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ABSTRACT: BACKGROUND: The aim of this study was to compare postoperative survival between hepatocellular carcinoma (HCC) patients with and without viral infection. METHODS: From among 398 HCC patients in our collected database, 377 who underwent surgery were enrolled. The patients were divided into 2 groups: group 1, those who had no hepatitis B virus or hepatitis C virus infection, and group 2, those who had hepatitis B virus or hepatitis C virus infection. Univariate analysis was performed to compare clinical factors, including viral infection, with overall survival. Kaplan-Meier analysis and the log-rank test were used to evaluate the overall and disease-free survival curves for the 2 groups. RESULTS: Univariate analysis showed that viral infection showed no such association. Moreover, Kaplan-Meier analysis and the log-rank test revealed no significant intergroup differences in either overall or disease-free survival. CONCLUSIONS: The presence or absence of viral infection shows no significant association with the postoperative survival of patients undergoing surgery for HCC.
American journal of surgery 03/2013; · 2.36 Impact Factor
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ABSTRACT: To establish methods for quantitative polymerase chain reaction (PCR) for hepcidin using RNAs isolated from paraffin-embedded sections and in situ hybridization of hepatocellular carcinoma (HCC).
Total RNA from paraffin-embedded sections was isolated from 68 paraffin-embedded samples of HCC. Samples came from 54 male and 14 female patients with a mean age of 66.8 ± 7.8 years. Quantitative PCR was performed. Immunohistochemistry and in situ hybridization for hepcidin were also performed.
Quantitative PCR for hepcidin using RNAs isolated from paraffin-embedded sections of HCC was performed successfully. The expression level of hepcidin mRNA in cancer tissues was significantly higher than that in non-cancer tissues. A method of in situ hybridization for hepcidin was established successfully, and this demonstrated that hepcidin mRNA was expressed in non-cancerous tissue but absent in cancerous tissue.
We have established novel methods for quantitative PCR for hepcidin using RNAs isolated from paraffin-embedded sections and in situ hybridization of HCC.
World Journal of Gastroenterology 07/2012; 18(28):3727-31. · 2.47 Impact Factor
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ABSTRACT: BACKGROUND: The current study was conducted to evaluate the safety and utility of intraoperative transhepatic biliary stenting (ITBS) in patients with unresectable malignant biliary obstruction (UMBO) diagnosed intraoperatively. METHODS: In this study, 50 patients who underwent ITBS for UMBO between April 2001 and May 2009 were retrospectively reviewed. For 26 patients who underwent preoperative percutaneous transhepatic biliary drainage (PTBD), the expandable metallic stent (EMS) was inserted intraoperatively by the PTBD route in a single stage. For 24 patients, the intrahepatic bile ducts were intentionally dilated by injection of saline via the endoscopic nasobiliary drainage or the percutaneous transhepatic gallbladder drainage route, and the puncture was performed under intraoperative ultrasound guidance followed by guidewire and catheter insertion. Thereafter, the EMS was placed in the same manner. The initial postoperative complications and long-term results of ITBS were evaluated. RESULTS: In all cases, ITBS was technically successful. Stenting alone was performed in 22 patients and stenting combined with other procedures in 28 patients. Hospital mortality occurred for three patients (6 %), and complication-related mortality occurred in two cases (4 %). There were nine cases (18 %) of postoperative complications. The median survival time was 179 days, and the EMS patency time was 137 days. During the follow-up period, EMS occlusion occurred in 23 cases (46 %). Best supportive care was a significant independent risk factor for early mortality within 100 days after ITBS (p = 0.020, odds ratio, 9.398). CONCLUSIONS: Single-stage ITBS is feasible for palliation of UMBO and seems to have a low complication rate.
Surgical Endoscopy 07/2012; · 4.01 Impact Factor
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ABSTRACT: Oral administration of triphenyltin chloride (TPT) (6 mg/100g body weight) inhibits insulin secretion by decreasing glucose-induced cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in pancreatic β-cells of the hamster. To test the possibility that the abnormal level of the [Ca(2+)](i) induced by TPT administration could be due to a defect in the metabolic signal of glucose in the β-cells, we tested the effects of TPT administration on the glucose-induced NAD(P)H and ATP production, and on the changes of membrane potential and [Ca(2+)](i) by glucose and high K(+) in the β-cells. The [Ca(2+)](i) was measured in islet cells loaded with fura-2. TPT administration significantly reduced the NAD(P)H and ATP production, the depolarization of plasma membrane, and insulin secretion by 15 mM glucose in islet cells. TPT administration also reduced the insulin secretion by 10mM dihydroxyacetone and glyceraldehyde. However, TPT administration did not affect the increase of [Ca(2+)](i) and the insulin secretion by 30 mMK(+) or 100 μM tolbutamide, and the membrane potential by 30 mMK(+), and the insulin secretion by 10mM α-ketoisocaproic acid and 0.5mM formycin A, an analog of ATP in the presence of 15 mM glucose. These results suggested that the pathogenesis of TPT-induced hyperglycemia in hamster involves the reduction of [Ca(2+)](i) and insulin secretion in response to K(ATP) channel-dependent depolarization, which is related to the decrease of NAD(P)H and ATP production in pancreatic islet cells after glucose metabolism.
Toxicology 06/2012; 299(2-3):165-71. · 3.68 Impact Factor
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ABSTRACT: The effect of a humanized anti-human leukocyte antigen-DR monoclonal antibody, IMMU-114, on the allogeneic immune response was investigated in vitro.
Responder peripheral blood mononuclear cells were cocultured with inactivated self or allogeneic stimulator peripheral blood mononuclear cells in the presence of control antibody or IMMU-114. Thymidine incorporation rates were then measured. Phenotypic changes in peripheral blood mononuclear cells and the intracellular Th1-type cytokines interleukin-2, interferon-γ, and tumor necrosis factor-α were analyzed using flow cytometry. The concentrations of interleukin-2, interferon-γ, and tumor necrosis factor-α in the mixed lymphocyte reaction culture medium were measured.
Thymidine incorporation rates at a 1:1 responder/stimulator ratio of allogeneic, allogeneic + IMMU-114, self, and self + IMMU-114 were 22,080.7 ± 602.4, 2,254.5 ± 118.1, 1,284.0 ± 227.8, and 494.5 ± 27.5 cpm, respectively (P = .038). IMMU-114 decreased the frequencies of human leukocyte antigen-DR-expressing CD16+56+ NK cells, CD19+ B cells, and CD3+25+ activated T cells.
Intracellular cytokine assay and measurement of Th1-type cytokines in the mixed lymphocyte reaction culture medium revealed that IMMU-114 significantly decreased the titers of interleukin-2, interferon-γ, and tumor necrosis factor-α. IMMU-114 significantly suppresses the allogeneic immune response in vitro, partly through inhibition of the Th1 response.
American journal of surgery 05/2012; 204(4):527-34. · 2.36 Impact Factor
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ABSTRACT: A B S T R A C T R E F E R E N C E S
Abstract
Background: The effects of Edaravone (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration were examined in a pig hepatectomy model.
Methods: One hour of ischemia was induced by occluding the vessels and the bile duct of the right and median lobes. About a 40% left hepatectomy was performed after reperfusion. Six animals received Edr (3 mg/kg/h) intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemodynamics, and levels of AST, ALT, LDH, and LA were compared between the groups. Expression of TGF-β1 and IL-6 mRNA in hepatic tissues was examined using RT-PCR. Apoptosis and cell proliferation were demonstrated by TUNEL and Ki-67 staining, respectively.
Results: Serum AST, LDH, and LA levels were significantly lower at 3 hours and 1 week after perfusion in animals that had received Edr. In the Edr group, hepatic tissues showed a greater tendency for the expression of TGF-β1 mRNA to be inhibited at 1 week, although the difference was not significant. Also at 1 week in the Edr group, TUNEL-positive cells in the hepatic sinusoidal endothelium were significantly fewer, and Ki-67-positive cells were significantly more numerous.
Conclusion: We conclude that Edr reduces hepatic injury and supports tissue regeneration after I/R injury in this pig model.
Archives of Clinical and Experimental Surgery (ACES). 04/2012; 1(3):142-150.
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ABSTRACT: The effect of an anti-human leukocyte antigen-DR (MHC class II) humanized monoclonal antibody, IMMU-114, against the human to bovine cellular response was investigated.
Human peripheral mononuclear cells (PBMCs) were cocultured with inactivated self-PBMCs (Self), bovine PBMCs with control antibody (Xeno), or bovine PBMCs with IMMU-114 (IMMU-114). Cellular responses were investigated by thymidine incorporation assay, CFSE (carboxyfluorescein diacetate succinimidyl ester)-mixed lymphocyte reaction, and cytokine production in culture medium.
Thymidine incorporation rates at a 1:1 responder to stimulator ratio for Xeno + control antibody, Xeno + IMMU-114, Self + control antibody, and Self + IMMU-114 were 14201.3 ± 1968.4, 513.0 ± 49.5, 952.7 ± 128.7, and 423.3 ± 138.8 cpm, respectively (P = 0.032). Those at a 1:2 ratio were 6518.0 ± 690.1, 896.6 ± 92.9, 1051.0 ± 123.6, and 736.0 ± 35.6 cpm, respectively (P = 0.036). CFSE-mixed lymphocyte reaction demonstrated that the frequencies of CFSE-low, CD4(+), and CD25(+) activating T cells in Self, Xeno, and IMMU-114 were 0.27 ± 0.04%, 3.65 ± 0.53%, and 1.23 ± 0.15%, respectively (P = 0.027). Cytokine production in culture medium indicated that IMMU-114 decreased Th1-type cytokines, including interleukin-2, interferon-γ, and tumor necrosis factor-α.
IMMU-114 effectively suppresses human to bovine cellular responses. The mechanism involves direct inhibition of the interaction between class II human leukocyte antigen-DR-positive cells and CD4(+) T cells, and indirect suppression of Th1 cytokine production.
Journal of Surgical Research 04/2012; 178(1):472-7. · 2.25 Impact Factor
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ABSTRACT: Hepcidin, a key regulator of iron homeostasis, is also a marker of acute inflammation. In the present study we investigated the changes in the serum hepcidin level and correlations between hepcidin and other markers of acute inflammation during the perioperative period in patients after abdominal surgery.
Serum hepcidin, hemoglobin (Hb), hematocrit (Ht), white blood cell (WBC) count, frequency of neutrophils, and C-reactive protein (CRP) were measured preoperatively (Pre), and on postoperative days (POD) 1, 3, 7, and 14.
In patients undergoing gastrectomy, the median levels of hepcidin preoperatively and on POD 1, 3, 7, and 14 were 6.5, 53.1, 31.7, 15.6, and 4.0 ng/dl, respectively (p < 0.0001). The corresponding levels in colectomy patients were 8.5, 78.3, 60.1, 49.7, and 8.4 ng/dl, respectively (p = 0.0002); those in hepatectomy patients were 6.6, 16.3, 3.5, 13.4, and 3.4 ng/dl, respectively (p = 0.0022); and those in patients undergoing surgery for diffuse peritonitis were 24.8, 50.1, 43.1, 31.2, and 31.7 ng/dl, respectively (p = 0.4933). There were no significant decreases in Hb and Ht in the patients undergoing gastrectomy, colectomy, or surgery for diffuse peritonitis. The level of hepcidin was significantly correlated with the WBC count, frequency of neutrophils, and CRP level during the perioperative period for all four types of operation.
Like other inflammatory markers, an increase in the level of hepcidin (i.e., a hepcidin storm) occurs in the acute phase after gastrectomy, colectomy, hepatectomy, and surgery for diffuse peritonitis.
World Journal of Surgery 02/2012; 36(4):800-6. · 2.36 Impact Factor
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ABSTRACT: Pancreatic fistula (PF) after pancreaticoduodenectomy (PD) is still a severe complication and a challenging problem. The common risk factors are the soft pancreas and small pancreatic duct of the remnant pancreas. Those two risk factors were recognized during surgery. On the other hand, a preoperatively determined risk factor of PF is unclarified. We conducted a retrospective analysis of 203 patients consecutively treated by PD from April 2000 to October 2010. PF was defined according to the criteria of the International Study Group of Pancreatic Fistula. Clinical and pre- and intraoperative data were compared between PF and non-PF patients. The recommended cutoff value of body mass index (BMI) as 20 kg/m(2) was defined by receiver operating characteristic curve analysis. PF occurred in 53 (26.1%) of 203 patients. In univariate analysis, BMI and soft remnant pancreas were found to be risk factors of PF (P = 0.027, P = 0.005). In multivariate analysis, BMI and soft pancreas were also risk factors of PF (P = 0.040, P = 0.005). Patients with PF had a significantly longer hospital stay than non-PF patients (P = 0.005). High BMI and soft pancreas were significant risk factors for PF.
The American surgeon 02/2012; 78(2):190-4. · 1.28 Impact Factor
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ABSTRACT: Primary hepatic leiomyosarcoma are rare tumors with less than 30 cases reported in the English literature. Non specific presentations and often diagnosis delayed until they reach a large size, is the norm with therapy leading to an often dismal prognosis. A 67-year-old man presented complaining of abdominal pain and a palpable abdominal mass since Jan 2010. Abdominal ultrasonography and abdominal computed tomography revealed a large tumor in the left lobe of the liver. Surgical exploration was undertaken and an extended left hepatectomy with extension onto the dorsal part of segment 8 preserving the MHV with partial resection of segment 6 was undertaken. The weight of the resected specimen was 1300 g of the left lobectomy specimen and 8 g of the segment 6 partial resection specimen. The pathology report confirmed the diagnosis of leiomyosarcoma. On immunohistochemistry, the tumor cells were positive for smooth muscle actin stain. The patient is on regular follow up and is currently 9 mo post resection with no evidence of recurrence. We report the case of a resected primary hepatic leiomyosarcoma and emphasize the need for a global database for these rare tumors to promote a better and broader understanding of this less understood subject.
World journal of gastrointestinal oncology. 10/2011; 3(10):148-52.
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ABSTRACT: To evaluate the influence of body mass index (BMI) on postoperative death in patients undergoing surgery for HCC.
Three hundred forty-two patients were enrolled, and divided into three groups: Group A, BMI <22.5; Group B, BMI ≥22.5 to <25; Group C, BMI ≥25. Univariate and multivariate analyses of postoperative death were performed to compare BMI with clinical factors. Kaplan-Meier analysis and log rank test were used to compare such outcome in Groups A, B, and C.
Kaplan-Meier analysis and log rank test revealed that Group A had a higher rate of postoperative death than Group B or C (P = 0.010). Univariate and multivariate analyses selected being underweight (Group B, C/Group A) (odds ratio, 1.829; 95% C.I., 1.091-3.068; P = 0.022) as one of the factors predictive of postoperative death, together with aspartate aminotransferase level (P = 0.042) and HCC growth pattern (P = 0.032).
BMI is a simple but important predictor of postoperative death in patients undergoing surgery for HCC, and is able to classify such patients into three independent groups.
Journal of Surgical Oncology 08/2011; 104(7):809-13. · 2.10 Impact Factor
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ABSTRACT: Few studies have investigated grading of liver metastasis (GLM) in patients with liver metastases from colorectal cancer (LM-CRC).
To screen for the most useful predictive factors in patients undergoing hepatic resection for LM-CRC, clinico-pathological factors were subjected to uni- and multivariate analyses.
One hundred and twenty-five patients were evaluated retrospectively. Univariate analyses using clinico-laboratory factors demonstrated that nomogram, gender, CRP, albumin, number of hepatic resections, liver metastasis (H) and GLM were related to postoperative death. Multivariate analysis using these seven factors disclosed that albumin (OR, 6.949; 95% CI, 1.994-24.22; p=0.002), CRP (OR, 6.977; 95% CI, 1.937-25.14; p=0.003) and GLM (OR, 2.819; 95% CI, 1.082-7.346; p=0.034) were associated with postoperative death. Kaplan-Meier analysis and log rank test revealed that higher GLM (p<0.001) and CRP (p<0.001) were associated with a higher rate of postoperative death. GLM was able to divide the patients into three independent groups with significantly different total nomogram counts (p<0.001, Kruskal-Wallis test).
GLM is able to classify patients with LM-CRC into three independent groups and offers reliable information for predicting postoperative death in such patients.
Hepato-gastroenterology 07/2011; 59(113):54-8. · 0.66 Impact Factor
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ABSTRACT: Glycated albumin (GA) is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells.
Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA) and GA was measured under three different glucose concentrations, 3 mM (G3), 7 mM (G7), and 15 mM (G15), with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS), and the expression of iNOS-mRNA was investigated by real-time PCR.
Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920), and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046), for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion.
GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.
Nutrition & Metabolism 04/2011; 8:20. · 2.88 Impact Factor
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ABSTRACT: Few studies have investigated the Glasgow Prognostic Score (GPS) in patients with hepatocellular carcinoma (HCC).
This study compared the prognostic value of the GPS and Cancer of the Liver Italian Program (CLIP) score in patients undergoing surgery for HCC.
A total of 398 patients were evaluated retrospectively. Kaplan-Meier analyses revealed that GPS (P < .001) and CLIP score (P < .001) were associated with overall survival. GPS could classify patients with low CLIP score (0 or 1) into 3 independent groups (P < .001). Univariate analyses selected GPS (P = .006) and CLIP score (P = .002) as the predictive factors associated with overall survival. Multivariate analysis using these 2 scoring systems disclosed that both GPS (P = .025) and CLIP score (P = .010) were associated with overall survival.
GPS is not only an important predictor of overall survival after surgical treatment of HCC as well as CLIP score, but also is able to clearly divide patients with low CLIP score into 3 independent groups.
American journal of surgery 03/2011; 203(1):101-6. · 2.36 Impact Factor
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Shohei Fuchinoue,
Yasuo Ishii, Tokihiko Sawada,
Toru Murakami,
Kazuhiro Iwadoh,
Akihito Sannomiya,
Ichiro Koyama,
Keiichi Kubota,
Tamotsu Tojimbara,
Ichiro Nakajima,
Satoshi Teraoka
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ABSTRACT: In 2002, we introduced the anti-CD20 chimeric antibody, rituximab, for ABO-incompatible kidney transplantation (ABO-IKT). Here, we report the 5-year outcome obtained using rituximab as part of the preoperative regimen for ABO-IKT.
Between January 2002 and December 2008, 408 patients underwent living-related kidney transplantation at our department. The patients were divided into three groups: group A (n=280), ABO-compatible kidney transplantation (ABO-CKT); group B (n=63), ABO-IKT without rituximab induction; and group C (n=50), ABO-IKT with rituximab induction. Basic immunosuppression was the same in all three groups except for the use of rituximab, which was administered at 100 mg (n=6), 200 mg (n=26), and 500 to 1000 mg (n=18).
The graft survival rates in groups A, B, and C were 99.2%, 96.8%, and 100% at 1 year, 93.8%, 94.9%, and 100% at 3 years, and 88.4%, 90.3%, and 100% at 5 years after transplantation, respectively. Serum creatinine levels in the three groups were not different at 1, 3, and 5 years after transplantation. The numbers of episodes of acute antibody-mediated rejection in groups A, B, and C were 7 (2.5%), 10 (15.9%), and 2 (4.0%), respectively (P=0.651), and acute cellular rejection was observed in 40 (14.3%), 6 (9.5%), and 2 (4.0%) patients, respectively (P=0.0957). There was no increased risk of cytomegalovirus infection in group C.
In the long term, inclusion of rituximab in the preoperative regimen yielded an even better outcome than that of ABO-CKT and rituximab-untreated ABO-IKT, without any increase in the risk of infection.
Transplantation 02/2011; 91(8):853-7. · 4.00 Impact Factor
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ABSTRACT: To assess and compare the predictive values of the hepatic Glasgow Prognostic Score (hGPS) and Cancer of the Liver Italian Program (CLIP) score in patients undergoing surgery for primary hepatocellular carcinoma (HCC).
The hGPS was calculated as follows: patients with an elevated level of C-reactive protein (CRP) (>0.3 mg/dl) were allocated a hGPS of 1 or 2 depending on the absence or presence of hypoalbuminemia (<3.5 g/dl), and patients without an elevation of the CRP level (≤ 0.3 mg/dl) were allocated a hGPS of 0.
Three hundred patients were evaluated. The hGPS divided patients into three independent groups, and that a hGPS of 2 predicted a higher mortality rate (P < 0.001) than a hGPS of 0 or 1. Univariate analysis demonstrated that hGPS (0, 1/2) (P = 0.010) was one of the factors predictive of postoperative mortality, along with the CLIP score (0, 1/≥ 2) (P = 0.021). Comparative analysis using these two factors showed that the hGPS was predictively superior to the CLIP score (P = 0.033).
The hGPS is able to divide patients undergoing surgery for primary HCC into three independent groups, and is considered to be an important factor predictive of postoperative mortality in such patients.
Journal of Surgical Oncology 01/2011; 103(8):801-6. · 2.10 Impact Factor
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ABSTRACT: The treatment strategy for hepatocellular carcinomas (HCCs)≤2 cm (HCC2-) is still controversial. In this study, we retrospectively analyzed clinicopathological data for HCC2- and HCCs>2 cm (HCC2+) to establish the treatment strategy for HCC2-.
Between April 2000 and December 2008, 206 patients with single HCC, who underwent hepatectomy for the first time, and whose outcomes could be tracked, were included in the study. There were 46 HCC2- and 160 HCC2+ patients. Survival and disease-free survival rates were compared between the two groups, in relation to various clinicopathological data.
The 1-, 3-, and 5-year overall survival rates were 100%, 92.6%, and 72.8% for HCC2- and 93.3%, 72.4%, and 57% for HCC2+, respectively (P=0.0098). The 1, 3, and 5-year disease-free survival rates were 86%, 42.6%, and 31% for HCC2-, and 64.7%, 35.9%, and 12.5% for HCC2+, respectively (P=0.0642). Survival rates were better for HCC2- than for HCC2+ in terms of abnormal serum des-gamma-carboxy prothrombin, Child-Pugh Class A, single infection with HBV or HCV, and operative method used for anatomical resection, irrespective of ICG R15. Disease-free survival rates were better for HCC2- than for HCC2+ in terms of Child-Pugh Class A, and operative method used for anatomical resection.
HCC2- has a better clinical outcome than HCC2+ after hepatic resection. Especially, HCC2- with an abnormal DCP value, Child-Pugh Class A, single infection with HBV or HCV, and anatomical resection, yields better outcomes. Even for HCC2- in patients with good liver function, anatomical resection is recommended.
World Journal of Surgery 11/2010; 35(2):377-85. · 2.36 Impact Factor
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Yuhki Sakuraoka, Tokihiko Sawada,
Toshie Okada,
Takayuki Shiraki,
Yoshikazu Miura,
Katsuya Hiraishi,
Tatsushi Ohsawa,
Masakazu Adachi,
Jun-ichi Takino,
Masayoshi Takeuchi,
Keiichi Kubota
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ABSTRACT: To investigate the proliferative effect of advanced glycation end-products (AGEs) and the role of their cellular receptor (RAGE) on hepatocellular carcinoma (HCC) cells, and the inhibitory effects of MK615, an extract from Japanese apricot, against AGEs were also evaluated.
Two HCC cell lines, HuH7 and HepG2, were used. Expression of RAGE was investigated by polymerase chain reaction, Western blotting, and flow cytometry (FACS). The effect of MK615 on RAGE expression was also evaluated by FACS. The proliferative effects of a control (unglycated bovine serum albumin), glucose-derived AGEs (Glc-AGE), and glyceraldehyde-derived AGEs (Glycer-AGE), and the anti-proliferative effect of MK615 against AGEs, were evaluated using MTT assays.
Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2. FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2. Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2. The growth indices for the control, Glc-AGE, and Glycer-AGE were 1.06 ± 0.08, 0.99 ± 0.04, and 1.38 ± 0.05, respectively, in HuH7 (P = 0.037), and were 1.03 ± 0.04, 1.04 ± 0.03, and 1.07 ± 0.05, respectively, in HepG2 (P > 0.05). When the cells were cultured simultaneously with Glycer-AGE and MK615, MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.
Only Glycer-AGE has a proliferative effect on HuH7, which expresses a higher level of RAGE. MK615 suppresses the proliferative effect of Glycer-AGE on HuH7 by decreasing the expression of RAGE.
World Journal of Gastroenterology 11/2010; 16(42):5334-41. · 2.47 Impact Factor
