RESULTS: The accuracy of the scores is described in the Table below. Based on the 95%CI, the NFS was equally accurate as the FIB-4 score, but significantly more accurate than the APRI, NIKEI and BARD scores. The FIB-4 was similar to the NIKEI and BARD scores, but significantly better than the APRI score. There was no a significant difference among the NIKEI, APRI and BARD scores. The NIKEI had the lowest indeterminate score value, but also the lowest NPV and PPV. CONCLUSIONS: This large independent validation analysis demonstrates the high accuracy of noninvasive scores to distinguish between patients with and without advanced fibrosis. Combining

the NPV and the PPV, the NFS seems the most accurate followed by the FIB-4, the APRI, the NIKEI and the BARD scores. Accuracy of the socre to distinguish between patients with

MAPK inhibitor and without advanced (stage 3/4) fibrosis AUROC (95%CI) Indeterminate score NPV (low find more cut-point) PPV (high cut-point) NFS •825 (.789,.861) 30% 89% 84% APRI .729 (.686,.771) 49% 86% 62% FIB-4 .814 (.777,.851) 29% 89% 76% NIKEI .749 (.711,.788) 1% 78% 55% BARD .744 (.702,.786) NA 78% 55% Disclosures: Charles D. Rice – Employment: Sanofi-Spouse; Management Position: SanofiSpouse; Stock Shareholder: Sanofi-Spouse Jacob George – Advisory Committees or Review Panels: Roche, BMS, MSD, Gilead, Janssen Christopher P. Day – Advisory Committees or Review Panels: Abbott; Board Membership: Abbott Paul Angulo – Grant/Research Support: NIDDK, Mochida, Genfit The following people have nothing to disclose: Elisabetta Bugianesi, Einar Bjornsson, Phunchai Charatcharoenwitthaya, Peter R. Mills Background: Recent evidence suggest that coffee consumption

could be of benefit for those In non-alcoholic fatty liver disease (NAFLD) patients at risk of developing hepatic fibrosis. The underlying mechanisms of hepatic benefits selleck chemical of coffee intake remain unclear. Aims: a) to assess if coffee administration influences hepatic inflammation and fibrosis or mitochondrial respiration in a dietary model of non-alcoholic steatohepatitis (NASH), b) to test the effect of caffeine on hepatic stellate cells (HSC). Methods: C57bl6 mice were fed a choline-deficient amino acid-defined (CDAA) diet for 22 weeks to induce NASH. Unfiltered coffee was added to drinking water during diet administration (CDAA-C and CSAA-C groups). Hepatic steatosis, inflammation, and fibrosis were scored histologically (hematoxylin-eosin and Sirius red staining). Hepatic triglyceride content (HTG) and mRNA expression of inflammatory markers such as TNF-α and MCP-1 as well as mitochondrial respiration were assessed. In addition, primary rat HSC were culture-activated and treated with caffeine for 96h (5 to 20mM) or its main metabolite 1, 7-dimethylxanthine (1, 7-DMX) (for 72h, 1mM).

The other two patients who developed PCH during antiviral therapy showed interface hepatitis with moderate plasma cell infiltration in liver histology and high serum IgG levels. Clinical features of the two patients with PCH during antiviral therapy could not be distinguished

from those of two patients who developed PCH after termination of antiviral therapy. The incidence of PCH in this study was similar to that in patients without antiviral therapy in our previous report, in which the incidence of PCH (de novo AIH) was 2.1% in 633 recipients.[12] Therefore, it is unknown whether antiviral therapy for HCV is involved in the development of PCH. However, in the present cases, PCH occurred immediately after selleck chemicals the termination of antiviral therapy, indicating that the cessation of interferon may have induced the disease. Several studies have shown an association between PCH (de novo AIH) and antiviral therapy for recurrent hepatitis C after liver transplantation.[2-8] In these studies, most of the patients developed PCH during antiviral therapy, and a few cases of PCH after the termination of antiviral

therapy have been reported. One study demonstrated two cases of de novo AIH that occurred after the end of antiviral therapy for recurrent hepatitis C after liver transplantation.[13] Tyrosine Kinase Inhibitor Library high throughput Both patients developed de novo AIH at 1 month after the termination of pegylated interferon plus ribavirin therapy, but hepatitis caused by HCV recurrence was not completely excluded in both cases because the patients’ sera tested positive for HCV RNA after termination of antiviral therapy. Berardi et al. reported nine liver transplant recipients with de novo AIH associated with antiviral treatment for hepatitis C recurrence.[5] While eight patients of the nine in their report had de novo AIH during antiviral therapy,

one patient who achieved SVR click here developed de novo AIH at 1 month after termination of antiviral therapy. Our present cases and these reported cases suggest that PCH can be induced by the termination of antiviral treatment. It is important that PCH is considered in differential diagnoses along with relapse of HCV in patients developing liver dysfunction just after the termination of interferon therapy. The present cases showed elevation of transaminase levels at 1 and 2 months after the cessation of antiviral therapy when the relapse of HCV usually occurs. As it takes several days to obtain the results of serum HCV RNA examination, it would be initially difficult to distinguish HCV relapse from the other causes of liver dysfunction. Liver biopsy should be immediately done and histological diagnosis using the scoring system for PCH is recommended to differentiate it from other causes of liver dysfunction, including hepatitis C relapse in this situation.

This may represent a critical element for surveillance strategies for gastric cancer. “
“This review summarizes important studies regarding Helicobacter

pylori therapy published from April 2012 up to March 2013. To begin with, the updated European Consensus Guidelines were published last year, highlighting the role of bismuth and nonbismuth quadruple regimen as first-line treatments. Cure rates for standard triple therapy remain acceptable in quite a few settings nowadays, and some reports on innovative triple therapies look promising. One study evaluating bismuth quadruple therapy as first-line therapy was reported. Regarding nonbismuth quadruple regimens, there is a trend of superiority emerging for the “concomitant” therapy over the “sequential” regimen. “Hybrid” therapy, a combination of sequential and concomitant selleck compound therapy, has also shown advantage over sequential therapy.

Levofloxacin-based therapies appear to be useful and versatile in second- and third-line therapies, with interesting results for newer generation quinolones, which may partially overcome antibiotic resistance. Some promising works have been reported for bismuth-based rescue therapy, using individualized therapies upon antimicrobial information, as well as for rifabutin fourth-line therapy. Probiotics appear to have an effect in terms of reducing side effects and improving compliance, but data on improvement of eradication rates remain controversial. A number of interesting articles have Kinase Inhibitor Library been published over the last year assessing many issues around Helicobacter pylori eradication therapy, including the updated European Consensus Guidelines on H. pylori therapy (Maastricht/Florence Consensus Report) [1]. This article

addresses the published literature over the last year pertaining to these topics. These focused selleck inhibitor primarily on assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized triple therapies and nonbismuth quadruple schemes. There was also progress in investigating antibiotic resistance rates and the rescue therapies required to deal with ensuing treatment failures, especially novel fluoroquinolones. There have also been advances in acid suppression and an evolution in the use of adjuvant therapies, especially probiotic therapies, which were extensively examined. What is without dispute is that the eradication of H. pylori remains a worthwhile goal to alleviate the burden of disease caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer. One particularly interesting paper looked at the role of H. pylori eradication in preventing rebleeding from peptic ulcers and showed virtually no recurrence in patients with complicated ulcers after H.

This may represent a critical element for surveillance strategies for gastric cancer. “
“This review summarizes important studies regarding Helicobacter

pylori therapy published from April 2012 up to March 2013. To begin with, the updated European Consensus Guidelines were published last year, highlighting the role of bismuth and nonbismuth quadruple regimen as first-line treatments. Cure rates for standard triple therapy remain acceptable in quite a few settings nowadays, and some reports on innovative triple therapies look promising. One study evaluating bismuth quadruple therapy as first-line therapy was reported. Regarding nonbismuth quadruple regimens, there is a trend of superiority emerging for the “concomitant” therapy over the “sequential” regimen. “Hybrid” therapy, a combination of sequential and concomitant find more therapy, has also shown advantage over sequential therapy.

Levofloxacin-based therapies appear to be useful and versatile in second- and third-line therapies, with interesting results for newer generation quinolones, which may partially overcome antibiotic resistance. Some promising works have been reported for bismuth-based rescue therapy, using individualized therapies upon antimicrobial information, as well as for rifabutin fourth-line therapy. Probiotics appear to have an effect in terms of reducing side effects and improving compliance, but data on improvement of eradication rates remain controversial. A number of interesting articles have Bortezomib cell line been published over the last year assessing many issues around Helicobacter pylori eradication therapy, including the updated European Consensus Guidelines on H. pylori therapy (Maastricht/Florence Consensus Report) [1]. This article

addresses the published literature over the last year pertaining to these topics. These focused this website primarily on assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized triple therapies and nonbismuth quadruple schemes. There was also progress in investigating antibiotic resistance rates and the rescue therapies required to deal with ensuing treatment failures, especially novel fluoroquinolones. There have also been advances in acid suppression and an evolution in the use of adjuvant therapies, especially probiotic therapies, which were extensively examined. What is without dispute is that the eradication of H. pylori remains a worthwhile goal to alleviate the burden of disease caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer. One particularly interesting paper looked at the role of H. pylori eradication in preventing rebleeding from peptic ulcers and showed virtually no recurrence in patients with complicated ulcers after H.

This may represent a critical element for surveillance strategies for gastric cancer. “
“This review summarizes important studies regarding Helicobacter

pylori therapy published from April 2012 up to March 2013. To begin with, the updated European Consensus Guidelines were published last year, highlighting the role of bismuth and nonbismuth quadruple regimen as first-line treatments. Cure rates for standard triple therapy remain acceptable in quite a few settings nowadays, and some reports on innovative triple therapies look promising. One study evaluating bismuth quadruple therapy as first-line therapy was reported. Regarding nonbismuth quadruple regimens, there is a trend of superiority emerging for the “concomitant” therapy over the “sequential” regimen. “Hybrid” therapy, a combination of sequential and concomitant Palbociclib nmr therapy, has also shown advantage over sequential therapy.

Levofloxacin-based therapies appear to be useful and versatile in second- and third-line therapies, with interesting results for newer generation quinolones, which may partially overcome antibiotic resistance. Some promising works have been reported for bismuth-based rescue therapy, using individualized therapies upon antimicrobial information, as well as for rifabutin fourth-line therapy. Probiotics appear to have an effect in terms of reducing side effects and improving compliance, but data on improvement of eradication rates remain controversial. A number of interesting articles have Fer-1 cost been published over the last year assessing many issues around Helicobacter pylori eradication therapy, including the updated European Consensus Guidelines on H. pylori therapy (Maastricht/Florence Consensus Report) [1]. This article

addresses the published literature over the last year pertaining to these topics. These focused check details primarily on assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized triple therapies and nonbismuth quadruple schemes. There was also progress in investigating antibiotic resistance rates and the rescue therapies required to deal with ensuing treatment failures, especially novel fluoroquinolones. There have also been advances in acid suppression and an evolution in the use of adjuvant therapies, especially probiotic therapies, which were extensively examined. What is without dispute is that the eradication of H. pylori remains a worthwhile goal to alleviate the burden of disease caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer. One particularly interesting paper looked at the role of H. pylori eradication in preventing rebleeding from peptic ulcers and showed virtually no recurrence in patients with complicated ulcers after H.

Our study attempted to identify the genetic risk factors associated with PU or ulcer bleeding. We investigated the identified 27 candidate SNPs of 23 genes associated with small bowel bleeding using DMET,[22] because these SNPs might be associated with GI bleeding including

PU bleeding among the patients taking LDA. Although these SNPs and additional two MK 1775 genes’ SNPS (ABCG2 c.421C > A(Q141K) rs2231142 and SLCO1B1*4_c.463C > A(P155T) rs11045819) for ulcer bleeding were investigated in our validation study, only the CHST2 SNP (rs6664) was significantly associated with ulcer or ulcer bleeding, as well as the SLCO1B1*1b haplotype. After adjustment for significant factors, the SLCO1B1*1b haplotype was Lumacaftor manufacturer associated with PU. Moreover, consistent with our previous reports,[6-8] cotreatment with statins or ARBs (or ACEIs) was significantly associated with PU and ulcer bleeding among patients taking LDA. A wide variety of anionic compounds, including statins, ACEIs, and ARBs, are actively transported from the portal blood into hepatocytes by OATP1B1, which is encoded by SLCO1B1.[15, 23, 24] Among the more than 40 mutations identified in SLCO1B1, A388G (Asn130Asp) and T521C (Val174Ala) occur frequently and have been extensively investigated. The T521C SNP has been consistently linked with reduced transport

activity of OATP1B1 both in vitro[15, 25-27] and in vivo,[23, 28, 29] and statin blood concentrations were reported to be higher in subjects with the 521C allele, which has been shown to be associated learn more with an increased risk of simvastatin-induced myopathy.[30] Two haplotypes with nonsynonymous variations, *1b harboring A388G and *15 harboring A388G and T521C, have been

frequently reported in Japanese. SLCO1B1*1b has been shown to have no altered transport activity from in vitro expression systems[15, 27, 31, 32]; however, an in vivo study suggested that the pravastatin blood concentration was significantly lower in *1b/*1b subjects than in *1a/*1a subjects.[33] Another major haplotype, SLCO1B1*15, has been reported to show impaired plasma membrane expression and reduced transport activity in vitro.[15, 27] Therefore, the SLCO1B1 521TT genotype as well as SLCO1B1*1b, which are thought to have the highest transport activity, may decrease statin and ARB blood concentrations and thus diminish the preventive effect of these drugs on aspirin-induced gastric mucosal injury, probably by reducing their concentrations in the stomach. We also found more significant difference in the frequency of the SLCO1B1*1b haplotype between the controls and not only the ulcer group, but also the bleeding group by analysis in the subgroup taking statins or ARBs; however, there was no significant difference in the subgroup not taking statins or ARBs. The SLCO1B1*1b haplotype could be a new risk marker for aspirin-induced mucosal injury especially in statin, ARB, or ACEI users.

Our study attempted to identify the genetic risk factors associated with PU or ulcer bleeding. We investigated the identified 27 candidate SNPs of 23 genes associated with small bowel bleeding using DMET,[22] because these SNPs might be associated with GI bleeding including

PU bleeding among the patients taking LDA. Although these SNPs and additional two Staurosporine nmr genes’ SNPS (ABCG2 c.421C > A(Q141K) rs2231142 and SLCO1B1*4_c.463C > A(P155T) rs11045819) for ulcer bleeding were investigated in our validation study, only the CHST2 SNP (rs6664) was significantly associated with ulcer or ulcer bleeding, as well as the SLCO1B1*1b haplotype. After adjustment for significant factors, the SLCO1B1*1b haplotype was Saracatinib associated with PU. Moreover, consistent with our previous reports,[6-8] cotreatment with statins or ARBs (or ACEIs) was significantly associated with PU and ulcer bleeding among patients taking LDA. A wide variety of anionic compounds, including statins, ACEIs, and ARBs, are actively transported from the portal blood into hepatocytes by OATP1B1, which is encoded by SLCO1B1.[15, 23, 24] Among the more than 40 mutations identified in SLCO1B1, A388G (Asn130Asp) and T521C (Val174Ala) occur frequently and have been extensively investigated. The T521C SNP has been consistently linked with reduced transport

activity of OATP1B1 both in vitro[15, 25-27] and in vivo,[23, 28, 29] and statin blood concentrations were reported to be higher in subjects with the 521C allele, which has been shown to be associated this website with an increased risk of simvastatin-induced myopathy.[30] Two haplotypes with nonsynonymous variations, *1b harboring A388G and *15 harboring A388G and T521C, have been

frequently reported in Japanese. SLCO1B1*1b has been shown to have no altered transport activity from in vitro expression systems[15, 27, 31, 32]; however, an in vivo study suggested that the pravastatin blood concentration was significantly lower in *1b/*1b subjects than in *1a/*1a subjects.[33] Another major haplotype, SLCO1B1*15, has been reported to show impaired plasma membrane expression and reduced transport activity in vitro.[15, 27] Therefore, the SLCO1B1 521TT genotype as well as SLCO1B1*1b, which are thought to have the highest transport activity, may decrease statin and ARB blood concentrations and thus diminish the preventive effect of these drugs on aspirin-induced gastric mucosal injury, probably by reducing their concentrations in the stomach. We also found more significant difference in the frequency of the SLCO1B1*1b haplotype between the controls and not only the ulcer group, but also the bleeding group by analysis in the subgroup taking statins or ARBs; however, there was no significant difference in the subgroup not taking statins or ARBs. The SLCO1B1*1b haplotype could be a new risk marker for aspirin-induced mucosal injury especially in statin, ARB, or ACEI users.

Our study attempted to identify the genetic risk factors associated with PU or ulcer bleeding. We investigated the identified 27 candidate SNPs of 23 genes associated with small bowel bleeding using DMET,[22] because these SNPs might be associated with GI bleeding including

PU bleeding among the patients taking LDA. Although these SNPs and additional two Crenolanib in vivo genes’ SNPS (ABCG2 c.421C > A(Q141K) rs2231142 and SLCO1B1*4_c.463C > A(P155T) rs11045819) for ulcer bleeding were investigated in our validation study, only the CHST2 SNP (rs6664) was significantly associated with ulcer or ulcer bleeding, as well as the SLCO1B1*1b haplotype. After adjustment for significant factors, the SLCO1B1*1b haplotype was STAT inhibitor associated with PU. Moreover, consistent with our previous reports,[6-8] cotreatment with statins or ARBs (or ACEIs) was significantly associated with PU and ulcer bleeding among patients taking LDA. A wide variety of anionic compounds, including statins, ACEIs, and ARBs, are actively transported from the portal blood into hepatocytes by OATP1B1, which is encoded by SLCO1B1.[15, 23, 24] Among the more than 40 mutations identified in SLCO1B1, A388G (Asn130Asp) and T521C (Val174Ala) occur frequently and have been extensively investigated. The T521C SNP has been consistently linked with reduced transport

activity of OATP1B1 both in vitro[15, 25-27] and in vivo,[23, 28, 29] and statin blood concentrations were reported to be higher in subjects with the 521C allele, which has been shown to be associated selleckchem with an increased risk of simvastatin-induced myopathy.[30] Two haplotypes with nonsynonymous variations, *1b harboring A388G and *15 harboring A388G and T521C, have been

frequently reported in Japanese. SLCO1B1*1b has been shown to have no altered transport activity from in vitro expression systems[15, 27, 31, 32]; however, an in vivo study suggested that the pravastatin blood concentration was significantly lower in *1b/*1b subjects than in *1a/*1a subjects.[33] Another major haplotype, SLCO1B1*15, has been reported to show impaired plasma membrane expression and reduced transport activity in vitro.[15, 27] Therefore, the SLCO1B1 521TT genotype as well as SLCO1B1*1b, which are thought to have the highest transport activity, may decrease statin and ARB blood concentrations and thus diminish the preventive effect of these drugs on aspirin-induced gastric mucosal injury, probably by reducing their concentrations in the stomach. We also found more significant difference in the frequency of the SLCO1B1*1b haplotype between the controls and not only the ulcer group, but also the bleeding group by analysis in the subgroup taking statins or ARBs; however, there was no significant difference in the subgroup not taking statins or ARBs. The SLCO1B1*1b haplotype could be a new risk marker for aspirin-induced mucosal injury especially in statin, ARB, or ACEI users.

DTI could not be performed at standard intervals for every patient due to different timing of admission to the hospital and of initial diagnosis. In one patient, MRI and DTI

were obtained three times: 21 days and 11 and 23 months after occurrence of the inciting lesion. Another patient was studied 5 times after the onset of disease: at 8, 12, 32, 38, and 44 months. In the remaining 8 patients, DTI was performed only once. The time interval between RG7204 order inciting lesion and DTI of patients ranged from 21 days to 60 months. Demographic and clinical profiles of patients with HOD are summarized in Table 1. Thirteen affected GMT were studied from 10 patients (both triangles from 3 patients). Thirteen GMTs were used from control subjects,

which were selected from age, sex, and side matched 10 neurologically normal population. All MRI examinations were performed in a 3T scanner (Trio, Siemens, Erlangen, Germany) using 8-channels head coil. Axial Turbo Spin Echo (TSE) T2, TSE T1, fluid-attenuated inversion recovery, sagittal, Selleckchem Birinapant and coronal TSE T2 were obtained. Single shot spin echo echo planar imaging (EPI) sequence was used to obtain diffusion weighted images (DWI). Sixty slices covering the whole brain were acquired with 2-mm × 2-mm × 2-mm isotropic resolution, time of repetition (TR) = 10,100 ms, time of echo (TE) = 100 ms, bandwidth = 1,300 Hz/pixels, field of view (FOV) = 256 × 256 mm, and find more scan time = 11.35 minutes. Parallel imaging was used with acceleration factor 2. The b-factor was set to 0 and 700 s/mm2. For generating the diffusion tensor, 60 uniformly distributed directions over the unit sphere were used. The DTI datasets were processed by using DTI task card software (Massachusetts General Hospital). The diffusivity along the fiber tract (axial diffusivity, λ//), the diffusivity perpendicular to the fiber tract (radial diffusivity, λ⊥), ADC and FA were calculated using the principal diffusivities: (1) Using the FA maps, FA color maps and EPI T2 weighted images (b = 0 DWI), ROIs were placed manually

on IO, the central tegmental tract, the superior cerebellar peduncle, the red nucleus, and the dentate nucleus of patients and the control subjects on consensus by two experienced radiologist (A.D., 16 years experience, and E.K., 8 years experience). The DWI datasets were chosen for ROIs selection, instead of other structural imaging data, to avoid any potential for misregistration related to patient motion and inconsistent geometric distortions between EPI and non-EPI sequence MR imaging. Furthermore, 2-mm isometric voxel DTI datasets allowed identification of different compartments of the brain stem.8 The size and the location of ROIs were standardized for each anatomical region. EPI T2, FA, and color FA were displayed alternatively to guide the selection of ROIs. Referring to anatomical knowledge, ROIs were placed on axial slices at five levels. Each ROI consisted of one slice only.

Accordingly, silencing of the PLK3 gene triggered hepatocarcinogenesis in a mouse model.18 Moreover, we frequently found LOH for the PLK4 gene in many HCC samples, with the highest incidence in HCCP. The PLK4 locus is located at the chromosomal band 4q28.1, which is frequently affected by LOH in HCC and whose crucial role in liver carcinogenesis has been envisaged.36, 37 In accordance with the latter

hypothesis, PLK4 heterozygosity resulted in spontaneous liver tumor development in a mouse model, which was associated with centrosome amplification and induction of chromosomal instability19 as characteristically observed in human check details HCC.37, 38 Thus, PLK4 might be one of the pivotal tumor suppressor genes located in the 4q28.1 chromosome region,

whose loss contributes to human hepatocarcinogenesis. Furthermore, we have investigated in more detail the role of PLK1 on cell cycle regulation in human HCC cell lines. Our data confirm the important function of PLK1 in regulating both the G2/M phase of the cell cycle and the apoptotic process, supporting previous observations in various cancer cell lines.25, 39, 40 In particular, the present findings indicate that PLK1 is able to inhibit apoptosis in a p53 family–dependent manner, as observed in Hep3B and HepG2 cell lines. It has been demonstrated that PLK1 interacts with the DNA binding domain of p53, thereby decreasing its stability and transcriptional activity.26 The latter mechanism might explain YAP-TEAD Inhibitor 1 the increased apoptosis rate reported in HepG2 cells (p53 wild-type) with subsequent down-regulation of antiapoptotic proteins following PLK1 silencing. Recently, a physical interaction between PLK1 and p73, another member of the p53 family, has been demonstrated in different cell lines.27, 28 Like p53, p73 transactivates many p53 target genes involved in cell cycle control and apoptosis. PLK1 is able to phosphorylate p73 at the threonine 27 residue within its transactivation domain, thereby abrogating its transcriptional activity.27, this website 28 We detected an increase in p73 protein level and its target genes following silencing of PLK1

expression in Hep3B and HepG2 cells. Up-regulation of the p73 protein was also observed in MCF7 breast cancer cells expressing the p53 gene,27 confirming that p73 induction by PLK1 is independent of p53 in different cellular contexts. In a recent report, a therapeutic approach using a PLK1 inhibitor resulted in dramatic tumor regression in nude mice bearing xenografts of HCT116 colorectal cancer cells in which the p53 gene was disrupted, suggesting a crucial function of PLK1 for the growth of p53-deficient tumor cells.41 Similarly, we show here that the growth of SNU-182 cells overexpressing Ha-Ras, FOXM1, and PLK1 is dramatically reduced and impaired when this axis is disrupted by either FOXM1 or PLK1 suppression through siRNA in vitro (Fig. 7D).