- [Show abstract] [Hide abstract] ABSTRACT: Objectives: Sentinel lymph node (SLN)-based diagnosis in gastric cancers has shown varied sensitivities and false-negative rates in several studies. Application of the reverse transcription-polymerase chain reaction (RT-PCR) in SLN diagnosis has recently been proposed.Methods: A total of 155 SLNs from 65 patients with cT1-2, N0 gastric cancer were examined. The histopathologic results were compared with results obtained by real-time RT-PCR for detecting molecular RNA (mRNA) of cytokeratin (CK)19, carcinoembryonic antigen (CEA), and CK20.Results: The sensitivity and specificity of the multiple marker RT-PCR assay standardized against the results of the postoperative histological examination were 0.778 (95% confidence interval [CI], 0.577-0.914) and 0.781 (95% CI, 0.700-0.850), respectively. In comparison, the sensitivity and specificity of intraoperative diagnosis were 0.819 (95% CI, 0.619-0.937) and 1.000 (95% CI, 0.972-1.000), respectively. The positive predictive value of the multiple-marker RT-PCR assay was 0.355 (95% CI, 0.192-0.546) for predicting non-SLN metastasis, which was lower than that of intraoperative diagnosis (0.813, 95% CI, 0.544-0.960).Conclusions: The real-time RT-PCR assay could detect SLN metastasis in gastric cancer. However, the predictive value of the real-time RT-PCR assay was lower than that of precise histopathologic examination and did not outweigh that of our intraoperative SLN diagnosis.
- [Show abstract] [Hide abstract] ABSTRACT: We analyzed the expression levels of fluoropyrimidine-metabolizing enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase [DPD], thymidine phosphorylase [TP] and orotate phosphoribosyltransferase [OPRT]) to identify potential biomarkers related to treatment outcomes in gastric cancer (GC) patients receiving adjuvant S-1 chemotherapy. In this study, 184 patients who received curative gastrectomy (D2 lymph node dissection) and adjuvant S-1 were included. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were performed to measure the protein and mRNA levels of TS, DPD, TP, and OPRT in tumor tissue. In univariate analysis, low intratumoral DPD protein expression was related to poorer 5-year disease-free survival (DFS; 78% vs. 88%; P = 0.068). Low intratumoral DPD mRNA expression (1st [lowest] quartile) was also related to poorer DFS (69% vs. 90%; P < 0.001) compared to high intratumoral DPD expression (2nd to 4th quartiles). In multivariate analyses, low intratumoral DPD protein or mRNA expression was related to worse DFS (P < 0.05), irrespective of other clinical variables. TS, TP, and OPRT expression levels were not related to treatment outcomes. Severe non-hematologic toxicities (grade ≥ 3) had a trend towards more frequent development in patients with low intratumoral DPD mRNA expression (29% vs. 16%; P = 0.068). In conclusion, GC patients with high intratumoral DPD expression did not have inferior outcome following adjuvant S-1 therapy compared with those with low DPD expression. Instead, low intratumoral DPD expression was related to poor DFS.
- [Show abstract] [Hide abstract] ABSTRACT: Background: It is unclear whether preoperative chemoradiotherapy (pCRT) increases the rate of sphincter-preserving surgery (SPS), avoiding abdominoperineal resection (APR), for the treatment of distal rectal cancer. We examined whether pCRT increases the likelihood of SPS based on changes in tumor height using pelvic magnetic resonance imaging (MRI). Methods: Between January 2009 and December 2013, 105 patients underwent long-course pCRT for locally advanced distal rectal cancer (≤5 cm from the anal verge) and were included in this study. The surgical procedures were analyzed in terms of radiologic findings, including the distance from the inferior margin of tumor to the superior margin of the anorectal ring (tumor height) measured by pelvic MRI before and after pCRT. Results: Eighty-six (81.9 %) patients underwent SPS. Overall clinical downstaging occurred in 48 (45.7 %) patients. Tumor height increased significantly after pCRT (from 15.0 ± 15.3 to 18.1 ± 16.9 mm, change 3.1 ± 9.7 mm, p = 0.01). The mean change in tumor height was not significantly different between patients who underwent SPS or APR (mean change 3.3 ± 9.6 vs. 2.3 ± 10.5 mm, p = 0.68). The mean change was significantly greater in the double-stapled anastomosis group than in the handsewn anastomosis group (mean change 5.6 ± 9.9 vs. -0.6 ± 8.6 mm, p = 0.02). Conclusions: This was the first MRI-based longitudinal study to show that pCRT does not appear to increase the likelihood of SPS in locally advanced distal rectal cancer, although it could improve the potential of double-stapled anastomoses.
- [Show abstract] [Hide abstract] ABSTRACT: Background/Aims There are several methods for obtaining tissue samples to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography (ERCP). However, each method has only limited sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush cytology, and forceps biopsy). Methods We retrospectively reviewed 168 patients with suspicious malignant biliary strictures who underwent double-tissue sampling (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011. Results Among the 168 patients reviewed, 117 patients (69.6%) were eventually diagnosed with malignancies. The diagnostic sensitivity for cancer was significantly higher in the TTS group than the DTS group (85.0% vs 64.9%, respectively; p=0.022). Furthermore, the combination of brush cytology and forceps biopsy was superior to the other method combinations in the DTS group. With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma), interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not for the non-cholangiocarcinoma patients (57.1% vs 57.1%, respectively). Conclusions TTS can provide an improved diagnostic accuracy in suspicious malignant biliary strictures, particularly for cholangiocarcinoma.
- [Show abstract] [Hide abstract] ABSTRACT: The objectives of this study were to study the expression status of markers associated with epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic ductal adenocarcinomas (PDACs) and to explore the prognostic value of these markers. Immunohistochemical stains for CD24, CD44, E-cadherin, N-cadherin, Snail, S100A4, Vimentin, urokinase-type plasminogen activator receptor, Ezrin, and matrix metalloproteinase 2 were performed on 67 resected PDACs. Proteins associated with EMT and metastasis were more frequently expressed in PDACs with poor differentiation, higher tumor stage, and lymphatic and perineural invasion. CD24 expression was associated with frequent expression of EMT markers (CD44 [P = 0.004], S100A4 [P < 0.001], Vimentin [P = 0.022], urokinase-type plasminogen activator receptor [P = 0.002], and Ezrin [P = 0.010]). CD24 and S100A4 expressions in PDAC were significant prognostic factors for early tumor recurrence (hazard risk [HR], 5.185 and 2.490, P = 0.048 and 0.009, respectively) and poor survival (HR, 11.977 and 3.202, P = 0.006 and 0.004, respectively). In addition, the interaction between CD24 and S100A4 expression status was a significant prognostic factor for poor survival (HR, 18.518, P = 0.003). The expression of markers of EMT and metastasis in PDACs was significantly associated with pathologic features of aggressiveness. CD24 and S100A4 expressions were significant predictors of poor survival; thus, immunohistochemistry for these markers in resected specimens may help to identify PDAC patients with a poor prognosis.
- [Show abstract] [Hide abstract] ABSTRACT: Obesity influences risk, progression and prognosis of various cancers including hepatocellular carcinoma (HCC). Adipose-tissue-derived adipokines has been considered to be involved in tumorigenesis and adiponecin, one such adipokine, has antiproliferative effect on obesity-related malignancies, though variable signal pathway mediated by adiponectin receptors-AdipoR1 and AdipoR2. In this study, we investigated expression of adiponectin and adiponectin receptors in tumor and non-tumorous hepatic tissues of HCC patients and its clinicopathological significance. We collected 75 HCC tissues and 70 non-tumorous hepatic tissues from HCC patients who underwent surgical resection. The tissue microarrays were constructed and immunohistochemical study for adiponectin, AdipoR1 and AipoR2 was performed. Adiponectin and AdipoR1 expression rates were significantly lower in HCC than non-neoplastic hepatic tissues (82.7 % vs. 97.1 % and 24.0 % vs. 90 %, P = 0.005 and <0.001, respectively). Immunopositivity for adiponectin was associated with small tumor size, low Edmonson-Steiner grade and absence of other organ invasion (P = 0.015, 0.021 and 0.028, respectively). AdipoR1 expression had association with absence of vascular invasion (P = 0.028) and AdipoR2 expression was correlated with lower histologic grade and low pathologic T-stage (P = 0.003 and 0.008, respectively). Cox regression analysis revealed that low expression of AdipoR1 and AdipoR2 were associated with increased risk of recurrence and death, respectively (hazard ration = 3.222 and 14.797, respectively). These findings suggest that loss of adiponectin, and adiponectin receptors expression is associated with aggressive clinicopathological features of HCC and AdipoR1 and AdipoR2 might serve as the independent prognostic factors for HCC patients.
- [Show abstract] [Hide abstract] ABSTRACT: Immunoglobulin G4 (IgG4)-related disease is a novel disease entity that can involve diverse organs, causing specific diseases, including autoimmune pancreatitis, sclerosing cholangitis, cholecystitis, inflammatory aortic aneurysm, and inflammatory pseudotumor. IgG4-related disease is characterized by elevated serum IgG4 concentrations, abundant IgG4 lymphoplasmacytic infiltration, and dramatic steroid responses. It is clinically important to differentiate this rare disease from primary sclerosing cholangitis and cholangiocarcinoma, because the treatment and prognosis of these two diseases are completely different. However, the preoperative diagnosis is challenging, and the disease is frequently misdiagnosed. If the serum level of IgG4 is within the normal range, the diagnosis of IgG4-related disease is more difficult. This article reports on a 59-year-old man with IgG4-related disease mimicking unresectable gallbladder cancer with normal serum IgG4 concentrations.
- [Show abstract] [Hide abstract] ABSTRACT: Hepatic progenitor cells (HPCs) are thought to play a role in hepatoblastoma, as hepatoblastomas are characterized by an immature histology and a wide variety of cell lineages. We aimed to investigate the extent of expression of HPCs marker and its clinical implication in hepatoblastoma. We collected 61 hepatoblastomas and 9 childhood hepatocellular carcinomas (HCCs) and performed immunohistochemistry for HPC markers, including cytokeratin 19 (CK19), octamer-binding transcription factor 3/4 (Oct-3/4), epithelial cell adhesion molecule (EpCAM), and delta-like 1 homolog (DLK1). Of the hepatoblastoma samples, 27/61 (44.3%), 21/61 (34.4%), 51/61 (83.6%) and 56/61 (91.8%) exhibited positivity for CK19, Oct-3/4, EpCAM and DLK-1, respectively. For HCCs, the rates of expression were 22.2% (CK19), 77.8% (EpCAM) and 77.8% (DLK-1). Oct-3/4 was not expressed in HCC cells. Hepatoblastomas with a poorly differentiated epithelial component had a higher incidence of CK19 and Oct-3/4 expression than those with a well differentiated epithelial component (p=0.005 and 0.037, respectively). Higher disease stage of hepatoblastoma was correlated with CK19 expression (p=0.043). Oct-3/4-positive hepatoblastomas were associated with short disease-free survival (p=0.035). Both hepatoblastomas and childhood HCCs, therefore, exhibit characteristics of HPCs, and the poor prognosis of patients with Oct-3/4-positive hepatoblastoma suggests that stem-like properties affect hepatoblastoma pathogenicity.
- [Show abstract] [Hide abstract] ABSTRACT: We summarize our experience in the pathological diagnosis of late complications of liver transplantation (LT) to better understand the causes of late allograft dysfunction in a population mostly composed of patients with hepatitis B virus (HBV) infection. We reviewed 361 post-transplant liver biopsies from 174 patients who underwent LT and first presented with liver function abnormalities 3 months post-procedure. The underlying diseases included HBV-associated liver disease (77%), toxic or alcoholic liver disease (10.3%), hepatitis C virus (HCV)-associated liver disease (8.6%), primary biliary cirrhosis (1.2%), primary sclerosing cholangitis (1.2%), and metabolic disease (1.7%). The three most common late complications were acute rejection (32.5%), recurrent disease (19.1%), and biliary complication (17.1%). Patients who underwent LT for HBV infection or for drug- or alcohol-related liver disease had a lower incidence of recurring disease than those who underwent transplantation for HCV infection. During post-transplantation months 3-12, acute rejection was the most common cause of allograft dysfunction and recurring disease was the leading cause for allograft dysfunction (p=0.039). The two primary causes of late allograft dysfunction have overlapping histological features, although acute rejection more frequently showed bile duct damage and vascular endothelialitis than recurring HBV infection, and recurring HBV infection had more frequent lobular activity and piecemeal necrosis. The causes of late liver allograft dysfunction are closely associated with the original liver diseases and the period after LT. Careful attention is required for differential diagnosis between acute rejection and recurrent HBV.
- [Show abstract] [Hide abstract] ABSTRACT: Purpose: Adiponectin, an adipocyte-secreted endogenous insulin sensitizer, appears to play an important role in progression of several malignancies. Expression of adiponectin receptors--AdipoR1 and AdipoR2--has been documented in gastric cancer (GC) cell lines, but its role in GCs is still controversial. We investigated expression level of 2 adiponectin receptors and correlated their expression with prognosis in GC patients. Methods: We immunohistochemically evaluated AdipoR1 and AdipoR2 expression in 59 non-neoplastic gastric mucosas, 48 gastric adenomas, 250 GCs, and 58 lymph nodes involved by metastatic GC and assessed its association with clinicopathologic characteristics. Results: Expression rates of both receptors increased stepwise in non-neoplastic gastric mucosa, gastric adenoma, intestinal-type GC, and metastatic GC (p < 0.001). AdipoR1 and AdipoR2 expression was observed in 85 (34.0 %) and 118 (47.2 %) GC cases, respectively. Expression rates were higher in intestinal-type GC than in diffuse-type GC (p < 0.001 and 0.016, respectively). AdipoR1 and AdipoR2 expression was more frequent in advanced GC than in early GC (p < 0.001, each) and was associated with lymphatic invasion (p = 0.046 and 0.001, respectively). AdipoR2 expression was associated with poor overall and disease-free survival (p = 0.001 and 0.007, respectively). AdipoR1 expression was associated with poor disease-free survival for intestinal-type GC patients (p = 0.046). In multivariate analysis, AdipoR2 was an independent prognostic factor for intestinal-type GC (p = 0.017). Conclusions: Adiponectin receptor expression is related to GC development and progression, especially intestinal-type GC. Thus, adiponectin receptor expression can serve as a prognostic marker in GC patients.
- [Show abstract] [Hide abstract] ABSTRACT: Although increased evidence has suggested that epithelial-mesenchymal transition has been implicated in cancer invasion and is associated with poor prognosis, its significance in cholangiocarcinoma remains unclear. We evaluated the levels of expression of epithelial-mesenchymal transition-related genes and proteins in 2 established human cholangiocarcinoma cell lines with different morphological characteristics and performed transwell cell invasion assays. Furthermore, we investigated the association between altered expression of 6 epithelial-mesenchymal transition-related proteins and clinical outcomes in human cholangiocarcinoma patients (n = 119) by immunohistochemistry using a tissue microarray approach. Comparative analysis of protein and messenger RNA expression revealed that the cell line with less differentiation (JCK) showed increased expression of mesenchymal markers and zinc-finger proteins and decreased expression of epithelial markers. The invasion activity of JCK cells was significantly higher than that of cells from OZ cell lines. Tissue microarray analysis revealed that the combined expression pattern of 6 epithelial-mesenchymal transition-related proteins predicted shortened disease-free survival (13.0 versus 22.0 months, P = .033) and overall survival (23.0 versus 63.0 months, P = .003) and was confirmed as an independent unfavorable prognostic factor for survival in multivariate survival analysis (disease-free survival, P = .028 for the 3 epithelial-mesenchymal transition-related markers; overall survival, P = .010 for the 6 epithelial-mesenchymal transition-related markers). In conclusion, our results suggest that altered expression of a number of epithelial-mesenchymal transition-related genes in tumor cells with poor differentiation may explain their increased invasive ability. Our results also suggest that altered expression of a suite of epithelial-mesenchymal transition-related proteins could be used as a tool to predict poor outcomes in human cholangiocarcinoma patients.
- [Show abstract] [Hide abstract] ABSTRACT: Aims and background: Differential diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma is sometimes difficult to accurately perform. Methods: Eight markers including cytokeratin 7 (CK7), cytokeratin 19 (CK19), MOC31, CD10, glypican 3 (GPC3), claudin 4, biglycan and high mobility group A1 (HMGA1) were immunohistochemically stained in samples from 179 surgically resected hepatocellular carcinomas and 127 intrahepatic cholangiocarcinomas, and the rates of marker expression were statistically compared. Results: With the exception of biglycan, 7 of the 8 markers were found to have significantly different expression patterns when comparing the two types of cancer (P <0.05). In intrahepatic cholangiocarcinomas, the expression rates of CK7, CK19, MOC31, claudin 4 and HMGA1 were 83.4%, 89.0%, 88.2%, 69.2%, and 31.5%, respectively. These rates of expression in intrahepatic cholangiocarcinomas were all higher than in those in hepatocellular carcinomas (CK7, 31.3%; CK19, 10.1%; MOC31, 34.0%; claudin 4, 11.2%; and HMGA1, 19.5%). The expression rates of GPC3, CD10, and biglycan were 72.6%, 39.7% and 10.0%, respectively, in hepatocellular carcinoma. These were higher than the rates found in intrahepatic cholangiocarcinomas (GPC3, 7.0%; CD10, 18.1%; and biglycan, 7.0%). In a multivariate logistic regression analysis, GPC3, CK19, MOC31 and claudin 4 were found to be independent markers for differentially diagnosing intrahepatic cholangiocarcinoma. Conclusions: Based on our results, GPC3 and CK19 can be used as first-line markers for differential diagnoses of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (accuracy rate, 73.5%), and additional combined screening for claudin 4 and MOC31 markers in GPC3(-) and CK19(-) tumors might increase the accuracy rate for distinguishing hepatocellular carcinoma from intrahepatic cholangiocarcinoma to 88.5%.
- [Show abstract] [Hide abstract] ABSTRACT: Shin E, Kim S-H, Jeong H-Y, Jang J-J, Lee K. Nuclear expression of S-phase kinase–associated protein 2 predicts poor prognosis of hepatocellular carcinoma. APMIS 2012; 120: 349–57. The S-phase kinase–associated protein 2 (Skp2), which ubiquitinates the cell cycle inhibitor p27Kip1 and targets it for degradation, is commonly overexpressed in human cancers and is associated with poor prognosis in several cancers. The aim of this study was to investigate Skp2 expression and its clinicopathologic significance in surgically resected hepatocellular carcinomas. We collected 359 hepatocellular carcinoma samples and evaluated Skp2 protein expression in cytoplasmic and nuclear fractions by immunohistochemistry using a tissue microarray method. Among the 359 patients, nuclear expression of Skp2 was observed in 41 (10.38%), and cytoplasmic expression of Skp2 was observed in 195 (49.37%). Of the several clinicopathologic variables examined, high Edmonson-Steiner grade and early recurrence correlated with nuclear expression of Skp2 (p = 0.000 and 0.022, respectively). Cytoplasmic expression of Skp2 correlated negatively with microvascular and macrovascular invasion, tumor size, histologic grade, and overall survival. Multivariate analysis revealed that nuclear expression of Skp2 correlated with short disease-free survival. Our findings suggest that nuclear expression of Skp2 may be used as an independent predictor of poor prognosis for hepatocellular carcinoma, whereas cytoplasmic expression of Skp2 may indicate less aggressive disease.
- [Show abstract] [Hide abstract] ABSTRACT: Heat shock protein 70 (HSP70) and glutamine synthetase (GS) have been proposed to be promising markers for the differentiation of malignant and benign hepatocellular lesions. The aim of this study was to investigate the clinicopathological significance of the expression of HSP70 and GS in surgically resected hepatocellular carcinoma (HCC). The authors collected 412 HCC samples and 120 non-neoplastic hepatic tissue samples and performed an immunohistochemical study. HSP70 staining was observed in 282 of 392 HCC samples (71.9%), and GS immunoreactivity was observed in 212 of 395 HCC cases (53.7%). Of the several clinicopathological parameters examined, microscopic vascular invasion, a large tumor size, and a high Edmonson-Steiner grade were found to be correlated with positive staining for HSP70 (P = 0.032, 0.002, and 0.012, respectively). Survival analysis showed a correlation between HSP70 expression and disease-free survival. GS was not found to be related to clinicopathological parameters. The findings of the present study suggest that HSP70 be viewed as a predictor of prognosis as well as a useful diagnostic marker for HCC.
- [Show abstract] [Hide abstract] ABSTRACT: Cluster differentiation 44 standard isoform (CD44s) is a transmembrane glycoprotein. CD44s is a known prognostic factor in various cancers, due to its involvement in tumor cell growth, invasion and metastasis. Its prognostic role, however, is debated because it can be a positive or negative prognostic factor depending on tumor type and is still an ambiguous prognostic indicator in other cancers, especially hepatocellular carcinoma (HCC). We investigated the relationship between CD44s expression and survival in HCC patients. A total of 260 HCC samples were collected to generate a tissue microarray. Staining of the arrays with a primary mouse CD44s monoclonal antibody was followed by evaluation of the relationship between CD44s expression and tumor differentiation. The effect of CD44s expression on patient survival was analyzed. CD44s protein expression correlated with histological grade (most and worst Edmondson grade) of the HCC (p=0.029 and p=0.039, respectively) and adversely affected the disease free survival period based on univariate and multivariate analyses (p=0.038 and p=0.077, respectively). High CD44s protein expression correlates with shorter disease free survival and poorly differentiated HCC. CD44s-targeted therapy may be efficacious for HCC treatment in the future.
- [Show abstract] [Hide abstract] ABSTRACT: We elucidated the genetic profile of hepatoblastomas (HBLs) to identify diagnostic and prognostic markers. RNA was extracted from 32 formalin-fixed, paraffin-embedded HBLs and corresponding nonneoplastic liver (NNL) tissues, and cDNA-mediated annealing, selection, extension, and ligation (DASL) chip assays were performed. Immunohistochemistry was performed to confirm the expression of Yin Yang 1 (YY1) protein in HBL. Twenty-four genes that were associated with signal transduction, cell-cell adhesion, cell cycle regulation, and apoptosis were differentially expressed in HBL and NNL tissues. Two apoptosis-associated genes, MYCN and BIRC5, were highly upregulated in HBL. Eight genes, including YY1 and IGF1, were upregulated in HBL cases that had a poor prognosis. Thirty-eight genes, including YY1, were differentially expressed according to histologic differentiation of HBL, and the immunohistochemical expression of YY1 was correlated with poor HBL differentiation. Thus, using DASL chip assays, we report the gene expression profiles of HBL, which suggest new candidate prognostic and diagnostic genetic markers and putative therapeutic targets for HBL.
- [Show abstract] [Hide abstract] ABSTRACT: Adenosquamous carcinoma arising in congenital choledochal cyst is very rare and herein we report a case thereof. A 37-year-old woman was referred for further evaluation of pancreas head mass and a hepatic nodule on CT. She had been diagnosed with congenital choledochal cyst at 22-years-old and received Roux-en-Y choledochojejunostomy at that time. Endoscopic ultrasonography-guided biopsy proved the pancreas head mass as a squamous cell carcinoma and liver biopsy also proved the liver mass as a metastatic squamous cell carcinoma. We performed pancreaticoduodenectomy and tumorectomy of metastatic liver nodule. Grossly, the primary lesion was located at intrapancreatic portion of choledochal cyst. Histologically, the primary lesion and hepatic nodule was metastatic adenosquamous carcinoma. So far, there have been only three cases of adenosquamous carcinoma arising in congenital choledochal cyst reported in English-language literature. This is another case and the first case reported in Korea.
- [Show abstract] [Hide abstract] ABSTRACT: This study aimed to better understand gene expression profiles of human hepatic stellate cell (HSC) activation and the relationship with the Wnt signaling pathway. The global transcript levels in platelet derived growth factor-BB (PDGF-BB)-stimulated hTERT HSCs were analyzed using oligonucleotide microarrays. Oligonucleotide microarrays with 19K human oligo chips were performed to obtain gene expression profiles associated with proliferation in human hTERT HSCs. The microarray data was verified by real time quantitative PCR and expression of the components of Wnt signaling was analyzed by Western blot. Microarray data showed 243 up-regulated and 265 down-regulated genes in PDGF-BB-treated HSCs. The changes in expression of glypican3 and BH3 interacting domain death agonist (BID) mRNA in real time quantitative PCR, especially among the highly up- or down-regulated genes, were statistically consistent with the microarray data. The Wnt signaling pathway components, frizzled10 (FZD10) and calcium/calmodulindependent protein kinase II alpha (CAMK2A), showed increased expression in the short time course microarray and the up-regulation of FZD10 also occurred at the protein level. Our data showed various gene expression profiles during activation of human HSC. The up-regulated expression of FZD10 and CAMK2A suggests that the Wnt/Ca(2+) signaling pathway is active in hTERT HSCs and may participate in HSC activation and proliferation.
Seoul National University Hospital
Sŏul, Seoul, South Korea
- Department of Pathology
Seoul National UniversitySŏul, Seoul, South Korea