Study of the expressions of p53 and bcl-2 genes, the telomerase activity and apoptosis in GIST patients

AIM: To explore the relationship between clinicobiological behavior and the expression levels of telomerase activity, apoptosis, p53 gene and bcl-2 gene in gastrointestinal stromal tumors (GISTs). METHODS: The intensity of telomerase activity, apoptosis, p 53 and bcl -2 expression in GISTs were detected by telomeric repeat amplification protocol, in situ end-labeling technique, and immunohistochemistry, respectively. RESULTS: The positive rates of telomerase activity of malignant GIST, potential malignant GIST and benign GIST were 85% (17/20), 22.8% (2/9) and 0 (0/9), respectively. The apoptosis indices of malignant GIST, potential malignant GIST, and benign GIST were 11.7 ± 5.4, 30.2 ± 5.6 and 45.2 ± 7.2, respectively. The intensity of telomerase activity and apoptosis were related to the biological characteristics of GISTs (85% vs 22.8%, 0, 0; P < 0.01 or 11.7 ± 5.4 vs 30.2 ± 5.6, 45.2 ± 7.2, 72.1 ± 9.3; P < 0.05). The intensity of telomerase activity was negatively correlated with cellular apoptosis (22.9 ± 8.4 vs 9.5 ± 5.7, P < 0.01). The intensity of telomerase activity was positively correlated with p53, bcl-2 expression (40.0% vs 78.9%, 40.0% vs 84.2%; P < 0.05). CONCLUSION: The detection of telomerase activity, apoptosis and its control genes in GIST will be helpful for the discrimination of the malignant and benign GIST and evaluation of the prognosis.     

全硫代反义寡核苷酸对乳腺癌MDA-MB-231细胞的影响

目的 本研究探讨全硫代反义寡核苷酸( PS-ASODN)对乳腺癌MDA-MB-231细胞端粒酶活性及细胞生长、迁移、侵袭的影响.方法 本实验将PS-ASODN经脂质体转染作用于乳腺癌MDA-MB-231细胞,将实验分为空白对照组、对照正义全硫代寡核苷酸(PS-SODN)组和不同剂量的PS-ASODN组;脂质体介导的PS-ASODN和PS-SODN作用于乳腺癌MDA-MB-231细胞后,分别采用四甲基偶氮唑蓝比色法(MTT)、酶联免疫吸附法(EUSA)、流式细胞术、Transwell小室迁移、侵袭实验检测细胞的体外增殖、端粒酶活性、细胞凋亡、细胞迁移、侵袭能力的影响.结果 终浓度为1、3及5 μmol/L的PS-ASODN对MDA-MB-231细胞端粒酶活性及细胞的增殖均有抑制作用,与空白对照组比较差异显著(P＜0.01),并呈一定剂量依赖性;ELISA法检测结果,1、3及5μmol/L的PS-ASODN对MDA-MB-231细胞作用72 h后端粒酶皆为阴性,表明端粒酶PS-ASODN能够抑制端粒酶活性,对照组端粒酶皆为阳性.1、3及5μmol/L的PS-ASODN作用24h可以明显抑制MDA-MB-231细胞的迁移和侵袭能力(P＜0.01).结论 PS-ASODN能有效抑制人乳腺癌MDA-MB -231细胞的生长、促进凋亡、抑制其侵袭和迁移能力,其机制可能是通过PS-ASODN降低端粒酶活性而实现.     

Effects of Linomide on growth and metastasis of implanted human gastric cancer in nude mice

ＥｆｅｃｔｓｏｆＬｉｎｏｍｉｄｅｏｎｇｒｏｗｔｈａｎｄｍｅｔａｓｔａｓｉｓｏｆｉｍｐｌａｎｔｅｄｈｕｍａｎｇａｓｔｒｉｃｃａｎｃｅｒｉｎｎｕｄｅｍｉｃｅＴＡＯＨｏｕＱｕａｎ，ＬＩＮＹａｎＺｈｅｎ，ＹＩＮＨａｏＲａｎ，ＧＵＱｉｎＬｏｎｇ，ＺＨＵ...     

Mechanism of QHF-cisplatin against hepatocellular carcinoma in a mouse model

AIM: To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma(HCC) and their mechanisms of action.METHODS: Sixty BALB/c mice were randomly divided into a model group(n = 48) and a normal control group(n = 12). An HCC xenograft tumor was created by injecting H22 cells directly into the liver parenchyma of the mice. The 48 BALB/c mice in the model group were randomly divided into four groups: QHF, DDP(cisplatin), QHF plus DDP, and model control. The inhibitory effects of these drugs on tumor growth were evaluated by calculating the rate of tumor growth inhibition. The mice were examined by observing their general condition, body weight and survival time. Changes in tumor tissue were observed under anoptical microscope. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and α-fetoprotein(AFP) levels in serum were measured. Hepatocyte growth factor(HGF), c-mesenchymal-epithelial transition(c-Met) factor, phosphorylated(p)-c-Met, p38, p-p38, extracellular signal-regulated kinase(ERK), p-ERK and vascular endothelial growth factor(VEGF) levels were evaluated in tumor and liver tissues using western blotting. RESULTS: Compared with the DDP group, a lower incidence of toxic reactions and a higher survival time were observed in the QHF plus DDP group. Tumor weight was significantly lower in the QHF, DDP and QHF plus DDP groups than in the model control group(0.24 ± 0.07, 0.18 ± 0.03 and 0.14 ± 0.01 g vs 0.38 ± 0.05 g, respectively), and the differences were statistically significant(P 0.01). The rate of tumor growth inhibition in the QHF, DDP and QHF plus DDP groups was 38.7%, 52.6% and 63.5%, respectively. AST, ALT and AFP levels in serum were significantly lower in the QHF, DDP and QHF plus DDP groups compared to the model control group(P 0.05). Similarly, HGF, p-c-Met, p-p38, p-ERK and VEGF levels in tumor tissue were significantly lower in the QHF, DDP and QHF plus DDP groups(P 0.05).CONCLUSION: QHF and DDP have an antiangiogenic effect on H22 HCC in mice. QHF inhibits tumor growth via blocking the HGF/c-Met signaling pathway, inhibiting p38, ERK and VEGF signaling.     

Intervention of mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

AIM: To investigate the effect of Mirtazapine on tumor growth, food intake, body weight, and nutritional status in gemcitabine-induced mild cachexia.METHODS: Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups. Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation. A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d, 13 d, and 16 d after tumor implantation. Tumor size, food intake, body weight, and nutritional status were measured during the experiment. All mice were sacrificed at day 28.RESULTS: (1) After 7 d of gemcitabine administration, body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period, food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant). After 21 d, mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g, P = 0.004). After 25 d, mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g, P = 0.014).CONCLUSION: Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice. Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice. It was believed to provide a potential therapeutic perspective for further studies on cachexia.     

microRNA194过表达抑制荷瘤小鼠肝癌细胞生长的实验研究*

目的 探讨microRNA194过表达对肝癌细胞生长的抑制作用及其具体作用机制。方法 通过细胞转染法构建过表达microRNA194的肝癌细胞Hep3B,并将其接种于Balb/c裸鼠建立荷瘤小鼠。30只Balb/c裸鼠被随机分配为microRNA194过表达组15只和对照组15只,采用荧光定量PCR法检测Hep3B细胞和荷瘤小鼠肝癌组织microRNA194水平,采用荧光定量PCR法和Western blot法分别检测肿瘤组织胰岛素样生长因子1受体（IGF1R）水平及其蛋白表达情况。结果 Hep3B细胞和荷瘤小鼠肝癌组织microRNA194 mRNA水平分别为（2.68±0.33）和（2.33±0.38）,均显著高于对照组【分别为（1.00±0.12）和（1.00±0.16）,P<0.01】;在肝癌细胞接种第11 d、16 d和21 d时,microRNA194过表达组小鼠肝肿瘤体积分别为（0.25±0.08）、（0.31±0.11）和（0.46±0.10）mm³,均显著小于对照组【分别为（0.56±0.13）、（0.73±0.20）和（0.95±0.22）mm³,P<0.01】;在肝癌细胞接种第21 d时,microRNA194过表达组小鼠肝肿瘤质量为（0.85±0.19）g,显著轻于对照组【（1.43±0.27）g,P<0.01】;microRNA194过表达组小鼠肝肿瘤IGF1R mRNA水平和其蛋白表达量分别为（0.78±0.12）和（0.81±0.17）,均显著低于对照组【分别为（1.0±0.16）和（1.0±0.11）,P<0.01】。结论 microRNA194过表达可以抑制肝癌细胞生长,有可能是通过抑制了下游靶基因IGF1R的表达而发挥作用的。     

Synchronous adenocarcinoma and gastrointestinal stromal tumors in the stomach

AIM:To review the clinicopathological characteristics of concurrent gastrointestinal stromal tumors(GISTs) and gastric adenocarcinoma.METHODS:We retrospectively analyzed eight cases of synchronous adenocarcinoma and GIST in the stomach that had been surgically resected with curative intent between March 2003 and December 2008 in Xinhua hospital and Ruijin hospital.The adenocarcinoma was determined to be the primary tumor based on the histological features.The GIST cells were diffusely and strongly positive for CD34 and CD117.RESULTS:The patients were six men and two women aged 47-80 years(average,68.6 years).GIST was preoperatively detected in only one patient.The average sizes of the gastric adenocarcinomas and GISTs were 6.000 ± 2.6186 cm and 1.825 ± 1.4370 cm,respectively.All GISTs were very low-or low-risk lesions that were detected during evaluation,staging,operation or follow-up for gastric adenocarcinoma.CONCLUSION:We hypothesized that the stomach was influenced by the same unknown carcinogen,resulting in a simultaneous proliferation of different cell lines(epithelial and stromal cell).     

Hydrogen-rich water protects against acetaminopheninduced hepatotoxicity in mice

AIM: To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water(HRW) in acetaminophen(APAP)-induced liver injury in mice.METHODS: Male mice were randomly divided into the following four groups: normal saline(NS) control group, mice received equivalent volumes of NS intraperitoneally(ip); HRW control group, mice were given HRW(same volume as the NS group); APAP + NS group, mice received NS ip for 3 d(5 mL /kg body weight, twice a day at 8 am and 5 pm) after APAP injection; APAP + HRW group, mice received HRW for 3 d(same as NS treatment) after APAP challenge.In the first experiment, mice were injected ip with a lethal dose of 750 mg/kg APAP to determine the 5-d survival rates.In the second experiment, mice were injected ip with a sub-lethal dose of 500 mg/kg.Blood and liver samples were collected at 24, 48, and 72 h after APAP injection to determine the degree of liver injury.RESULTS :Treatment with HRW resulted ina significant increase in the 5-d survival rate compared with the APAP + NS treatment group(60% vs 26.67%, P 0.05).HRW could significantly decrease the serum alanine aminotransferase level(24 h: 4442 ± 714.3 U/L vs 6909 ± 304.8 U/L, P 0.01; 48 h: 3782 ± 557.5 U/L vs 5111 ± 404 U/L, P 0.01; and3255 ± 337.4 U/L vs 3814 ± 250.2 U/L, P 0.05, respectively) and aspartate aminotransferase level(24 h: 4683 ± 443.4 U/L vs 5307 ± 408.4 U/L, P 0.05; 48 h: 3392 ± 377.6 U/L vs 4458 ± 423.6 U/L, P 0.01; and 3354 ± 399.4 U/L vs 3778 ± 358 U/L, respectively) compared with the APAP treatment group.The alkaline phosphatase, total bilirubin and lactate dehydrogenase levels had the same result.Seventy-two hours after APAP administration, liver samples were collected for pathological examination and serum was collected to detect the cytokine levels.The liver index(5.16% ± 0.26% vs 5.88% ± 0.073%, P 0.05) and percentage of liver necrosis area(27.73% ± 0.58% vs 36.87% ± 0.49%, P 0.01) were significantly lower in the HRW-treated animals.The malonyldialdehyde(MDA) contents were significantly reduced in the HRW pretreatment group, but they were increased in the APAP-treated group(10.44 ± 1.339 nmol/mg protein vs 16.70 ± 1.646 nmol/mg protein, P 0.05).A decrease in superoxide dismutase(SOD) activity in the APAP treatment group and an increase of SOD in the HRW treatment group were also detected(9.74 ± 0.46 U/mg protein vs 12.1 ± 0.67 U/mg protein, P 0.05).Furthermore, HRW could significantly increase the glutathione(GSH) contents(878.7 ± 76.73 mg/g protein vs 499.2 ± 48.87 mg/g protein) compared with the APAP treatment group.Meanwhile, HRW could reduce the inflammation level(serum TNF-α: 399.3 ± 45.50 pg/L vs 542.8 ± 22.38 pg/L, P 0.05; and serum IL-6: 1056 ± 77.01 pg/L vs 1565 ± 42.11 pg/L, P 0.01, respectively).In addition, HRW could inhibit 4-HNE, nitrotyrosine formation, JNK phosphorylation, connexin 32 and cytochrome P4502 E expression.Simultaneously, HRW could facilitate hepatocyte mitosis to promote liver regeneration.CONCLUSION: HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.     

Coexistence of hyperlipidemia and acute cerebral ischemia/reperfusion induces severe liver damage in a rat model

AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.     

Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?

AIM:To investigate the protective effect of clodronatecontaining liposomes against severe acute pancreatitis(SAP)-triggered acute gastric mucosal injury(AGMI) in rats.METHODS:Clodronate- and phosphate-buffered saline(PBS)-containing liposomes were prepared by reverse-phase evaporation.The SAP rat model was established by injecting sodium taurocholate into the pancreatic subcapsular space.Sprague-Dawley rats were randomly divided into three groups:control(C),SAP plus PBS-containing liposome(P) and SAP plus clodronate-containing liposome(T).Serum tumor necrosis factor(TNF)-α levels were estimated by ELISA.Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin(HE) staining.Apoptotic cells were detected by terminal deoxynucleotidyl transferase d UTP nick end labeling staining.The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining.RESULTS:The liposomes had a mean diameter of 150 ± 30 nm.The TNF-α levels were significantly higher in the P group than that in the C group(2 h,145.13 ± 11.50 vs 23.2 ± 2.03; 6 h,245.06 ± 12.11 vs 30.28 ± 6.07,P < 0.05),and they were significantly lower in the T group than that in the P group(2 h,93.24 ± 23.11 vs 145.13 ± 11.50; 6 h,135.18 ± 13.10 vs 245.06 ± 12.11,P < 0.05).The pathological scores of the pancreas were lower in the T group than in the P group(2 h,1.88 ± 0.83 vs 4.13 ± 0.83; 6 h,2.87 ± 0.64 vs 6.25 ± 0.88,P < 0.01).The pathological scores of the gastric mucosa were also lower in the T group than in the P group(2 h,1.12 ± 0.64 vs 2 ± 0.75; 6 h,1.58 ± 0.53 vs 3 ± 1.31,P < 0.05).In addition,increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group.Clodronate-containing liposomes decreased the CD68 levels in the mucosa of the T group.The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group(2 h,15.7 ± 0.92 vs 11.5 ± 1.64; 6 h,21.12 ± 1.06 vs 12.6 ± 2.44,P < 0.01).CONCLUSION:Gastric macrophages contribute to the pathogenesis of gastric injury in SAP.Clodronatecontaining liposomes have protective effects against AGMI in rats with SAP.     

Intravenous infusion of mesenteric lymph from severe intraperitoneal infection rats causes lung injury in healthy rats

AIM:To investigate whether mesenteric lymph from rats with severe intraperitoneal infection(SII)induces lung injury in healthy rats.METHODS:Twenty adult male specific pathogen-free Wistar rats were divided into two groups.Animals in the SII group received intraperitoneal injection of Escherichia coli(E.coli)at a dose of 0.3 mL/100 g.Control rats underwent the same procedure,but were injected with normal saline rather than E.coli.We ligated and drained the mesenteric lymphatic vessels and collected the mesenteric lymph.Mesenteric lymph collected from SII or control rats was infused intravenously into male healthy rats at a rate of 1 mL/h for 4 h.At the end of the infusion,all rats were sacrificed.Lungs were removed and examined histologically,and wet-to-dry weight(W/D)ratio and myeloperoxidase(MPO)activity were determined.Enzyme-linked immunosorbent assay(ELISA)was performed to determine the levels of the proinflammatory cytokines tumor necrosis factor(TNF)-αand interleukin(IL)-6.We performed Western blot to investigate the activation of Toll-like receptor(TLR)-4,and nuclear factor(NF)-κB p65.RESULTS:Compared with the control infusion group,there were obvious pathological changes in the SII group.The W/D ratio was significantly increased in the SII compared to control infusion group(5.86±0.06vs 5.37±0.06,P<0.01).MPO activity significantly increased in the SII infusion rats with a mean level of0.86±0.02 U/g compared to 0.18±0.05 U/g in the control group(P<0.01).The concentrations of TNF-αand IL-6 were significantly increased in the SII infusion group.The concentration of TNF-αwas significantly increased in the SII infusion rats compared to control infusion rats(2104.46±245.91 vs 1475.13±137.82pg/mL,P<0.01).The concentration of IL-6 was significantly increased in the SII infusion rats with a mean level of 50.56±2.85 pg/mL compared to 43.29±2.02 pg/mL(P<0.01).The expression levels of TLR-4(7496.68±376.43 vs 4589.02±233.16,P<0.01)and NF-κB(8722.19±323.96 vs 6498.91±338.76,P<0.01)were significantly increased in the SII infusion group compared to the control infusion group.The infusion of SII lymph,but not control lymph,caused lung injury.CONCLUSION:The results indicate that SII lymph is sufficient to induce acute lung injury.     

High dose glargine alters the expression profiles of microRNAs in pancreatic cancer cells

AIM: To investigate the effect of high dose glargine on the expression profiles of microRNAs in human pancreatic cancer cells.METHODS: Real-time polymerase chain reaction array (RT-PCR) was applied to investigate miRNAs differentially expressed in Sw1990 cells treated with or without 100 IU/L glargine. Stem-loop RT-PCR was used to confirm the results of the array assay in Sw1990 and Panc-1 cells. The effects of miR-95 on cell growth, apoptosis, invasion and migration abilities were respectively examined by CCK8 assay, apoptosis assay, Matrigel invasion and migration assay in Sw1990 and Panc-1 cells. Nude mice xenograft models with Sw1990 cells were built to investigate pancreatic cancer growth in vivo after transfection by the lentivirus pGLV3-GFP- miR-95.RESULTS: Ten miRNAs were significantly up-regulated and 2 miRNAs down-regulated in glargine treated Sw1990 cells when compared with non-treated cells (2.48-fold changes on average, P < 0.01). miR-95, miR-134 and miR-34c-3p are the top three miRNAs regulated by glargine (3.65-fold, 2.67-fold and 2.60-fold changes respectively, P < 0.01) in Sw1990 cells. Stem-loop RT-PCR confirmed that high dose glargine up-regulated the expression of miR-95 and miR-134 in both Sw1990 and Panc-1 cells. The most obvious change is the apparent increase of miR-95. Forced expression of miR-95 significantly increased cell proliferation (Sw1990: 2.510 ± 0.129 vs 2.305 ± 0.187, P < 0.05; Panc-1: 2.439 ± 0.211 vs 2.264 ± 0.117, P < 0.05), invasion (Sw1990: 67.90 ± 12.33 vs 47.30 ± 5.89, P < 0.01; Panc-1: 37.80 ± 8.93 vs 30.20 ± 5.14, P < 0.01), migration (Sw1990: 101 ± 6.00 vs 51.20 ± 8.34, P < 0.01; Panc-1: 91.80 ± 9.22 vs 81.50 ± 7.47, P < 0.01) and inhibited cell apoptosis (Sw1990: 22.05% ± 1.92% vs 40.32% ± 1.93%, P < 0.05; Panc-1: 20.17% ± 0.85% vs 45.60% ± 1.43%, P < 0.05) when compared with paired negative controls, whereas knockdown of miR-95 obtained the opposite effect. Nude mice xenograft models confirmed that miR-95 promoted the growth of pancreatic cancer in vivo when compared with negative control (tumor volume: 373.82 ± 23.67 mL vs 219.69 ± 17.82 mL, P < 0.05).CONCLUSION: These observations suggested that modulation of miRNA expression may be an important mechanism underlying the biological effects of glargine.     

Role of ascites adenosine deaminase in differentiating between tuberculous peritonitis and peritoneal carcinomatosis

AIM: To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis (TBP) and peritoneal carcinomatosis (PC).METHODS: A retrospective analysis of data was performed on consecutive patients who underwent peritoneoscopic and abdominal computed tomography (CT) evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients (36.0%) and 25 patients (33.3%) were diagnosed with TBP and PC, respectively. Diagnosis was confirmed by peritoneoscopic biopsy.RESULTS: Serum c-reactive protein (7.88 ± 6.62 mg/dL vs 3.12 ± 2.69 mg/dL, P = 0.01), ascites adenosine deaminase (66.76 ± 32.09 IU/L vs 13.89 ± 8.95 IU/L, P < 0.01), ascites lymphocyte proportion (67.77 ± 23.41% vs 48.36 ± 18.78%, P < 0.01), and serum-ascites albumin gradient (0.72 ± 0.49 g/dL vs 1.05 ± 0.50 g/dL, P = 0.03) were significantly different between the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohydrate antigen 19-9 showed significant difference between two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group (77.8% vs 40.7%) whereas nodular involvement was more common in the PC group (14.8% vs 40.7%, P = 0.04). From receiver operating characteristic (ROC) curves ascites adenosines deaminase (ADA) showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differential diagnosis; sensitivity, specificity, positive predictive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively.CONCLUSION: Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differential diagnosis of TBP and PC.     

Effects of tetrandrine on gastric mucosa and liver in portal hypertensive rats

ＥｆｅｃｔｓｏｆｔｅｔｒａｎｄｒｉｎｅｏｎｇａｓｔｒｉｃｍｕｃｏｓａａｎｄｌｉｖｅｒｉｎｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓＭＵＹｉ，ＳＨＥＮＹａｏＺｏｎｇａｎｄＣＨＵＹｉＦａｎｇＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｇａｓｔｒｉｃｍ...     

I_κB kinase-beta inhibitor attenuates hepatic fibrosis in mice

AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice rec...