skills were largely intact but generative language was characterized by semantic-based associations, evident in tangential and associative content, and phonology-based associations, evident in rhyming, in the context of prominent executive dysfunction. We suggest this pattern is underpinned by a failure to terminate or inhibit verbal associations resulting in a ‘loosening’ of associations at the level of conceptual preparation for spoken language. “
“A common cause of neuropsychological impairment in older adults is cerebral small vessel disease (SVD), but little is known as to whether lack of awareness of neuropsychological impairment is a feature of this clinical condition.


“It has been argued that executive tests should capture ce


“It has been argued that executive tests should capture central aspects of executive functions in everyday life such as initiating and monitoring parallel actions in low-structured environments (so-called multitasking; see Burgess, 2000). We present a cooking task in order to assess

executive function impairments in brain-damaged patients, which focuses on a central feature of multitasking, the interleaving of tasks (Burgess, 2000). Behavioural performance of 21 brain-damaged patients (stroke, traumatic brain injury) and of a group of matched controls was analysed on the basis of a standardized protocol. In comparison to controls, the patients explored less, RAD001 solubility dmso were less successful in monitoring their actions and corrected errors less efficiently. Interleaving of actions was observed less frequently

in patients, with respect to both cooking itself as well as to subordinate goals (e.g., cleaning up). Interleaving proved efficient, as it was associated with less time to complete Smoothened Agonist ic50 the task. Patients’ scores in the cooking task correlated with performance in both the Behavioural Assessment of the Dysexecutive Syndrome (BADS) Zoo Map Test and the BADS Six Elements Test, but not with tests of attention, verbal memory, or figural fluency, thus demonstrating convergent and discriminant validity. In summary, our task demonstrates that cooking can provide a valid testing ground for assessing a central aspect of everyday medchemexpress multitasking demands, namely, the interleaving of actions. “
“All electrostimulation studies on arithmetic have so far solely reported general errors. Nonetheless, a classification of the errors during stimulation can inform us about underlying arithmetic processes. The present electrostimulation study was performed in a case of left parietal glioma. The patient’s erroneous responses suggested that calculation was mainly applied for addition and a combination of retrieval and calculation was mainly applied for multiplication. The findings of the present single-case study encourage follow

up with further data collection with the same paradigm. “
“We report a case of probable Alzheimer’s disease who presented with the unusual feature of disinhibited rhyming. Core language skills were largely intact but generative language was characterized by semantic-based associations, evident in tangential and associative content, and phonology-based associations, evident in rhyming, in the context of prominent executive dysfunction. We suggest this pattern is underpinned by a failure to terminate or inhibit verbal associations resulting in a ‘loosening’ of associations at the level of conceptual preparation for spoken language. “
“A common cause of neuropsychological impairment in older adults is cerebral small vessel disease (SVD), but little is known as to whether lack of awareness of neuropsychological impairment is a feature of this clinical condition.

037) and pathological grade (P = 0021)

037) and pathological grade (P = 0.021). RAD001 manufacturer Moreover, the overall survival of patients with negative IGFBP7 expression was significantly (P = 0.003) poorer than that of IGFBP7-positive patients. Cox regression analyses showed that IGFBP7 expression was an independent

predictor of overall survival (P = 0.02). Conclusion: The expression of IGFBP7 is significantly reduced in gastric cancer, which is associated with higher T stage and differentiation grade. IGFBP7 may serve as a prognostic marker as well as a potential therapeutic target for gastric cancer. Key Word(s): 1. gastric neoplasm; 2. RT PCR; 3. Western blotting; 4. survival analysis; Presenting Author: WEIHAO SUN Additional Authors: XIAOLIN LI, HAO ZHANG, KUN SUN, KAI ZHANG Corresponding Author: WEIHAO SUN Affiliations: The First Affiliated Hospital of Nanjing Medical University Objective: The current study evaluated the antitumor effects of Harmine (HM) on human gastric cancer both in vitro and in vivo. Methods: Growth inhibitory activity was assayed by the Methyl thiazolyl Smoothened Agonist concentration tetrazolium (MTT) assay, apoptotic staining and Flow cytometry analysis. The wound-healing and transwell invasion assays were performed to evaluate the effect of HM on inhibiting tumor invasion and metastasis. The protein expressions involved in regulating apoptosis

and invasion and metastasis were detected by western blot. Results: HM inhibited the proliferation of human gastric cancer cell lines BGC-823 and SGC-7901 in a dose- and time-dependent manner. In addition, HM effectively promoted the apoptosis of gastric cancer cells (Fig. 1) through dose-dependently inhibiting the expression of cyclooxygenase-2 (COX-2) (Fig. 2). Moreover, HM could induce apoptosis through a direct impact on many apoptosis-related proteins, such as Bcl-2 and Bax (Fig. 2). Most importantly, HM dramatically inhibited migration and invasion of gastric cancer by down-regulating the matrix metalloproteinase-2 (MMP-2) expression regulated by COX-2. In vivo, HM suppressed gastric xenograft tumor growth significantly. Fig. 1 Apoptosis

of BGC-823 and SGC-7901 cells detected by Flow cytometry. BGC-823 and SGC-7901 cells were treated with harmine at 0, 4, 8, and 16 μg/ml 上海皓元 for 24 hours. (A, B) Representative annexin V-FITC/PI stained BGC-823 (A) and SGC-7901 (B) cells. (C, D) The histograms on the right represent the rates of apoptotic cells in BGC-823 and SGC-7901 groups. All data represent the mean ± SD of three independent experiments. *P < 0.05, **P < 0.01 vs. control (0 μg/ml). Fig. 2 Effects of harmine on the COX-2, Bcl-2 and Bax protein expressions in BGC-823 and SGC-7901 cells. BGC-823 and SGC-7901 cells were treated with harmine at 0, 4, 8, and 16 μg/ml for 24 hours. (A, B) Representative COX-2, Bcl-2 and Bax protein expressions in BGC-823 (A) and SGC-7901 (B) cells detected by western blot analysis.