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Sample records for human gastric juice

  1. Human gastric juice contains chitinase that can degrade chitin.

    PubMed

    Paoletti, Maurizio G; Norberto, Lorenzo; Damini, Roberta; Musumeci, Salvatore

    2007-01-01

    Chitin digestion by humans has generally been questioned or denied. Only recently chitinases have been found in several human tissues and their role has been associated with defense against parasite infections and to some allergic conditions. In this pilot study we tested the gastric juices of 25 Italian subjects on the artificial substrates 4-methylumbelliferyl-beta-D-N,N',diacetylchitobiose or/and fluorescein isothiocyanate (FITC) chitin to demonstrate the presence of a chitinase activity. Since this chitinase activity was demonstrated at acidic pH, it is currently referred to acidic mammalian chitinase (AMCase). AMCase activity was present in gastric juices of twenty of 25 Italian patients in a range of activity from 0.21 to 36.27 nmol/ml/h and from 8,881 to 1,254,782 fluorescence emission (CPS), according to the used methods. In the remaining five of 25 gastric juices, AMCase activity was almost absent in both assay methods. An allosamidine inhibition test and the measurement at different pH values confirmed that this activity was characteristic of AMCase. The absence of activity in 20% of the gastric juices may be a consequence of virtual absence of chitinous food in the Western diet. PMID:17587796

  2. A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices

    SciTech Connect

    Schlosser, Paul M. Sasso, Alan F.

    2014-10-15

    Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. - Highlights: • Hexavalent chromium (Cr-VI) reduction in gastric juices is a key detoxifying step. • pH-dependent Cr-VI reduction rates are explained using known chemical speciation. • Reduction in rodents appears to involve multiple pools of electron donors. • Reduction appears to continue after 60 min, although more slowly than initial rates.

  3. Gastric Emptying After Pickle-Juice Ingestion in Rested, Euhydrated Humans

    PubMed Central

    Miller, Kevin C.; Mack, Gary W.; Knight, Kenneth L.

    2010-01-01

    Abstract Context: Small volumes of pickle juice (PJ) relieve muscle cramps within 85 seconds of ingestion without significantly affecting plasma variables. This effect may be neurologic rather than metabolic. Understanding PJ's gastric emptying would help to strengthen this theory. Objective: To compare gastric emptying and plasma variables after PJ and deionized water (DIW) ingestion. Design: Crossover study. Setting: Laboratory. Patients or Other Participants: Ten men (age  =  25.4 ± 0.7 years, height  =  177.1 ± 1.6 cm, mass  =  78.1 ± 3.6 kg). Intervention(s): Rested, euhydrated, and eunatremic participants ingested 7 mL·kg−1 body mass of PJ or DIW on separate days. Main Outcome Measure(s): Gastric volume was measured at 0, 5, 10, 20, and 30 minutes postingestion (using the phenol red dilution technique). Percentage changes in plasma volume and plasma sodium concentration were measured preingestion (−45 minutes) and at 5, 10, 20, and 30 minutes postingestion. Results: Initial gastric volume was 624.5 ± 27.4 mL for PJ and 659.5 ± 43.8 mL for DIW (P > .05). Both fluids began to empty within the first 5 minutes (volume emptied: PJ  =  219.2 ± 39.1 mL, DIW  =  305.0 ± 40.5 mL, P < .05). Participants who ingested PJ did not empty further after the first 5 minutes (P > .05), whereas in those who ingested DIW, gastric volume decreased to 111.6 ± 39.9 mL by 30 minutes (P < .05). The DIW group emptied faster than the PJ group between 20 and 30 minutes postingestion (P < .05). Within 5 minutes of PJ ingestion, plasma volume decreased 4.8% ± 1.6%, whereas plasma sodium concentration increased 1.6 ± 0.5 mmol·L−1 (P < .05). Similar changes occurred after DIW ingestion. Calculated plasma sodium content was unchanged for both fluids (P > .05). Conclusions: The initial decrease in gastric volume with both fluids is likely attributable to gastric distension. Failure of the PJ group to empty afterward is likely due to PJ

  4. Comparison of Gastric Microbiota Between Gastric Juice and Mucosa by Next Generation Sequencing Method

    PubMed Central

    Sung, Jihee; Kim, Nayoung; Kim, Jaeyeon; Jo, Hyun Jin; Park, Ji Hyun; Nam, Ryoung Hee; Seok, Yeong-Jae; Kim, Yeon-Ran; Lee, Dong Ho; Jung, Hyun Chae

    2016-01-01

    Background: Not much is known about the role of gastric microbiota except for Helicobacter pylori in human health and disease. In this study, we aimed to detect human gastric microbiota in both gastric mucosa and gastric juice by barcoded 454-pyrosequencing of the 16S rRNA gene and to compare the results from mucosa and juice. Methods: Gastric biopsies and stomach juices were collected from 4 subjects who underwent standard endoscopy at Seoul National University Bundang Hospital. Gastric microbiota of antral mucosa, corpus mucosa samples, and gastric fluids were analyzed by barcoded 454-pyrosequencing of the 16S rRNA gene. The analysis focused on bacteria, such as H. pylori and nitrosating or nitrate-reducing bacteria. Results: Gastric fluid samples showed higher diversity compared to that of gastric mucosa samples. The mean of operational taxonomic units was higher in gastric fluid than in gastric mucosa. The samples of gastric fluid and gastric mucosa showed different composition of phyla. The composition of H. pylori and Proteobacteria was higher in mucosa samples compared to gastric fluid samples (H. pylori, 66.5% vs. 3.3%, P = 0.033; Proteobacteria, 75.4% vs. 26.3%, P = 0.041), while Actinobacteria, Bacteroidetes, and Firmicutes were proportioned relatively less in mucosa samples than gastric fluid. However there was no significant difference. (Actinobacteria, 3.5% vs. 20.2%, P = 0.312; Bacteroidetes, 6.0% vs. 14.8%, P = 0.329; Firmicutes, 12.8% vs. 33.4%, P = 0.246). Conclusions: Even though these samples were small, gastric mucosa could be more effective than gastric fluid in the detection of meaningful gastric microbiota by pyrosequencing. PMID:27051651

  5. A revised model of ex-vivo reduction of hexavalent chromium in human and rodent gastric juices.

    PubMed

    Schlosser, Paul M; Sasso, Alan F

    2014-10-15

    Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. PMID:25151221

  6. N-nitroso compounds, genotoxins and their precursors in gastric juice from humans with and without precancerous lesions of the stomach.

    PubMed

    Pignatelli, B; Malaveille, C; Chen, C; Hautefeuille, A; Thuillier, P; Muñoz, N; Moulinier, B; Berger, F; De Montclos, H; Ohshima, H

    1991-01-01

    We are investigating the interrelationships between levels of total N-nitroso compounds (NOC), genotoxic activity (both before and after nitrosation), degree of bacterial colonization in gastric juice and degree of severity or absence of precancerous lesions of the stomach. The mean level of constitutive total NOC in gastric juice was similar in the different groups of patients, but it was higher in acidic gastric juice (n = 30) than in gastric juice at pH greater than 4.5 (n = 12). Acid-catalysed nitrosation of gastric juice in vitro increased the concentration of total NOC by up to several thousand fold, to a maximum of 1330 mumol/l. Genotoxicity, expressed as SOS-inducing potency per 100 microliters of gastric juice was measurable in only 20% of gastric juice samples tested. After acid-catalysed nitrosation, however, all samples showed genotoxic activity, the mean SOS-inducing potency being four to seven times greater than the corresponding constitutive value. There was no association between the mean SOS-inducing potency of gastric juice and the severity of precancerous lesions. The mean SOS-inducing potency of neutral or basic gastric juice was slightly greater than that of acidic samples. In a kinetic study on N-nitrosation of gastric juice in vitro, a mixture of amino and amido substrates was nitrosated; both qualitative and quantitative individual differences in nitrosatable substrates in gastric juice were seen. Fractionation of acidic, neutral and basic nitrosated gastric juice samples revealed a preponderance of nonvolatile, unknown NOC with varying polarities. The results of our study suggest that only pH determines the nature and level of precursors of NOC and of nitrosation-dependent genotoxins in gastric juice. PMID:1855844

  7. Effect of human and simulated gastric juices on the digestion of whey proteins and carboxymethylcellulose-stabilised O/W emulsions.

    PubMed

    Malinauskytė, Ernesta; Ramanauskaitė, Jovita; Leskauskaitė, Daiva; Devold, Tove G; Schüller, Reidar B; Vegarud, Gerd E

    2014-12-15

    In this study, we analysed the impact of carboxymethylcellulose (CMC) on lipid digestion and physicochemical properties of whey proteins (WP)-stabilised emulsions during in vitro digestion with either artificial or human gastrointestinal juices. The emulsions were made by adsorbing WP on the fat droplets and subsequently adding CMC, which does not interact with the adsorbed proteins. The limited hydrolysis of lipids and their higher physical stability was recorded for WP-stabilised emulsions in the presence of CMC under simulated gastrointestinal conditions. The possible mechanism by which CMC lowers the digestion of WP-stabilised emulsions is related to the limited interaction of fat droplets with gastrointestinal fluids due to the extended thickening network formed by CMC in the continuous phase. The digestion of WP- and CMC-stabilised emulsions in the in vitro model with human gastric fluids led to greater lipid hydrolysis, although the enzymatic activity in both in vitro models was observed at the same level. PMID:25038655

  8. In vitro studies of the digestion of caprine whey proteins by human gastric and duodenal juice and the effects on selected microorganisms.

    PubMed

    Almaas, Hilde; Holm, Halvor; Langsrud, Thor; Flengsrud, Ragnar; Vegarud, Gerd E

    2006-09-01

    The in vitro digestion of caprine whey proteins was investigated by a two-step degradation assay, using human gastric juice (HGJ) at pH 2.5 and human duodenal juice (HDJ) at pH 7.5. Different protein and peptide profiles were observed after the first (HGJ) and second (HDJ) enzymatic degradation. The minor whey proteins serum albumin, lactoferrin and Ig were rapidly degraded by HGJ, while alpha-lactalbumin (alpha-LA) and beta-lactoglobulin (beta-LG) were more resistant and survived both 30 and 45 min of the enzymatic treatment. Further digestion with HDJ still showed intact beta-LG, and the main part of alpha-LA also remained unchanged. The protein degradation by HGJ and HDJ was also compared with treatment by commercial enzymes, by using pepsin at pH 2.5, and a mixture of trypsin and chymotrypsin at pH 7.5. The two methods resulted in different caprine protein and peptide profiles. The digests after treatment with HGJ and HDJ were screened for antibacterial effects on some selected microorganisms, Escherichia coli, Bacillus cereus, Lactobacillus rhamnosus GG and Streptococcus mutans. Active growing cells of E. coli were inhibited by the digestion products from caprine whey obtained after treatment with HGJ and HDJ. Cells of B. cereus were inhibited only by whey proteins obtained after reaction with HGJ, while the products after further degradation with HDJ demonstrated no significant effect. Screenings performed on cells of Lb. rhamnosus GG and S. mutans all showed no signs of inhibition. PMID:16925863

  9. An infrared spectroscopy method to detect ammonia in gastric juice.

    PubMed

    Giovannozzi, Andrea M; Pennecchi, Francesca; Muller, Paul; Balma Tivola, Paolo; Roncari, Silvia; Rossi, Andrea M

    2015-11-01

    Ammonia in gastric juice is considered a potential biomarker for Helicobacter pylori infection and as a factor contributing to gastric mucosal injury. High ammonia concentrations are also found in patients with chronic renal failure, peptic ulcer disease, and chronic gastritis. Rapid and specific methods for ammonia detection are urgently required by the medical community. Here we present a method to detect ammonia directly in gastric juice based on Fourier transform infrared spectroscopy. The ammonia dissolved in biological liquid samples as ammonium ion was released in air as a gas by the shifting of the pH equilibrium of the ammonium/ammonia reaction and was detected in line by a Fourier transform infrared spectroscopy system equipped with a gas cell for the quantification. The method developed provided high sensitivity and selectivity in ammonia detection both in pure standard solutions and in a simulated gastric juice matrix over the range of diagnostic concentrations tested. Preliminary analyses were also performed on real gastric juice samples from patients with gastric mucosal injury and with symptoms of H. pylori infection, and the results were in agreement with the clinicopathology information. The whole analysis, performed in less than 10 min, can be directly applied on the sample without extraction procedures and it ensures high specificity of detection because of the ammonia fingerprint absorption bands in the infrared spectrum. This method could be easily used with endoscopy instrumentation to provide information in real time and would enable the endoscopist to improve and integrate gastroscopic examinations. PMID:26377936

  10. Downregulated MicroRNA-133a in Gastric Juice as a Clinicopathological Biomarker for Gastric Cancer Screening.

    PubMed

    Shao, Juan; Fang, Peng-Hua; He, Biao; Guo, Li-Li; Shi, Ming-Yi; Zhu, Yan; Bo, Ping; Zhen-Wen, Zhen-Wen

    2016-01-01

    Circulatory miR-133a is a marker shared by several types of cancer. In this study we evaluated the feasibility of using miR-133a levels in gastric juice to screen for gastric cancer. A total of 204 samples of gastric juice and mucosa from gastric cancer, atrophic gastritis, gastric ulcer, superficial gastritis and healthy cases were collected by gastroscopy. The results showed that miR-133a levels in gastric juice and carcinoma tissues of patients with gastric cancer were significantly downregulated and positively correlated. Moreover, miR-133a in gastric juice has high operability, high reliability, high sensitivity, high specificity and relative stability, fit for clinical diagnosis of gastric cancer. PMID:27268657

  11. Characterization and morphology analysis of degradable poly(L-lactide) film in in-vitro gastric juice incubation

    NASA Astrophysics Data System (ADS)

    Chang, Hao-Ming; Huang, Chun-Chiang; Tsai, Hsieh-Chih; Imae, Toyoko; Hong, Po-Da

    2012-12-01

    The purpose of this study was to evaluate the use of the biodegradable poly(L-lactide) (PLLA) as a gastro-jejunal tube anchored in the duodenum for duodenal exclusion. PLLA film was fabricated using a hot melting process to a thickness of around 40-50 μm and was then immersed in human gastric juice to estimate the in vitro biodegradability behavior. PLLA film was more biodegradable in human gastric juice than in HCl and PBS. Measurements of weight loss indicated that 60% of original the PLLA was lost after 42 days of incubation. Surface functional group characterization, thermal stability, and surface morphology of the degraded PLLA film in human gastric juice showed that the decomposed sections of the PLLA film were primarily from the amorphous region. The degradation of the PLLA film in human gastric juice began with the erosion of continuous nanocavities in the range of 100-200 nm on the PLLA surface over the course of 21 days. The PLLA film collapsed and spiral PLLA fiber was obtained after 42 days of decomposing in human gastric juice.

  12. Microbiological profiles of sputum and gastric juice aspirates in Cystic Fibrosis patients.

    PubMed

    Al-Momani, H; Perry, A; Stewart, C J; Jones, R; Krishnan, A; Robertson, A G; Bourke, S; Doe, S; Cummings, S P; Anderson, A; Forrest, T; Griffin, S M; Brodlie, M; Pearson, J; Ward, C

    2016-01-01

    Gastro-Oesophageal Reflux (GOR) is a key problem in Cystic Fibrosis (CF), but the relationship between lung and gastric microbiomes is not well understood. We hypothesised that CF gastric and lung microbiomes are related. Gastric and sputum cultures were obtained from fifteen CF patients receiving percutaneous endoscopic gastrostomy feeding. Non-CF gastric juice data was obtained through endoscopy from 14 patients without lung disease. Bacterial and fungal isolates were identified by culture. Molecular bacterial profiling used next generation sequencing (NGS) of the 16S rRNA gene. Cultures grew bacteria and/or fungi in all CF gastric juice and sputa and in 9/14 non-CF gastric juices. Pseudomonas aeruginosa(Pa) was present in CF sputum in 11 patients, 4 had identical Pa strains in the stomach. NGS data from non-CF gastric juice samples were significantly more diverse compared to CF samples. NGS showed CF gastric juice had markedly lower abundance of normal gut bacteria; Bacteroides and Faecalibacterium, but increased Pseudomonas compared with non-CF. Multivariate partial least squares discriminant analysis demonstrated similar bacterial profiles of CF sputum and gastric juice samples, which were distinct from non-CF gastric juice. We provide novel evidence suggesting the existence of an aerodigestive microbiome in CF, which may have clinical relevance. PMID:27245316

  13. Microbiological profiles of sputum and gastric juice aspirates in Cystic Fibrosis patients

    PubMed Central

    Al-momani, H.; Perry, A.; Stewart, C. J.; Jones, R.; Krishnan, A.; Robertson, A. G.; Bourke, S.; Doe, S.; Cummings, S. P.; Anderson, A.; Forrest, T.; Griffin, S. M.; Brodlie, M.; Pearson, J.; Ward, C.

    2016-01-01

    Gastro-Oesophageal Reflux (GOR) is a key problem in Cystic Fibrosis (CF), but the relationship between lung and gastric microbiomes is not well understood. We hypothesised that CF gastric and lung microbiomes are related. Gastric and sputum cultures were obtained from fifteen CF patients receiving percutaneous endoscopic gastrostomy feeding. Non-CF gastric juice data was obtained through endoscopy from 14 patients without lung disease. Bacterial and fungal isolates were identified by culture. Molecular bacterial profiling used next generation sequencing (NGS) of the 16S rRNA gene. Cultures grew bacteria and/or fungi in all CF gastric juice and sputa and in 9/14 non-CF gastric juices. Pseudomonas aeruginosa(Pa) was present in CF sputum in 11 patients, 4 had identical Pa strains in the stomach. NGS data from non-CF gastric juice samples were significantly more diverse compared to CF samples. NGS showed CF gastric juice had markedly lower abundance of normal gut bacteria; Bacteroides and Faecalibacterium, but increased Pseudomonas compared with non-CF. Multivariate partial least squares discriminant analysis demonstrated similar bacterial profiles of CF sputum and gastric juice samples, which were distinct from non-CF gastric juice. We provide novel evidence suggesting the existence of an aerodigestive microbiome in CF, which may have clinical relevance. PMID:27245316

  14. LC determination of dinitrosopiperazine in simulated gastric juice.

    PubMed

    Walash, M I; Belal, F; Ibrahim, F; Hefnawy, M; Eid, M

    2001-12-01

    A simple and specific reversed phase HPLC method for the determination of dinitrosopiperazine in simulated gastric juice using UV detection was reported. The chromatographic resolution of the analyte and the internal standard isosorbide dinitrate was performed without extraction from the gastric juice on a reversed phase ODS column. Isocratic elution was carried out with methanol-0.02 M sodium dihydrogen phosphate (60:40 v/v, pH 3.0) at a flow rate of 1.0 ml min(-1) with UV detection at 238 nm. The calibration graph was linear over the concentration range 0.072-2.88 microg ml(-1) of dinitrosopiperazine with minimum detectability (S/N=2) of 0.01 microg ml(-1) (8 x 10(-8) M). Inter-day and intra-day precisions calculated as % RSD were in the range 0.32-0.38% and 0.19-0.25% respectively. Inter-day and intra-day accuracies calculated as % error were in the range 0.18-0.21 and 0.08-0.11% respectively. The proposed method was successfully applied to the study of the possible in-vivo production of DNPZ under the standard nitrosation conditions recommended by WHO. PMID:11600313

  15. Antigens with glycoprotein structure in the gastric juice. I. Immunological and chemical determinations.

    PubMed

    Vântu, A; Voiculet, N; Ivănescu, M; Balaban, C

    1978-01-01

    To demonstrate the presence of specific antigens in the normal and malignant gastric juice the immunological and chemical features of certain antigens with glycoprotein structure from malignant gastric jucice and gastric tumors were studied comparatively with those of antigens obtained from normal gastric juice and gastric tissue. The investigation was carried out in tumor tissue extracts from 7 patients with malignant gastric tumors and in gastric juice from 45 patients with other non-cancerous diseases. From the five fractions obtained, which gave immunoelectrophoretic precipitin lines in the beta and alpha-globulin regions with the antiserum against total normal gastric juice, a single specific was separated by means of successive chromatographies on sephadex G--100 and DEAE-Sephadex -a--50 (eluted in NaCl concentration gradient). This fraction represented 11.1 per cent of the total proteins. None of the five fractions could be identified with carcinoembryonic antigen (value in gastric juice and gastric malignant tumors = 2 to 10 ng per mg lyophilized products). PMID:635406

  16. The changes of metabolism balance of zinc and copper in gastric juice with widely varying dietary zinc intake.

    PubMed

    Leung, P L; Li, X L

    1993-10-01

    The concentrations of zinc and copper in gastric juice of humans who had widely varying dietary zinc intake were evaluated. In order to compare this with zinc and copper levels of normal dietary individuals, we also determined the zinc and copper levels in healthy individuals' plasma and in cancer patient's natural tissue, all of whom had normal diets. The correlation coefficients between zinc and copper were 0.71, 0.45, and 0.55, respectively, in gastric juice, plasma, and tissue of normal dietary subjects. Such correlation changed and was destroyed when there was a high zinc level in gastric juice. When gastric juice zinc level changed from mean value 16.8 mumol/L to 262.5 mumol/L, the correlation coefficient varied from 0.71 to -0.04, and the copper level also varied from mean value 8.96 mumol/L to 4.89 mumol/L. These findings probably give the evidence to suggest that a high zinc level will restrain the copper level and break the balance of the human body's zinc and copper metabolism. PMID:7505097

  17. Dissociation of Intrinsic Factor from its Antibody: Application to Study of Pernicious Anaemia Gastric Juice Specimens

    PubMed Central

    Rose, Michael S.; Chanarin, I.

    1969-01-01

    Intrinsic factor antibody may sometimes be concealed in the gastric secretions of pernicious anaemia subjects, being complexed with residual amounts of intrinsic factor. A method is described for dissociating intrinsic factor from its antibody. Antibody to the vitamin-B12-binding site of intrinsic factor was identified in 16 (57%) out of 28 samples of pernicious anaemia gastric juice after dissociation but in only 10 before dissociation. There was no clear relationship between the incidence of antibody in the serum and in the gastric juice of these patients. PMID:5764247

  18. Longer resistance of some DNA traits from BT176 maize to gastric juice from gastrointestinal affected patients.

    PubMed

    Ferrini, A M; Mannoni, V; Pontieri, E; Pourshaban, M

    2007-01-01

    The presence of antibiotic resistance marker genes in genetically engineered plants is one of the most controversial issues related to Genetically Modified Organism (GMO)-containing food, raising concern about the possibility that these markers could increase the pool of antibiotic resistance genes. This study investigates the in vitro survival of genes bla and cryIA(b) of maize Bt176 in human gastric juice samples. Five samples of gastric juice were collected from patients affected by gastro-esophageal reflux or celiac disease and three additional samples were obtained by pH modification with NaHCO3. DNA was extracted from maize Bt176 and incubated with samples of gastric juices at different times. The survival of the target traits (bla gene, whole 1914 bp gene cry1A(b), and its 211 bp fragment) was determined using PCR. The stability of the target genes was an inverse function of their lengths in all the samples. Survival in samples from untreated subjects was below the normal physiological time of gastric digestion. On the contrary, survival time in samples from patients under anti-acid drug treatment or in samples whose pH was modified, resulted strongly increased. Our data indicate the possibility that in particular cases the survival time could be so delayed that, as a consequence, some traits of DNA could reach the intestine. In general, this aspect must be considered for vulnerable consumers (people suffering from gastrointestinal diseases related to altered digestive functionality, physiological problems or drug side-effects) in the risk analysis usually referred to healthy subjects. PMID:17346434

  19. A Rapid and Accurate Method to Evaluate Helicobacter pylori Infection, Clarithromycin Resistance, and CYP2C19 Genotypes Simultaneously From Gastric Juice.

    PubMed

    Kuo, Chao-Hung; Liu, Chung-Jung; Yang, Ching-Chia; Kuo, Fu-Chen; Hu, Huang-Ming; Shih, Hsiang-Yao; Wu, Meng-Chieh; Chen, Yen-Hsu; Wang, Hui-Min David; Ren, Jian-Lin; Wu, Deng-Chyang; Chang, Lin-Li

    2016-05-01

    Because Helicobacter pylori (H pylori) would cause carcinogenesis of the stomach, we need sufficient information for deciding on an appropriate strategy of eradication. Many factors affect the efficacy of eradication including antimicrobial resistance (especially clarithromycin resistance) and CYP2C19 polymorphism. This study was to survey the efficiency of gastric juice for detecting H pylori infection, clarithromycin resistance, and CYP2C19 polymorphism.The specimens of gastric juice were collected from all patients while receiving gastroscopy. DNA was extracted from gastric juice and then urease A and cag A were amplified by polymerase chain reaction (PCR) for detecting the existence of H pylori. By PCR-restriction fragment length polymorphism (PCR-RFLP), the 23S rRNA of H pylori and CYP2C19 genotypes of host were examined respectively. During endoscopy examination, biopsy-based specimens were also collected for rapid urease test, culture, and histology. The blood samples were also collected for analysis of CYP2C19 genotypes. We compared the results of gastric juice tests with the results of traditional clinical tests.When compared with the results from traditional clinical tests, our results from gastric juice showed that the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy to detect H pylori infection were 92.1% (105/114), 92.9% (143/154), 90.5% (105/116), 94.1% (143/152), and 92.5% (248/268), respectively. The SEN, SPE, PPV, and NPV to detect clarithromycin resistance were 97.3% (36/37), 91.5% (43/47), 90.0% (36/40), and 97.7% (43/44), respectively. By using PCR-RFLP, the consistency of human CYP2C19 gene polymorphism from blood samples and gastric juice was as high as 94.9% (149/157).The manipulated gastric juice is actually an effective diagnostic sample for evaluation of H pylori existence, clarithromycin resistance, and host CYP2C19 polymorphism. PMID:27227911

  20. A Rapid and Accurate Method to Evaluate Helicobacter pylori Infection, Clarithromycin Resistance, and CYP2C19 Genotypes Simultaneously From Gastric Juice

    PubMed Central

    Kuo, Chao-Hung; Liu, Chung-Jung; Yang, Ching-Chia; Kuo, Fu-Chen; Hu, Huang-Ming; Shih, Hsiang-Yao; Wu, Meng-Chieh; Chen, Yen-Hsu; Wang, Hui-Min David; Ren, Jian-Lin; Wu, Deng-Chyang; Chang, Lin-Li

    2016-01-01

    Abstract Because Helicobacter pylori (H pylori) would cause carcinogenesis of the stomach, we need sufficient information for deciding on an appropriate strategy of eradication. Many factors affect the efficacy of eradication including antimicrobial resistance (especially clarithromycin resistance) and CYP2C19 polymorphism. This study was to survey the efficiency of gastric juice for detecting H pylori infection, clarithromycin resistance, and CYP2C19 polymorphism. The specimens of gastric juice were collected from all patients while receiving gastroscopy. DNA was extracted from gastric juice and then urease A and cag A were amplified by polymerase chain reaction (PCR) for detecting the existence of H pylori. By PCR-restriction fragment length polymorphism (PCR-RFLP), the 23S rRNA of H pylori and CYP2C19 genotypes of host were examined respectively. During endoscopy examination, biopsy-based specimens were also collected for rapid urease test, culture, and histology. The blood samples were also collected for analysis of CYP2C19 genotypes. We compared the results of gastric juice tests with the results of traditional clinical tests. When compared with the results from traditional clinical tests, our results from gastric juice showed that the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and accuracy to detect H pylori infection were 92.1% (105/114), 92.9% (143/154), 90.5% (105/116), 94.1% (143/152), and 92.5% (248/268), respectively. The SEN, SPE, PPV, and NPV to detect clarithromycin resistance were 97.3% (36/37), 91.5% (43/47), 90.0% (36/40), and 97.7% (43/44), respectively. By using PCR-RFLP, the consistency of human CYP2C19 gene polymorphism from blood samples and gastric juice was as high as 94.9% (149/157). The manipulated gastric juice is actually an effective diagnostic sample for evaluation of H pylori existence, clarithromycin resistance, and host CYP2C19 polymorphism. PMID:27227911

  1. DBGC: A Database of Human Gastric Cancer.

    PubMed

    Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

    2015-01-01

    The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do. PMID:26566288

  2. A chemometric optimization of method for determination of nitrosamines in gastric juices by GC-MS.

    PubMed

    Akyüz, Mehmet; Ata, Şevket; Dinç, Erdal

    2016-01-01

    A chemometrically optimized isolation procedure combined with gas chromatography-mass spectrometry detection technique has been proposed for quantitative determination of trace levels of nitrosamines in gastric juice samples of patients with the gastrointestinal tract problems. The extraction conditions of each nitrosamine were optimized using regression modelling based on central composite design. The extraction conditions for all nitrosamines were selected to be 10.7 min for extraction time, 4.2 for pH and 23 for 2-propanol percentage in extraction solution. The obtained recoveries of nitrosamines ranged from 94.0 (NDMA) to 99.3 (NDPheA) %, and the precision of this method, as indicated by the relative standard deviations was within the range of 0.7 (NDPheA) and 2.6 (NDMA) %. The detection limits obtained from calculations by using GC-MS results based on S/N=3 were found within the range from 0.3 to 1.1 pg/mL. Total nitrosamine concentrations were found at the highest concentration up to 2431.12 pg/mL in cancer patients, whereas they were found at the lowest concentration down to 12.18 pg/mL in gastritis patients. The classification results of the gastric juice samples in different patient groups were very satisfactory, allowing 100% of patients to be correctly grouped. A new mathematical model has been developed allowing for the classification of gastric juices with a 93.1% success rate based on just the ratio of MNPIZ to DNPIZ. The ratio of MNPIZ to DNPIZ might be considered as a biomarker for the classification of gastric juices of patients and might act as an indicator of increased risk for stomach cancer. PMID:26342445

  3. Effects of simulated gastric juice on color stability, surface roughness and microhardness of laboratory-processed composites.

    PubMed

    Cengiz, Seda; Sarac, Sinasi; Özcan, Mutlu

    2014-01-01

    Medical problems such as gastroesophageal reflux disease can cause considerable damage to restorations in the oral environment. This study evaluated the effects of gastric juice on the surface characteristics of different types of laboratory-processed indirect composites with different filler particles and polymerization modes. Specimens were prepared from Tescera (TES; Bisco), Sinfony (SIN; 3M ESPE), Solidex (SOL; Shofu), and Adoro (AD; Ivoclar Vivadent). Before exposing the specimens to simulated gastric juice for 24 h, color, surface roughness, and microhardness were measured on one half of the polished flat surface of each specimen. After exposure to the simulated gastric juice, the same tests were repeated on the other half of specimen surface. Results indicated that gastric juice had a significant impact on color change (p<0.001). AD showed the largest surface roughness change among the resins (p<0.001). Gastric juice also significantly affected the microhardness of the materials, and AD and TES showed statistically similar change in microhardness (p>0.05). PMID:24882109

  4. Mechanism for high PCO2 in gastric juice: roles of bicarbonate secretion and CO2 diffusion.

    PubMed

    Stevens, M H; Thirlby, R C; Feldman, M

    1987-10-01

    The partial pressure of CO2 (PCO2) in gastric juice often exceeds the PCO2 of blood. CO2 in gastric juice may originate from blood and enter luminal fluid by diffusion, or CO2 may be produced in the lumen of the stomach from the reaction of HCO3- and H+. Because CO2 production from HCO3- is dependent on acid (low pH), we suppressed acid secretion with intravenous cimetidine to estimate to what extent appearance of CO2 in luminal fluid is due to production from HCO3-. When denervated fundic pouches of dogs were distended with saline, the PCO2 of the solution increased to the PCO2 of blood in approximately 20 min, with the initial rate of appearance of CO2 in the pouch solution only minimally affected by cimetidine. Thereafter, PCO2 of luminal fluid continued to increase to 50-60 mmHg in the absence of cimetidine, whereas PCO2 of luminal fluid remained approximately equal to that of blood when cimetidine was infused (P less than 0.001, cimetidine vs. control). The mean pH in the pouch solution remained between 6.3 and 6.9 during cimetidine infusion but decreased to 4.75 without cimetidine (P less than 0.001). In additional experiments, an acidic solution with high PCO2 (242 +/- 3 mmHg) was infused into the fundic pouches. PCO2 in luminal fluid decreased rather slowly toward plasma PCO2, requiring 240 min for luminal fluid PCO2 to decrease to 56 +/- 2 mmHg. Thus the permeability of the gastric mucosa to luminal CO2 was relatively low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3116857

  5. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.

    PubMed

    Ding, Lin; El Zaatari, Mohamad; Merchant, Juanita L

    2016-01-01

    This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, "humanized" versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model. PMID:27573785

  6. The use of election paramagnetic resonance spectroscopy in early preformulation experiments: the impact of different experimental formulations on the release of a lipophilic spin probe into gastric juice.

    PubMed

    Bittner, B; Isel, H; Mountfield, R J

    2001-03-01

    The lipophilic spin probe TEMPOL-benzoate was dissolved in different experimental formulations, including polyethylene glycol 400 (PEG 400), Miglyol, glycerol monooleate (GMO), and Cremophor RH-40. Samples were measured by electron paramagnetic resonance (EPR) spectroscopy before and after addition to human gastric juice. The distance between the first and the third peak in the EPR spectrum (2a(N)) was measured to monitor the polarity of the spin probe's microenvironment. Moreover, the ratio between the signal amplitudes of the second and the third peak (a/b ratio) was used to monitor the mobility of the spin probe in a certain formulation. Thus, by calculating 2a(N) and the a/b ratio of the EPR spectra it was possible to determine a potential release of the spin probe from different formulations into gastric juice. It was found that oily and surface-active vehicles (Miglyol, Cremophor RH-40, and GMO) were more suitable to protect a lipophilic compound from being released within a gastric environment than PEG 400. Our results demonstrate that EPR spectroscopy seems to be a promising tool in early preformulation experiments to monitor the release of spin probes from formulations of different nature. This kind of experiment can be of value for the optimization of exploratory formulations. PMID:11226824

  7. Exposure to gastric juice may not cause adenocarcinogenesis of the esophagus

    PubMed Central

    Cheng, Peng; Li, Jian-Sheng; Zhang, Lian-Feng; Chen, Yong-Zhong; Gong, Jun

    2013-01-01

    AIM: To determine the effects of gastric juice on the development of esophageal adenocarcinoma (EAC). METHODS: A animal model of duodenogastroesophageal reflux was established in Sprague-Dawley rats undergoing esophagoduodenostomy. The development of EAC and forestomach adenocarcinoma was investigated 40 wk after the treatment. Intraluminal pH and bile of the forestomach were measured. RESULTS: There were no significant differences in pH (t = 0.117, P = 0.925) or bile (χ2 = 0.036, P = 0.85) in the forestomach before and 40 wk after esophagoduodenostomy. There were also no significant differences between the model and controls during esophagoduodenostomy or 40 wk after esophagoduodenostomy. The incidence of intestinal metaplasia (88%) and intestinal metaplasia with dysplasia and adenocarcinoma (28%) in the esophagus in the model was higher than in the controls 40 wk after surgery (χ2 = 43.06, P < 0.001 and χ2 = 9.33, P = 0.002, respectively) and in the forestomach in the model (χ2 = 32.05, P < 0.001 and χ2 = 8.14, P = 0.004, respectively). The incidence rates of inflammation in the esophagus and forestomach were 100% and 96%, respectively (χ2 = 1.02, P = 0.31) in the model, which was higher than in the esophageal control (6.8%) (χ2 = 42.70, P < 0.001). CONCLUSION: Gastric juice exposure may not cause intestinal metaplasia with dysplasia or adenocarcinoma of the forestomach and may not be related to EAC. PMID:23613638

  8. Effect of Aronia melanocarpa fruit juice on indomethacin-induced gastric mucosal damage and oxidative stress in rats.

    PubMed

    Valcheva-Kuzmanova, S; Marazova, K; Krasnaliev, I; Galunska, B; Borisova, P; Belcheva, A

    2005-04-01

    Aronia melanocarpa fruits are rich in phenolic substances-mainly flavonoids from the anthocyanin subclass. The anthocyanins are water-soluble plant pigments with antioxidant, anti-inflammatory, antimicrobial, hepatoprotective, gastroprotective and other activities. We studied the effect of A. melanocarpa fruit juice (AMFJ) on indomethacin-induced gastric mucosal damage in rats and its possible relation to the oxidative status. AMFJ (5, 10 and 20 ml kg(-1)) was applied orally as a pretreatment 1 h before the subcutaneous administration of indomethacin (30 mg kg(-1)). Gastric ulcer formation was estimated morphometrically and histopathologically 4h after the indomethacin administration. Malondialdehyde (MDA) in rat plasma and gastric mucosa and also reduced glutathione (GSH) and oxidized glutathione (GSSG) in gastric mucosa were determined and used as biochemical markers of the oxidative status. AMFJ-pretreatment diminished the number and area of indomethacin-induced gastric lesions. Histopathological examination of rat stomachs demonstrated that AMFJ induced an increase in gastric mucus production and a reduction of the depth and severity of indomethacin-induced mucosal lesions. AMFJ dose-dependently reduced the elevated indomethacin plasma and gastric MDA levels and at the doses of 10 and 20 ml kg(-1) they were not significantly different from the control values. Neither indomethacin-treatment, nor AMFJ-pretreatment had a significant influence on GSH and GSSG gastric mucosal levels. These results demonstrated that indomethacin-induced gastric mucosal damage was accompanied by the development of oxidative stress, evidenced by the accumulation of MDA. AMFJ-pretreatment decreased the gastric lesions caused by indomethacin. It could be suggested that this effect of AMFJ was probably due to the increased mucus production and interference with oxidative stress development as evidenced by the decreased plasma and gastric mucosal MDA. PMID:15945278

  9. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

    PubMed

    Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

    2016-08-01

    Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity. PMID:26429932

  10. Voltammetric determination of N-nitrosoderivatives of atenolol and propranolol in simulated gastric juice.

    PubMed

    Belal, F; al-Deeb, O A; al-Majed, A A; Gad-Kariem, E A

    1999-10-30

    A highly sensitive and simple voltammetric method is proposed for the determination of N-nitrosoatenolol (NA) and N-nitrosopropranolol (NP) in simulated gastric juice. The method is based on measuring the differential-pulse polarographic peak produced by NA and NP in Britton-Robinson buffers of pH 3 and 4 for NA and NP, respectively. Both compounds yielded diffusion-controlled current with diffusion-current constants of 7.23 +/- 0.03 and 9.46 +/- 0.06 for NA and NP, respectively. The current-concentration plots were rectilinear over the range 0.16-9.6 micrograms ml-1 with minimum detectability (S/N = 2) of 0.015 microgram ml-1 (5 x 10(-8) M) for NA; for NP the range was 0.08-8.0 micrograms ml-1 with minimum detectability (S/N = 2) of 0.009 microgram ml-1 (3 x 10(-8) M). The proposed method was successfully applied to study the possible in vivo production of the nitroso-derivatives under the standard nitrosation reaction conditions recommended by WHO. The method is characterized by simplicity and higher sensitivity as compared with the reported HPLC method. PMID:10575740

  11. Honey and Apoptosis in Human Gastric Mucosa

    PubMed Central

    Ghaffari, Aida; Somi, Mohammad H; Safaiyan, Abdolrasoul; Modaresi, Jabiz; Ostadrahimi, Alireza

    2012-01-01

    Background: Gastric cancer is the fourth most common malignancy in the world. Honey is a complex mixture of special biological active constituents. Honey possesses antioxidant and antitumor properties. Nutritional studies have indicated that consumption of honey modulates the risk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisive role in precancerous changes. Our chief study was conducted to assess the relationship between consumption of honey and apoptosis in human gastric mucosa. Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred to two hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62 subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire (FFQ) and apoptosis was detected by TUNEL technique. We tested polynomial curve to find the best fit between honey consumption and apoptosis. Results: A positive relation between honey consumption and apoptosis was found (P=0.024). Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honey amount) - 0.533(honey amount)2 +1.833×10-5(honey amount)7. Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis in gastric mucosa. PMID:24688918

  12. Effect of gastric acid suppressants on human gastric motility

    PubMed Central

    Parkman, H; Urbain, J; Knight, L; Brown, K; Trate, D; Miller, M; Maurer, A; Fisher, R

    1998-01-01

    Background—The effect of histamine H2 receptor antagonists on gastric emptying is controversial. 
Aims—To determine the effects of ranitidine, famotidine, and omeprazole on gastric motility and emptying. 
Patients and methods—Fifteen normal subjects underwent simultaneous antroduodenal manometry, electrogastrography (EGG), and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of fasting manometry and EGG recording, subjects received either intravenous saline, ranitidine, or famotidine, followed by another 30 minutes recording and then three hours of postprandial recording after ingestion of a radiolabelled meal. Images were obtained every 10-15 minutes for three hours to measure gastric emptying and assess antral contractility. Similar testing was performed after omeprazole 20 mg daily for one week. 
Results—Fasting antral phase III migrating motor complexes (MMCs) were more common after ranitidine (9/15 subjects, 60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%) compared with placebo (4/14, 29%; p<0.05). Postprandially, ranitidine, famotidine, and omeprazole slowed gastric emptying, increased the amplitude of DAS contractions, increased the EGG power, and increased the antral manometric motility index. 
Conclusions—Suppression of gastric acid secretion with therapeutic doses of gastric acid suppressants is associated with delayed gastric emptying but increased antral motility. 

 Keywords: gastric motility; gastric emptying; histamine H2 receptor antagonists; proton pump inhibitors; gastric acid secretion; scintigraphy PMID:9536950

  13. Human Gastric Epithelial Cells Contribute to Gastric Immune Regulation by Providing Retinoic Acid to Dendritic Cells

    PubMed Central

    Bimczok, Diane; Kao, John Y.; Zhang, Min; Cochrun, Steven; Mannon, Peter; Peter, Shajan; Wilcox, Charles M.; Mönkemüller, Klaus E.; Harris, Paul R.; Grams, Jayleen M.; Stahl, Richard D.; Smith, Phillip D.; Smythies, Lesley E.

    2014-01-01

    Despite the high prevalence of chronic gastritis caused by H. pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule, retinol, and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of retinol synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric DCs. Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation. PMID:25249167

  14. Metabolomic studies of human gastric cancer: review.

    PubMed

    Jayavelu, Naresh Doni; Bar, Nadav S

    2014-07-01

    Metabolomics is a field of study in systems biology that involves the identification and quantification of metabolites present in a biological system. Analyzing metabolic differences between unperturbed and perturbed networks, such as cancerous and non-cancerous samples, can provide insight into underlying disease pathology, disease prognosis and diagnosis. Despite the large number of review articles concerning metabolomics and its application in cancer research, biomarker and drug discovery, these reviews do not focus on a specific type of cancer. Metabolomics may provide biomarkers useful for identification of early stage gastric cancer, potentially addressing an important clinical need. Here, we present a short review on metabolomics as a tool for biomarker discovery in human gastric cancer, with a primary focus on its use as a predictor of anticancer drug chemosensitivity, diagnosis, prognosis, and metastasis. PMID:25009381

  15. Pharmacokinetics of flavanone glycosides after ingestion of single doses of fresh-squeezed orange juice versus commercially processed orange juice in healthy humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Orange juice is a rich source of flavonoids known to be beneficial to cardiovascular health in humans. The objective of this study was to analyze the pharmacokinetics of the main flavanone glycosides, hesperidin and narirutin, in humans after the consumption of two types of orange juice, fresh squee...

  16. [Quantitative evaluation of 90Sr, 137Cs, 239Pu, 241Am transfer from polluted soil to gastric and intestine juice of cows].

    PubMed

    Chizhevskiĭ, I V

    2001-01-01

    Quantitative parameters of 90Sr, 137Cs, 239Pu and 241Am transfer from solid phase of soil to gastric, intestine juice of cows as well as to imitating solutions have been estimated on the base of results of laboratory incubation experiments. A prevailing role of enzyme complex and microflora of gastrointestinal tract in radionuclides transfer from solid phase of soil to solution has been shown. PMID:11605246

  17. Stability of free and encapsulated Lactobacillus acidophilus ATCC 4356 in yogurt and in an artificial human gastric digestion system.

    PubMed

    Ortakci, F; Sert, S

    2012-12-01

    The objective of this study was to determine the effect of encapsulation on survival of probiotic Lactobacillus acidophilus ATCC 4356 (ATCC 4356) in yogurt and during artificial gastric digestion. Strain ATCC 4356 was added to yogurt either encapsulated in calcium alginate or in free form (unencapsulated) at levels of 8.26 and 9.47 log cfu/g, respectively, and the influence of alginate capsules (1.5 to 2.5mm) on the sensorial characteristics of yogurts was investigated. The ATCC 4356 strain was introduced into an artificial gastric solution consisting of 0.08 N HCl (pH 1.5) containing 0.2% NaCl or into artificial bile juice consisting of 1.2% bile salts in de Man, Rogosa, and Sharpe broth to determine the stability of the probiotic bacteria. When incubated for 2h in artificial gastric juice, the free ATCC 4356 did not survive (reduction of >7 log cfu/g). We observed, however, greater survival of encapsulated ATCC 4356, with a reduction of only 3 log cfu/g. Incubation in artificial bile juice (6 h) did not significantly affect the viability of free or encapsulated ATCC 4356. Moreover, statistically significant reductions (~1 log cfu/g) of both free and encapsulated ATCC 4356 were observed during 4-wk refrigerated storage of yogurts. The addition of probiotic cultures in free or alginate-encapsulated form did not significantly affect appearance/color or flavor/odor of the yogurts. However, significant deficiencies were found in body/texture of yogurts containing encapsulated ATCC 4356. We concluded that incorporation of free and encapsulated probiotic bacteria did not substantially change the overall sensory properties of yogurts, and encapsulation in alginate using the extrusion method greatly enhanced the survival of probiotic bacteria against an artificial human gastric digestive system. PMID:23021757

  18. A new gastric juice peptide, BPC. An overview of the stomach-stress-organoprotection hypothesis and beneficial effects of BPC.

    PubMed

    Sikirić, P; Petek, M; Rucman, R; Seiwerth, S; Grabarević, Z; Rotkvić, I; Turković, B; Jagić, V; Mildner, B; Duvnjak, M

    1993-01-01

    The possibility that the stomach, affected by general stress, might initiate a counter-response has not until recently been considered in theories of stress. We suggest that the stomach, as the most sensitive part of the gastrointestinal tract and the largest neuroendocrine organ in the body, is crucial for the initiation of a full stress response against all noxious stress pathology. The end result would be a strong protection of all organs invaded by 'stress'. Consistent with this assumption, this coping response is best explained in terms of 'organoprotection'. Endogenous organoprotectors (eg prostaglandins, somatostatin, dopamine) are proposed as mediators. Such an endogenous counteraction could even be afforded by their suitable application. A new gastric juice peptide, M(r) 40,000, named BPC, was recently isolated. Herein, a 15 amino acid fragment (BPC 157), thought to be essential for its activity, has been fully characterized and investigated. As has been demonstrated for many organoprotective agents using different models of various tissue lesions, despite the poorly understood final mechanism, practically all organ systems appear to benefit from BPC activity. These effects have been achieved in many species using very low dosages (mostly microgram and ng/kg range) after ip, ig, and intramucosal (local) application. The effect was apparent already after one application. Long lasting activity was also demonstrated. BPC was highly effective when applied simultaneously with noxious agents or in already pathological, as well as chronical, conditions. Therefore, it seems that BPC treatment does not share any of the so far known limitations for 'conventional organoprotectors'. No influence on different basal parameters and no toxicity were observed. These findings provide a breakthrough in stress theory. BPC, as a possible endogenous free radical scavenger and organoprotection mediator, could be a useful prototype of a new class of drugs, organoprotective agents

  19. Prognostic role of neuroendocrine cell differentiation in human gastric carcinoma

    PubMed Central

    Zhang, Tingting; Su, Dan; Mao, Zhiyuan; Guo, Xiaochuan; Wang, Lijie; Bai, Li

    2015-01-01

    The objective of the current study was to investigate the significance and biologic characteristic of neuroendocrine cell differentiation (NED) in gastric carcinoma by comparing the prognosis and clinicopathologic characteristics between patients with or without NED. Retrospective analyses of neuroendocrine markers, neuron specific enolase (NSE), chromogranin A (CgA), and synaptophysin (Syn) were performed in 174 human gastric carcinoma patients. NED association was found in 21.3% gastric carcinoma patients, with or without NED, and was correlated with tumor location, cancer emboli, infiltrative depth, TNM stage and distant metastasis (P < 0.05 in each case). The 1-year and 3-year survival rate of the patients who suffered from gastric carcinoma with NED were significantly lower than those without NED. The overall survival time of patients with NED was shorter than those with gastric carcinoma without NED, with a significant difference between the two types (P = 0.037). Cumulatively, gastric carcinoma patients with NED had shorter postoperative survival time and poorer prognosis. PMID:26221337

  20. Pulsed electric fields-processed orange juice consumption increases plasma vitamin C and decreases F2-isoprostanes in healthy humans.

    PubMed

    Sánchez-Moreno, Concepción; Cano, M Pilar; de Ancos, Begoña; Plaza, Lucía; Olmedilla, Begoña; Granado, Fernando; Elez-Martínez, Pedro; Martín-Belloso, Olga; Martín, Antonio

    2004-10-01

    Orange juice, a rich source of vitamin C, accounts for 60% of all fruit juices and juice-based drinks consumed in western Europe. Orange juice preservation is currently accomplished by traditional pasteurization. Pulsed electric fields (PEF) have been studied as a nonthermal food preservation method. Food technology needs in the area of processing are driven by nutrition. Therefore, the objectives of this study were to assess the bioavailability of vitamin C from pulsed electric fields-treated orange juice in comparison with freshly squeezed orange juice and its impact on 8-epiPGF(2alpha) concentrations (biomarker of lipid peroxidation) in a healthy human population. Six subjects consumed 500 mL/day of pulsed electric fields-treated orange juice and six subjects consumed 500 mL/day of freshly squeezed orange juice for 14 days, corresponding to an intake of about 185 mg/day of ascorbic acid. On the first day of the study, subjects drank the juice in one dose, and on days 2-14 they consumed 250 mL in the morning and 250 mL in the afternoon. Blood was collected every hour for 6 hours on the first day and again on days 7 and 14. In the dose-response study, the maximum increase in plasma vitamin C occurred 4 hours postdose. Vitamin C remained significantly higher on days 7 and 14 in both orange juice groups. Plasma 8-epiPGF(2alpha) concentrations was lower at the end of the study (P < 0.001) in both groups. Plasma levels of vitamin C and 8-epiPGF(2alpha) were inversely correlated. Pulsed electric fields-preservation of orange juice retains the vitamin C bioavailability and antioxidant properties of fresh juice with a longer shelf-life. PMID:15542351

  1. Mutagens, N-nitroso compounds and their precursors in gastric juice from patients with and without precancerous lesions of the stomach.

    PubMed

    Pignatelli, B; Malaveille, C; Rogatko, A; Hautefeuille, A; Thuillier, P; Muñoz, N; Moulinier, B; Berger, F; De Montclos, H; Lambert, R

    1993-01-01

    This study examined whether elevated risk of gastric cancer is associated with high levels of total N-nitroso compounds (NOC), their precursors and nitrosation-dependent genotoxins in gastric juice (GJ). An improved method for quantifying total NOC was used and genotoxicity was assayed in E. coli. Results from patients (n = 210) with or without precancerous lesions of the stomach and living in three areas with up to 8-fold variations in gastric cancer risk (U.K., France, Colombia) were compared. The level of nitrite (range < 1-472 mumol/l) was found to increase with the pH of GJ from the three countries and was dependent on country of collection. The levels of NOC (range: < or = 0.01-8.0 mumol/l) in GJ were not affected by stomach histology and country of collection. NOC levels increased linearly with nitrite concentrations, but the slope of the regression line was greater for acidic GJ (pH < or = 4). These data together suggest that chemical nitrosation contributes at least as much as other nitrosation pathways to the intragastric formation of NOC. Acid-catalysed nitrosation of GJ in vitro increased the NOC concentration (range: 7-1332 mumol/l) up to several 1000-fold but this increase was not predictive of gastric cancer risk either by country or by stomach histology. After acid-catalysed nitrosation, direct genotoxicity (SOS-inducing potency) was significantly higher in GJ with original pH > 4 and highest in samples from Colombia. The results (a) provide no support that intragastric total NOC levels are elevated in subjects with precancerous stomach lesions or living in a high risk area for stomach cancer; (b) confirm that a high nitrite level and elevated pH in GJ are strongly associated, the level of nitrite being associated with precancerous stomach conditions only in Colombia; (c) reveal the presence of precursor compounds in GJ, that after nitrosation yield direct mutagens that probably contain NOC and other substances. As their concentrations were

  2. Identification of a Cranberry Juice Product that Inhibits Enteric CYP3A-Mediated First-Pass Metabolism in Humans

    PubMed Central

    Ngo, Ngoc; Yan, Zhixia; Graf, Tyler N.; Carrizosa, Daniel R.; Kashuba, Angela D. M.; Dees, E. Claire; Oberlies, Nicholas H.; Paine, Mary F.

    2009-01-01

    An in vivo study in rats showed a cranberry juice product to inhibit the intestinal first-pass metabolism of the CYP3A substrate nifedipine. However, a clinical study involving the CYP3A probe substrate midazolam and a different cranberry juice product showed no interaction. Because the composition of bioactive components in natural products can vary substantially, a systematic in vitro-in vivo approach was taken to identify a cranberry juice capable of inhibiting enteric CYP3A in humans. First, the effects of five cranberry juices, coded A through E, were evaluated on midazolam 1′-hydroxylation activity in human intestinal microsomes. Juice E was the most potent, ablating activity at 0.5% juice (v/v) relative to control. Second, juice E was fractionated to generate hexane-, chloroform-, butanol-, and aqueous-soluble fractions. The hexane- and chloroform-soluble fractions at 50 μg/ml were the most potent, inhibiting by 77 and 63%, respectively, suggesting that the CYP3A inhibitors reside largely in these more lipophilic fractions. Finally, juice E was evaluated on the oral pharmacokinetics of midazolam in 16 healthy volunteers. Relative to water, juice E significantly increased the geometric mean area under the curve (AUC)0-∞ of midazolam by ∼30% (p = 0.001), decreased the geometric mean 1′-hydroxymidazolam/midazolam AUC0-∞ ratio by ∼40% (p < 0.001), and had no effect on geometric mean terminal half-life, indicating inhibition of enteric, but not hepatic, CYP3A-mediated first-pass metabolism of midazolam. This approach both showed a potential drug interaction liability with cranberry juice and substantiated that rigorous in vitro characterization of dietary substances is required before initiation of clinical drug-diet interaction studies. PMID:19114462

  3. Glutathione prevents ethanol induced gastric mucosal damage and depletion of sulfhydryl compounds in humans.

    PubMed Central

    Loguercio, C; Taranto, D; Beneduce, F; del Vecchio Blanco, C; de Vincentiis, A; Nardi, G; Romano, M

    1993-01-01

    Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione significantly decreased the extent of ethanol induced macroscopic injury to the mucosa of the gastric body and antrum. Glutathione's protective effect is associated with appreciable inhibition of ethanol induced depletion of gastric sulfhydryl compounds. This is the first report of protection against ethanol induced gastric mucosal damage by a sulfhydryl containing agent in humans. PMID:8432465

  4. Mechanism-based inhibition of recombinant human cytochrome P450 3A4 by tomato juice extract.

    PubMed

    Sunaga, Katsuyoshi; Ohkawa, Kenichi; Nakamura, Kenichi; Ohkubo, Atsuko; Harada, Sonoko; Tsuda, Tadashi

    2012-01-01

    This study investigates whether tomato juice can inhibit cytochrome P450 (CYP) 3A4-mediated drug metabolism. Three commercially available, additive-free tomato juices, along with homogenized fresh tomato, were analyzed for their ability to inhibit testosterone 6β-hydroxylation activity using human recombinant CYP3A4. Results were compared to that of grapefruit juice. Ethyl acetate extracts of the tomato juices moderately reduced residual activity of CYP3A4 testosterone 6β-hydroxylation activity by 19.3-26.2% with 0-min preincubation. Residual activity was strongly reduced by 69.9-83.5% at 20-min preincubation, a reduction similar to that of grapefruit juice extract, known to contain constituents of mechanism-based inhibitors. One juice extract (tomato juice C) showed irreversible dose- and preincubation time-dependent and partial nicotinamide adenine dinucleotide phosphate (NADPH)-dependent inhibition of CYP3A4 activity. Furthermore, we examined whether the CYP3A4 inhibitory effect of tomato juice was substrate dependent by examining midazolam 1'-hydroxylation activity and nifedipine oxidation activity, in addition to testosterone 6β-hydroxylation activity. Tomato juice showed a potent inhibitory effect on nifedipine oxidation activity, which was comparable to that on testosterone 6β-hydroxylation activity; however, it showed a weak inhibitory effect on midazolam 1'-hydroxylation activity. We conclude that tomato juice contains one or more mechanism-based and competitive inhibitor(s) of CYP3A4. Additionally, significant CYP3A4 inhibitory activity did not result from lycopene, a major compound in tomato. Although the active compound was uncertain, a strong CYP3A4 inhibitory activity was observed in other solanaceous plants, i.e., potato, eggplant, sweet pepper, and capsicum. Therefore, responsible compounds in tomato are likely commonly shared among solanaceous vegetables. PMID:22382318

  5. The role of the obestatin/GPR39 system in human gastric adenocarcinomas

    PubMed Central

    Alén, Begoña O.; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S.; Beiras, Andrés; Casanueva, Felipe F.; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P.; Pazos, Yolanda

    2016-01-01

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer. PMID:26716511

  6. Aloe-emodin-induced apoptosis in human gastric carcinoma cells.

    PubMed

    Chen, Sheng-Hsuan; Lin, Kai-Yuan; Chang, Chun-Chao; Fang, Chia-Lang; Lin, Chih-Ping

    2007-11-01

    The purpose of this study was to investigate the anticancer effect of aloe-emodin, an anthraquinone compound present in the leaves of Aloe vera, on two distinct human gastric carcinoma cell lines, AGS and NCI-N87. We demonstrate that aloe-emodin induced cell death in a dose- and time-dependent manner. Noteworthy is that the AGS cells were generally more sensitive than the NCI-N87 cells. Aloe-emodin caused the release of apoptosis-inducing factor and cytochrome c from mitochondria, followed by the activation of caspase-3, leading to nuclear shrinkage and apoptosis. In addition, exposure to aloe-emodin suppressed the casein kinase II activity in a time-dependent manner and was accompanied by a reduced phosphorylation of Bid, a downstream substrate of casein kinase II and a pro-apoptotic molecule. These preclinical studies suggest that aloe-emodin represents a suitable and novel chemotherapeutic drug candidate for the treatment of human gastric carcinoma. PMID:17637488

  7. Organotypic slice cultures of human gastric and esophagogastric junction cancer.

    PubMed

    Koerfer, Justus; Kallendrusch, Sonja; Merz, Felicitas; Wittekind, Christian; Kubick, Christoph; Kassahun, Woubet T; Schumacher, Guido; Moebius, Christian; Gaßler, Nikolaus; Schopow, Nikolas; Geister, Daniela; Wiechmann, Volker; Weimann, Arved; Eckmann, Christian; Aigner, Achim; Bechmann, Ingo; Lordick, Florian

    2016-07-01

    Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μm slices and cultivated in 6-well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8, AE1/3) were applied for determining tumor cellularity, Ki-67 for proliferation, and cleaved caspase-3 staining for apoptosis. The slices were analyzed under naive conditions and following 2-4 days in vitro exposure to 5-FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response. PMID:27073068

  8. Fate of Escherichia coli O157 Cells Inoculated into Lightly Pickled Chinese Cabbage during Processing, Storage and Incubation in Artificial Gastric Juice.

    PubMed

    Inatsu, Yasuhiro; Ohata, Yukiko; Ananchaipattana, Chiraporn; Latiful Bari, Md; Hosotani, Yukie; Kawasaki, Susumu

    2016-01-01

    Fate of Escherichia coli O157 cells was evaluated when inoculated into each step after production of lightly pickled Chinese cabbage. The efficacy of surface sterilization by 100 mg/L of chlorine water for 10 min on raw leaves (6.0 log CFU/g) was 2.2 log CFU/g reduction. No meaningful change of the population of E. coli O157 (3.5 log CFU/g to 1.5 log MPN/g) contaminated into 19 kinds of products was observed. These results indicated the difficulty of estimating the viable count of the cells between contaminated on farms and further processing and storage steps. The population of E. coli O157 (3 log CFU/g to 1 log MPN/g) inoculated into the Chinese cabbage products was reduced less than 0.6 log CFU/g after 2 h-incubation at 37℃ in artificial gastric juice. Prevention from initial contamination of E. coli O157 on the ingredients of Chinese cabbage products is important to reduce the risk of food poisoning because the reduction of the bacterial counts after processing and consumption are limited. PMID:27009510

  9. Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion.

    PubMed

    Bibo-Verdugo, Betsaida; O'Donoghue, Anthony J; Rojo-Arreola, Liliana; Craik, Charles S; García-Carreño, Fernando

    2016-04-01

    Crustaceans are a diverse group, distributed in widely variable environmental conditions for which they show an equally extensive range of biochemical adaptations. Some digestive enzymes have been studied by purification/characterization approaches. However, global analysis is crucial to understand how digestive enzymes interplay. Here, we present the first proteomic analysis of the digestive fluid from a crustacean (Homarus americanus) and identify glycosidases and peptidases as the most abundant classes of hydrolytic enzymes. The digestion pathway of complex carbohydrates was predicted by comparing the lobster enzymes to similar enzymes from other crustaceans. A novel and unbiased substrate profiling approach was used to uncover the global proteolytic specificity of gastric juice and determine the contribution of cysteine and aspartic acid peptidases. These enzymes were separated by gel electrophoresis and their individual substrate specificities uncovered from the resulting gel bands. This new technique is called zymoMSP. Each cysteine peptidase cleaves a set of unique peptide bonds and the S2 pocket determines their substrate specificity. Finally, affinity chromatography was used to enrich for a digestive cathepsin D1 to compare its substrate specificity and cold-adapted enzymatic properties to mammalian enzymes. We conclude that the H. americanus digestive peptidases may have useful therapeutic applications, due to their cold-adaptation properties and ability to hydrolyze collagen. PMID:26613762

  10. Technological characterization and survival of the exopolysaccharide-producing strain Lactobacillus delbrueckii subsp. lactis 193 and its bile-resistant derivative 193+ in simulated gastric and intestinal juices.

    PubMed

    Burns, Patricia; Vinderola, Gabriel; Reinheimer, Jorge; Cuesta, Isabel; de Los Reyes-Gavilán, Clara G; Ruas-Madiedo, Patricia

    2011-08-01

    The capacity of lactic acid bacteria to produce exopolysaccharides (EPS) conferring microorganisms a ropy phenotype could be an interesting feature from a technological point of view. Progressive adaptation to bile salts might render some lactobacilli able to overcome physiological gut barriers but could also modify functional properties of the strain, including the production of EPS. In this work some technological properties and the survival ability in simulated gastrointestinal conditions of Lactobacillus delbrueckii subsp. lactis 193, and Lb. delbrueckii subsp. lactis 193+, a strain with stable bile-resistant phenotype derived thereof, were characterized in milk in order to know whether the acquisition of resistance to bile could modify some characteristics of the microorganism. Both strains were able to grow and acidify milk similarly; however the production of ethanol increased at the expense of the aroma compound acetaldehyde in milk fermented by the strain 193+, with respect to milk fermented by the strain 193. Both microorganisms produced a heteropolysaccharide composed of glucose and galactose, and were able to increase the viscosity of fermented milks. In spite of the higher production yield of EPS by the bile-resistant strain 193+, it displayed a lower ability to increase viscosity than Lb. delbrueckii subsp. lactis 193. Milk increased survival in simulated gastric juice; the presence of bile improved adhesion to the intestinal cell line HT29-MTX in both strains. However, the acquisition of a stable resistance phenotype did not improve survival in simulated gastric and intestinal conditions or the adhesion to the intestinal cell line HT29-MTX. Thus, Lb. delbrueckii subsp. lactis 193 presents suitable technological properties for the manufacture of fermented dairy products; the acquisition of a stable bile-resistant phenotype modified some properties of the microorganism. This suggests that the possible use of bile-resistant derivative strains should be

  11. Lectin staining patterns in human gastric mucosae with and without exposure to Helicobacter pylori

    PubMed Central

    Melo-Junior, Mario R.; Cavalcanti, Carmelita L.B.; Pontes-Filho, Nicodemos T.; Carvalho Jr, Luiz B.; Beltrão, Eduardo I. C.

    2008-01-01

    The aim of the present study was to evaluate qualitative changes in the glycoconjugate expression in human gastric tissue of positive and negative patients for Helicobacter pylori, through lectins: Wheat Germ Agglutinin (WGA) and Concanavalin A (Con A). The lectins recognized differently the glycoconjugates in the superficial mucous layer at the gastric tissues. The results suggest a significant change in the carbohydrate moieties present on the surface of the gastric cells during infection. PMID:24031208

  12. Increased programmed death-ligand-1 expression in human gastric epithelial cells in Helicobacter pylori infection

    PubMed Central

    Wu, Y-Y; Lin, C-W; Cheng, K-S; Lin, C; Wang, Y-M; Lin, I-T; Chou, Y-H; Hsu, P-N

    2010-01-01

    B7-H1 [programmed death-ligand-1 (PD-L1)] is a B7-family member that binds to programmed death-1 (PD-1). Recently, deficiency of PD-L1 has been demonstrated to result in accelerated gastric epithelial cell damage in gastritis, and PD-L1 is suggested to play a critical role in regulating T cell homeostasis. Here, we aimed to gain more insight into gastric PD-L1 expression, regulation and function during Helicobacter pylori infection. PD-L1 expression in human gastric epithelial cells was analysed using Western blotting, quantitative polymerase chain reaction and fluorescence activated cell sorter analysis. Furthermore, co-culture experiments of human gastric epithelial cells with primary human T cells or Jurkat T cells were conducted. PD-L1 expression in primary human gastric epithelial cells was strongly enhanced by H. pylori infection and activated T cells, and augmented markedly by further stimulation with interferon-γ or tumour necrosis factor-α. Moreover, PD-L1 expression in gastric epithelial cells significantly induced apoptosis of T cells. Our results indicate that a novel bidirectional interaction between human gastric epithelial cells and lymphocytes modulates PD-L1 expression in human gastric epithelial cells, contributing to the unique immunological properties of the stomach. PMID:20646001

  13. Yoghurt impacts on the excretion of phenolic acids derived from colonic breakdown of orange juice flavanones in humans.

    PubMed

    Roowi, Suri; Mullen, William; Edwards, Christine A; Crozier, Alan

    2009-05-01

    Human urine was collected over a 24 h period after the consumption of 250 mL of (i) water, (ii) orange juice, and (iii) orange juice plus 150 mL of full fat natural yoghurt. The orange juice contained 168 micromol of hesperetin-7-O-rutinoside and 18 micromol of naringenin-7-O-rutinoside. GC-MS analysis of the urine identified nine phenolic acids, five of which, 3-hydroxyphenylacetic acid, 3-hydroxyphenylhydracrylic acid, dihydroferulic acid, 3-methoxy-4-hydroxyphenylhydracrylic acid and 3-hydroxyhippuric acid, were associated with orange juice consumption indicating that they were derived from colonic catabolism of hesperetin-7-O-rutinoside. The overall 0-24 h excretion of the five phenolic acids was 6.7 +/- 1.8 micromol after drinking water and this increased significantly (p < 0.05) to 62 +/- 18 micromol, equivalent to 37% of the ingested flavanones, following orange juice consumption. When the orange juice was ingested with yoghurt excretion fell back markedly to 9.3 +/- 4.4 micromol. This was not due to a difference in mouth to caecum transit time, as measured with breath hydrogen production, though possibly there may have been a slowing of the bulk of the meal reaching the large intestine which may then have altered the catabolism of the flavanones to phenolic acids by the colonic microbiota. PMID:19415668

  14. The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?

    PubMed Central

    Compare, Debora

    2015-01-01

    Introduction Although long thought to be a sterile organ, due to its acid production, the human stomach holds a core microbiome. Aim To provide an update of findings related to gastric microbiota and its link with gastric diseases. Methods We conducted a systematic review of the literature. Results The development of culture-independent methods facilitated the identification of many bacteria. Five major phyla have been detected in the stomach: Firmicutes, Bacteroidites, Actinobacteria, Fusobacteria and Proteobacteria. At the genera level, the healthy human stomach is dominated by Prevotella, Streptococcus, Veillonella, Rothia and Haemophilus; however, the composition of the gastric microbiota is dynamic and affected by such factors as diet, drugs and diseases. The interaction between the pre-existing gastric microbiota and Helicobacter pylori infection might influence an individual’s risk of gastric disease, including gastric cancer. Conclusions The maintenance of bacterial homeostasis could be essential for the stomach’s health and highlights the chance for therapeutic interventions targeting the gastric microbiota, even if gastric pH, peristalsis and the mucus layer may prevent bacteria colonization; and the definition of gastric microbiota of the healthy stomach is still an ongoing challenging task. PMID:26137299

  15. Human gastric cancer, Helicobacter pylori and bracken carcinogens: A connecting hypothesis.

    PubMed

    Oliveros-Bastidas, Alberto; Calcagno-Pissarelli, María Pía; Naya, Marlene; Ávila-Núñez, Jorge Luis; Alonso-Amelot, Miguel E

    2016-03-01

    Long term infection of Helicobacter pylori (Hp) virulent strains is a key factor in the genesis of human gastric cancer, and so are certain dietary proinflammatory and genotoxic compounds. Carcinogenic bracken fern (Pteridium spp.) is one of these. Toxins from this plant are consumed as bracken culinary preparations, through milk and meat of bracken-exposed livestock, and drain waters from bracken swards. Bracken toxin ptaquiloside (PtQ), a suspected human carcinogen, elicits complex responses in animals leading to death. PtQ and Hp might cooperate in gastric pathologies. This paper presents an hypothesis on PtQ-Hp association leading to the enhancement of carcinogenesis in the human gastric environment that might explain the high gastric cancer incidence and death rates among Hp-infected people living in bracken zones at two levels: (1) The macroscopic scale comprising the flow of PtQ in the human diet. (2) the microscopic scale encompassing (A) gastric luminal medium; (B) gastric mucus structure and mucin degradation elicited by Hp; (C) bacterial pH gradient modification of the gastric mucosa that favors PtQ survival and its penetration into epithelial tissue; (D) combined PtQ/Hp effects on gastric immune and inflammatory responses; (E) PtQ-Hp complementary activity at selected cell signaling cascades and genome disturbance. PMID:26632203

  16. Immunohistochemical study of DNA topoisomerase II in human gastric disorders.

    PubMed Central

    Yabuki, N.; Sasano, H.; Kato, K.; Ohara, S.; Toyota, T.; Nagura, H.; Miyaike, M.; Nozaki, N.; Kikuchi, A.

    1996-01-01

    Topoisomerase II (topo II) separates chromosomes at the end of mitosis and is also the target for various chemotherapeutic agents. Expression of this enzyme has been demonstrated to increase rapidly at the end of the S to G2/M phase and decrease after the completion of mitosis. We immunolocalized topo II in specimens of both normal and neoplastic human gastric mucosas to evaluate expression of this enzyme. Three different antibodies were used for the immunostaining of topo II (anti-topo II alpha isoform, anti-topo II beta isoform and anti-topo II alpha and -beta isoforms). There were no significant differences in topo II labeling index (LI) between frozen and paraffin-embedded tissue sections obtained from the same cases. Topo II LI was significantly correlated with Ki67 LI in all of the specimens examined. The area of cells positive for Topo II was much narrower than that of Ki67 in the normal gastric glands, and the pattern of Topo II immunolocalization in both adenomas and adenocarcinomas was also essentially the same as that of Ki67. The topo II LI values (positive cells/1000 cells) for normal gastric gland, adenoma, intestinal-type adenocarcinoma, and diffuse-type adenocarcinoma were 114.7 +/- 2.2, 266.7 +/- 18.8, 277.6 +/- 19.2, and 324.5 +/- 5.3, respectively. Significant differences in topo II LI and topo II/Ki67 index were observed between normal and neoplastic mucosas (P < 0.0001) and between adenomas or intestinal-type adenocarcinoma and diffuse-type adenocarcinoma (P < 0.001 and P < 0.01, respectively). Simultaneous measurement of topo II alpha and nuclear DNA content by two-parameter flow cytometry revealed that the Jurkat cell line established from acute lymphocytic leukemia cells expressed the enzyme in cells at other than S and G2/M phases of the cell cycle whereas topo-II alpha-positive cells were predominantly observed in S and G2/M phases of the cell cycle in the cells from normal lymph nodes. These findings suggest that dys-regulation or

  17. A Review and Critical Analysis of the Scientific Literature Related to 100% Fruit Juice and Human Health12

    PubMed Central

    Hyson, Dianne A

    2015-01-01

    The association between the consumption of pure (100%) fruit juice (PFJ) and human health is uncertain. The current review summarizes data published between 1995 and 2012 related to PFJ with a focus on juices that are widely available and studied in forms representing native juice without supplemental nutrients or enhanced phytochemical content. The effects of apple, cranberry, grape, grapefruit, orange, and pomegranate PFJ intake on outcomes linked to cancer, cardiovascular disease, cognition, hypertension, inflammation, oxidation, platelet function, urinary tract infection, and vascular reactivity are reviewed. Implications for bodyweight regulation are also addressed. The collective data are provocative although challenges and unanswered questions remain. There are many plausible mechanisms by which PFJ might be protective, and investigation of its effects on human health and disease prevention must remain an active area of research. PMID:25593142

  18. A review and critical analysis of the scientific literature related to 100% fruit juice and human health.

    PubMed

    Hyson, Dianne A

    2015-01-01

    The association between the consumption of pure (100%) fruit juice (PFJ) and human health is uncertain. The current review summarizes data published between 1995 and 2012 related to PFJ with a focus on juices that are widely available and studied in forms representing native juice without supplemental nutrients or enhanced phytochemical content. The effects of apple, cranberry, grape, grapefruit, orange, and pomegranate PFJ intake on outcomes linked to cancer, cardiovascular disease, cognition, hypertension, inflammation, oxidation, platelet function, urinary tract infection, and vascular reactivity are reviewed. Implications for bodyweight regulation are also addressed. The collective data are provocative although challenges and unanswered questions remain. There are many plausible mechanisms by which PFJ might be protective, and investigation of its effects on human health and disease prevention must remain an active area of research. PMID:25593142

  19. Juice of Bryophyllum pinnatum (Lam.) inhibits oxytocin-induced increase of the intracellular calcium concentration in human myometrial cells.

    PubMed

    Simões-Wüst, A P; Grãos, M; Duarte, C B; Brenneisen, R; Hamburger, M; Mennet, M; Ramos, M H; Schnelle, M; Wächter, R; Worel, A M; von Mandach, U

    2010-10-01

    The use of preparations from Bryophyllum pinnatum in tocolysis is supported by both clinical (retrospective comparative studies) and experimental (using uterus strips) evidence. We studied here the effect of B. pinnatum juice on the response of cultured human myometrial cells to stimulation by oxytocin, a hormone known to be involved in the control of uterine contractions by increasing the intracellular free calcium concentration ([Ca2+]i). In this work, [Ca2+]i was measured online during stimulation of human myometrial cells (hTERT-C3 and M11) with oxytocin, which had been pre-incubated in the absence or in the presence of B. pinnatum juice. Since no functional voltage-gated Ca2+ channels could be detected in these myometrial cells, the effect of B. pinnatum juice was as well studied in SH-SY5Y neuroblastoma cells, which are known to have such channels and can be depolarised with KCl. B. pinnatum juice prevented the oxytocin-induced increase in [Ca2+]i in hTERT-C3 human myometrial cells in a dose-dependent manner, achieving a ca. 80% inhibition at a 2% concentration. Comparable results were obtained with M11 human primary myometrial cells. In hTERT-C3 cells, prevention of the oxytocin-induced increase in [Ca2+]i was independent of the extracellular Ca2+ concentration and of voltage-dependent Ca2+-channels. B. pinnatum juice delayed, but did not prevent the depolarization-induced increase in [Ca2+]i in SH-SY5Y cells. Taken together, the data suggest a specific and concentration-dependent effect of B. pinnatum juice on the oxytocin signalling pathway, which seems to corroborate its use in tocolysis. Such a specific mechanism would explain the rare and minor side-effects in tocolysis with B. pinnatum as well as its high therapeutic index. PMID:20381326

  20. 21 CFR 156.145 - Tomato juice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Tomato juice. 156.145 Section 156.145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION VEGETABLE JUICES Requirements for Specific Standardized Vegetable Juices § 156.145 Tomato juice. (a) Identity—(1) Definition. Tomato...

  1. Gene cataloging and expression profiling in human gastric cancer cells by expressed sequence tags.

    PubMed

    Kim, Nam-Soon; Hahn, Yoonsoo; Oh, Jung-Hwa; Lee, Ju-Yeon; Oh, Kyung-Jin; Kim, Jeong-Min; Park, Hong-Seog; Kim, Sangsoo; Song, Kyu-Sang; Rho, Seung-Moo; Yoo, Hyang-Sook; Kim, Yong Sung

    2004-06-01

    To understand the molecular mechanism associated with gastric carcinogenesis, we identified genes expressed in gastric cancer cell lines and tissues. Of 97,609 high-quality ESTs sequenced from 36 cDNA libraries, 92,545 were coalesced into 10,418 human Unigene clusters (Build 151). The gene expression profile was produced by counting the cluster frequencies in each library. Although the profiles of highly expressed genes varied greatly from library to library, those genes related to cell structure formation, heat shock proteins, the glycolysis pathway, and the signaling pathway were highly represented in human gastric cancer cell lines and in primary tumors. Conversely, the genes encoding immunoglobulins, ribosomal proteins, and digestive proteins were down-regulated in gastric cancer cell lines and tissues compared to normal tissues. The transcription levels of some of these genes were confirmed by RT-PCR. We found that genes related to cell adhesion, apoptosis, and cytoskeleton formation were particularly up-regulated in the gastric cancer cell lines established from malignant ascites compared to those from primary tumors. This comprehensive molecular profiling of human gastric cancer should be useful for elucidating the genetic events associated with human gastric cancer. PMID:15177556

  2. Oxidative-stress-related proteome changes in Helicobacter pylori-infected human gastric mucosa.

    PubMed Central

    Baek, Hye Yeon; Lim, Joo Weon; Kim, Hyeyoung; Kim, Jung Mogg; Kim, Joo Sung; Jung, Hyun Chae; Kim, Kyung Hwan

    2004-01-01

    Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration and gastric carcinoma. Proteomic analysis of the human gastric mucosa from the patients with erosive gastritis, peptic ulcer or gastric cancer, which were either infected or not with H. pylori, was used to determine the differentially expressed proteins by H. pylori in the human gastric mucosa in order to investigate the pathogenic mechanism of H. pylori -induced gastric diseases. Prior to the experiment, the expression of the main 18 proteins were identified in the gastric mucosa and used for a proteome map of the human gastric mucosa. Using two-dimensional electrophoresis of the protein isolated from the H. pylori -infected tissues, Coomassie Brilliant Blue staining and computerized analysis of the stained gel, the expression of eight proteins were altered in the H. pylori -infected tissues compared with the non-infected tissues. MS analysis (matrix-assisted laser desorption/ionization-time of flight MS) of the tryptic fragment and a data search allowed the the identification of the four increased proteins (78 kDa glucose-regulated protein precursor, endoplasmin precursor, aldehyde dehydrogenase 2 and L-lactate dehydrogenase B chain) and the four decreased proteins (intracellular chloride channel protein 1, glutathione S-transferase, heat-shock protein 60 and cytokeratin 8) caused by H. pylori infection in the gastric mucosa. These proteins are related to cell proliferation, carcinogenesis, cytoskeletal function and cellular defence mechanism. The common feature is that these proteins are related to oxidative-stress-mediated cell damage. In conclusion, the established gastric mucosal proteome map might be useful for detecting the disease-related protein changes. The H. pylori -induced alterations in protein expression demonstrate the involvement of oxidative stress in the pathogenesis of H. pylori -induced gastric diseases, including inflammation, ulceration and carcinogenesis

  3. Nutraceutical Improvement Increases the Protective Activity of Broccoli Sprout Juice in a Human Intestinal Cell Model of Gut Inflammation.

    PubMed

    Ferruzza, Simonetta; Natella, Fausta; Ranaldi, Giulia; Murgia, Chiara; Rossi, Carlotta; Trošt, Kajetan; Mattivi, Fulvio; Nardini, Mirella; Maldini, Mariateresa; Giusti, Anna Maria; Moneta, Elisabetta; Scaccini, Cristina; Sambuy, Yula; Morelli, Giorgio; Baima, Simona

    2016-01-01

    Benefits to health from a high consumption of fruits and vegetables are well established and have been attributed to bioactive secondary metabolites present in edible plants. However, the effects of specific health-related phytochemicals within a complex food matrix are difficult to assess. In an attempt to address this problem, we have used elicitation to improve the nutraceutical content of seedlings of Brassica oleracea grown under controlled conditions. Analysis, by LC-MS, of the glucosinolate, isothiocyanate and phenolic compound content of juices obtained from sprouts indicated that elicitation induces an enrichment of several phenolics, particularly of the anthocyanin fraction. To test the biological activity of basal and enriched juices we took advantage of a recently developed in vitro model of inflamed human intestinal epithelium. Both sprouts' juices protected intestinal barrier integrity in Caco-2 cells exposed to tumor necrosis factor α under marginal zinc deprivation, with the enriched juice showing higher protection. Multivariate regression analysis indicated that the extent of rescue from stress-induced epithelial dysfunction correlated with the composition in bioactive molecules of the juices and, in particular, with a group of phenolic compounds, including several anthocyanins, quercetin-3-Glc, cryptochlorogenic, neochlorogenic and cinnamic acids. PMID:27529258

  4. Study of the Gastric Emptying in Humans: Biomagnetic Assessments

    NASA Astrophysics Data System (ADS)

    Hernández, E.; Córdova, T.; Huerta-Franco, R.; Sosa, M.; Vargas-Luna, M.

    2006-09-01

    Biomagnetic studies of the gastrointestinal system can be carried out in two ways. Recording the magnetic field produced by the myenteric nervous system or created by any oral contrast mean as magnetic tracers or markers. In the first case, a SQUID magnetometer is demanded while a fluxgate magnetometer is enough in the second case. In this work, a magnetic marker was ingested by 8 healthy volunteers, in three gastric volume conditions, to measure the luminal content volume effect in the gastric emptying and to perform the quantification of the peristaltic frequencies in gastric and duodenum tract segments. The average emptying times for low luminal content, relative to the emptying time when the intake was the highest, were 43.6 ± 15.6 % and 77.3 ± 47.0 %. These results show that the biomagnetic technique is a powerful modality to estimate the effects of the gastric volume in the gastric emptying and a way to record the peristaltic frequencies.

  5. Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling.

    PubMed

    Kirman, Christopher R; Suh, Mina; Hays, Sean M; Gürleyük, Hakan; Gerads, Russ; De Flora, Silvio; Parker, William; Lin, Shu; Haws, Laurie C; Harris, Mark A; Proctor, Deborah M

    2016-09-01

    To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (<0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment. PMID:27396814

  6. Modeling human development and disease in pluripotent stem cell-derived gastric organoids

    PubMed Central

    McCracken, Kyle W.; Catá, Emily M.; Crawford, Calyn M.; Sinagoga, Katie L.; Schumacher, Michael; Rockich, Briana E.; Tsai, Yu-Hwai; Mayhew, Christopher N.; Spence, Jason R.; Zavros, Yana; Wells, James M.

    2014-01-01

    Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world’s population and are largely due to chronic H. pylori infection1–3. Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis4, and there is no experimental model of normal human gastric mucosa. Here we report the de novo generation of three-dimensional human gastric tissue in vitro through the directed differentiation of human pluripotent stem cells (hPSCs). We identified that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signaling pathways and three-dimensional growth are sufficient to generate human gastric organoids (hGOs). Developing hGOs progressed through molecular and morphogenetic stages that were nearly identical to the developing antrum of the mouse stomach. Organoids formed primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signaling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. Using hGOs to model pathogenesis of human disease, we found that H. pylori infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signaling and induction of epithelial proliferation. Together, these studies describe a novel and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease. PMID:25363776

  7. Oxygenated hemoglobin diffuse reflectance ratio for in vitro detection of human gastric pre-cancer

    NASA Astrophysics Data System (ADS)

    Li, L. Q.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Zhong, H. Q.; Li, X. Y.; Zhao, Q. L.; Guo, X.

    2010-07-01

    Oxygenated hemoglobin diffuse reflectance (DR) ratio (R540/R575) method based on DR spectral signatures is used for early diagnosis of malignant lesions of human gastric epithelial tissues in vitro. The DR spectra for four different kinds of gastric epithelial tissues were measured using a spectrometer with an integrating sphere detector in the spectral range from 400 to 650 nm. The results of measurement showed that the average DR spectral intensity for the epithelial tissues of normal stomach is higher than that for the epithelial tissues of chronic and malignant stomach and that for the epithelial tissues of chronic gastric ulcer is higher than that for the epithelial tissues of malignant stomach. The average DR spectra for four different kinds of gastric epithelial tissues show dips at 542 and 577 nm owing to absorption from oxygenated Hemoglobin (HbO2). The differences in the mean R540/R575 ratios of HbO2 bands are 6.84% between the epithelial tissues of normal stomach and chronic gastric ulcer, 14.7% between the epithelial tissues of normal stomach and poorly differentiated gastric adenocarcinoma and 22.6% between the epithelial tissues of normal stomach and undifferentiated gastric adenocarcinoma. It is evident from results that there were significant differences in the mean R540/R575 ratios of HbO2 bands for four different kinds of gastric epithelial tissues in vitro ( P < 0.01).

  8. Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis

    PubMed Central

    Wang, Hai-Sheng; Nie, Xiaobo; Wu, Rui-Bing; Yuan, Hong-Wei; Ma, Yue-Hong; Liu, Xiu-Lan; Zhang, Jian-Yu; Deng, Xiu-Ling; Na, Qin; Jin, Hai-Yan; Bian, Yan-Chao; Gao, Yu-Min; Wang, Yan-Dong; Chen, Wei-Dong

    2016-01-01

    Aberrant activation of Wnt/β-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer. PMID:27390525

  9. Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue

    PubMed Central

    Wen, Yanghui; Da, Mingxu; Zhang, Yongbin; Peng, Lingzhi; Yao, Jibin; Duan, Yaoxing

    2015-01-01

    Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ2 test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (< 5 cm) compared with large tumors (≥ 5 cm), with a statistically significant difference respectively (P = 0.016, P = 0.009). A decline linear trend appeared when analyzing the statistical difference of VDR expression among normal, premalignant, and malignant gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer. PMID:26722516

  10. Potential prognostic, diagnostic and therapeutic markers for human gastric cancer

    PubMed Central

    Tsai, Ming-Ming; Wang, Chia-Siu; Tsai, Chung-Ying; Chi, Hsiang-Cheng; Tseng, Yi-Hsin; Lin, Kwang-Huei

    2014-01-01

    The high incidence of gastric cancer (GC) and its consequent mortality rate severely threaten human health. GC is frequently not diagnosed until a relatively advanced stage. Surgery is the only potentially curative treatment. Thus, early screening and diagnosis are critical for improving prognoses in patients with GC. Gastroscopy with biopsy is an appropriate method capable of aiding the diagnosis of specific early GC tumor types; however, the stress caused by this method together with it being excessively expensive makes it difficult to use it as a routine method for screening for GC on a population basis. The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of GC. Here, we review the serum-based tumor markers for GC and their clinical significance, focusing on discoveries from microarray/proteomics research. We also review tissue-based GC tumor markers and their clinical application, focusing on discoveries from immunohistochemical research. This review provides a brief description of various tumor markers for the purposes of diagnosis, prognosis and therapeutics, and we include markers already in clinical practice and various forthcoming biomarkers. PMID:25320517

  11. Inhibition of human and rat CYP1A1 enzyme by grapefruit juice compounds.

    PubMed

    Santes-Palacios, Rebeca; Romo-Mancillas, Antonio; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

    2016-09-01

    Cytochrome P4501A1 is involved in the metabolism of carcinogenic polycyclic aromatic hydrocarbons; therefore, its inhibition interferes with the carcinogenesis process induced by these compounds in rats. The human and rat CYP1A1 differ by 21% in amino acid sequence, including the active site of the enzyme; this difference may be an important factor when results obtained using animal models are interpolated to humans. Based on its previously reported CYP inhibitory properties, we studied the effects of two molecules contained within grapefruit juice, naringenin and 6',7'-dihydroxybergamottin, on human and rat CYP1A1 activity. For this purpose, the kinetics of inhibition as well as computational simulations were used. Naringenin and 6',7'-dihydroxybergamottin were found to be competitive inhibitors of human and rat CYP1A1. Additionally, naringenin exerted a mixed type inhibition effect on rat CYP1A1. Computational docking showed that inhibitors might block the oxidation of 7-ethoxyresorufin by binding to the CYP1A1 active site. Our results demonstrate the differences in CYP inhibitory mechanisms for the same molecule when CYP from different species are considered. PMID:27444380

  12. Roles of ZIC family genes in human gastric cancer.

    PubMed

    Ma, Gang; Dai, Weijie; Sang, Aiyu; Yang, Xiaozhong; Li, Qianjun

    2016-07-01

    The human zinc finger of the cerebellum (ZIC)family genes, comprised of 5 members, which are vertebrate homologues of the Drosophila odd-paired gene and encode zinc-finger transcription factors, have been shown to be involved in various diseases, including cancer. However, the roles of ZICs in human gastric cancer (GC) have not yet been fully elucidated. This study aimed to investigate the expression patterns of ZICs and determine their clinical significance in GC. The mRNA and protein expression levels of ZIC1-5 were detected by RT-qPCR and western blot analysis, respectively using 60 pairs of human GC and matched normal mucosa tissues. The expression pattern and subcellular localization of ZIC1 in 160 pairs of human GC and matched normal mucosa tissues were verified by immunohistochemistry. Moreover, the associations of ZIC1 expression with various clinicopathological characteristics and patient prognosis were evaluated. The mRNA and protein expression levels of ZIC1 were both found to be significantly decreased in the GC tissues compared to matched normal mucosa tissues (GC vs. normal, 2.15±0.69 vs. 4.28±0.95; P<0.001); however, ZIC2-5 expression exhibited no significant difference between the cancer and normal tissue samples. In addition, the downregulation of ZIC1 (ZIC1-low) was more frequently observed in the GC tissues with positive lymph node metastasis (P=0.006), an advanced TNM stage (P<0.001) and a great depth of invasion (P=0.01). Notably, a low ZIC1 expression was significantly associated with a poor disease-free and overall survival. Furthermore, multivariate analysis revealed that ZIC1 expression was an independent prognostic marker for patients with GC. In conclusion, among the human ZIC family genes, the dysregulation of ZIC1, but not of ZIC2, ZIC3, ZIC4 and ZIC5, may play a crucial role in the progression of GC. ZIC1 may thus serve as a novel molecular marker to predict the progression, survival and relapse of patients with GC. PMID

  13. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers

    PubMed Central

    Hanley, Michael J; Masse, Gina; Harmatz, Jerold S; Cancalon, Paul F; Dolnikowski, Gregory G; Court, Michael H; Greenblatt, David J

    2013-01-01

    Aim The present study evaluated the possibility of drug interactions involving blueberry juice (BBJ) and substrate drugs whose clearance is dependent on cytochromes P4503A (CYP3A) and P4502C9 (CYP2C9). Methods A 50:50 mixture of lowbush and highbush BBJ was evaluated in vitro as an inhibitor of CYP3A activity (hydroxylation of triazolam and dealkylation of buspirone) and of CYP2C9 activity (flurbiprofen hydroxylation) using human liver microsomes. In clinical studies, clearance of oral buspirone and oral flurbiprofen was studied in healthy volunteers with and without co-treatment with BBJ. Results BBJ inhibited CYP3A and CYP2C9 activity in vitro, with 50% inhibitory concentrations (IC50) of less than 2%, but without evidence of mechanism-based (irreversible) inhibition. Grapefruit juice (GFJ) also inhibited CYP3A activity, but inhibitory potency was increased by pre-incubation, consistent with mechanism-based inhibition. In clinical studies, GFJ significantly increased area under the plasma concentration−time curve (AUC) for the CYP3A substrate buspirone. The geometric mean ratio (GMR = AUC with GFJ divided by AUC with water) was 2.12. In contrast, the effect of BBJ (GMR = 1.39) was not significant. In the study of flurbiprofen (CYP2C9 substrate), the positive control inhibitor fluconazole significantly increased flurbiprofen AUC (GMR = 1.71), but BBJ had no significant effect (GMR = 1.03). Conclusion The increased buspirone AUC associated with BBJ is quantitatively small and could have occurred by chance. BBJ has no effect on flurbiprofen AUC. The studies provide no evidence for concern about clinically important pharmacokinetic drug interactions of BBJ with substrate drugs metabolized by CYP3A or CYP2C9. PMID:22943633

  14. Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity.

    PubMed

    Guo, L Q; Fukuda, K; Ohta, T; Yamazoe, Y

    2000-07-01

    With juices of grapefruit and related fruits, possible relationships between contents of six different furanocoumarins and extents of inhibition of microsomal CYP3A activity have been studied in vitro. Microsomal CYP3A-mediated testosterone 6beta-hydroxylation was inhibited by the addition of a fruit juice (2.5%, v/v) from eight different grapefruit sources, two sweeties, three pomelos, and one sour orange, whereas no clear inhibition was observed with two sweet orange juices. The inhibitory component in grapefruit juice resides mainly in the precipitate rather than in the supernatant after centrifugation. Higher amounts of (R)-6',7'-dihydroxybergamottin (DHB) were distributed in the supernatant, whereas GF-I-1, GF-I-2, GF-I-4, and the newly isolated GF-I-5 and GF-I-6 were detected predominantly in the precipitate. Mixing of five representative furanocoumarins at their detectable levels in grapefruit juice reproduced roughly the inhibitory potencies of grapefruit juice, but omission of any of the components resulted in decreased potencies. These results suggested that all the major furanocoumarins contributed to the CYP3A inhibitory properties of grapefruit juice. Furthermore, all six furanocoumarins showed stronger CYP3A inhibitory potencies after preincubation in the presence of NADPH, suggesting that both competitive and mechanism-based inhibition occur in a grapefruit juices-drug interaction. PMID:10859150

  15. Novel method to assess gastric emptying in humans: the Pellet Gastric Emptying Test

    NASA Technical Reports Server (NTRS)

    Choe, S. Y.; Neudeck, B. L.; Welage, L. S.; Amidon, G. E.; Barnett, J. L.; Amidon, G. L.

    2001-01-01

    To further validate the Pellet Gastric Emptying Test (PGET) as a marker of gastric emptying, a randomized, four-way crossover study was conducted with 12 healthy subjects. The study consisted of oral co-administration of enteric coated caffeine (CAFF) and acetaminophen (APAP) pellets in four treatment phases: Same Size (100 kcal), Fasted, Small Liquid Meal (100 kcal), and Standard Meal (847 kcal). The time of first appearance of measurable drug marker in plasma, t(initial), was taken as the emptying time for the markers. Co-administration of same size enteric coated pellets of CAFF and APAP (0.7 mm in diameter) revealed no statistically significant differences in t(initial) values indicating that emptying was dependent only on size and not on chemical make-up of the pellets. Co-administration of different size pellets indicated that the smaller 0.7-mm diameter (CAFF) pellets were emptied and absorbed significantly earlier than the larger 3.6-mm diameter (APAP) pellets with both the Small Liquid Meal (by 35 min) and the Standard Meal (by 33 min) (P<0.05). The differences in emptying of the pellets were not significant in the Fasted Phase. The results suggest that the pellet gastric emptying test could prove useful in monitoring changes in transit times in the fasted and fed states and their impact on drug absorption.

  16. Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

    PubMed Central

    Magalhães, Ana; Marcos-Pinto, Ricardo; Nairn, Alison V.; Rosa, Mitche dela; Ferreira, Rui M.; Junqueira-Neto, Susana; Freitas, Daniela; Gomes, Joana; Oliveira, Patrícia; Santos, Marta R.; Marcos, Nuno T.; Xiaogang, Wen; Figueiredo, Céu; Oliveira, Carla; Dinis-Ribeiro, Mário; Carneiro, Fátima; Moremen, Kelley W.; David, Leonor; Reis, Celso A.

    2015-01-01

    Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local proinflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity. PMID:26144047

  17. Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection

    PubMed Central

    Xiao, Hua; Zhang, Yan; Kim, Yong; Kim, Sung; Kim, Jae Joon; Kim, Kyoung Mee; Yoshizawa, Janice; Fan, Liu-Yin; Cao, Cheng-Xi; Wong, David T. W.

    2016-01-01

    Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation. PMID:26911362

  18. Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection.

    PubMed

    Xiao, Hua; Zhang, Yan; Kim, Yong; Kim, Sung; Kim, Jae Joon; Kim, Kyoung Mee; Yoshizawa, Janice; Fan, Liu-Yin; Cao, Cheng-Xi; Wong, David T W

    2016-01-01

    Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation. PMID:26911362

  19. Inhibitory effects of dobutamine on human gastric adenocarcinoma

    PubMed Central

    Zheng, Hui-Xia; Wu, Li-Na; Xiao, Hong; Du, Qian; Liang, Jian-Fang

    2014-01-01

    AIM: To explore the inhibitory effects of dobutamine on gastric adenocarcinoma cells. METHODS: Dobutamine was used to treat gastric adenocarcinoma cells (SGC-7901) and cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of dobutamine combined with cisplatin on cell viability were also analyzed. Cell migration was studied using the wound healing assay, and cell proliferation was analyzed using the colony formation assay. A cell invasion assay was carried out using Transwell cell culture chambers. The cell cycle and cell apoptosis were analyzed by flow cytometry. Western blot and immunocytochemistry were performed to determine the expression of Yes-associated protein (YAP) in treated cells. RESULTS: Dobutamine significantly inhibited cell growth, migration, cell colony formation, and cell invasion into Matrigel. Dobutamine also arrested the cell cycle at G1/S phase, and increased the rate of apoptosis of gastric adenocarcinoma cells. The expression of YAP was detected mainly in the nucleus in the absence of dobutamine. However, reduced expression of phosphorylated YAP was mainly found in the cytosol following treatment with dobutamine. CONCLUSION: Dobutamine has significant inhibitory effects on gastric adenocarcinoma cells and may be used in neoadjuvant therapy not only for gastric cancer, but also for other tumors. PMID:25493021

  20. Flavonoid Fraction of Orange and Bergamot Juices Protect Human Lung Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Stress.

    PubMed

    Ferlazzo, Nadia; Visalli, Giuseppa; Smeriglio, Antonella; Cirmi, Santa; Lombardo, Giovanni Enrico; Campiglia, Pietro; Di Pietro, Angela; Navarra, Michele

    2015-01-01

    It has been reported that oxidant/antioxidant imbalance triggers cell damage that in turn causes a number of lung diseases. Flavonoids are known for their health benefits, and Citrus fruits juices are one of the main food sources of these secondary plant metabolites. The present study was designed to evaluate the effect of the flavonoid fraction of bergamot and orange juices, on H2O2-induced oxidative stress in human lung epithelial A549 cells. First we tested the antioxidant properties of both extracts in cell-free experimental models and then we assayed their capability to prevent the cytotoxic effects induced by H2O2. Our results demonstrated that both Citrus juice extracts reduce the generation of reactive oxygen species and membrane lipid peroxidation, improve mitochondrial functionality, and prevent DNA-oxidative damage in A549 cells incubated with H2O2. Our data indicate that the mix of flavonoids present in both bergamot and orange juices may be of use in preventing oxidative cell injury and pave the way for further research into a novel healthy approach to avoid lung disorders. PMID:26221182

  1. Discovery of human urinary biomarkers of aronia-citrus juice intake by HPLC-q-TOF-based metabolomic approach.

    PubMed

    Llorach, Rafael; Medina, Sonia; García-Viguera, Cristina; Zafrilla, Pilar; Abellán, José; Jauregui, Olga; Tomás-Barberán, Francisco A; Gil-Izquierdo, Angel; Andrés-Lacueva, Cristina

    2014-06-01

    Metabolomics has emerged in the field of food and nutrition sciences as a powerful tool for doing profiling approaches. In this context, HPLC-q-TOF-based metabolomics approach was applied to unveil changes in the urinary metabolome in human subjects (n = 51, 23 men and 28 women) after regular aronia-citrus juice (AC-juice) intake (250 mL/day) during 16 weeks compared to individuals given a placebo beverage. Samples were analyzed by HPLC-q-TOF followed by multivariate data analysis (orthogonal signal filtering-partial least square discriminant analysis) that discriminated relevant mass features related to AC-juice intake. The results showed that biomarkers of AC-juice intake including metabolites coming from metabolism of food components as proline betaine, ferulic acid, and two unknown mercapturate derivatives were identified. Discovery of new biomarkers of food intake will help in the building up of the food metabolome and facilitate future insights into the mechanisms of action of dietary components in population health. PMID:24616048

  2. Flavonoid Fraction of Orange and Bergamot Juices Protect Human Lung Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Stress

    PubMed Central

    Ferlazzo, Nadia; Visalli, Giuseppa; Smeriglio, Antonella; Cirmi, Santa; Lombardo, Giovanni Enrico; Campiglia, Pietro; Di Pietro, Angela; Navarra, Michele

    2015-01-01

    It has been reported that oxidant/antioxidant imbalance triggers cell damage that in turn causes a number of lung diseases. Flavonoids are known for their health benefits, and Citrus fruits juices are one of the main food sources of these secondary plant metabolites. The present study was designed to evaluate the effect of the flavonoid fraction of bergamot and orange juices, on H2O2-induced oxidative stress in human lung epithelial A549 cells. First we tested the antioxidant properties of both extracts in cell-free experimental models and then we assayed their capability to prevent the cytotoxic effects induced by H2O2. Our results demonstrated that both Citrus juice extracts reduce the generation of reactive oxygen species and membrane lipid peroxidation, improve mitochondrial functionality, and prevent DNA-oxidative damage in A549 cells incubated with H2O2. Our data indicate that the mix of flavonoids present in both bergamot and orange juices may be of use in preventing oxidative cell injury and pave the way for further research into a novel healthy approach to avoid lung disorders. PMID:26221182

  3. Living cells of probiotic Bifidobacterium bifidum YIT 10347 detected on gastric mucosa in humans.

    PubMed

    Shibahara-Sone, H; Gomi, A; Iino, T; Kano, M; Nonaka, C; Watanabe, O; Miyazaki, K; Ohkusa, T

    2016-06-01

    The probiotic strain Bifidobacterium bifidum YIT 10347 has been demonstrated to inhibit Helicobacter pylori activity, prevent injury to the gastric mucosa, and improve general gastric malaise symptoms in H. pylori positive patients. This study aimed to investigate the adhering activity and localisation of B. bifidum YIT 10347 to gastric cells and tissue in vitro, and in human in vivo to clarify the mechanism of its beneficial effects on the stomach. The in vitro study found the adhesion rate of B. bifidum YIT 10347 to human gastric epithelial cells was about 10 times higher than that of lactic acid bacteria and other bifidobacteria. In the human study, 5 H. pylori negative and 12 H. pylori positive subjects ingested milk fermented with B. bifidum YIT 10347. B. bifidum YIT 10347 cells were measured by RT-qPCR for in gastric biopsy samples. Living B. bifidum YIT 10347 cells were detected in the biopsy samples in H. pylori negative subjects (105 cells/g and 104 cells/g at 1 h and 2 h after ingestion, respectively) and H. pylori positive subjects (104 cells/g at 1 h after the ingestion). Moreover, immunostaining analysis of tissue sections found that B. bifidum YIT 10347 cells were located at the interstitial mucin layer of the stomach. These results suggest that cells of probiotic B. bifidum YIT 10347 adhered to the human gastric mucosa in a live state, and that the higher adhering activity of B. bifidum YIT 10347 to the gastric mucosa may be involved in its beneficial effects on the human stomach. PMID:26925600

  4. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice.

    PubMed

    Erlund, I; Meririnne, E; Alfthan, G; Aro, A

    2001-02-01

    The flavanones naringenin and hesperetin exhibit estrogenic, anticarcinogenic and antioxidative properties. Orange juice and grapefruit juice contain high amounts of these compounds, and therefore their intake from the diet can be relatively high. No data are available regarding plasma concentrations or plasma kinetics of flavanones. The objectives of this study were to develop methods allowing the analysis of naringenin and hesperetin from plasma and urine and to study their plasma kinetics and urinary excretion. We also wanted to assess whether plasma or urine flavanone concentrations can be used as biomarkers of intake. Healthy volunteers ingested orange juice (five women and three men) or grapefruit juice (two women and three men) once (8 mL/kg). Eleven blood samples and urine were collected between 0 and 24 h after juice administration. Flavanones were analyzed by HPLC with electrochemical detection. Naringenin and hesperetin were bioavailable from the studied juices, but interindividual variation in bioavailability was remarkable. The resulting plasma concentrations were comparatively high, and the peak plasma concentrations (C(max)) were 0.6 +/- 0.4 micromol/L (means +/- SD) for naringenin from orange juice and 6.0 +/- 5.4 micromol/L for naringenin from grapefruit juice. The corresponding value for hesperetin from orange juice was 2.2 +/- 1.6 micromol/L. The elimination half-lives were between 1.3 and 2.2 h, and therefore plasma concentrations reflect short-term intake. The relative urinary excretion varied depending on the flavanone source and dose and was 30.2 +/- 25.5% and 1.1 +/- 0.8% for naringenin from grapefruit juice and orange juice, respectively, and 5.3 +/- 3.1% for hesperetin from orange juice. The considerable difference in the relative urinary excretion of naringenin from the two juices was most likely caused by dose-dependent renal clearance rather than differences in bioavailability (as indicated by the similar C(max)-to-dose ratios). The

  5. Microvessel density is a prognostic marker of human gastric cancer

    PubMed Central

    Zhao, Hong-Chuan; Qin, Rong; Chen, Xiao-Xin; Sheng, Xia; Wu, Ji-Feng; Wang, Dao-Bin; Chen, Gui-Hua

    2006-01-01

    AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis. METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohistochemical staining. To assess tumor angiogenesis, MVD was determined by immunohistochemical staining of endothelial protein factor VIII-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer. PMID:17171787

  6. Probiotic and technological properties of Lactobacillus spp. strains from the human stomach in the search for potential candidates against gastric microbial dysbiosis.

    PubMed

    Delgado, Susana; Leite, Analy M O; Ruas-Madiedo, Patricia; Mayo, Baltasar

    2014-01-01

    This work characterizes a set of lactobacilli strains isolated from the stomach of healthy humans that might serve as probiotic cultures. Ten different strains were recognized by rep-PCR and PFGE fingerprinting among 19 isolates from gastric biopsies and stomach juice samples. These strains belonged to five species, Lactobacillus gasseri (3), Lactobacillus reuteri (2), Lactobacillus vaginalis (2), Lactobacillus fermentum (2) and Lactobacillus casei (1). All ten strains were subjected to a series of in vitro tests to assess their functional and technological properties, including acid resistance, bile tolerance, adhesion to epithelial gastric cells, production of antimicrobial compounds, inhibition of Helicobacter pylori, antioxidative activity, antibiotic resistance, carbohydrate fermentation, glycosidic activities, and ability to grow in milk. As expected, given their origin, all strains showed good resistance to low pH (3.0), with small reductions in counts after 90 min exposition to this pH. Species- and strain-specific differences were detected in terms of the production of antimicrobials, antagonistic effects toward H. pylori, antioxidative activity and adhesion to gastric epithelial cells. None of the strains showed atypical resistance to a series of 16 antibiotics of clinical and veterinary importance. Two L. reuteri strains were deemed as the most appropriate candidates to be used as potential probiotics against microbial gastric disorders; these showed good survival under gastrointestinal conditions reproduced in vitro, along with strong anti-Helicobacter and antioxidative activities. The two L. reuteri strains further displayed appropriated technological traits for their inclusion as adjunct functional cultures in fermented dairy products. PMID:25642213

  7. Probiotic and technological properties of Lactobacillus spp. strains from the human stomach in the search for potential candidates against gastric microbial dysbiosis

    PubMed Central

    Delgado, Susana; Leite, Analy M. O.; Ruas-Madiedo, Patricia; Mayo, Baltasar

    2015-01-01

    This work characterizes a set of lactobacilli strains isolated from the stomach of healthy humans that might serve as probiotic cultures. Ten different strains were recognized by rep-PCR and PFGE fingerprinting among 19 isolates from gastric biopsies and stomach juice samples. These strains belonged to five species, Lactobacillus gasseri (3), Lactobacillus reuteri (2), Lactobacillus vaginalis (2), Lactobacillus fermentum (2) and Lactobacillus casei (1). All ten strains were subjected to a series of in vitro tests to assess their functional and technological properties, including acid resistance, bile tolerance, adhesion to epithelial gastric cells, production of antimicrobial compounds, inhibition of Helicobacter pylori, antioxidative activity, antibiotic resistance, carbohydrate fermentation, glycosidic activities, and ability to grow in milk. As expected, given their origin, all strains showed good resistance to low pH (3.0), with small reductions in counts after 90 min exposition to this pH. Species- and strain-specific differences were detected in terms of the production of antimicrobials, antagonistic effects toward H. pylori, antioxidative activity and adhesion to gastric epithelial cells. None of the strains showed atypical resistance to a series of 16 antibiotics of clinical and veterinary importance. Two L. reuteri strains were deemed as the most appropriate candidates to be used as potential probiotics against microbial gastric disorders; these showed good survival under gastrointestinal conditions reproduced in vitro, along with strong anti-Helicobacter and antioxidative activities. The two L. reuteri strains further displayed appropriated technological traits for their inclusion as adjunct functional cultures in fermented dairy products. PMID:25642213

  8. Adenoviral Delivery of the EMX2 Gene Suppresses Growth in Human Gastric Cancer

    PubMed Central

    Li, Jie; Mo, Minli; Chen, Zhao; Chen, Zhe; Sheng, Qing; Mu, Hang; Zhang, Fang; Zhang, Yi; Zhi, Xiu-Yi; Li, Hui; He, Biao; Zhou, Hai-Meng

    2012-01-01

    Background EMX2 is a human orthologue of the Drosophila empty spiracles homeobox gene that has been implicated in embryogenesis. Recent studies suggest possible involvement of EMX2 in human cancers; however, the role of EMX2 in carcinogenesis needs further exploration. Results In this study, we reported that down-regulation of EMX2 expression was significantly correlated with EMX2 promoter hypermethylation in gastric cancer. Restoring EMX2 expression using an adenovirus delivery system in gastric cancer cell lines lacking endogenous EMX2 expression led to inhibition of cell proliferation and Wnt signaling pathway both in vitro and in a gastric cancer xenograft model in vivo. In addition, we observed that animals treated with the adenoviral EMX2 expression vector had significantly better survival than those treated with empty adenoviral vector. Conclusion Our study suggests that EMX2 is a putative tumor suppressor in human gastric cancer. The adenoviral-EMX2 may have potential as a novel gene therapy for the treatment of patients with gastric cancer. PMID:23029345

  9. [Biologic and molecular genetic properties of a transplantable human primary gastric cancer in nude mice].

    PubMed

    Chen, S S

    1989-05-01

    A human primary gastric cancer tissue (adenocarcinoma II-III) was transplanted into nude mice (SWISS/DF. nu/nu). It has been transferred for 8 generations at 56 sites in 28 nude mice with transplantable rate of 100%. The transplanted tumor is designated as transplantable human primary gastric cancer-1 in nude mice (THPGC-1). The growth of THPGC-1 is rather rapid and the size of transplanted tumor reaches 1 cm2, 4-5 weeks after transfer. The morphology and histochemistry of the original tumor were retained well in the initial and serial transplanted tumors. THPGC-1 could secret carcinoembryonic antigen (CEA). After intravenous or intraperitoneal injection of 131I-antiCEA monoclonal antibody into the THPGC-1 bearing nude mice, the radiolabeled antibody was concentrated and localized in the tumor as shown by gamma-camera analysis. Similar pattern of lactate dehydrogenase isoenzyme was observed both in primary gastric cancer tissue and THPGC-1 tissue. Chromosomal examination revealed that THPGC-1 was human aneuploid ones. Southern blot analysis showed that the pattern of repetitive DNA bands and the structures of 28s, rDNA, c-H-ras and c-myc genes in THPGC-1 were identical to the original primary gastric cancer DNA. The results suggest that THPGC-1 be a reliable model for the research of the molecular biology of cancer cells and experimental gastric cancer diagnosis and treatment. PMID:2693024

  10. Inhibition selectivity of grapefruit juice components on human cytochromes P450.

    PubMed

    Tassaneeyakul, W; Guo, L Q; Fukuda, K; Ohta, T; Yamazoe, Y

    2000-06-15

    Five compounds including furanocoumarin monomers (bergamottin, 6', 7'-dihydroxybergamottin (DHB)), furanocoumarin dimers (4-¿¿6-hydroxy-71-¿(1-hydroxy-1-methyl)ethyl-4-methyl-6-(7-oxo-7H- furo¿3,2-g1benzopyran-4-yl)-4-hexenyl]oxy]-3,7-dimethyl- 2-octenyl]oxy]-7H-furo[3,2-g]¿1benzopyran-7-one (GF-I-1) and 4-¿¿6-hydroxy-7¿¿4-methyl-1-(1-methylethenyl)-6-(7-oxo-7H-furo¿3, 2-g1benzopyran-4-yl)-4-hexenylŏxy-3, 7-dimethyl-2-octenylŏxy-7H-furo¿3,2-g1benzopyran-7-one (GF-I-4)), and a sesquiterpene nootkatone have been isolated from grapefruit juice and screened for their inhibitory effects toward human cytochrome P450 (P450) forms using selective substrate probes. Addition of ethyl acetate extract of grapefruit juice into an incubation mixture resulted in decreased activities of CYP3A4, CYP1A2, CYP2C9, and CYP2D6. All four furanocoumarins clearly inhibited CYP3A4-catalyzed nifedipine oxidation in concentration- and time-dependent manners, suggesting that these compounds are mechanism-based inhibitors of CYP3A4. Of the furanocoumarins investigated, furanocoumarin dimers, GF-I-1 and GF-I-4, were the most potent inhibitors of CYP3A4. Inhibitor concentration required for half-maximal rate of inactivation (K(I)) values for bergamottin, DHB, GF-I-1, and GF-I-4 were calculated, respectively, as 40.00, 5. 56, 0.31, and 0.13 microM, whereas similar values were observed on their inactivation rate constant at infinite concentration of inhibitor (k(inact), 0.05-0.08 min(-1)). Apparent selectivity toward CYP3A4 does occur with the furanocoumarin dimers. In contrast, bergamottin showed rather stronger inhibitory effect on CYP1A2, CYP2C9, CYP2C19, and CYP2D6 than on CYP3A4. DHB inhibited CYP3A4 and CYP1A2 activities at nearly equivalent potencies. Among P450 forms investigated, CYP2E1 was the least sensitive to the inhibitory effect of furanocoumarin components. A sesquiterpene nootkatone has no significant effect on P450 activities investigated except for CYP2A6 and CYP2C19

  11. Gastric digestion of α-lactalbumin in adult human subjects using capsule endoscopy and nasogastric tube sampling.

    PubMed

    Sullivan, Louise M; Kehoe, Joseph J; Barry, Lillian; Buckley, Martin J M; Shanahan, Fergus; Mok, K H; Brodkorb, André

    2014-08-28

    In the present study, structural changes in the milk protein α-lactalbumin (α-LA) and its proteolysis were investigated for the potential formation of protein-fatty acid complexes during in vivo gastric digestion. Capsule endoscopy allowed visualisation of the digestion of the test drinks, with nasogastric tubes allowing sampling of the gastric contents. A total of ten healthy volunteers had nasogastric tubes inserted into the stomach and ingested test drinks containing 50 g/l of sucrose and 25 g/l of α-LA with and without 4 g/l of oleic acid (OA). The samples of gastric contents were collected for analysis at 3 min intervals. The results revealed a rapid decrease in the pH of the stomach of the subjects. The fasting pH of 2·31 (SD 1·19) increased to a pH maxima of pH 6·54 (SD 0·29) after ingestion, with a subsequent decrease to pH 2·22 (SD 1·91) after 21 min (n 8). Fluorescence spectroscopy and Fourier transform IR spectroscopy revealed partial protein unfolding, coinciding with the decrease in pH below the isoelectric point of α-LA. The activity of pepsin in the fasting state was found to be 39 (SD 12) units/ml of gastric juice. Rapid digestion of the protein occurred: after 15 min, no native protein was detected using SDS-PAGE; HPLC revealed the presence of small amounts of native protein after 24 min of gastric digestion. Mirocam® capsule endoscopy imaging and video clips (see the online supplementary material) revealed that gastric peristalsis resulted in a heterogeneous mixture during gastric digestion. Unfolding of α-LA was observed during gastric transit; however, there was no evidence of a cytotoxic complex being formed between α-LA and OA. PMID:24967992

  12. Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

    NASA Astrophysics Data System (ADS)

    Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

    2008-02-01

    Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

  13. Expression of interleukin-8 correlates with vascularity in human gastric carcinomas.

    PubMed Central

    Kitadai, Y.; Haruma, K.; Sumii, K.; Yamamoto, S.; Ue, T.; Yokozaki, H.; Yasui, W.; Ohmoto, Y.; Kajiyama, G.; Fidler, I. J.; Tahara, E.

    1998-01-01

    Interleukin (IL)-8 is a multifunctional cytokine that can stimulate the division of endothelial cells. We examined the expression of IL-8 mRNA using Northern blot analysis and in situ mRNA hybridization (ISH) and protein production using enzyme-linked immunosorbent assay and immunohistochemistry in 8 human gastric carcinoma cell lines and 39 gastric carcinomas and corresponding normal mucosa (34 surgical specimens and 5 biopsy specimens). Of the 8 human gastric carcinoma cell lines, 6 expressed 1.8-kb IL-8 mRNA and secreted various levels of IL-8 protein. The expression of IL-8 by TMK-1 cells was induced by exposure to IL-1 alpha, epidermal growth factor, and transforming growth factor-alpha, shown previously to be autocrine growth stimulators for human gastric carcinoma cells. In tumor tissues, most of the tumors (28 of 34 surgical specimens and 4 of 5 biopsy specimens) expressed IL-8 at higher levels than the corresponding normal mucosa. ISH and immunohistochemical analyses revealed that IL-8 mRNA and protein were localized in the cytoplasm of tumor cells. The number of blood vessels in the gastric carcinomas was determined by using antibodies against CD34. The level of IL-8 mRNA in the neoplasms strongly correlated with vascularization (Spearman correlation, r = 0.812; P = 0.001). The data suggest that IL-8 produced by tumor cells may regulate neovascularization and, hence, the growth and spread of human gastric carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9422527

  14. PEITC reverse multi-drug resistance of human gastric cancer SGC7901/DDP cell line.

    PubMed

    Tang, Tao; Song, Xin; Liu, Yu-Fen; Wang, Wen-Yue

    2014-04-01

    Gastric cancer is one of the leading causes of cancer death in the world and nearly all patients who respond initially to cisplatin later develop drug resistance, indicating multi-drug resistance is an essential aspect of the failure of treatment. Phenethyl isothiocyanate (PEITC) has been implicated in inhibiting metastasis of several types of human cancer. However, the effect and potential mechanism of PEITC reversed multi-drug resistance of human gastric cancer is not fully clear. We have identified the role of PEITC in multi-drug resistance reversal of human gastric cancer SGC7901/DDP cell line. PEITC inhibited cisplatin-resistant human SGC7901/DDP cell growth in a dose-dependent manner, causing increased apoptosis, ROS generation, glutathione depletion, accumulation of Rhodamine-123, decreased expression of P-glycoprotein and cell cycle arrest. mRNA and protein expression of the multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), survivin, and Mad2 was decreased, and phosphorylation of Akt and transcriptional activation of NF-κB were suppressed. PEITC may be useful as the therapeutic strategy for overcoming multi-drug resistance through suppressing the PI3K-Akt pathway in human gastric cancer. PMID:23956061

  15. Characterization, Purification of Poncirin from Edible Citrus Ougan (Citrus reticulate cv. Suavissima) and Its Growth Inhibitory Effect on Human Gastric Cancer Cells SGC-7901

    PubMed Central

    Zhu, Xiaoyan; Luo, Fenglei; Zheng, Yixiong; Zhang, Jiukai; Huang, Jianzhen; Sun, Chongde; Li, Xian; Chen, Kunsong

    2013-01-01

    Poncirin is a bitter flavanone glycoside with various biological activities. Poncirin was isolated from four different tissues (flavedo, albedo, segment membrane, and juice sac) of Ougan fruit (Citrus reticulate cv. Suavissima). The highest content of poncirin was found in the albedo of Ougan fruit (1.37 mg/g DW). High speed counter-current chromatography (HSCCC) combined with D101 resin chromatography was utilized for the separation and purification of poncirin from the albedo of Ougan fruit. After this two-step purification, poncirin purity increased from 0.14% to 96.56%. The chemical structure of the purified poncirin was identified by both HPLC-PDA and LC-MS. Poncirin showed a significant in vitro inhibitory effect on the growth of the human gastric cancer cells, SGC-7901, in a dose-dependent manner. Thus, poncirin from Ougan fruit, may be beneficial for gastric cancer prevention. The purification method demonstrated here will be useful for further studies on the pharmacological mechanism of poncirin activity, as well as for guiding the consumption of Ougan fruit. PMID:23615464

  16. Survival and expression of acid resistance genes in Shiga toxin-producing Escherichia coli acid adapted in pineapple juice and exposed to synthetic gastric fluid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aims: The aim of this research was to examine relative transcriptional expression of acid resistance (AR) genes, rpoS, gadA and adiA, in O157:H7 and non-O157 Shiga toxin-producing Escherichia coli (STEC) serotypes after adaptation to pineapple juice (PJ) and subsequently to determine survival with e...

  17. Reversal of radiocontrast medium toxicity in human renal proximal tubular cells by white grape juice extract.

    PubMed

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Russo, Domenico; Mattivi, Fulvio; De Sarro, Giovambattista; Navarra, Michele; Michael, Ashour

    2015-03-01

    Radiocontrast media (RCM)-induced nephrotoxicity (CIN) is a major clinical problem accounting for 12% of all hospital-acquired cases of acute kidney injury. The pathophysiology of CIN is not well understood, but direct toxic effects on renal cells have been postulated as contributing to CIN. We have investigated the effect of a white grape (Vitis vinifera) juice extract (WGJe) on human renal proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium diatrizoate. WGJe caused an increase in phosphorylation of the prosurvival kinases Akt and ERK1/2 in HK-2 cells. Treatment of HK-2 cells with 75 mgI/ml sodium diatrizoate for 2.5h and then further incubation (for 27.5h) after removal of the RCM caused a drastic decrease in cell viability. However, pre-treatment with WGJe, prior to incubation with diatrizoate, dramatically improved cell viability. Analysis of key signaling molecules by Western blotting showed that diatrizoate caused a drastic decrease in phosphorylation of Akt (Ser473), FOXO1 (Thr24) and FOXO3a (Thr32) during the initial 2.5h incubation period, and WGJe pre-treatment caused a reversal of these effects. Further analysis by Western blotting of samples from HK-2 cells cultured for longer periods of time (for up to 27.5h after an initial 2.5h exposure to diatrizoate with or without WGJe pre-treatment) showed that WGJe pre-treatment caused a negative effect on phosphorylation of p38, NF-κB (Ser276) and pERK1/2 whilst having a positive effect on the phosphorylation of Akt, FOXO1/FOXO3a and maintained levels of Pim-1 kinase. WGJe may alleviate RCM toxicity through modulation of signaling molecules that are known to be involved in cell death and cell survival and its possible beneficial effects should be further investigated. PMID:25603236

  18. [Gastric uptake of gallium67 in the human immunodeficiency virus infection].

    PubMed

    Escalera Temprado, T; Banzo Marraco, J; Abós Olivares, M D; Olave Rubio, M T; Prats Rivera, E; García López, F; Razola Alba, P

    2004-02-01

    Nowadays, the human immunodeficiency virus infection (HIV) is a chronic disease. In the frequent clinical situations with fever, lymph nodes and loss weight it is necessary to determine their etiology, for establishing a specific treatment. Gastrointestinal opportunistic infections or gastric lymphomatous or sarcomatous process, which can accumulate Ga67, may be present in the patient with acquired immunodeficiency syndrome. We report 2 cases with gastric uptake in which endoscopy and biopsy was obtained. In the first one, with previous treatment with omeprazol and almalgate for gastroesophagic reflux, endoscopy and biopsy were normal and in the second patient an Helicobacter pylori infection was diagnosed. We think that gastric uptake of Ga67 in HIV patients, must indicate to the clinician to rule out associated pathologies. PMID:14974895

  19. Differential growth factor induction and modulation of human gastric epithelial regeneration

    SciTech Connect

    Tetreault, Marie-Pier; Chailler, Pierre; Rivard, Nathalie; Menard, Daniel . E-mail: Daniel.Menard@USherbrooke.ca

    2005-05-15

    While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGF{alpha}, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGF{beta} pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGF{alpha} exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGF{alpha} and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair.

  20. Morphological evidence of neutrophil-tumor cell phagocytosis (cannibalism) in human gastric adenocarcinomas.

    PubMed

    Caruso, R A; Muda, A O; Bersiga, A; Rigoli, L; Inferrera, C

    2002-01-01

    The phenomenon of neutrophil-tumor cell emperipolesis or phagocytosis has been documented by light microscopy in various human carcinomas, but little is known about the cellular pathological processes and the morphological changes involved. In an attempt to clarify the nature of this phenomenon, the authors' ultrastructural studies on the relationships among neutrophils and tumor cells in human gastric carcinomas are reviewed and analyzed. At the electron microscopy level, apoptotic neutrophils were found within vacuoles of adenocarcinoma cells in 2 cases. They showed either early apoptotic morphology with perinuclear chromatin aggregation but cytoplasm integrity or late apoptotic morphology with uniform, collapsed nucleus and tightly packed cytoplasmic granules. A light microscopy review of 200 cases of resected gastric carcinomas identified 22 cases (11%) that were characterized by neutrophil-tumor cell phagocytosis (cannibalism). TUNEL staining confirmed the presence of apoptotic neutrophils within the cytoplasm of the tumor cells. This study provides light and electron microscopic evidence of apoptotic neutrophils phagocytosed by gastric adenocarcinoma cells. The morphological features of neutrophil-tumor cell phagocytosis (cannibalism) would suggest a particular mechanism of tumor-immune escape in human gastric carcinoma. PMID:12396242

  1. Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells

    PubMed Central

    Das, Soumita; Sarkar, Arup; Ryan, Kieran A.; Fox, Sarah; Berger, Alice H.; Juncadella, Ignacio J.; Bimczok, Diane; Smythies, Lesley E.; Harris, Paul R.; Ravichandran, Kodi S.; Crowe, Sheila E.; Smith, Phillip D.; Ernst, Peter B.

    2014-01-01

    After Helicobacter pylori infection in humans, gastric epithelial cells (GECs) undergo apoptosis due to stimulation by the bacteria or inflammatory cytokines. In this study, we assessed the expression and function of brain angiogenesis inhibitor 1 (BAI1) in the engulfment of apoptotic GECs using human tissue and cells. After induction of apoptosis by H. pylori or camptothecin, there was a 5-fold increase in the binding of apoptotic GECs to THP-1 cells or peripheral blood monocyte-derived macrophages as assayed by confocal microscopy or conventional and imaging flow cytometry. Binding was impaired 95% by pretreating apoptotic cells with annexin V, underscoring the requirement for phosphatidylserine recognition. The phosphatidylserine receptor BAI1 was expressed in human gastric biopsy specimens and gastric phagocytes. To confirm the role of BAI1 in apoptotic cell clearance, the functional domain of BAI1 was used as a competitive inhibitor or BAI1 expression was inhibited by small interfering RNA. Both approaches decreased binding and engulfment >40%. Exposing THP-1 cells to apoptotic cells inhibited IL-6 production from 1340 to <364 pg/ml; however, this decrease was independent of phagocytosis. We conclude that recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti-inflammatory effects.—Das, S., Sarkar, A., Ryan, K. A., Fox, S., Berger, A. H., Juncadella, I. J., Bimczok, D., Smythies, L. E., Harris, P. R., Ravichandran, K. S., Crowe, S. E., Smith, P. D., Ernst, P. B. Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells. PMID:24509909

  2. Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma.

    PubMed

    Zhang, Bingchang; Wang, Fen; Dai, Lianzhi; Cai, Heguo; Zhan, Yanyan; Gang, Song; Hu, Tianhui; Xia, Chun; Zhang, Bing

    2016-02-16

    Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma. PMID:26811493

  3. Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma

    PubMed Central

    Zhang, Bingchang; Wang, Fen; Dai, Lianzhi; Cai, Heguo; Zhan, Yanyan; Gang, Song; Hu, Tianhui; Xia, Chun; Zhang, Bing

    2016-01-01

    Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma. PMID:26811493

  4. Predictive value of CHFR and MLH1 methylation in human gastric cancer

    PubMed Central

    Li, Yazhuo; Yang, Yunsheng; Lu, Youyong; Herman, James G.; Brock, Malcolm V.; Zhao, Po; Guo, Mingzhou

    2016-01-01

    Background Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. Methods The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan–Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. Results The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3 % (35/102), 21.6 % (22/102), 12.7 % (13/102), 9.8 % (10/102), and 0 % (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95 % CI, 0.069–0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95 % CI, 1.064–8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). Conclusions CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a

  5. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer.

    PubMed

    Kolin, David L; Sy, Keiyan; Rotondo, Fabio; Bassily, Mena N; Kovacs, Kalman; Brezden-Masley, Christine; Streutker, Catherine J; Yousef, George M

    2014-09-01

    The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer. PMID:25153389

  6. EGFR, HER-2 and KRAS in canine gastric epithelial tumors: a potential human model?

    PubMed

    Terragni, Rossella; Casadei Gardini, Andrea; Sabattini, Silvia; Bettini, Giuliano; Amadori, Dino; Talamonti, Chiara; Vignoli, Massimo; Capelli, Laura; Saunders, Jimmy H; Ricci, Marianna; Ricci, Marianna; Ulivi, Paola; Ulivi, Paola

    2014-01-01

    Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥ 1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer. PMID:24454858

  7. EGFR, HER-2 and KRAS in Canine Gastric Epithelial Tumors: A Potential Human Model?

    PubMed Central

    Bettini, Giuliano; Amadori, Dino; Talamonti, Chiara; Vignoli, Massimo; Capelli, Laura; Saunders, Jimmy H.; Ricci, Marianna; Ulivi, Paola

    2014-01-01

    Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer. PMID:24454858

  8. 21 CFR 73.260 - Vegetable juice.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Vegetable juice. 73.260 Section 73.260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.260 Vegetable juice. (a) Identity. (1) The color additive vegetable juice is prepared either...

  9. Bergamot juice extract inhibits proliferation by inducing apoptosis in human colon cancer cells.

    PubMed

    Visalli, Giuseppa; Ferlazzo, Nadia; Cirmi, Santa; Campiglia, Pietro; Gangemi, Sebastiano; Di Pietro, Angela; Calapai, Gioacchino; Navarra, Michele

    2014-01-01

    Colorectal cancer (CRC) is a leading cause of cancer mortality in the industrialized world, second to lung cancer. A lot of evidences highlight that a diet rich in fruits and vegetables may reduce the risk of some types of cancer including CRC. In this study we demonstrate that Citrus bergamia juice extracts (BJe) reduces CRC cell growth by multiple mechanisms. Low BJe concentrations inhibit MAPKs pathway and alter apoptosis-related proteins, that in turn induce cell cycle arrest and apoptosis in HT-29 cells. Instead, high concentrations of BJe induce oxidative stress causing DNA damage. Our study highlights the role of BJe as modulator of cell apoptosis in CRC cells and strengthens our previous hypothesis that the flavonoid fraction of bergamot juice may play a role as anti-cancer drug. PMID:25173561

  10. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells

    PubMed Central

    Lan, Huiyin; Tang, Zaiming; Jin, Hongchuan; Sun, Yi

    2016-01-01

    MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts as an indirect inhibitor of CRL by blocking cullin neddylation. Given that CRLs components are up-regulated, whereas neddylation modification is over-activated in a number of human cancers, MLN4924 was found to be effective in growth suppression of cancer cells. Whether MLN4924 is effective against gastric cancer cells, however, remains elusive. Here we showed that in gastric cancer cells, MLN4924 rapidly inhibited cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies in combination with siRNA knockdown-based rescue experiments revealed that MLN4924 induced the accumulation of a number of CRL substrates, including CDT1/ORC1, p21/p27, and PHLPP1 to trigger DNA damage response and induce growth arrest at the G2/M phase, to induce senescence, as well as autophagy, respectively. MLN4924 also significantly suppressed migration by transcriptionally activating E-cadherin and repressing MMP-9. Taken together, our study suggest that neddylation modification and CRL E3 ligase are attractive gastric cancer targets, and MLN4924 might be further developed as a potent therapeutic agent for the treatment of gastric cancer. PMID:27063292

  11. Anticancer activity of CopA3 dimer peptide in human gastric cancer cells.

    PubMed

    Lee, Joon Ha; Kim, In-Woo; Kim, Sang-Hee; Yun, Eun-Young; Nam, Sung-Hee; Ahn, Mi-Young; Kang, Dong-Chul; Hwang, Jae Sam

    2015-06-01

    CopA3 is a homodimeric α-helical peptide derived from coprisin which is a defensin-like antimicrobial peptide that was identified from the dung beetle, Copris tripartitus. CopA3 has been reported to have anticancer activity against leukemia cancer cells. In the present study, we investigated the anticancer activity of CopA3 in human gastric cancer cells. CopA3 reduced cell viability and it was cytotoxic to gastric cancer cells in the MTS and LDH release assay, respectively. CopA3 was shown to induce necrotic cell death of the gastric cancer cells by flow cytometric analysis and acridine orange/ethidium bromide staining. CopA3-induced cell death was mediated by specific interactions with phosphatidylserine, a membrane component of cancer cells. Taken together, these data indicated that CopA3 mainly caused necrosis of gastric cancer cells, probably through interactions with phosphatidylserine, which suggests the potential utility of CopA3 as a cancer therapeutic. PMID:25047444

  12. Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells.

    PubMed

    Lan, Huiyin; Tang, Zaiming; Jin, Hongchuan; Sun, Yi

    2016-01-01

    MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts as an indirect inhibitor of CRL by blocking cullin neddylation. Given that CRLs components are up-regulated, whereas neddylation modification is over-activated in a number of human cancers, MLN4924 was found to be effective in growth suppression of cancer cells. Whether MLN4924 is effective against gastric cancer cells, however, remains elusive. Here we showed that in gastric cancer cells, MLN4924 rapidly inhibited cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies in combination with siRNA knockdown-based rescue experiments revealed that MLN4924 induced the accumulation of a number of CRL substrates, including CDT1/ORC1, p21/p27, and PHLPP1 to trigger DNA damage response and induce growth arrest at the G2/M phase, to induce senescence, as well as autophagy, respectively. MLN4924 also significantly suppressed migration by transcriptionally activating E-cadherin and repressing MMP-9. Taken together, our study suggest that neddylation modification and CRL E3 ligase are attractive gastric cancer targets, and MLN4924 might be further developed as a potent therapeutic agent for the treatment of gastric cancer. PMID:27063292

  13. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

    PubMed

    Kang, J Y; Teng, C H; Wee, A; Chen, F C

    1995-05-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli. PMID:7541007

  14. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.

    PubMed Central

    Kang, J Y; Teng, C H; Wee, A; Chen, F C

    1995-01-01

    Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli. Images p665-a PMID:7541007

  15. Purification and assay of secretory lithostathine in human pancreatic juice by fast protein liquid chromatography.

    PubMed Central

    Mariani, A; Mezzi, G; Malesci, A

    1995-01-01

    Impaired secretion of lithostathine, a pancreatic glycoprotein capable of inhibiting the growth of CaCO3 crystals, has been reported in chronic calcifying pancreatitis. Controversial results were obtained, however, using immunoassays with different antibodies. The aim of this study was to purify and to measure juice lithostathine by a non-immunological method. Fast protein liquid chromatography (FPLC) on a cation exchange column eluted by a sodium chloride gradient, was used. The conditions appropriate to separate secretory (S) from hydrolysed (H) isoforms of immunopurified lithostathine were also used for juice analysis. Pancreatic juice was collected by endoscopic cannulation of the major pancreatic duct, after secretin stimulation, from eight patients with chronic pancreatitis (CP) and from eight controls. In all samples, S-isoforms of lithostathine (ranging from 16 to 19 Mr at SDS-PAGE) were the only constituent of two of the 15 peaks in which FPLC resolved the pancreatic proteins. The nature of these two peaks was confirmed by their coelution with immunopurified S-lithostathine and by immunoblot analysis with polyclonal anti-lithostathine antibodies. The ratio between the area of S-lithostathine peaks and the total area of proteic eluates, was always lower in CP patients (5.3 micrograms/mg of protein, median value; 0.2-15.4, range) than in controls (35.2 micrograms/mg; 16.6-55.9). It is concluded that lithostathine can be purified and measured in pancreatic juice by FPLC. Our results with a nonimmunological assay confirm a reduced secretion of lithostathine in patients with CP. Images Figure 2 Figure 4 Figure 5 PMID:7737574

  16. Human postprandial gastric emptying of 1-3-millimeter spheres.

    PubMed

    Meyer, J H; Elashoff, J; Porter-Fink, V; Dressman, J; Amidon, G L

    1988-06-01

    Microspheres of pancreatin should empty from the stomachs of patients with pancreatic insufficiency as fast as food. The present study was undertaken in 26 healthy subjects to identify the size of spheres that would empty from the stomach with food and to determine whether different meals alter this size. Spheres of predefined sizes were labeled with 113mIn or 99mTc. Using a gamma-camera, we studied the concurrent gastric emptying of spheres labeled with 113mIn and of chicken liver labeled with 99mTc in 100-g, 154-kcal or 420-g, 919-kcal meals, or the concurrent emptying of 1-mm vs. larger spheres. One-millimeter spheres emptied consistently (p less than 0.01, paired t-test) faster than 2.4- or 3.2-mm spheres when ingested together with either the 420- or 100-g meals. Thus, in the 1-3-mm range of diameters, sphere size was a more important determinant of sphere emptying than meal size. Statistical analyses indicated that spheres 1.4 +/- 0.3 mm in diameter with a density of 1 empty at the same rate as 99mTc-liver. Our data indicate some commercially marketed microspheres of pancreatin will empty too slowly to be effective in digestion of food. PMID:3360258

  17. Human postprandial gastric emptying of 1-3-millimeter spheres

    SciTech Connect

    Meyer, J.H.; Elashoff, J.; Porter-Fink, V.; Dressman, J.; Amidon, G.L.

    1988-06-01

    Microspheres of pancreatin should empty from the stomachs of patients with pancreatic insufficiency as fast as food. The present study was undertaken in 26 healthy subjects to identify the size of spheres that would empty from the stomach with food and to determine whether different meals alter this size. Spheres of predefined sizes were labeled with /sup 113m/In or /sup 99m/Tc. Using a gamma-camera, we studied the concurrent gastric emptying of spheres labeled with /sup 113m/In and of chicken liver labeled with /sup 99m/Tc in 100-g, 154-kcal or 420-g, 919-kcal meals, or the concurrent emptying of 1-mm vs. larger spheres. One-millimeter spheres emptied consistently (p less than 0.01, paired t-test) faster than 2.4- or 3.2-mm spheres when ingested together with either the 420- or 100-g meals. Thus, in the 1-3-mm range of diameters, sphere size was a more important determinant of sphere emptying than meal size. Statistical analyses indicated that spheres 1.4 +/- 0.3 mm in diameter with a density of 1 empty at the same rate as /sup 99m/Tc-liver. Our data indicate some commercially marketed microspheres of pancreatin will empty too slowly to be effective in digestion of food.

  18. Physico-chemical evaluation of bitter and non-bitter Aloe and their raw juice for human consumption.

    PubMed

    Azam, M M; Kumar, S; Pancholy, A; Patidar, M

    2014-11-01

    In addition to Aloe vera which is bitter in taste, a non-bitter Aloe is also found in arid part of Rajasthan. This non-bitter Aloe (NBA) is sporadically cultivated as vegetable and for health drink. In spite of its cultivation and various uses, very little information is available about its detailed botanical parameters and chemical characters. This study aims to evaluate the physico-chemical characters of NBA through employing floral morphology, leaf characters and leaf gel and to compare them with those of A. vera. Of eleven floral characters studied, eight characters of NBA were significantly different from that of A. vera. Most visible difference was observed in their reproductive shoots which are highly branched in NBA (5.21 inflorescence/shoot) as compared to A. vera (1.5 inflorescence/shoot). NBA produces less leaf-biomass (-29.32 %) with less leaf-thickness (-31.44 %) but higher leaf length, width, and no. of spine/side by 17.56 %, 21.34 % and 16.11 %, respectively, with significant difference as compared to A. vera. But its polysaccharide content (0.259 %) is at par with that of A. vera. The raw juice from the leaf of NBA has very low aloin content (4.1 ppm) compared to that from A. vera (427.3 ppm) making it a safer health drink compared to the one obtained from A. vera. Thus, NBA raw juice emerged as suitable alternative to A. vera juice for human consumption. PMID:26396351

  19. GLP-1 receptor is expressed in human stomach mucosa: analysis of its cellular association and distribution within gastric glands.

    PubMed

    Broide, Efrat; Bloch, Olga; Ben-Yehudah, Gilad; Cantrell, Dror; Shirin, Haim; Rapoport, Micha J

    2013-09-01

    The stomach is a target organ of the incretin hormone glucagon-like peptide-1 (GLP-1). However, the cellular expression and glandular distribution of its receptor (GLP-1R) in human gastric mucosa are not known. We determined the expression of GLP-1R in different regions of human stomach mucosa and its specific cellular association and distribution within gastric glands. Tissue samples from stomach body and antrum were obtained from 20 patients during routine esophagogastroduodenoscopy. mRNA encoding GLP-1R protein expression was evaluated by RT-PCR. Determination of cell types bearing GLP-1R, their localization, and their frequency in gastric glands in different gastric regions were estimated by immunohistochemical morphological analysis. Levels of GLP-1R mRNA were similar in body and antrum. GLP-1R immunoreactivity was found throughout the gastric mucosa in various types of glandular cells. The highest frequency of GLP-1R immunoreactive cells was found in the neck area of the principal glands in cells morphologically identified as parietal cells. GLP-1R immunostaining was also found on enteroendocrine-like cells in the pyloric glands. This study provides the first description of GLP-1R expression in human gastric glands and its specific cellular association. Our data suggest that GLP-1 may act directly on the gastric mucosa to modulate its complex functions. PMID:23803499

  20. Popular species of edible mushrooms as a good source of zinc to be released to artificial digestive juices.

    PubMed

    Zajac, M; Muszynska, B; Kala, K; Sikora, A; Opoka, W

    2015-10-01

    Because fruiting bodies of edible mushrooms accumulate elements very effectively, in this study for the first time we aimed at determining the degree of the release of zinc(II) ions to artificial digestive juices imitating the human gastrointestinal tract from freeze-dried popular edible mushroom fruiting bodies, such as Agaricus bisporus, Boletus badius and Cantharellus cibarius. For the analysis, anodic stripping voltammetry method was used. The amount of zinc released to artificial saliva within 1 minute ranged from 0.03 to 1.14 mg/100 g d.w. In gastric juice, the amounts were higher and ranged from 0.75 to 2.07 mg/100 g d.w. depending on the incubation time. After incubation of the freeze-dried edible mushroom fruiting bodies for 1 minute in artificial saliva, 15 in artificial gastric juice and then 150 minutes in artificial intestinal juice, it was found that the concentration of the released zinc in artificial intestinal juice was the highest and amounted to 6.44 mg/100 g d.w. The total average amount of zinc released from Boletus badius was the highest and this was estimated at 4.13 mg/100 g d.w. For the remaining two investigated species of A. bisporus and C. cibarius, the total amounts of zinc released into artificial digestive juices were only slightly lower and were estimated at 2.23 and 3.29 mg/100 g d.w. on average, respectively. It was demonstrated for the first time that mushrooms release zinc to artificial digestive juices imitating conditions in the human digestive tract and are a good source of this element. PMID:26579582

  1. The newly synthesized anticancer drug HUHS1015 is useful for treatment of human gastric cancer.

    PubMed

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nakao, Shuhei; Shimizu, Tadashi; Tanaka, Akito; Nishizaki, Tomoyuki

    2015-03-01

    Naftopidil is clinically for treatment of benign prostate hyperplasia, and emerging evidence has pointed to its anticancer effect. To obtain the anticancer drug with the potential greater than that of naftopidil, we have newly synthesized the naftopidil analogue HUHS1015. The present study investigated the mechanism underlying HUHS1015-induced apoptosis of human gastric cancer cells and assessed the possibility for clinical use as an innovative anticancer drug. HUHS1015 reduced cell viability for MKN28 human well-differentiated gastric adenocarcinoma cell line and MKN45 human poorly differentiated gastric adenocarcinoma cell line in a concentration (0.3-100 μM)-dependent manner more effectively than cisplatin, a chemo-drug widely used. In the flow cytometry using propidium iodide (PI) and annexin V, HUHS1015 significantly increased the population of PI-positive and annexin V-negative cells, corresponding to primary necrosis and that of PI-positive and annexin V-positive cells, corresponding to late apoptosis/secondary necrosis, both in the two cell types. HUHS1015 significantly activated caspase-3, caspase-4, and caspase-8 in MKN45 cells, while no obvious caspase activation was found in MKN28 cells. HUHS1015 upregulated expression of the tumor necrosis factor α (TNFα) mRNA and protein in MKN45 cells, allowing activation of caspase-8 through TNF receptor and the effector caspase-3. HUHS1015 clearly inhibited tumor growth in mice inoculated with MKN45 cells, with the survival rate higher than that for the anticancer drugs cisplatin, paclitaxel, and irinotecan. The results of the present study show that HUHS1015 induces caspase-independent and caspase-dependent apoptosis of MKN28 and MKN45 human gastric cancer cells, respectively, and effectively suppresses MKN45 cell proliferation. PMID:25567349

  2. Clearance of bile and trypsin in rat lungs following aspiration of human gastric fluid

    PubMed Central

    Leung, Jason H.; Chang, Jui-Chih; Foltz, Emily; Bell, Sadé M.; Pi, Cinthia; Azad, Sassan; Everett, Mary Lou; Holzknecht, Zoie E.; Sanders, Nathan L.; Parker, William; Davis, R. Duane; Keshavjee, Shaf; Lin, Shu S.

    2016-01-01

    ABSTRACT Purpose: In the clinical setting, there is no reliable tool for diagnosing gastric aspiration. A potential way of diagnosing gastric fluid aspiration entails bronchoalveolar lavage (BAL) with subsequent examination of the BAL fluid for gastric fluid components that are exogenous to the lungs. The objective of this study was to determine the longevity of the gastric fluid components bile and trypsin in the lung, in order to provide an estimate of the time frame in which assessment of these components in the BAL might effectively be used as a measure of aspiration. Materials and Methods: Human gastric fluid (0.5 mg/kg) was infused in the right lung of intubated male Fischer 344 rats (n = 30). Animals were sacrificed at specified times following the experimentally induced aspiration, and bronchoalveolar lavage fluid (BALF) was collected. Bile concentrations were analyzed by an enzyme-linked chromatogenic method, and the concentration of trypsin was quantified using an ELISA. Data were analyzed using non-linear regression and a one-phase decay equation. Results: In this experimental model, the half-life of bile was 9.3 hours (r 2 = 0.81), and the half-life of trypsin was 9.0 hours (r 2 = 0.68). Conclusions: The half-lives of bile and trypsin in the rodent aspiration model suggest that the ability to detect aspiration may be limited to a few days post-aspiration. If studies using rats are any indication, it may be most effective to collect BAL samples within the first 24 hours of suspected aspiration events in order to detect aspiration. PMID:26873328

  3. Pitanga (Eugenia uniflora L.) fruit juice and two major constituents thereof exhibit anti-inflammatory properties in human gingival and oral gum epithelial cells.

    PubMed

    Josino Soares, Denise; Walker, Jessica; Pignitter, Marc; Walker, Joel Michael; Imboeck, Julia Maria; Ehrnhoefer-Ressler, Miriam Margit; Montenegro Brasil, Isabella; Somoza, Veronika

    2014-11-01

    Pitanga, Eugenia uniflora L., is a tropical fruit, which may be consumed as juice. While beneficial health effects of Eugenia uniflora L. leaf extracts have extensively been studied, limited data are available on an anti-inflammatory potential of pitanga juice. The aim of the presented study was to investigate anti-inflammatory properties of pitanga juice with regards to a prevention of inflammation-related periodontal diseases. For this purpose, six healthy volunteers swirled pitanga juice, containing 35% pitanga pulp, for 10 min. Thereafter, oral gum epithelial cells were harvested using a sterile brush and stimulated with lipopolysaccharides from Porphyromonas gingivalis (PG-LPS) for 6 h. Furthermore, human gingival fibroblasts (HGF-1) were used to elucidate the anti-inflammatory potential of pitanga juice constituents, cyanidin-3-glucoside and oxidoselina-1,3,7(11)-trien-8-one, in juice representative concentrations of 119 μg ml(-1) and 30 μg ml(-1), respectively. For the first time, an anti-inflammatory impact of pitanga juice on gingival epithelial cells was shown by means of an attenuation of IL-8 release by 55 ± 8.2% and 52 ± 11% in non-stimulated and PG-LPS-stimulated cells, respectively. In addition, both cyanidin-3-glucoside and oxidoselina-1,3,7(11)-trien-8-one reduced the LPS-stimulated CXCL8 mRNA expression by 50 ± 15% and 37 ± 18% and IL-8 release by 52 ± 9.9% and 45 ± 3.7% in HGF-1 cells, when concomitantly incubated with 10 μg ml(-1)PG-LPS for 6 h, revealing an anti-inflammatory potential of the volatile compound oxidoselina-1,3,7(11)-trien-8-one for the first time. PMID:25228206

  4. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer

    PubMed Central

    Bennett, M; O'Connell, J; O'Sullivan, G; Roche, D; Brady, C; Kelly, J; Collins, J; Shanahan, F

    1999-01-01

    Background—Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. 
Aim—To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. 
Specimens—Thirty paraffin wax embedded human gastric adenocarcinomas. 
Methods—FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). 
Results—Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. 
Conclusions—Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer. 

 Keywords: Fas ligand; gastric cancer; immune escape; apoptosis; tumour; mRNA PMID:9895372

  5. Detection of human papillomavirus DNA in gastric carcinoma specimens in a high-risk region of Iran

    PubMed Central

    Fakhraei, Farzaneh; Haghshenas, Mohammad Reza; Hosseini, Vahid; Rafiei, Alireza; Naghshvar, Farshad; Alizadeh-Navaei, Reza

    2016-01-01

    Gastric cancer is the fourth most common type of cancer worldwide and is associated with high mortality rates. The incidence of gastric cancer varies widely in different geographical regions. For example, in Iran, the most northern and northwestern regions are considered to be high-risk areas for gastric cancer. The aim of the present study was to determine the distribution of human papillomavirus (HPV) genotypes among patients with gastric carcinoma in Mazandaran province, Northern Iran, which is a high-risk area. A total of 100 paraffin-embedded tissue samples were obtained from 70 males and 30 females with gastric carcinoma, diagnosed between 2006 and 2013, in the Imam Khomeini Hospital (Sari, Iran). GP5+/GP6+ general primers were applied for detection of HPV DNA in the specimens. Positive samples were then selected and high-risk HPV genotyping was performed. The samples were analyzed by polymerase chain reaction and five (5%) samples were identified to be positive for HPV DNA [four male (5.7%) and one female (3.3%)]. Three (60%) samples were positive for HPV-16, one (20%) sample was positive for HPV-18 and one (20%) sample was positive for HPV-45. Following pathological diagnosis, 88 samples were identified as gastric adenocarcinoma, nine samples were gastric lymphoma, and three samples were gastric and esophagus adenocarcinoma. According to the findings of the present study and the rate of HPV infection in patients with gastric carcinoma, an association between HPV infection and gastric carcinoma in subjects from Northern Iran was not identified. PMID:27588180

  6. Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts

    PubMed Central

    Ge, Sai; Zhang, Qiyue; He, Qiong; Zou, Jianling; Liu, Xijuan; Li, Na; Tian, Tiantian; Zhu, Yan; Gao, Jing; Shen, Lin

    2016-01-01

    Famitinib (SHR1020), a novel multi-targeted tyrosine kinase inhibitor, has antitumor activity against several solid tumors via targeting vascular endothelial growth factor receptor 2, c-Kit and platelet-derived growth factor receptor β. The present study investigated famitinib's activity against human gastric cancer cells in vitro and in vivo. Cell viability and apoptosis were measured, and cell cycle analysis was performed following famitinib treatment using 3-(4,5-dimethylthiazol −2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and western blotting. Subsequently, cluster of differentiation 34 staining was used to evaluate microvessel density. BGC-823-derived xenografts in nude mice were established to assess drug efficacy in vivo. Famitinib inhibited cell proliferation by inducing cell cycle arrest at the G2/M phase and caused cell apoptosis in a dose-dependent manner in gastric cancer cell lines. In BGC-823 xenograft models, famitinib significantly slowed tumor growth in vivo via inhibition of angiogenesis. Compared with other chemotherapeutics such as 5-fluorouracil, cisplatin or paclitaxel alone, famitinib exhibited the greatest tumor suppression effect (>85% inhibition). The present study demonstrated for the first time that famitinib has efficacy against human gastric cancer in vitro and in vivo, which may lay the foundations for future clinical trials. PMID:27602110

  7. Exploratory study of oral mucosal colonization of human gastric Helicobacter pylori in mice

    PubMed Central

    Wan, Xueqin; Tang, Dongsheng; Zhang, Xiaohuan; Li, Hongming; Cui, Zhixin; Hu, Sijuan; Huang, Ming

    2014-01-01

    In this study, human gastric Helicobacter pylori (Hp) was closely attached to the pre-treated mouse buccal mucosa by using artificial oral film to induce the growth and colonization of Hp on the buccal mucosa in mice. Sixty BALB/c mice were divided into three groups, in which Hp biofilm colonization was detected in three mice in Hp film group (Hp mesh biofilm accumulation under an optical microscope; Hp accumulated colonization under an electron microscope). There were no Hp biofilms detected in Hp smear group or the control group with black film. In this study, human gastric Hp was first used to artificially induce the growth and colonization of Hp on the buccal mucosa in mice. The mouse model of oral infection with Hp was initially established, providing animal experimental evidences for oral conditions of growth and colonization of Hp on the buccal mucosa in mice, and providing a workable animal modeling method for further research of joint infection of Hp on the mouth and stomach, as well as the relationship between oral Hp and gastric Hp. PMID:24753744

  8. Juice and phenolic fractions of the berry Aristotelia chilensis inhibit LDL oxidation in vitro and protect human endothelial cells against oxidative stress.

    PubMed

    Miranda-Rottmann, Soledad; Aspillaga, Augusto A; Pérez, Druso D; Vasquez, Luis; Martinez, Alvaro L F; Leighton, Federico

    2002-12-18

    Oxidative modification of low-density lipoprotein (LDL) particles is a key event in the development of atherosclerosis. Oxidized LDL induces oxidative stress and modifies gene expression in endothelial cells. Berries constitute a rich dietary source of phenolic antioxidants. We found that the endemic Chilean berry Aristotelia chilensis (ach) has higher phenol content and scores better for total radical-trapping potential and total antioxidant reactivity in in vitro antioxidant capacity tests, when compared to different commercial berries. The juice of ach is also effective in inhibiting copper-induced LDL oxidation. In human endothelial cell cultures, the addition of ach juice significantly protects from hydrogen peroxide-induced intracellular oxidative stress and is dose-dependent. The aqueous, anthocyanin-rich fraction of ach juice accounts for most of ach's antioxidant properties. These results show that ach is a rich source of phenolics with high antioxidant capacity and suggest that it may have antiatherogenic properties. PMID:12475268

  9. Imaging normal and cancerous human gastric muscular layer in transverse and longitudinal sections by multiphoton microscopy.

    PubMed

    Zhou, Yi; Kang, Deyong; Yang, Zhenrong; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Zhou, Yongjian; Chen, Jianxin

    2016-07-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) has been widely used for imaging microstructure of biological tissues. In this article, we used MPM to investigate the microstructure changes of normal and cancerous human gastric muscular layer in transverse and longitudinal sections. The results displayed different patterns of microstructure changes of smooth muscular tissue, cell morphology and interstitial fibers in transverse and longitudinal sections, being similar to standard histopathological images but without the need for tissue processing. Our study demonstrated that MPM can bring more detailed complementary information on tissue architecture through observing transverse and longitudinal sections of tissues, which are the important pathological information when the pathologists diagnose the gastrointestinal lesions. These observations indicate that MPM could be an important potential tool to provide real-time pathological diagnosis for gastric cancer in the future. SCANNING 38:357-364, 2016. © 2015 Wiley Periodicals, Inc. PMID:26435529

  10. Nitric Oxide-mediated Relaxation by High K in Human Gastric Longitudinal Smooth Muscle.

    PubMed

    Kim, Young Chul; Choi, Woong; Yun, Hyo-Young; Sung, Rohyun; Yoo, Ra Young; Park, Seon-Mee; Yun, Sei Jin; Kim, Mi-Jung; Song, Young-Jin; Xu, Wen-Xie; Lee, Sang Jin

    2011-12-01

    This study was designed to elucidate high-K(+)induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high K(+) (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high K(+) (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high K(+)-induced relaxation. K(+) channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium (Ba(2+)) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent K(+) channel (K(V)) blocker, inhibited high K(+)-induced relaxation, hence reversing to tonic contraction. High K(+)-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and K(V) channel blocker sensitive high K(+)-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high K(+)-induced relaxation which was activated by NO/sGC pathway and by K(V) channel dependent mechanism. PMID:22359479

  11. Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells

    PubMed Central

    Shiozaki, Atsushi; Shimizu, Hiroki; Ichikawa, Daisuke; Konishi, Hirotaka; Komatsu, Shuhei; Kubota, Takeshi; Fujiwara, Hitoshi; Okamoto, Kazuma; Iitaka, Daisuke; Nakashima, Shingo; Nako, Yoshito; Liu, Mingyao; Otsuji, Eigo

    2014-01-01

    AIM: To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells. METHODS: Knockdown experiments were conducted with claudin 1 small interfering RNA (siRNA), and the effects on the cell cycle, apoptosis, migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells. The gene expression profiles of cells were analyzed by microarray and bioinformatics. RESULTS: The knockdown of claudin 1 significantly inhibited cell proliferation, migration and invasion, and increased apoptosis. Microarray analysis identified 245 genes whose expression levels were altered by the knockdown of claudin 1. Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway, which involved MMP7, TNF-SF10, TGFBR1, and CCL2. Furthermore, TNF- and nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1. TNF-α treatment increased claudin 1 expression and cell migration in MKN28 cells. Microarray analysis indicated that the depletion of claudin 1 inhibited 80% of the TNF-α-induced mRNA expression changes. Further, TNF-α did not enhance cell migration in the claudin 1 siRNA transfected cells. CONCLUSION: These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells. A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer. PMID:25548484

  12. Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

    PubMed Central

    Seitz, H K; Egerer, G; Simanowski, U A; Waldherr, R; Eckey, R; Agarwal, D P; Goedde, H W; von Wartburg, J P

    1993-01-01

    As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p < 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p < 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people. Images Figure

  13. Furocoumarins from grapefruit juice and their effect on human CYP 3A4 and CYP 1B1 isoenzymes.

    PubMed

    Girennavar, Basavaraj; Poulose, Shibu M; Jayaprakasha, Guddadarangavvanahally K; Bhat, Narayan G; Patil, Bhimanagouda S

    2006-04-15

    Bioactive compounds present in grapefruit juice are known to increase the bioavailability of certain medications by acting as potent CYP 3A4 inhibitors. An efficient technique has been developed for isolation and purification of three furocoumarins. The isolated compounds have been tested for the inhibition of human CYP 1B1 isoform using specific substrates. Grapefruit juice was extracted with ethyl acetate (EtOAc) and the dried extract was loaded onto silica gel column chromatography. Further, column fractions were subjected to preparative HPLC to obtain three compounds. The purity of these compounds was analyzed by HPLC and structures were determined by NMR studies. The identified compounds, bergamottin, 6',7'-dihydroxybergamottin (DHB), and paradisin-A, were tested for their inhibitory effects on hydroxylase and O-dealkylase activities of human cytochrome P450 isoenzymes CYP 3A4 and CYP 1B1. Paradisin-A was found to be a potent CYP 3A4 inhibitor with an IC50 of 1.2 microM followed by DHB and bergamottin. All three compounds showed a substantial inhibitory effect on CYP 3A4 below 10 microM. Inhibitory effects on CYP 1B1 exhibited a greater variation due to the specificity of substrates. Paradisin A showed an IC50 of 3.56+/-0.12 microM for the ethoxy resorufin O-dealkylase (EROD) activity and 33.56+/-0.72 microM for the benzyloxy resorufin (BROD). DHB and bergamottin showed considerable variations for EROD and BROD activities with an IC50 of 7.17 microM and 13.86 microM, respectively. PMID:16338240

  14. Astaxanthin Inhibits Proliferation of Human Gastric Cancer Cell Lines by Interrupting Cell Cycle Progression

    PubMed Central

    Kim, Jung Ha; Park, Jong-Jae; Lee, Beom Jae; Joo, Moon Kyung; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae

    2016-01-01

    Background/Aims Astaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines. Methods The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed. Results The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27kip-1 increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner. Conclusions Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27kip-1. PMID:26470770

  15. /sup 99m/Tc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying

    SciTech Connect

    Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

    1983-08-01

    A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t/sup 1///sup 2/ for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis.

  16. Suppression of IL-8-Src signalling axis by 17β-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.

    PubMed

    Liu, Chung-Jung; Kuo, Fu-Chen; Wang, Chiu-Lin; Kuo, Chao-Hung; Wang, Sophie S W; Chen, Chiao-Yun; Huang, Yaw-Bin; Cheng, Kuang-Hung; Yokoyama, Kazunari K; Chen, Chun-Lin; Lu, Chien-Yu; Wu, Deng-Chyang

    2016-05-01

    Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17β -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17β-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17β-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells. PMID:26945908

  17. MiRNA Expression Profile for the Human Gastric Antrum Region Using Ultra-Deep Sequencing

    PubMed Central

    Hamoy, Igor G.; Darnet, Sylvain; Burbano, Rommel; Khayat, André; Gonçalves, André Nicolau; Alencar, Dayse O.; Cruz, Aline; Magalhães, Leandro; Araújo Jr., Wilson; Silva, Artur; Santos, Sidney; Demachki, Samia; Assumpção, Paulo; Ribeiro-dos-Santos, Ândrea

    2014-01-01

    Background MicroRNAs are small non-coding nucleotide sequences that regulate gene expression. These structures are fundamental to several biological processes, including cell proliferation, development, differentiation and apoptosis. Identifying the expression profile of microRNAs in healthy human gastric antrum mucosa may help elucidate the miRNA regulatory mechanisms of the human stomach. Methodology/Principal Findings A small RNA library of stomach antrum tissue was sequenced using high-throughput SOLiD sequencing technology. The total read count for the gastric mucosa antrum region was greater than 618,000. After filtering and aligning using with MirBase, 148 mature miRNAs were identified in the gastric antrum tissue, totaling 3,181 quality reads; 63.5% (2,021) of the reads were concentrated in the eight most highly expressed miRNAs (hsa-mir-145, hsa-mir-29a, hsa-mir-29c, hsa-mir-21, hsa-mir-451a, hsa-mir-192, hsa-mir-191 and hsa-mir-148a). RT-PCR validated the expression profiles of seven of these highly expressed miRNAs and confirmed the sequencing results obtained using the SOLiD platform. Conclusions/Significance In comparison with other tissues, the antrum’s expression profile was unique with respect to the most highly expressed miRNAs, suggesting that this expression profile is specific to stomach antrum tissue. The current study provides a starting point for a more comprehensive understanding of the role of miRNAs in the regulation of the molecular processes of the human stomach. PMID:24647245

  18. Different gastric microbiota compositions in two human populations with high and low gastric cancer risk in Colombia

    PubMed Central

    Yang, Ines; Woltemate, Sabrina; Piazuelo, M. Blanca; Bravo, Luis E.; Yepez, Maria Clara; Romero-Gallo, Judith; Delgado, Alberto G.; Wilson, Keith T.; Peek, Richard M.; Correa, Pelayo; Josenhans, Christine; Fox, James G.; Suerbaum, Sebastian

    2016-01-01

    Inhabitants of Túquerres in the Colombian Andes have a 25-fold higher risk of gastric cancer than inhabitants of the coastal town Tumaco, despite similar H. pylori prevalences. The gastric microbiota was recently shown in animal models to accelerate the development of H. pylori-induced precancerous lesions. 20 individuals from each town, matched for age and sex, were selected, and gastric microbiota analyses were performed by deep sequencing of amplified 16S rDNA. In parallel, analyses of H. pylori status, carriage of the cag pathogenicity island and assignment of H. pylori to phylogeographic groups were performed to test for correlations between H. pylori strain properties and microbiota composition. The gastric microbiota composition was highly variable between individuals, but showed a significant correlation with the town of origin. Multiple OTUs were detected exclusively in either Tumaco or Túquerres. Two operational taxonomic units (OTUs), Leptotrichia wadei and a Veillonella sp., were significantly more abundant in Túquerres, and 16 OTUs, including a Staphylococcus sp. were significantly more abundant in Tumaco. There was no significant correlation of H. pylori phylogeographic population or carriage of the cagPAI with microbiota composition. From these data, testable hypotheses can be generated and examined in suitable animal models and prospective clinical trials. PMID:26729566

  19. [Drugs from the classes of tricyclic antidepressives and antiepileptics, nitrosatable under simulated human gastric conditions].

    PubMed

    Ziebarth, D; Schramm, T; Töppel, A

    1989-01-01

    The nitrosatability of Pryleugan (imipramine), Herphonal (trimipramine), and Finlepsin (carbamazepine) was investigated under simulated human gastric conditions using a colorimetric measuring method. All of them proved to be nitrosatable even at very low nitrite concentrations. In the presence of ascorbic acid, the formation of N-nitroso compounds under model conditions was inhibited markedly. N-nitroso-dihydrodibenzazepine and N-nitroso-dibenzazepine could be identified by thin layer chromatography as main products. The biological effects of these N-nitroso compounds are not known up to now. PMID:2802933

  20. Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

    PubMed Central

    Chang, Yuan; Niu, Wei; Lian, Pei-Long; Wang, Xian-Qiang; Meng, Zhi-Xin; Liu, Yi; Zhao, Rui

    2016-01-01

    AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor (VEGF) and prognosis in gastric cancer. METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density (MVD) (endocan-MVD), VEGF and vascular endothelial growth factor receptor 2 (VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student’s t-test or an analysis of variance test. Spearman’s rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. Long-term survival of these patients was analysed using univariate and multivariate analyses. RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues (108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type (P > 0.05), while endocan-MVD was associated with tumour size, Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage (P < 0.05). According to the Spearman’s rank correlation analysis, endocan-MVD had a positive correlation with VEGF (r = 0.167, P = 0.047) and VEGFR2 (r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD (17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor. CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer. PMID:27340359

  1. Inhibition of sphingolipid metabolism enhances resveratrol chemotherapy in human gastric cancer cells.

    PubMed

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-09-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 μM) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells. PMID:24009836

  2. Luteolin Induces Apoptosis by Up-regulating miR-34a in Human Gastric Cancer Cells.

    PubMed

    Wu, Hao; Huang, Min; Liu, Yatian; Shu, Yongqian; Liu, Ping

    2015-12-01

    Luteolin (39, 49, 5, 7-tetrahydroxyflavone) is a natural flavonoid that exists in several types of vegetables, fruits, and medicinal herbs that inhibits tumorigenesis in different types of cancer. In this study, we demonstrate luteolin-mediated regulation of cell apoptosis in a gastric cancer cell line through inhibition of the apoptosis regulatory protein Bcl-2. MTT and flow cytometric analysis indicate that luteolin inhibits cell proliferation and induces apoptosis in gastric cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that miR-34a expression is downregulated in the majority of human primary gastric cancer tissues (8/12, 66.7%), compared with adjacent, pair-matched non-tumor tissues. Target analysis indicated that micro RNA (miR)-34a directly regulates Bcl-2, and miR-34a overexpression decreased Bcl-2 protein level in gastric cancer cells. We also found that luteolin upregulates miR-34a expression and downregulates Bcl-2 expression. Furthermore, anti-miR-34a oligonucleotides (AMO) partly reverse luteolin-induced Bcl-2 downregulation in gastric cancer cells. Based on these results, we can draw the conclusion that luteolin partly decreases Bcl-2 expression through upregulating miR-34a expression. This study shows for the first time that the miR-34a pathway plays an important role in luteolin-induced apoptosis in gastric cancer cells. PMID:24988056

  3. Effect of Citrus bergamia juice on human neuroblastoma cells in vitro and in metastatic xenograft models.

    PubMed

    Navarra, M; Ursino, M R; Ferlazzo, N; Russo, M; Schumacher, U; Valentiner, U

    2014-06-01

    Neuroblastoma is the most common extracranial pediatric solid tumor with poor prognosis in children with disseminated stage of disease. A number of studies show that molecules largely distributed in commonly consumed fruits and vegetables may have anti-tumor activity. In this study we evaluate the effect of Citrus bergamia (bergamot) juice (BJ) in vitro and in a spontaneous metastatic neuroblastoma SCID mouse model. Qualitative and quantitative characterizations of BJ flavonoid fractions were performed by RP-HPLC/PDA/MS. We show that BJ significantly affects SK-N-SH and LAN-1 cell proliferation in vitro, but fails to reduce primary tumor weight in vivo. Moreover, BJ reduced cell adhesiveness and invasion of LAN-1 and SK-N-SH cells in vitro and the number of pulmonary metastases under consideration of the number of tumor cells in the blood in mice inoculated with LAN-1 cells in vivo. These effects without any apparent sign of systemic toxicity confirm the potential clinical interest of BJ and lay the basis for further investigation in cancer. PMID:24594241

  4. Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells

    PubMed Central

    Hahm, Sahng-Wook; Park, Jieun; Park, Kun-Young; Son, Yong-Suk; Han, Hyungchul

    2016-01-01

    Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF (100 μg/mL) significantly induced (P<0.05) the G1 phase cell cycle arrest. Additionally, the apoptotic cell population was greater (P<0.05) in OHF (200 μg/mL) treated AGS cells when compared to the control. The expression of genes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells. PMID:27069903

  5. Basis of decreased risk of gastric cancer in severe atrophic gastritis with eradication of Helicobacter pylori.

    PubMed

    Tari, Akira; Kitadai, Yasuhiko; Sumii, Masaharu; Sasaki, Atsunori; Tani, Hiroshi; Tanaka, Sinji; Chayama, Kazuaki

    2007-01-01

    Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover. PMID:17151803

  6. Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo.

    PubMed

    Mao, Zong-Lei; He, Song-Bing; Sheng, Wei-Hua; Dong, Xiao-Qiang; Yang, Ji-Cheng

    2013-11-01

    Chemotherapy is the primary treatment for both resectable and advanced gastric carcinoma, yet multiple drug resistance (MDR) of gastric carcinoma remains a significant therapeutic obstacle. The development of novel strategies to reduce MDR in gastric carcinoma would yield a better outcome following chemotherapy. ING4, a member of the inhibitor of growth (ING) tumor-suppressor family, possesses antitumor and radiosensitization or chemosensitization effects in a variety of human cancers. The present study investigated the effects and possible mechanisms of action of adenovirus-mediated ING4 (AdVING4) on the reversion of human gastric carcinoma cell MDR in vitro and in vivo in nude mouse xenografts. The data showed that the expression of ING4 mRNA and protein was dramatically downregulated (or lost) in gastric carcinoma SGC7901/CDDP cells after CDDP-induced MDR phenotype and in the parental SGC7901 cells. AdVING4‑induced ING4 expression reversed MDR and induced apoptosis of SGC7901/CDDP cells in vitro and in vivo in the SGC7901/CDDP xenograft tumors. Furthermore, AdVING4 substantially downregulated the expression of MDR-related proteins P-gp and MRP1 and apoptosis‑related proteins Bcl-2 and survivin, but upregulated the expression of apoptosis-related protein Bax in the SGC7901/CDDP xenograft tissues. The reversion effects elicited by AdVING4 on gastric cancer cell MDR were closely associated with the downregulation of ATP-binding cassette transporters and activation of apoptotic pathways. Thus, these findings suggest that AdVING4 may be a feasible modulator for the MDR phenotype of gastric carcinoma cells. PMID:23969950

  7. microRNA-25 Inhibits Cell Apoptosis of Human Gastric Adenocarcinoma Cell Line AGS via Regulating CCNE1 and MYC

    PubMed Central

    Zhang, Yong; Peng, Zheng; Zhao, Yunshan; Chen, Lin

    2016-01-01

    Background Gastric carcinoma is the second leading cause of cancer death. microRNAs play vital roles in regulating expression of related oncogenes. microRNA-25 (miR-25) has been found to be up-regulated in gastric carcinoma. However, its roles in affecting cell apoptosis of gastric carcinoma and the related mechanism remain elusive. This study aimed to uncover the influences of miR-25 on gastric carcinoma cell apoptosis and the possible functional mechanisms involved. Material/Methods Human gastric adenocarcinoma cell line AGS was used and transfected with lentivirus containing miR-25-specifc inhibitor sponge or expression vector to analyze the effects of miR-25. Results miR-25 had higher expression in AGS than in human gastric epithelial cell line GES-1 (P<0.01). Inhibition of miR-25 by its sponge in AGS cells resulted in suppressed cell viability (P<0.01) and promoted cell apoptosis (P<0.01), while overexpression of miR-25 abrogated these effects (P<0.01 and P<0.05), indicating that miR-25 can promote cell viability and inhibit cell apoptosis in AGS cells. Expression analysis of related factors by Western blot showed that inhibiting miR-25 led to the up-regulation of F-box and WD repeat domain-containing 7 (FBXW7, P<0.01) and the down-regulation of FBXW7 substrates, cyclin E1 (CCNE1, P<0.01), and v-myc avian myelocytomatosis viral oncogene homolog (MYC, P<0.001). Conclusions These results indicate that miR-25 has anti-apoptosis roles in AGS cells, possibly via inhibiting FBXW7 and thus promoting oncogenes, such as CCNE1 and MYC. This study provides basic evidence for using miR-25 as a possible therapeutic target in treating gastric carcinoma. PMID:27120728

  8. Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans.

    PubMed

    Pereira-Caro, Gema; Oliver, Christine M; Weerakkody, Rangika; Singh, Tanoj; Conlon, Michael; Borges, Gina; Sanguansri, Luz; Lockett, Trevor; Roberts, Susan A; Crozier, Alan; Augustin, Mary Ann

    2015-07-01

    Orange juice (OJ) flavanones are bioactive polyphenols that are absorbed principally in the large intestine. Ingestion of probiotics has been associated with favorable changes in the colonic microflora. The present study examined the acute and chronic effects of orally administered Bifidobacterium longum R0175 on the colonic microflora and bioavailability of OJ flavanones in healthy volunteers. In an acute study volunteers drank OJ with and without the microencapsulated probiotic, whereas the chronic effects were examined when OJ was consumed after daily supplementation with the probiotic over 4 weeks. Bioavailability, assessed by 0-24h urinary excretion, was similar when OJ was consumed with and without acute probiotic intake. Hesperetin-O-glucuronides, naringenin-O-glucuronides, and hesperetin-3'-O-sulfate were the main urinary flavanone metabolites. The overall urinary excretion of these metabolites after OJ ingestion and acute probiotic intake corresponded to 22% of intake, whereas excretion of key colon-derived phenolic and aromatic acids was equivalent to 21% of the ingested OJ (poly)phenols. Acute OJ consumption after chronic probiotic intake over 4 weeks resulted in the excretion of 27% of flavanone intake, and excretion of selected phenolic acids also increased significantly to 43% of (poly)phenol intake, corresponding to an overall bioavailability of 70%. Neither the probiotic bacterial profiles of stools nor the stool moisture, weight, pH, or levels of short-chain fatty acids and phenols differed significantly between treatments. These findings highlight the positive effect of chronic, but not acute, intake of microencapsulated B. longum R0175 on the bioavailability of OJ flavanones. PMID:25801290

  9. Da0324, an inhibitor of nuclear factor-κB activation, demonstrates selective antitumor activity on human gastric cancer cells

    PubMed Central

    Jin, Rong; Xia, Yiqun; Chen, Qiuxiang; Li, Wulan; Chen, Dahui; Ye, Hui; Zhao, Chengguang; Du, Xiaojing; Shi, Dengjian; Wu, Jianzhang; Liang, Guang

    2016-01-01

    Background The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. Methods The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. Results High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation

  10. Endogenous Hydrogen Sulfide Enhances Cell Proliferation of Human Gastric Cancer AGS Cells.

    PubMed

    Sekiguchi, Fumiko; Sekimoto, Teruki; Ogura, Ayaka; Kawabata, Atsufumi

    2016-01-01

    Hydrogen sulfide (H2S), the third gasotransmitter, is endogenously generated by certain H2S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H2S affects the proliferation of cancer cells, although the effects of H2S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H2S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and β-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H2S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H2S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions. PMID:27150157

  11. Anti-cancer effect of rubropunctatin against human gastric carcinoma cells BGC-823.

    PubMed

    Zheng, Yunquan; Xin, Yanwen; Shi, Xianai; Guo, Yanghao

    2010-11-01

    The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR) and its cytotoxic activities against human gastric adenocarcinoma BGC-823 cells were studied both in vitro and in vivo. Rubropunctatin inhibited the proliferation of BGC-823 cells with an inhibitory concentration (IC₅₀) of 12.57 μM, while it exhibited no significant toxicity to normal gastric epithelial cell GES-1 at the same concentration. Treatment of BGC-823 cells with rubropunctatin resulted in a dose- and time-dependent apoptosis, as validated by the increase in the percentage of cells in sub-G1 phase and phosphotidylserine externalization. The in vivo experimental data demonstrated that rubropunctatin could offer similar therapeutic benefits in comparison with the same dose of taxol. After five times of intravenous injection, tumor weight in BGC-823-bearing nude mice reduced 23.5% at the dose of 8 mg/kg and 37.7% at the dose of 32 mg/kg, respectively. The expressions of 30 genes related to induction of apoptosis were found up-regulated significantly. The two most expressed genes were tumor necrosis factor (TNF) and DNA-damage inducible transcript 3. TNF was considered as a major mediator of apoptosis induced by rubropunctatin. This is the first report describing the anti-proliferative effect of rubropunctatin and its apoptosis mechanism on BGC-823 cells. Rubropunctatin has potential to be developed as a new natural anti-cancer agent. PMID:20730532

  12. Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori.

    PubMed

    Watanabe, Tatsuro; Takahashi, Atsushi; Suzuki, Kaori; Kurusu-Kanno, Miki; Yamaguchi, Kensei; Fujiki, Hirota; Suganuma, Masami

    2014-05-15

    Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. Tipα acts as a homodimer with 38-kDa protein, whereas del-Tipα is an inactive monomer. H. pylori isolated from gastric cancer patients secreted large amounts of Tipα, which are incorporated into gastric cancer cells by directly binding to nucleolin on the cell surface, which is a receptor of Tipα. The binding complex induces expression of TNF-α and chemokine genes, and activates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). To understand the mechanisms of Tipα in tumor progression, we looked at numerous effects of Tipα on human gastric cancer cell lines. Induction of cell migration and elongation was found to be mediated through the binding to surface nucleolin, which was inhibited by the nucleolin-targeted siRNAs. Tipα induced formation of filopodia in MKN-1 cells, suggesting invasive morphological changes. Tipα enhanced the phosphorylation of 11 cancer-related proteins in serine, threonine and tyrosine, indicating activation of MEK-ERK signal cascade. Although the downregulation of E-cadherin was not shown in MKN-1 cells, Tipα induced the expression of vimentin, a significant marker of the epithelial-mesenchymal transition (EMT). It is of great importance to note that Tipα reduced the Young's modulus of MKN-1 cells determined by atomic force microscopy: This shows lower cell stiffness and increased cell motility. The morphological changes induced in human gastric cancer cells by Tipα are significant phenotypes of EMT. This is the first report that Tipα is a new inducer of EMT, probably associated with tumor progression in human gastric carcinogenesis. PMID:24249671

  13. The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions.

    PubMed Central

    Soman, N R; Correa, P; Ruiz, B A; Wogan, G N

    1991-01-01

    The TPR-MET oncogenic rearrangement was originally observed in an in vitro transformed human osteosarcoma cell line. Recently, we detected the expression of this rearrangement at very low levels in several cell lines derived from human tumors of nonhematopoietic origin using a highly sensitive method based on polymerase chain reaction amplification of the transcript. We report here the results of analysis of TPR-MET expression in cell lines derived from human gastric tumors and 22 biopsy samples of human gastric mucosa showing cancer or precursor lesions. The rearranged RNA was expressed in all four cell lines as well as in biopsy samples from 12 of the 22 patients. Overexpression of TPR-MET RNA in superficial gastritis lesions with hyperplasia of glandular neck cells suggests the possible involvement of this oncogene at an early stage of gastric tumorigenesis. Analysis of gastric biopsy samples for RAS gene mutations showed base substitutions occurring in the codon 12 region of Ki- and Ha-RAS genes in four cases, including two precursor lesions. Images PMID:2052572

  14. Plasma and Electrolyte Changes in Exercising Humans After Ingestion of Multiple Boluses of Pickle Juice

    PubMed Central

    McKenney, Michael A.; Miller, Kevin C.; Deal, James E.; Garden-Robinson, Julie A.; Rhee, Yeong S.

    2015-01-01

    Context: Twenty-five percent of athletic trainers administer pickle juice (PJ) to treat cramping. Anecdotally, some clinicians provide multiple boluses of PJ during exercise but warn that repeated ingestion of PJ may cause hyperkalemia. To our knowledge, no researchers have examined the effect of ingesting multiple boluses of PJ on the same day or the effect of ingestion during exercise. Objective: To determine the short-term effects of ingesting a single bolus or multiple boluses of PJ on plasma variables and to characterize changes in plasma variables when individuals ingest PJ and resume exercise. Design: Crossover study. Setting: Laboratory. Patients or Other Participants: Nine euhydrated men (age = 23 ± 4 years, height = 180.9 ± 5.8 cm, mass = 80.7 ± 13.8 kg, urine specific gravity = 1.009 ± 0.005). Intervention(s): On 3 days, participants rested for 30 minutes, and then a blood sample was collected. Participants ingested 0 or 1 bolus (1 mL·kg−1 body weight) of PJ, donned sweat suits, biked vigorously for 30 minutes (approximate temperature = 37°C, relative humidity = 18%), and had a blood sample collected. They either rested for 60 seconds (0- and 1-bolus conditions) or ingested a second 1 mL·kg−1 body weight bolus of PJ (2-bolus condition). They resumed exercise for another 35 minutes. A third blood sample was collected, and they exited the environmental chamber and rested for 60 minutes (approximate temperature = 21°C, relative humidity = 18%). Blood samples were collected at 30 and 60 minutes postexercise. Main Outcome Measure(s): Plasma sodium concentration, plasma potassium concentration, plasma osmolality, and changes in plasma volume. Results: The number of PJ boluses ingested did not affect plasma sodium concentration, plasma potassium concentration, plasma osmolality, or changes in plasma volume over time. The plasma sodium concentration, plasma potassium concentration, and plasma osmolality did not exceed 144.6 mEq·L−1 (144.6 mmol

  15. Electrolyte and Plasma Responses After Pickle Juice, Mustard, and Deionized Water Ingestion in Dehydrated Humans

    PubMed Central

    Miller, Kevin C.

    2014-01-01

    Context: Some athletes ingest pickle juice (PJ) or mustard to treat exercise-associated muscle cramps (EAMCs). Clinicians warn against this because they are concerned it will exacerbate exercise-induced hypertonicity or cause hyperkalemia. Few researchers have examined plasma responses after PJ or mustard ingestion in dehydrated, exercised individuals. Objective: To determine if ingesting PJ, mustard, or deionized water (DIW) while hypohydrated affects plasma sodium (Na+) concentration ([Na+]p), plasma potassium (K+) concentration ([K+]p), plasma osmolality (OSMp), or percentage changes in plasma volume or Na+ content. Design: Crossover study. Setting: Laboratory. Patients or Other Participants: A total of 9 physically active, nonacclimated individuals (age = 25 ± 2 years, height = 175.5 ± 9.0 cm, mass = 78.6 ± 13.8 kg). Intervention(s): Participants exercised vigorously for 2 hours (temperature = 37°C ± 1°C, relative humidity = 24% ± 4%). After a 30-minute rest, a baseline blood sample was collected, and they ingested 1 mL/kg body mass of PJ or DIW. For the mustard trial, participants ingested a mass of mustard containing a similar amount of Na+ as for the PJ trial. Postingestion blood samples were collected at 5, 15, 30, and 60 minutes. Main Outcome Measure(s): The dependent variables were [Na+]p, [K+]p, OSMp, and percentage change in plasma Na+ content and plasma volume. Results: Participants became 2.9% ± 0.6% hypohydrated and lost 96.8 ± 27.1 mmol (conventional unit = 96.8 ± 27.1 mEq) of Na+, 8.4 ± 2 mmol (conventional unit = 8.4 ± 2 mEq) of K+, and 2.03 ± 0.44 L of fluid due to exercise-induced sweating. They ingested approximately 79 mL of PJ or DIW or 135.24 ± 22.8 g of mustard. Despite ingesting approximately 1.5 g of Na+ in the PJ and mustard trials, no changes occurred within 60 minutes postingestion for [Na+]p, [K+]p, OSMp, or percentage changes in plasma volume or Na+ content (P > .05). Conclusions: Ingesting a small bolus of PJ or large

  16. Inhibitory effects of fruit juices on CYP3A activity.

    PubMed

    Kim, Hyunmi; Yoon, Yune-Jung; Shon, Ji-Hong; Cha, In-June; Shin, Jae-Gook; Liu, Kwang-Hyeon

    2006-04-01

    There have been very limited reports on the effects of commercial fruit juices on human CYP3A activity. Therefore, the inhibitory effects of readily available commercial fruit juices on midazolam 1'-hydroxylase activity, a marker of CYP3A, were evaluated in pooled human liver microsomes. The fruit juices investigated were black raspberry, black mulberry, plum, and wild grape. White grapefruit, pomegranate, and orange juice were used as positive and negative controls. The black mulberry juice showed the most potent inhibition of CYP3A except for grapefruit juice. The inhibition depended on the amount of a fruit juice added to the incubation mixture. The inhibitory potential of human CYP3A was in the order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. The IC(50) values of all fruit juices tested were reduced after preincubation with microsomes in the presence of the NADPH-generating system, suggesting that a mechanism-based inhibitory component was present in these fruit juices, as in the case of grapefruit. The results suggest that, like grapefruit juice, commercial fruit juices also have the potential to inhibit CYP3A-catalzyed midazolam 1'-hydroxylation. Therefore, in vivo studies investigating the interactions between fruit juices such as black mulberry and wild grape and CYP3A substrates are necessary to determine whether inhibition of CYP3A activity by fruit juices is clinically relevant. PMID:16415112

  17. Aronia melanocarpa juice induces a redox-sensitive p73-related caspase 3-dependent apoptosis in human leukemia cells.

    PubMed

    Sharif, Tanveer; Alhosin, Mahmoud; Auger, Cyril; Minker, Carole; Kim, Jong-Hun; Etienne-Selloum, Nelly; Bories, Pierre; Gronemeyer, Hinrich; Lobstein, Annelise; Bronner, Christian; Fuhrmann, Guy; Schini-Kerth, Valérie B

    2012-01-01

    Polyphenols are natural compounds widely present in fruits and vegetables, which have antimutagenic and anticancer properties. The aim of the present study was to determine the anticancer effect of a polyphenol-rich Aronia melanocarpa juice (AMJ) containing 7.15 g/L of polyphenols in the acute lymphoblastic leukemia Jurkat cell line, and, if so, to clarify the underlying mechanism and to identify the active polyphenols involved. AMJ inhibited cell proliferation, which was associated with cell cycle arrest in G(2)/M phase, and caused the induction of apoptosis. These effects were associated with an upregulation of the expression of tumor suppressor p73 and active caspase 3, and a downregulation of the expression of cyclin B1 and the epigenetic integrator UHRF1. AMJ significantly increased the formation of reactive oxygen species (ROS), decreased the mitochondrial membrane potential and caused the release of cytochrome c into the cytoplasm. Treatment with intracellular ROS scavengers prevented the AMJ-induced apoptosis and upregulation of the expression of p73 and active caspase 3. The fractionation of the AMJ and the use of identified isolated compounds indicated that the anticancer activity was associated predominantly with chlorogenic acids, some cyanidin glycosides, and derivatives of quercetin. AMJ treatment also induced apoptosis of different human lymphoblastic leukemia cells (HSB-2, Molt-4 and CCRF-CEM). In addition, AMJ exerted a strong pro-apoptotic effect in human primary lymphoblastic leukemia cells but not in human normal primary T-lymphocytes. Thus, the present findings indicate that AMJ exhibits strong anticancer activity through a redox-sensitive mechanism in the p53-deficient Jurkat cells and that this effect involves several types of polyphenols. They further suggest that AMJ has chemotherapeutic properties against acute lymphoblastic leukemia by selectively targeting lymphoblast-derived tumor cells. PMID:22412883

  18. Aronia melanocarpa Juice Induces a Redox-Sensitive p73-Related Caspase 3-Dependent Apoptosis in Human Leukemia Cells

    PubMed Central

    Sharif, Tanveer; Alhosin, Mahmoud; Auger, Cyril; Minker, Carole; Kim, Jong-Hun; Etienne-Selloum, Nelly; Bories, Pierre; Gronemeyer, Hinrich; Lobstein, Annelise; Bronner, Christian; Fuhrmann, Guy; Schini-Kerth, Valérie B.

    2012-01-01

    Polyphenols are natural compounds widely present in fruits and vegetables, which have antimutagenic and anticancer properties. The aim of the present study was to determine the anticancer effect of a polyphenol-rich Aronia melanocarpa juice (AMJ) containing 7.15 g/L of polyphenols in the acute lymphoblastic leukemia Jurkat cell line, and, if so, to clarify the underlying mechanism and to identify the active polyphenols involved. AMJ inhibited cell proliferation, which was associated with cell cycle arrest in G2/M phase, and caused the induction of apoptosis. These effects were associated with an upregulation of the expression of tumor suppressor p73 and active caspase 3, and a downregulation of the expression of cyclin B1 and the epigenetic integrator UHRF1. AMJ significantly increased the formation of reactive oxygen species (ROS), decreased the mitochondrial membrane potential and caused the release of cytochrome c into the cytoplasm. Treatment with intracellular ROS scavengers prevented the AMJ-induced apoptosis and upregulation of the expression of p73 and active caspase 3. The fractionation of the AMJ and the use of identified isolated compounds indicated that the anticancer activity was associated predominantly with chlorogenic acids, some cyanidin glycosides, and derivatives of quercetin. AMJ treatment also induced apoptosis of different human lymphoblastic leukemia cells (HSB-2, Molt-4 and CCRF-CEM). In addition, AMJ exerted a strong pro-apoptotic effect in human primary lymphoblastic leukemia cells but not in human normal primary T-lymphocytes. Thus, the present findings indicate that AMJ exhibits strong anticancer activity through a redox-sensitive mechanism in the p53-deficient Jurkat cells and that this effect involves several types of polyphenols. They further suggest that AMJ has chemotherapeutic properties against acute lymphoblastic leukemia by selectively targeting lymphoblast-derived tumor cells. PMID:22412883

  19. Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich acai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers.

    PubMed

    Mertens-Talcott, Susanne U; Rios, Jolian; Jilma-Stohlawetz, Petra; Pacheco-Palencia, Lisbeth A; Meibohm, Bernd; Talcott, Stephen T; Derendorf, Hartmut

    2008-09-10

    The acai berry is the fruit of the acai palm and is traditionally consumed in Brazil but has gained popularity abroad as a food and functional ingredient, yet little information exists on its health effect in humans. This study was performed as an acute four-way crossover clinical trial with acai pulp and clarified acai juice compared to applesauce and a non-antioxidant beverage as controls. Healthy volunteers (12) were dosed at 7 mL/kg of body weight after a washout phase and overnight fast, and plasma was repeatedly sampled over 12 h and urine over 24 h after consumption. Noncompartmental pharmacokinetic analysis of total anthocyanins quantified as cyanidin-3-O-glucoside showed Cmax values of 2321 and 1138 ng/L at t max times of 2.2 and 2.0 h, and AUC last values of 8568 and 3314 ng h L(-1) for pulp and juice, respectively. Nonlinear mixed effect modeling identified dose volume as a significant predictor of relative oral bioavailability in a negative nonlinear relationship for acai pulp and juice. Plasma antioxidant capacity was significantly increased by the acai pulp and applesauce. Individual increases in plasma antioxidant capacity of up to 2.3- and 3-fold for acai juice and pulp, respectively were observed. The antioxidant capacity in urine, generation of reactive oxygen species, and uric acid concentrations in plasma were not significantly altered by the treatments. Results demonstrate the absorption and antioxidant effects of anthocyanins in acai in plasma in an acute human consumption trial. PMID:18693743

  20. Enhancement of iron(II)-dependent reduction of nitrite to nitric oxide by thiocyanate and accumulation of iron(II)/thiocyanate/nitric oxide complex under conditions simulating the mixture of saliva and gastric juice.

    PubMed

    Takahama, Umeo; Hirota, Sachiko

    2012-01-13

    Iron(III) ingested as a food component or supplement for iron deficiencies can react with salivary SCN(-) to produce Fe(SCN)(2+) and can be reduced to iron(II) by ascorbic acid in the stomach. Iron(II) generated in the stomach can react with salivary nitrite and SCN(-) to produce nitric oxide (NO) and FeSCN(+), respectively. The purpose of this investigation is to make clear the reactions among nitrite, SCN(-), iron ions, and ascorbic acid under conditions simulating the mixture of saliva and gastric juice. Iron(II)-dependent reduction of nitrite to NO was enhanced by SCN(-) in acidic buffer solutions, and the oxidation product of iron(II) reacted with SCN(-) to produce Fe(SCN)(2+). Almost all of the NO produced was autoxidized to N(2)O(3) under aerobic conditions. Iron(II)-dependent production of NO was also observed in acidified saliva. Under anaerobic conditions, NO transformed Fe(SCN)(2+) and FeSCN(+) to Fe(SCN)NO(+) in acidic buffer solutions. Fe(SCN)NO(+) was also formed under aerobic conditions when excess ascorbic acid was added to iron(II)/nitrite/SCN(-) systems in acidic buffer solutions and acidified saliva. The Fe(SCN)NO(+) formed was transformed to Fe(SCN)(2+) and iron(III) at pH 2.0 and pH 7.4, respectively, by O(2). Salivary glycoproteins could complex with iron(III) in the stomach preventing the formation of Fe(SCN)(2+). Ascorbic acid reduced iron(III) to iron(II) to react with nitrite and SCN(-) as described above. The above results suggest (i) that iron(II) can have toxic effects on the stomach through the formation of reactive nitrogen oxide species from NO when supplemented without ascorbic acid and through the formation of both reactive nitrogen oxide species and Fe(SCN)NO(+) when supplemented with ascorbic acid, and (ii) that the toxic effects of iron(III) seemed to be smaller than and similar to those of iron(II) when supplemented without and with ascorbic acid, respectively. Possible mechanisms that cause oxidative stress on the stomach

  1. Gastric Emptying and Curding of Pasteurized Donor Human Milk and Mother's Own Milk in Preterm Infants.

    PubMed

    Perrella, Sharon L; Hepworth, Anna R; Gridneva, Zoya; Simmer, Karen N; Hartmann, Peter E; Geddes, Donna T

    2015-07-01

    We evaluated the effects of fortification and composition on gastric emptying and curding in un/fortified pairs of mother's own milk (MOM, n = 17) and pasteurized donor human milk (PDHM, n = 15) in preterm infants. Retained meal proportions (%) and curding were determined from sonography. Immediate and subsequent postprandial % were higher for PDHM (23%, P = 0.026; 15%, P = 0.006) and fortified meals (31.5%; 8.8%, both P < 0.001), whereas higher casein, whey, and lactose concentrations were associated with lower immediate postprandial % (all P < 0.006). Curding did not affect emptying. Influences of fortification, pasteurization, and differing breast milk compositions are small and unlikely implicated in preterm feeding intolerance. PMID:25729886

  2. MicroRNA-190 regulates FOXP2 genes in human gastric cancer

    PubMed Central

    Jia, Wen-Zhuo; Yu, Tao; An, Qi; Yang, Hua; Zhang, Zhu; Liu, Xiao; Xiao, Gang

    2016-01-01

    Objective To investigate how microRNA-190 (miR-190) regulates FOXP2 genes in gastric cancer (GC) cell line SGC7901. Methods We identified that miR-190 could target FOXP2 genes by using dual luciferase enzyme assay. Precursor fragment transfection of miR-190 was performed with GC cell line SGC7901 and human gastric mucosal cell line GES-1. miR-190 expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and FOXP2 protein expression was measured by Western blotting. Results FOXP2-3′-untranslated region (UTR) in miR-190 transfection group was significantly decreased as compared with other groups. There were no significant differences in fluorescence signals of FOXP2mut-3′-UTR in each group. Therefore, it was assumed that miR-190 can target FOXP2 genes. Through RT-PCR verification, it was observed that the expression level of miR-190 was significantly higher in GC cell line SGC7901 than in human gastric mucosa cell line GES-1 after transfection with miR-190 mimics. The expression level of miR-190 was significantly higher in GES-1 cells than in SGC7901 cells after transfection with miR-190 inhibitors. Western blotting results showed the expression level of FOXP2 was significantly lower in GC cell line SGC7901 than in GES-1 cells. Compared with blank, mimics control, and inhibitors control groups, the miR-190 mimics group showed significantly enhanced proliferation, migration, and invasion abilities, while miR-190 inhibitors group showed decreased abilities toward proliferation, migration, and invasion (P<0.05). The transcription level of miR-190 and the expression level of FOXP2 in tumor tissues and adjacent normal tissues in GC patients were verified to be consistent with those of cell line experiments. Conclusion Upregulation of miR-190 can lead to downregulation of FOXP2 protein expression. miR-190 may serve as a potential target for GC diagnosis. PMID:27382302

  3. The role of K+ conductances in regulating membrane excitability in human gastric corpus smooth muscle

    PubMed Central

    Lee, Ji Yeon; Ko, Eun-ju; Ahn, Ki Duck; Kim, Sung

    2015-01-01

    Changes in resting membrane potential (RMP) regulate membrane excitability. K+ conductance(s) are one of the main factors in regulating RMP. The functional role of K+ conductances has not been studied the in human gastric corpus smooth muscles (HGCS). To examine the role of K+ channels in regulation of RMP in HGCS we employed microelectrode recordings, patch-clamp, and molecular approaches. Tetraethylammonium and charybdotoxin did not affect the RMP, suggesting that BK channels are not involved in regulating RMP. Apamin, a selective small conductance Ca2+-activated K+ channel (SK) blocker, did not show a significant effect on the membrane excitability. 4-Aminopyridine, a Kv channel blocker, caused depolarization and increased the duration of slow wave potentials. 4-Aminopyridine also inhibited a delayed rectifying K+ current in isolated smooth muscle cells. End-product RT-PCR gel detected Kv1.2 and Kv1.5 in human gastric corpus muscles. Glibenclamide, an ATP-sensitive K+ channel (KATP) blocker, did not induce depolarization, but nicorandil, a KATP opener, hyperpolarized HGCS, suggesting that KATP are expressed but not basally activated. Kir6.2 transcript, a pore-forming subunit of KATP was expressed in HGCS. A low concentration of Ba2+, a Kir blocker, induced strong depolarization. Interestingly, Ba2+-sensitive currents were minimally expressed in isolated smooth muscle cells under whole-cell patch configuration. KCNJ2 (Kir2.1) transcript was expressed in HGCS. Unique K+ conductances regulate the RMP in HGCS. Delayed and inwardly rectifying K+ channels are the main candidates in regulating membrane excitability in HGCS. With the development of cell dispersion techniques of interstitial cells, the cell-specific functional significance will require further analysis. PMID:25591864

  4. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    SciTech Connect

    Suzuki, Kanayo; Sakaguchi, Minoru; Tanaka, Satoshi; Yoshimoto, Tadashi; Takaoka, Masanori

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  5. 21 CFR 73.260 - Vegetable juice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Vegetable juice. 73.260 Section 73.260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.260 Vegetable juice. (a) Identity. (1) The color...

  6. 21 CFR 73.260 - Vegetable juice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Vegetable juice. 73.260 Section 73.260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... coloring foods. (b) Uses and restrictions. Vegetable juice may be safely used for the coloring of...

  7. 21 CFR 73.260 - Vegetable juice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Vegetable juice. 73.260 Section 73.260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... coloring foods. (b) Uses and restrictions. Vegetable juice may be safely used for the coloring of...

  8. 21 CFR 73.260 - Vegetable juice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Vegetable juice. 73.260 Section 73.260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... coloring foods. (b) Uses and restrictions. Vegetable juice may be safely used for the coloring of...

  9. Anthocyanins are bioavailable in humans following an acute dose of cranberry juice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research suggests that anthocyanins from berry fruit may affect a variety of physiological responses, including endothelial function, but little information is available regarding the pharmacokinetics of these flavonoids in humans. To determine the pharmacokinetics of cranberry anthocyanins a study ...

  10. Fluid intake and industrial processing in apple juice induced chronic non-specific diarrhoea.

    PubMed Central

    Hoekstra, J H; van den Aker, J H; Ghoos, Y F; Hartemink, R; Kneepkens, C M

    1995-01-01

    Dietary factors have been shown to contribute to the occurrence or persistence of chronic non-specific diarrhoea (CNSD). Among these are low dietary fat, high fluid consumption, and the consumption of apple juice. Prompted by the clinical impression that freshly pressed and unprocessed ('cloudy') apple juice was less likely to induce diarrhoea than normal, enzymatically processed ('clear') apple juice, both juices were compared in terms of carbohydrate malabsorption, gastric emptying, and effects on defecation patterns. Clear and cloudy apple juice differ in their fibre and non-absorbable monosaccharide and oligosaccharide contents. Ten healthy children aged 3.6 to 5.9 years ingested 10 ml/kg of clear and cloudy apple juice; in five of them it was enriched with 40 mg of [1-13C]-glycine. Clear apple juice resulted in increased (> or = 20 ppm) breath hydrogen excretion in 8/10, compared with 5/10 after cloudy apple juice; peak breath hydrogen was higher in the clear apple juice group (35 (4) and 18 (3) ppm, respectively). Gastric emptying as determined by means of labelled breath carbon dioxide (13CO2) excretion was similar with both juices. In a four week crossover clinical trial 12 children, formerly diagnosed as having CNSD, were given extra clear fluids (excluding fruit juices; > or = 50% over basal consumption), clear apple juice, or cloudy apple juice, for five day periods. Extra fluids and cloudy apple juice did not influence stool frequency and consistency compared with the basal period. In contrast, clear apple juice significantly promoted diarrhoea. It is suggested that, in addition to fructose, the increased availability of non-absorbable monosaccharides and oligosaccharides as a result of the enzymatic processing of apple pulp is an important aetiological factor in apple juice induced CNSD. PMID:7574855

  11. Bolus consumption of a specifically designed fruit juice rich in anthocyanins and ascorbic acid did not influence markers of antioxidative defense in healthy humans.

    PubMed

    Ellinger, Sabine; Gordon, André; Kürten, Mira; Jungfer, Elvira; Zimmermann, Benno F; Zur, Berndt; Ellinger, Jörg; Marx, Friedhelm; Stehle, Peter

    2012-11-14

    Exotic fruits such as açai, camu-camu, and blackberries rich in natural antioxidants (ascorbic acid, anthocyanins) are marketed as "functional" foods supporting a pro-/antioxidant balance. Confirming data from human studies are lacking. Within a randomized controlled crossover trial, 12 healthy nonsmokers ingested 400 mL of a blended juice of these fruits or a sugar solution (control). Blood was drawn before and afterward to determine antioxidants in plasma, markers of antioxidant capacity [trolox equivalent antioxidant capacity, Folin-Ciocalteu reducing capacity, total oxidant scavenging capacity (TOSC)] and oxidative stress [isoprostane, DNA strand breaks in leukocytes in vivo], and their resistance versus H₂O₂-induced strand breaks. Compared with sugar solution, juice consumption increased plasma ascorbic acid and maintained TOSC and partly Folin-Ciocalteu reducing capacity (both P values < 0.05). Strand breaks in vivo increased after ingestion of both beverages (P < 0.001), probably due to postprandial and/or circadian effects. This anthocyanin-rich fruit juice may stabilize the pro-/antioxidant balance in healthy nonsmokers without affecting markers of oxidative stress. PMID:23072538

  12. HOXB5 induces invasion and migration through direct transcriptional up-regulation of β-catenin in human gastric carcinoma.

    PubMed

    Hong, Chang-Soo; Jeong, Oh; Piao, Zhengri; Guo, Chen; Jung, Mi-Ran; Choi, Chan; Park, Young-Kyu

    2015-12-15

    HOX (homeobox) genes encode a family of transcriptional regulators, which have an important role in morphogenesis and differentiation during embryonic development. Their deregulated expression is involved in the carcinogenesis of many human solid tumours. In the present study, we show that HOXB5 mRNA was significantly overexpressed in gastric cancer tissues compared with adjacent normal tissues. HOXB5-up-regulated cancer cells showed increased invasion and migration activity, but no change in proliferation activity, whereas HOXB5-down-regulated cells showed decreased invasion and migration activity. Up-regulation of HOXB5 resulted in up-regulation of β-catenin, whereas inhibition of HOXB5 expression by siRNA led to the down-regulation of β-catenin. Moreover, a significant correlation between HOXB5 and CTNNB1 (β-catenin) mRNA expression was detected in gastric cancer tissues. Furthermore, we found that HOXB5 binds directly to the CTNNB1 promoter region and activates the transcriptional expression of β-catenin, as well as its downstream target genes, encoding cyclin D1 and c-Myc, leading to an increase in the invasion and migration activity of human gastric cancer cells. Thus HOXB5 may be an important regulator of the Wnt/β-catenin signalling pathway, thereby contributing to gastric cancer progression and metastasis. PMID:26467157

  13. Importance of luminal and mucosal zinc in the mechanism of experimental gastric ulcer healing.

    PubMed

    Opoka, W; Adamek, D; Plonka, M; Reczynski, W; Bas, B; Drozdowicz, D; Jagielski, P; Sliwowski, Z; Adamski, P; Brzozowski, T

    2010-10-01

    Zinc has been reported to exert a gastroprotective action against various experimental gastric lesions suggesting that this trace element is involved in the integrity of the gastric mucosa. Compounds containing zinc, such as polaprezinc, were developed in Japan and used as an antiulcer drugs in the treatment of human peptic ulcer disease. However, the precise mechanism of Zn(2+) containing compounds and their effects on mucosal integrity, gastroprotection and ulcer healing remain unclear. We have determined the efficacy of zinc hydroaspartate, a compound containing Zn(2+), in the mechanism of gastric secretion and ulcer healing in rats with chronic gastric ulcers induced by acetic acid (initial ulcer area = 28 mm(2)). Rats with gastric ulcers were randomized into two groups: A) with gastric fistulas (GF) and B) without gastric fistulas and received a daily treatment with zinc hydroaspartate (32-130 mg/kg-d i.g.) for 3, 7 and 14 days. At the termination of each treatment, the area of gastric ulcers were examined by planimetry, the gastric blood flow (GBF) at ulcer margin was assessed by laser Doppler flowmetry and H(2)-gas clearance methods. The venous blood was withdrawn for a measurement of plasma gastrin levels by radioimmunoassay (RIA). The concentration of Zn(2+) in the gastric juice and mucosa at the ulcer margin were determined by differential pulse anodic stripping voltammetry (DPASV) and flame atomic absorption spectrometry (FAAS) methods and the gastric biopsy samples were taken for histopathological assessment of the quality of ulcer healing. The ulcers healed gradually, with the ulcer area in the vehicle control rats being diminished by 15%, 48% and 78% upon ulcer induction at 3, 7 and 14 days, respectively. Zinc hydroaspartate dose-dependently inhibited the area of gastric ulcer, the dose reducing this area by 50% (ID(50)) being about 60 mg/kg-d. The mucosal concentration of Zn(2+) significantly was unchanged from the baseline immediately after ulcer

  14. Gastrospheres of human gastric mucosa cells: an in vitro model of stromal and epithelial stem cell niche reconstruction.

    PubMed

    Santos, Carlos A N; Andrade, Leonardo R; Costa, Márcia H M; Souza, Heitor S P; Granjeiro, José M; Takiya, Christina M; Borojevic, Radovan; Nasciutti, Luiz E

    2016-08-01

    The molecular characterization of mechanisms involved in the gastrointestinal tract disorders needs an in vitro 3D culture model able to mimic the in vivo gastric microenvironment. Herein, we propose a 3D coculture system where gastric epithelial and stromal cells are grown together building spherical and solid structures using the NASA bioreactor - cell culture system (RCCS), a bioreactor. Epithelial and stromal cells from human antral gastric mucosa were isolated from endoscopic gastric biopsies. Thereafter, these cells were mechanically and enzymatically dispersed by treatment with dispase and collagenase, respectively. Using specific culture procedures, these cells formed 3D structures by using a RCCS, named "gastrospheres". Briefly, gastrospheres were obtained by initial seeding of 2.5x10⁴ cells/well in 96 well culture plates. At 24 h after their formation, they were transferred into RCCS, and maintained for 7, 14, 21, and 28 days. The gastrospheres were morphologically characterized by immunocytochemisty to evaluate extracellular matrix (ECM), and by electron microscopy. These analysis of gastrospheres revealed that the epithelial cells were cytokeratin (CK) and lectin reactive and were arranged in the outer layer; stromal cells presented long cytoplasmic processes and were localized inside the gastrosphere. They were vimentin (VIM) and α-smooth muscle actin (α-SMA) positive and expressed ECM components such as laminin (LN), fibronectin (FN), and type IV collagen (CIV). Electron microscopy revealed groups of cohesive gastric cells surrounded by complex stromal structures, with multiple microvilli, and tight cellular junctions interspersed with extracellular matrix fibrils and fibers. The presence of some nestin-positive cells was observed in the inner region of the gastrospheres, suggesting an intermediary localization between epithelial and stromal cells. Altogether, our data suggest that in vitro gastrospheres recapitulate the in vivo gastric niche

  15. Long noncoding RNAs in gastric cancer: functions and clinical applications

    PubMed Central

    Wang, Jiajun; Sun, Jingxu; Wang, Jun; Song, Yongxi; Gao, Peng; Shi, Jinxin; Chen, Ping; Wang, Zhenning

    2016-01-01

    Over the last two decades, genome-wide studies have revealed that only a small fraction of the human genome encodes proteins; long noncoding RNAs (lncRNAs) account for 98% of the total genome. These RNA molecules, which are >200 nt in length, play important roles in diverse biological processes, including the immune response, stem cell pluripotency, cell proliferation, apoptosis, differentiation, invasion, and metastasis by regulating gene expression at the epigenetic, transcriptional, and posttranscriptional levels. However, the detailed molecular mechanisms underlying lncRNA function are only partially understood. Recent studies showed that many lncRNAs are aberrantly expressed in gastric cancer (GC) tissues, gastric juice, plasma, and cells, and these alterations are linked to the occurrence, progression, and outcome of GC. Here, we review the current knowledge of the biological functions and clinical aspects of lncRNAs in GC. PMID:26929639

  16. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

    PubMed Central

    Tsai, Ming-Ming; Wang, Chia-Siu; Tsai, Chung-Ying; Huang, Hsiang-Wei; Chi, Hsiang-Cheng; Lin, Yang-Hsiang; Lu, Pei-Hsuan; Lin, Kwang-Huei

    2016-01-01

    Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets. PMID:27322246

  17. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    SciTech Connect

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  18. Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells.

    PubMed

    Gao, Shiyong; Tan, Huixin; Zhu, Nan; Gao, Haiyu; Lv, Chunyu; Gang, Jian; Ji, Yubin

    2016-06-01

    Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC50) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells. PMID:27082253

  19. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer.

    PubMed

    Tsai, Ming-Ming; Wang, Chia-Siu; Tsai, Chung-Ying; Huang, Hsiang-Wei; Chi, Hsiang-Cheng; Lin, Yang-Hsiang; Lu, Pei-Hsuan; Lin, Kwang-Huei

    2016-01-01

    Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients' survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets. PMID:27322246

  20. Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity.

    PubMed

    De Flora, Silvio; Camoirano, Anna; Micale, Rosanna T; La Maestra, Sebastiano; Savarino, Vincenzo; Zentilin, Patrizia; Marabotto, Elisa; Suh, Mina; Proctor, Deborah M

    2016-09-01

    Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (±SE) Cr(VI)-reducing ability of post-meal samples (20.4±2.6μgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2±2.3μgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3±1.9 and 25.6±2.8μgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. PMID:27404458

  1. Effect of Static Magnetic Field on Oxidant/Antioxidant Parameters in Cancerous and Noncancerous Human Gastric Tissues

    PubMed Central

    Öztürk, Bahadır; Durak, Zahide Esra; Büber, Süleyman; Kocaoğlu, Ender Hilmi

    2016-01-01

    Aim. To investigate the effects of static magnetic field (SMF) on oxidant and antioxidant parameters of the cancerous and noncancerous human gastric tissues. Materials and Methods. Gastric tissues obtained from patients with gastric cancer were used in the study. SMF was created by using two static magnets. Before and after treatment with SMF, oxidant and antioxidant parameters were measured in the tissue samples. Results. In the cancerous tissue, superoxide dismutase (SOD) activity was found higher and malondialdehyde (MDA) level was found lower as compared with noncancerous tissue. SMF affects oxidant/antioxidant parameters differently in the cancerous and noncancerous tissues. In this regard, SMF causes increase in SOD activity and decrease in MDA level in the noncancerous tissue. However, it decreases SOD and glutathione peroxidase (GSH-Px) activities and increases MDA level and catalase (CAT) activity in the cancerous tissue. There were no differences between nitric oxide (NO) and nitric oxide synthase (NOS) parameters in or among the cancerous and noncancerous tissues. Conclusions. SMF accelerates peroxidation reactions possibly by suppressing SOD and GSH-Px enzymes in the cancerous gastric tissue. This event caused by SMF might play part in the death of cancer cells, which may be a good supportive vehicle for the cancer therapy. PMID:27313958

  2. Effect of Static Magnetic Field on Oxidant/Antioxidant Parameters in Cancerous and Noncancerous Human Gastric Tissues.

    PubMed

    Öztürk, Bahadır; Durak, Zahide Esra; Büber, Süleyman; Kocaoğlu, Ender Hilmi

    2016-01-01

    Aim. To investigate the effects of static magnetic field (SMF) on oxidant and antioxidant parameters of the cancerous and noncancerous human gastric tissues. Materials and Methods. Gastric tissues obtained from patients with gastric cancer were used in the study. SMF was created by using two static magnets. Before and after treatment with SMF, oxidant and antioxidant parameters were measured in the tissue samples. Results. In the cancerous tissue, superoxide dismutase (SOD) activity was found higher and malondialdehyde (MDA) level was found lower as compared with noncancerous tissue. SMF affects oxidant/antioxidant parameters differently in the cancerous and noncancerous tissues. In this regard, SMF causes increase in SOD activity and decrease in MDA level in the noncancerous tissue. However, it decreases SOD and glutathione peroxidase (GSH-Px) activities and increases MDA level and catalase (CAT) activity in the cancerous tissue. There were no differences between nitric oxide (NO) and nitric oxide synthase (NOS) parameters in or among the cancerous and noncancerous tissues. Conclusions. SMF accelerates peroxidation reactions possibly by suppressing SOD and GSH-Px enzymes in the cancerous gastric tissue. This event caused by SMF might play part in the death of cancer cells, which may be a good supportive vehicle for the cancer therapy. PMID:27313958

  3. Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans.

    PubMed

    Stalmach, Angelique; Edwards, Christine A; Wightman, Jolynne D; Crozier, Alan

    2012-03-01

    The in vitro gastrointestinal stability of (poly)phenolic compounds in Concord grape juice was compared with recoveries in ileal fluid after the ingestion of the juice by ileostomists. Recoveries in ileal fluid indicated that 67% of hydroxycinnamate tartarate esters, and smaller percentages of the intake of other (poly)phenolic compounds, pass from the small intestine to the colon. The juice was also ingested by healthy subjects with an intact functioning colon. Peak plasma concentrations (C(max) ) ranged from 1.0 nmol/L for petunidin-3-O-glucoside to 355 nmol/L for dihydrocoumaric acid. Urinary excretion, as an indicator of bioavailability, varied from 0.26% for total anthocyanins to 24% for metabolites of hydroxycinnamate tartarate esters. The C(max) times of the anthocyanins indicated that their low level absorption occurred in the small intestine in contrast to hydroxycinnamate metabolites which were absorbed in both the small and the large intestine where the colonic microflora appeared responsible for hydrogenation of the hydroxycinnamate side chain. The bioavailability of the complex mixture of (poly)phenolic compounds in Concord grape juice, was very similar to that observed in previous studies when compounds were either fed individually or as major components in products containing a restricted spectrum of (poly)phenolic compounds. PMID:22331633

  4. Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells

    PubMed Central

    Agarwal, Rajesh

    2013-01-01

    Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2–5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2 and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 µl water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical

  5. Patient-Derived Gastric Carcinoma Xenograft Mouse Models Faithfully Represent Human Tumor Molecular Diversity

    PubMed Central

    Fan, Shuqiong; Zhang, Meizhuo; Fu, Haihua; Liu, Yuanjie; Yin, Xiaolu; Chen, Hao; Xie, Liang; Zhang, Jingchuan; Gavine, Paul R.; Gu, Yi; Ni, Xingzhi; Su, Xinying

    2015-01-01

    Patient-derived cancer xenografts (PDCX) generally represent more reliable models of human disease in which to evaluate a potential drugs preclinical efficacy. However to date, only a few patient-derived gastric cancer xenograft (PDGCX) models have been reported. In this study, we aimed to establish additional PDGCX models and to evaluate whether these models accurately reflected the histological and genetic diversities of the corresponding patient tumors. By engrafting fresh patient gastric cancer (GC) tissues into immune-compromised mice (SCID and/or nude mice), thirty two PDGCX models were established. Histological features were assessed by a qualified pathologist based on H&E staining. Genomic comparison was performed for several biomarkers including ERBB1, ERBB2, ERBB3, FGFR2, MET and PTEN. These biomarkers were profiled to assess gene copy number by fluorescent in situ hybridization (FISH) and/or protein expression by immunohistochemistry (IHC). All 32 PDGCX models retained the histological features of the corresponding human tumors. Furthermore, among the 32 models, 78% (25/32) highly expressed ERBB1 (EGFR), 22% (7/32) were ERBB2 (HER2) positive, 78% (25/32) showed ERBB3 (HER3) high expression, 66% (21/32) lost PTEN expression, 3% (1/32) harbored FGFR2 amplification, 41% (13/32) were positive for MET expression and 16% (5/32) were MET gene amplified. Between the PDGCX models and their parental tumors, a high degree of similarity was observed for FGFR2 and MET gene amplification, and also for ERBB2 status (agreement rate = 94~100%; kappa value = 0.81~1). Protein expression of PTEN and MET also showed moderate agreement (agreement rate = 78%; kappa value = 0.46~0.56), while ERBB1 and ERBB3 expression showed slight agreement (agreement rate = 59~75%; kappa value = 0.18~0.19). ERBB2 positivity, FGFR2 or MET gene amplification was all maintained until passage 12 in mice. The stability of the molecular profiles observed across subsequent passages within the

  6. Estimation of gastric residence time of the Heidelberg capsule in humans: effect of varying food composition

    SciTech Connect

    Mojaverian, P.; Ferguson, R.K.; Vlasses, P.H.; Rocci, M.L. Jr.; Oren, A.; Fix, J.A.; Caldwell, L.J.; Gardner, C.

    1985-08-01

    In animal and human studies, the gastric emptying of large (greater than 1 mm) indigestible solids is due to the activity of the interdigestive migrating myoelectric complex. The gastric residence time (GRT) of an orally administered, nondigestible, pH-sensitive, radiotelemetric device (Heidelberg capsule) was evaluated in three studies in healthy volunteers. In 6 subjects, the GRT of the Heidelberg capsule was compared with the half-emptying time (t1/2) of diethylenetriaminepentaacetic acid labeled with technetium 99m after a 4-ml/kg liquid fatty meal. The mean (+/-SD) GRT (4.3 +/- 1.4 h) was significantly (p less than 0.001) longer than the mean t1/2 (1.1 +/- 0.3 h); the GRT was prolonged compared with the t1/2 in each subject. In a randomized, crossover trial in 10 subjects, frequent feeding caused a dramatic prolongation in mean GRT of the capsule compared with the fasting state (greater than 14.5 vs. 0.5 h, p less than 0.005). In another crossover study in 6 subjects, the GRT of the capsule was evaluated after an overnight fast, a standard breakfast including solid food, and a liquid meal (i.e., 200 ml of diluted light cream). The mean GRT was 2.6 +/- 0.9 h after the liquid meal vs. 1.2 +/- 0.8 h after fasting (p less than 0.025). The mean GRT after the breakfast was 4.8 +/- 1.5 h, which was significantly greater than that after fasting (p less than 0.001) and after the liquid meal (p less than 0.01). These data suggest that the GRT of the Heidelberg capsule is a marker of the interdigestive migrating myoelectric complex in humans, the interdigestive migrating myoelectric complex can be markedly delayed by frequent feedings with solids, and the interdigestive migrating myoelectric complex is delayed by both liquid and solid meals.

  7. Chelidonine induces mitotic slippage and apoptotic-like death in SGC-7901 human gastric carcinoma cells.

    PubMed

    Qu, Zhongyuan; Zou, Xiang; Zhang, Xiujuan; Sheng, Jiejing; Wang, Yumeng; Wang, Jiaqi; Wang, Chao; Ji, Yubin

    2016-02-01

    The aim of the present study was to investigate the effect of chelidonine on mitotic slippage and apoptotic-like death in SGC-7901 human gastric cancer cells. The MTT assay was performed to detect the antiproliferative effect of chelidonine. Following treatment with chelidonine (10 µmol/l), the ultrastructure changes in SGC-7901, MCF-7 and HepG2 cells were observed by transmission electron microscopy. The effects of chelidonine on G2/M phase arrest and apoptosis of SGC-7901 cells were determined by flow cytometry. Indirect immunofluorescence assay and laser scanning confocal microscopy (LSCM) were used to detect the phosphorylation level of histone H3 (Ser10) and microtubule formation was detected using LSCM following immunofluorescent labeling. Subsequent to treatment with chelidonine (10 µmol/l), expression levels of mitotic slippage-associated proteins, including BUB1 mitotic checkpoint serine/threonine kinase B (BubR1), cyclin-dependent kinase 1 (Cdk1) and cyclin B1, and apoptosis-associated protein, caspase-3 were examined by western blotting at 24, 48 and 72 h. The half maximal inhibitory concentration of chelidonine was 23.13 µmol/l over 48 h and chelidonine induced G2/M phase arrest of cells. The phosphorylation of histone H3 at Ser10 was significantly increased following treatment with chelidonine for 24 h, indicating that chelidonine arrested the SGC-7901 cells in the M phase. Chelidonine inhibited microtubule polymerization, destroyed microtubule structures and induced cell cycle arrest in the M phase. Giant cells were observed with multiple micronuclei of varying sizes, which indicated that following a prolonged arrest in the M phase, the cells underwent mitotic catastrophe. Western blotting demonstrated that the protein expression levels of BubR1, cyclin B1 and Cdk1 decreased significantly between 48 and 72 h. Low expression levels of BubR1 and inactivation of the cyclin B1-Cdk1 complex results in the cells being arrested at mitosis and leads to

  8. Chromosome band 16q24 is frequently deleted in human gastric cancer.

    PubMed

    Mori, Y; Matsunaga, M; Abe, T; Fukushige, S; Miura, K; Sunamura, M; Shiiba, K; Sato, M; Nukiwa, T; Horii, A

    1999-05-01

    We have analysed the loss of heterozygosity (LOH) on chromosome bands 16q22-q24 in 24 primary gastric cancer tissues and found three regions of frequent allelic loss (16q22, 16q24.1-q24.3 and 16q24.3). The region for the most frequent allelic loss (63%) was in 16q24.1-q24.3. LOH of this region had no relationship with histological subtype, but a significant association between LOH and microscopic lymphangial invasion was observed. Although not significant, vascular and gastric wall invasions are also associated with LOH. The region includes the locus for the H-cadherin gene. Therefore we examined the genetic and epigenetic alterations of this gene. Markedly reduced expression was observed in gastric cancer cell lines compared with that of normal gastric mucosa. However, no mutation was found in this gene in any of the gastric cancer tissues or the gastric cancer cell lines. Furthermore, we analysed the methylation status of the 5'-flanking region of the gene, but no significant association was found. We suggest that some other tumour suppressor gene(s) in 16q24.1-q24.3 may be responsible for gastric carcinogenesis. PMID:10408866

  9. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity.

    PubMed

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng; Cao, Zhifei

    2015-09-01

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. PMID:25982451

  10. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

    SciTech Connect

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng Cao, Zhifei

    2015-09-01

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.

  11. Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT-YB1-MDR1 Signaling Pathway.

    PubMed

    Mo, Dongliang; Fang, Hongbo; Niu, Kaifeng; Liu, Jing; Wu, Meng; Li, Shiyou; Zhu, Tienian; Aleskandarany, Mohammed A; Arora, Arvind; Lobo, Dileep N; Madhusudan, Srinivasan; Balajee, Adayabalam S; Chi, Zhenfen; Zhao, Yongliang

    2016-05-15

    Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic and chemotherapeutic significance of RECQL4 in human gastric cancer, which has yet to be determined. We observed significant increases in RECQL4 mRNA or protein in >70% of three independent sets of human gastric cancer specimens examined, relative to normal gastric tissues. Strikingly, high RECQL4 expression in primary tumors correlated well with poor survival and gastric cancer lines with high RECQL4 expression displayed increased resistance to cisplatin treatment. Mechanistic investigations revealed a novel role for RECQL4 in transcriptional regulation of the multidrug resistance gene MDR1, through a physical interaction with the transcription factor YB1. Notably, ectopic expression of RECQL4 in cisplatin-sensitive gastric cancer cells with low endogenous RECQL4 was sufficient to render them resistant to cisplatin, in a manner associated with YB1 elevation and MDR1 activation. Conversely, RECQL4 silencing in cisplatin-resistant gastric cancer cells with high endogenous RECQL4 suppressed YB1 phosphorylation, reduced MDR1 expression, and resensitized cells to cisplatin. In establishing RECQL4 as a critical mediator of cisplatin resistance in gastric cancer cells, our findings provide a therapeutic rationale to target RECQL4 or the downstream AKT-YB1-MDR1 axis to improve gastric cancer treatment. Cancer Res; 76(10); 3057-66. ©2016 AACR. PMID:27013200

  12. Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells.

    PubMed

    Xu, Mei-Ying; Lee, Dong Hwa; Joo, Eun Ji; Son, Kun Ho; Kim, Yeong Shik

    2013-09-01

    In this study, we investigated the anticancer mechanism of akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides in human gastric cancer cell lines. It was shown that AS-induced cell death is caused by autophagy and apoptosis in AGS cells. The apoptosis-inducing effect of AS was characterized by annexin V/propidium (PI) staining, increase of sub-G1 phase and caspase-3 activation, while the autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF1) decreased AS-induced cell death and caspase-3 activation, but caspase-3 inhibitor Ac-DEVD-CHO did not affect LC3-II accumulation or AS-induced cell viability, suggesting that AS induces autophagic cell death and autophagy contributes to caspase-3-dependent apoptosis. Furthermore, AS activated p38/c-Jun N-terminal kinase (JNK), which could be inhibited by BaF1, and caspase-3 activation was attenuated by both SB202190 and SP600125, indicating that AS-induced autophagy promotes mitogen-activated protein kinases (MAPKs)-mediated apoptosis. Taken together, these results demonstrate that AS induces autophagic and apoptotic cell death and autophagy plays the main role in akebia saponin PA-induced cell death. PMID:23850994

  13. Lupeol enhances inhibitory effect of 5-fluorouracil on human gastric carcinoma cells.

    PubMed

    Liu, Yan; Bi, Tingting; Dai, Wei; Wang, Gang; Qian, Liqiang; Shen, Genhai; Gao, Quangen

    2016-05-01

    Lupeol, a dietary triterpene present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including cancer-preventive and anti-cancer effects in vitro and in vivo. Here, we investigated the anti-cancer efficacy and adjuvant chemotherapy action of lupeol in gastric cancer (GC) cells (SGC7901 and BGC823) and explored the underlying mechanisms. Cells were treated with lupeol and/or 5-fluorouracil (5-Fu) and subjected to cell viability, colony formation, apoptosis, western blot, semiquantitative RT-PCR, and xenograft tumorigenicity assay. Our results showed that lupeol and 5-Fu inhibited the proliferation of SGC7901 and BGC823 cells, and combination treatment with lupeol and 5-Fu resulted in a combination index < 1, indicating a synergistic effect. Co-treatment with lupeol and 5-Fu induced apoptosis through up-regulating the expressions of Bax and p53 and down-regulating the expressions of survivin and Bcl-2. Furthermore, co-treatment displayed more efficient inhibition of tumor weight and volume on BGC823 xenograft mouse model than single-agent treatment with 5-Fu or lupeol. Taken together, our findings highlight that lupeol sensitizes GC to 5-Fu treatment, and combination treatment with lupeol and 5-Fu would be a promising therapeutic strategy for human GC treatment. PMID:26892272

  14. Apoptosis of human gastric carcinoma cells induced by Euphorbia esula latex

    PubMed Central

    Fu, Zhao-Ying; Han, Xiao-Dong; Wang, Ai-Hong; Liu, Xiao-Bin

    2016-01-01

    AIM: To investigate the effect of Euphorbia esula (E. esula) extract in inhibiting proliferation and inducing apoptosis in SGC-7901 cells. METHODS: E. esula extract at different concentrations was used to inhibit proliferation and induce apoptosis of human gastric carcinoma SGC-7901 cells. Inhibition of proliferation was detected with thiazolyl blue assay, and apoptosis was detected with fluorescence microscopy, transmission electron microscopy, and flow cytometry. The mechanisms were studied by measurement of caspase-3 and caspase-8 activities and Bax and Bcl2 mRNA expression. RESULTS: The thiazolyl blue assay showed that SGC-7901 cell viability and proliferation were inhibited significantly by E. esula extract in a time- and concentration-dependent manner. Fluorescence microscopy revealed that the cell nuclei showed the characteristic changes of apoptosis, such as uneven staining and chromatin marginalization. Some key features of apoptosis were also observed under transmission electron microscopy, which included cellular shrinkage and the foaming or bubbling phenomenon. When the cells were analyzed by flow cytometry, a sub-G1 peak could be seen clearly. Spectrophotometric assay of caspase-3 and caspase-8 activities in the treated cells showed an approximately two-fold increase. Reverse transcription polymerase chain reaction showed that Bax mRNA expression was upregulated, while Bcl2 mRNA expression was downregulated. CONCLUSION: E. esula extract inhibited proliferation and induced apoptosis in SGC-7901 cells, in a caspase-dependent manner, involving upregulation of Bax and downregulation of Bcl2. PMID:27053848

  15. Identification of Serum Biomarkers for Gastric Cancer Diagnosis Using a Human Proteome Microarray.

    PubMed

    Yang, Lina; Wang, Jingfang; Li, Jianfang; Zhang, Hainan; Guo, Shujuan; Yan, Min; Zhu, Zhenggang; Lan, Bin; Ding, Youcheng; Xu, Ming; Li, Wei; Gu, Xiaonian; Qi, Chong; Zhu, Heng; Shao, Zhifeng; Liu, Bingya; Tao, Sheng-Ce

    2016-02-01

    We aimed to globally discover serum biomarkers for diagnosis of gastric cancer (GC). GC serum autoantibodies were discovered and validated using serum samples from independent patient cohorts encompassing 1,401 participants divided into three groups, i.e. healthy, GC patients, and GC-related disease group. To discover biomarkers for GC, the human proteome microarray was first applied to screen specific autoantibodies in a total of 87 serum samples from GC patients and healthy controls. Potential biomarkers were identified via a statistical analysis protocol. Targeted protein microarrays with only the potential biomarkers were constructed and used to validate the candidate biomarkers using 914 samples. To provide further validation, the abundance of autoantibodies specific to the biomarker candidates was analyzed using enzyme-linked immunosorbent assays. Receiver operating characteristic curves were generated to evaluate the diagnostic accuracy of the serum biomarkers. Finally, the efficacy of prognosis efficacy of the final four biomarkers was evaluated by analyzing the clinical records. The final panel of biomarkers consisting of COPS2, CTSF, NT5E, and TERF1 provides high diagnostic power, with 95% sensitivity and 92% specificity to differentiate GC patients from healthy individuals. Prognosis analysis showed that the panel could also serve as independent predictors of the overall GC patient survival. The panel of four serum biomarkers (COPS2, CTSF, NT5E, and TERF1) could serve as a noninvasive diagnostic index for GC, and the combination of them could potentially be used as a predictor of the overall GC survival rate. PMID:26598640

  16. A comparison between the gastric and salivary concentration of iodide, pertechnetate, and bromide in man

    PubMed Central

    Harden, R. McG.; Alexander, W. D.; Shimmins, J.; Chisholm, D.

    1969-01-01

    The concentration of iodide (I−) and pertechnetate (TcO4−) and bromide (Br−) has been measured simultaneously in gastric juice and parotid saliva. The combined gastric and salivary clearance for iodide and pertechnetate is more than twice the clearance of these ions by the thyroid gland. The concentration of the ions was in the order I−>TcO4−>Br− in both gastric juice and saliva. Differences exist between the secretion of iodide, pertechnetate, and bromide. Bromide, in contrast to iodide and pertechnetate, was found to be more concentrated in gastric juice than in saliva. The ratio of the iodide to pertechnetate clearance was greater in gastric juice than in saliva. PMID:5358585

  17. Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells.

    PubMed

    Lee, Hyun Sook; Hong, Ji Eun; Kim, Eun Ji; Kim, Sun Hyo

    2014-01-01

    Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer. PMID:24911042

  18. Farnesoid X receptor signal is involved in deoxycholic acid-induced intestinal metaplasia of normal human gastric epithelial cells.

    PubMed

    Li, Shu; Chen, Xin; Zhou, Lu; Wang, Bang-Mao

    2015-11-01

    The farnesoid X receptor (FXR) signaling pathway is known to be involved in the metabolism of bile acid, glucose and lipid. In the present study, we demonstrated that 400 µmol/l deoxycholic acid (DCA) stimulation promotes the proliferation of normal human gastric epithelial cells (GES-1). In addition, DCA activated FXR and increased the expression of intestinal metaplasia genes, including caudal-related homeobox transcription factor 2 (Cdx2) and mucin 2 (MUC2). The treatment of FXR agonist GW4064/antagonist guggulsterone (Gug.) significantly increased/decreased the expression levels of FXR, Cdx2 and MUC2 protein in DCA-induced GES-1 cells. GW4064/Gug. also enhanced/reduced the nuclear factor-κB (NF-κB) activity and binding of the Cdx2 promoter region and NF-κB, the most common subunit p50 protein. Taken together, the results indicated that DCA is capable of modulating the expression of Cdx2 and the downstream MUC2 via the nuclear receptor FXR-NF-κB activity in normal gastric epithelial cells. FXR signaling pathway may therefore be involved in the intestinal metaplasia of human gastric mucosa. PMID:26324224

  19. Biomagnetic and bioelectric detection of gastric slow wave activity in normal human subjects – a correlation study

    PubMed Central

    Somarajan, S; Muszynski, ND; Obioha, C; Richards, WO; Bradshaw, LA

    2012-01-01

    We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes, and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in MGG and in mucosal electrodes (r =0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes. PMID:22735166

  20. Influence of experimental hypokinesia on gastric secretory function

    NASA Technical Reports Server (NTRS)

    Markova, O. O.; Vavryshchuk, V. I.; Rozvodovskyy, V. I.; Proshcheruk, V. A.

    1980-01-01

    The gastric secretory function of rats was studied in 4, 8, 16 and 30 day hypokinesia. Inhibition of both the gastric juice secretory and acid producing functions was found. The greatest inhibition was observed on day 8 of limited mobility. By days 16 and 30 of the experiment, a tendency of the gastric secretory activity to return to normal was observed, although it remained reduced.

  1. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand

    PubMed Central

    Venkatarame Gowda Saralamma, Venu; Nagappan, Arulkumar; Hong, Gyeong Eun; Lee, Ho Jeong; Yumnam, Silvia; Raha, Suchismita; Heo, Jeong Doo; Lee, Sang Joon; Lee, Won Sup; Kim, Eun Hee; Kim, Gon Sup

    2015-01-01

    Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer. PMID:26393583

  2. MicroRNA-106a functions as an oncogene in human gastric cancer and contributes to proliferation and metastasis in vitro and in vivo.

    PubMed

    Zhu, Meng; Zhang, Ning; He, Shuixiang; Yan, Ruirui; Zhang, Jun

    2016-06-01

    Mounting evidences has shown that miRNAs are involved in the development and progression of gastric cancer acts as tumor suppressor genes or oncogenes. In our previous studies, we have found that the up-regulation of miR-106a occurs frequently in human gastric cancer tissues compared with that of normal tissues. Here, we investigate the role of the ectopic expressed miR-106a in the progression and metastasis of gastric cancer in vitro and in vivo. FFPE samples have the priority to be included and qRT-PCR was used to detect the miR-106a expression. Human gastric cancer cells and immortalized gastric epithelial cell were selected and the miR-106a mimic and inhibitor were transfected. Cell growth was determined by MTT method. The flow cytometric analysis for cell apoptosis and transwell assays for evaluating the cell migration and invasion were conducted. Luciferase assay and western blot confirmed the direct binding site of miR-106a and its target. BALB/c nude mice were randomly divided to explore the implantation of gastric cancer cells transfected with miR-106a antagomir. Abnormal over-expression of miR-106a significantly promoted gastric cancer cell proliferation, metastasis, inhibited the cell apoptosis. Functional experiment ascertained that miR-106a interacted with FAS and mediated caspase3 pathway. Knockdown of miR-106a leaded to the attenuation of gastric cancer implantation capacity in vivo. Moreover, expression of TIMP2 was inversely associated with miR-106a in nodule tissues. Apoptotic body was also seen under electron microscope accompanied by silencing of miR-106a. Together, this data indicated that miR-106a may act as an oncogene and contribute to gastric cancer development. PMID:27142596

  3. Low molecular weight phenolics of grape juice and winemaking byproducts: antioxidant activities and inhibition of oxidation of human low-density lipoprotein cholesterol and DNA strand breakage.

    PubMed

    de Camargo, Adriano Costa; Regitano-d'Arce, Marisa Aparecida Bismara; Biasoto, Aline Camarão Telles; Shahidi, Fereidoon

    2014-12-17

    Bioactive compounds belonging to phenolic acids, flavonoids, and proanthocyanidins of grape juice and winemaking byproducts were identified and quantified by HPLC-DAD-ESI-MS(n). The concentration of phenolic compounds in different grape cultivars was in the order Tempranillo > Cora > Syrah > Isabel. The insoluble-bound fraction was most prominent, contributing 63 and 79% to the total for Isabel and Tempranillo, respectively. Juice-processing byproducts had a higher content of free than esterified phenolics, but the opposite was noted for winemaking byproducts. Insoluble-bound phenolics were up to 15 and 10 times more effective as antioxidants than those of free and esterified fractions, respectively, as evaluated by the DPPH, ABTS, and H2O2 scavenging activities and reducing power determinations. In general, insoluble-bound phenolics (100 ppm) were more effective in inhibiting copper-induced human LDL-cholesterol oxidation than free and esterified phenolics, exhibiting equal or higher efficacy than catechin. Phenolic extracts from all fractions inhibited peroxyl radical-induced DNA strand breakage. These findings shed further light for future studies and industrial application of grape byproducts, which may focus not only on the soluble phenolics but also on the insoluble-bound fraction. PMID:25417599

  4. Antioxidant effectiveness of phenolic apple juice extracts and their gut fermentation products in the human colon carcinoma cell line caco-2.

    PubMed

    Bellion, Phillip; Hofmann, Thomas; Pool-Zobel, Beatrice L; Will, Frank; Dietrich, Helmut; Knaup, Bastian; Richling, Elke; Baum, Matthias; Eisenbrand, Gerhard; Janzowski, Christine

    2008-08-13

    Apples represent a major dietary source of antioxidative polyphenols. Their metabolic conversion by the gut microflora might generate products that protect the intestine against oxidative damage. We studied the antioxidant effectiveness of supernatants of fermented apple juice extracts (F-AEs, 6 and 24 h fermentation) and of selected phenolic degradation products, identified by HPLC-DAD-ESI-MS. Cell free antioxidant capacity of unfermented apple juice extracts (AEs) was decreased after fermentation by 30-50%. In the human colon carcinoma cell line Caco-2, F-AEs (containing <0.5% of original AE-phenolics) decreased the reactive oxygen species (ROS) level more efficiently than the F-blank (fermented without AE) but were less effective than the respective AEs. Similarly, antioxidant effectiveness of individual degradation products was lower compared to respective AE constituents. Glutathione level was slightly increased and oxidative DNA damage slightly decreased by fermented AE03, rich in quercetin glycosides. In conclusion, F-AEs/degradation products exhibit antioxidant activity in colon cells but to a lesser extent than the respective unfermented AEs/constituents. PMID:18624411

  5. Effect of sodium bicarbonate on aspirin-induced damage and potential difference changes in human gastric mucosa

    PubMed Central

    Bowen, Bruce K; Krause, William J; Ivey, Kevin J

    1977-01-01

    Two aspirin tablets in 100 ml fluid will produce microscopical damage to the human stomach. A study was performed to determine whether a small amount of sodium bicarbonate (equivalent to one-third of a teaspoonful of baking soda) could protect against this damage. Sequential gastric biopsy specimens were taken from 15 healthy subjects before, during, and after intragastric instillation of one of the following isotonic solutions: saline; sodium bicarbonate; 600 mg aspirin suspended in sodium bicarbonate; and aspirin suspended in saline. On a separate day the same solutions were instilled, but gastric transmucosal potential differences were monitored. Light microscopy and scanning electron microscopy of the biopsy specimens showed occasional mucous degranulation of mucosal surface cells, but no cell damage during instillation of sodium bicarbonate. Light microscopy studies 10 minutes after aspirin in saline showed damage in 20% of surface cells, with focal areas of cellular disruption and microscopic erosions, but only 3·4% of cells were damaged after aspirin in bicarbonate and there were no erosions. Electron microscopy showed a damaged honeycombed appearance of surface epithelium after aspirin in saline and a normal cobblestone appearance after aspirin in bicarbonate. Aspirin dissolved in bicarbonate failed to induce the usual fall in potential difference. These findings indicate that sodium bicarbonate in amounts equivalent to one-third of a teaspoonful of baking soda protects the gastric mucosa against aspirin-induced damage and prevents the usual fall in potential difference after aspirin. ImagesFIG 2FIG 3FIG 4 PMID:922417

  6. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study.

    PubMed

    Di Lorenzo, Chiara; Sangiovanni, Enrico; Fumagalli, Marco; Colombo, Elisa; Frigerio, Gianfranco; Colombo, Francesca; Peres de Sousa, Luis; Altindişli, Ahmet; Restani, Patrizia; Dell'Agli, Mario

    2016-01-01

    Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)α-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases. PMID:27447609

  7. Accumulation of abasic sites induces genomic instability in normal human gastric epithelial cells during Helicobacter pylori infection.

    PubMed

    Kidane, D; Murphy, D L; Sweasy, J B

    2014-01-01

    Helicobacter pylori infection of the human stomach is associated with inflammation that leads to the release of reactive oxygen and nitrogen species (RONs), eliciting DNA damage in host cells. Unrepaired DNA damage leads to genomic instability that is associated with cancer. Base excision repair (BER) is critical to maintain genomic stability during RONs-induced DNA damage, but little is known about its role in processing DNA damage associated with H. pylori infection of normal gastric epithelial cells. Here, we show that upon H. pylori infection, abasic (AP) sites accumulate and lead to increased levels of double-stranded DNA breaks (DSBs). In contrast, downregulation of the OGG1 DNA glycosylase decreases the levels of both AP sites and DSBs during H. pylori infection. Processing of AP sites during different phases of the cell cycle leads to an elevation in the levels of DSBs. Therefore, the induction of oxidative DNA damage by H. pylori and subsequent processing by BER in normal gastric epithelial cells has the potential to lead to genomic instability that may have a role in the development of gastric cancer. Our results are consistent with the interpretation that precise coordination of BER processing of DNA damage is critical for the maintenance of genomic stability. PMID:25417725

  8. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma

    PubMed Central

    Hedner, Charlotta; Borg, David; Nodin, Björn; Karnevi, Emelie; Jirström, Karin; Eberhard, Jakob

    2016-01-01

    Background Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma. Methods Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology. Results and Discussion High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods. PMID:26844548

  9. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study

    PubMed Central

    Di Lorenzo, Chiara; Sangiovanni, Enrico; Fumagalli, Marco; Colombo, Elisa; Frigerio, Gianfranco; Colombo, Francesca; Peres de Sousa, Luis; Altindişli, Ahmet; Restani, Patrizia; Dell’Agli, Mario

    2016-01-01

    Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)α-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases. PMID:27447609

  10. Different digestion of caprine whey proteins by human and porcine gastrointestinal enzymes.

    PubMed

    Eriksen, Ellen K; Holm, Halvor; Jensen, Einar; Aaboe, Ragnhild; Devold, Tove G; Jacobsen, Morten; Vegarud, Gerd E

    2010-08-01

    The objective of the present study was twofold: first to compare the degradation patterns of caprine whey proteins digested with either human digestive juices (gastric or duodenal) or commercial porcine enzymes (pepsin or pancreatic enzymes) and second to observe the effect of gastric pH on digestion. An in vitro two-step assay was performed at 37 degrees C to simulate digestion in the stomach (pH 2, 4 or 6) and the duodenum (pH 8). The whey proteins were degraded more efficiently by porcine pepsin than by human gastric juice at all pH values. Irrespective of the enzyme source, gastric digestion at pH 2 followed by duodenal digestion resulted in the most efficient degradation. Lactoferrin, serum albumin and the Ig heavy chains were highly degraded with less than 6 % remaining after digestion. About 15, 56 and 50 % Ig light chains, beta-lactoglobulin (beta-LG) and alpha-lactalbumin remained intact, respectively, when digested with porcine enzymes compared with 25, 74 and 81 % with human digestive juices. For comparison, purified bovine beta-LG was digested and the peptide profiles obtained were compared with those of the caprine beta-LG in the digested whey. The bovine beta-LG seemed to be more extensively cleaved than the caprine beta-LG in the whey. Commercial enzymes appear to digest whey proteins more efficiently compared with human digestive juices when used at similar enzyme activities. This could lead to conflicting results when comparing human in vivo protein digestion with digestion using purified enzymes of non-human species. Consequently the use of human digestive juices might be preferred. PMID:20307348

  11. Prognostic value of decreased expression of RBM4 in human gastric cancer

    PubMed Central

    Yong, Hongmei; Zhu, Huijun; Zhang, Shu; Zhao, Wei; Wang, Wei; Chen, Chen; Ding, Guipeng; Zhu, Lun; Zhu, Ziyuan; Liu, Huaidong; Zhang, Yongjie; Wen, Jinbo; Kang, Xing; Zhu, Jin; Feng, Zhenqing; Liu, Baorui

    2016-01-01

    RNA-binding motif 4 (RBM4) is a multifunctional protein that participates in regulating alternative splicing and mRNA translation. Its reduced expression has been associated with poor overall survival in lung cancer, breast cancer and ovarian cancer. We assessed RBM4 protein expression levels with immunohistochemistry in tissue microarrays containing malignant gastric cancer tissues and benign tissues from 813 patients. We also examined the expression levels of RBM4 mRNA in twenty-five paired gastric cancer samples and adjacent noncancerous tissues. Both RBM4 protein and mRNA expression levels were significantly lower in gastric cancer tissues compared with the adjacent noncancerous tissues. There was a significant association between reduced RBM4 protein expression and differentiation (P < 0.001), lymph node metastasis (P = 0.026), TNM state (P = 0.014) and distant metastasis (P = 0.036). Patients with reduced RBM4 expression (P < 0.001, CI = 0.315–0.710) and TNM stage III and IV (P < 0.001, CI = 4.757–11.166) had a poor overall survival. These findings suggest that RBM4 is a new biomarker in gastric cancer, as the reduced expression of this protein is correlated with poor differentiation, lymph node status and distant metastasis. Further, lower RBM4 expression is an independent prognostic marker for gastric cancer. PMID:27324405

  12. NHE1 activity contributes to migration and is necessary for proliferation of human gastric myofibroblasts.

    PubMed

    Czepán, Mátyás; Rakonczay, Zoltán; Varró, Andrea; Steele, Islay; Dimaline, Rod; Lertkowit, Nantaporn; Lonovics, János; Schnúr, Andrea; Biczó, György; Geisz, Andrea; Lázár, György; Simonka, Zsolt; Venglovecz, Viktória; Wittmann, Tibor; Hegyi, Péter

    2012-03-01

    Myofibroblasts play central roles in wound healing, deposition of the extracellular matrix and epithelial function. Their functions depend on migration and proliferation within the subepithelial matrix, which results in accelerated cellular metabolism. Upregulated metabolic pathways generate protons which need to be excreted to maintain intracellular pH (pH(i)). We isolated human gastric myofibroblasts (HGMs) from surgical specimens of five patients. Then we characterized, for the first time, the expression and functional activities of the Na(+)/H(+) exchanger (NHE) isoforms 1, 2 and 3, and the functional activities of the Na(+)/HCO(3)(-) cotransporter (NBC) and the anion exchanger (AE) in cultured HGMs using microfluorimetry, immunocytochemistry, reverse transcription polymerase chain reaction and immunoblot analysis. We showed that NHE1-3, NBC and AE activities are present in HGMs and that NHE1 is the most active of the NHEs. In scratch wound assays we also demonstrated (using the selective NHE inhibitor HOE-642) that carbachol and insulin like growth factor II (IGF-II) partly stimulate migration of HGMs in a NHE1-dependent manner. EdU incorporation assays revealed that IGF-II induces proliferation of HGMs which is inhibited by HOE-642. The results indicate that NHE1 is necessary for IGF-II-induced proliferation response of HGMs. Overall, we have characterized the pH(i) regulatory mechanisms of HGMs. In addition, we demonstrated that NHE1 activity contributes to both IGF-II- and carbachol-stimulated migration and that it is obligatory for IGF-II-induced proliferation of HGMs. PMID:22138972

  13. The NMDA receptor NR2A subunit regulates proliferation of MKN45 human gastric cancer cells

    SciTech Connect

    Watanabe, Kanako; Kanno, Takeshi; Oshima, Tadayuki; Miwa, Hiroto; Tashiro, Chikara; Nishizaki, Tomoyuki

    2008-03-07

    The present study investigated proliferation of MKN28 and MKN45 human gastric cancer cells regulated by the N-methyl-D-aspartate (NMDA) receptor subunit. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) inhibited proliferation of MKN45 cells, but not MKN28 cells. Of the NMDA subunits such as NR1, NR2 (2A, 2B, 2C, and 2D), and NR3 (3A and 3B), all the NMDA subunit mRNAs except for the NR2B subunit mRNA were expressed in both MKN28 and MKN45 cells. MKN45 cells were characterized by higher expression of the NR2A subunit mRNA and lower expression of the NR1 subunit mRNA, but MKN28 otherwise by higher expression of the NR1 subunit mRNA and lower expression of the NR2A subunit mRNA. MKN45 cell proliferation was also inhibited by silencing the NR2A subunit-targeted gene. For MKN45 cells, AP5 or knocking-down the NR2A subunit increased the proportion of cells in the G{sub 1} phase of cell cycling and decreased the proportion in the S/G{sub 2} phase. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G{sub 1} phase; in other words, the NR2A subunit promotes MKN45 cell proliferation by accelerating cell cycling.

  14. Inhibitory effect of vitamin K1 on growth and polyamine biosynthesis of human gastric and colon carcinoma cell lines.

    PubMed

    Linsalata, Michele; Orlando, Antonella; Tutino, Valeria; Notarnicola, Maria; D'Attoma, Benedetta; Russo, Francesco

    2015-08-01

    Gastric and colon cancers remain the leading cause of cancer mortality throughout the world. Since the gastrointestinal tract works in a constant link with the external environment, chemoprevention by dietary constituents could represent a possible approach to reduce cancer risk. Dietary vitamin K1 (VK1) has been shown to prevent the growth of many types of cancer cells. However, no data are available on possible different susceptibility to VK1 by gastric or colon neoplastic cell lines. Moreover, the exact mechanism of action of VK1 is still object of investigation, even if it has been reported that VK1 may induce cell cycle arrest and apoptosis. Therefore, molecules affecting cell growth such as the natural polyamines could be of interest in VK1 action. The aim of the present study was to investigate the effects of increasing concentrations of VK1 (from 10 to 200 µM) administered up to 72 h, on the cell proliferation and apoptosis of a gastric (HGC-27) and a colon (SW480) cancer cell line. Additionally, the polyamine biosynthesis and the MAPK pathway were also examined. VK1 treatments caused an inhibition of cell proliferation and an induction of apoptosis in both cell lines, with a concomitant significant decrease of the polyamine biosynthesis, increased phospho-ERK 1/2 expression was also observed. A different proliferative behavior and a different response to VK1 by gastric and colon cancer cells was evident, with colon cells showing a more pronounced susceptibility to VK1 action. VK1 is safe and without known toxicities in adult humans, consequently it could be effective in prevention and treatment of selected gastrointestinal neoplasms. Protocols based on the use of VK1, along with polyamine inhibitors and/or analogues, could represent a suitable alternative option for improving the efficacy of chemoprevention and treatment in future strategies for gastrointestinal cancer management. PMID:26043965

  15. 3,3'-Diindolylmethane induces anti-human gastric cancer cells by the miR-30e-ATG5 modulating autophagy.

    PubMed

    Ye, Yang; Fang, Yanfei; Xu, Wenxia; Wang, Qiang; Zhou, Jianwei; Lu, Rongzhu

    2016-09-01

    3,3'-Diindolylmethane (DIM), a class of relatively non-toxic indole derivatives from cruciferous vegetables, has been reported as a promising anticancer phytochemical, but the underlying molecular mechanism is not completely elucidated. In the present study we report a novel regulation of autophagy by DIM in human gastric cancer cells. We found that DIM dose-dependently inhibited the growth of gastric cancer cells in vitro and in vivo. Moreover, ATG5 and LC3 were activated by DIM in gastric cancer cells. Furthermore, miR-30e was down-regulated by DIM and miR-30e targeted the 3'-UTR of ATG5 to inhibit its translation. Overall, these results suggest that DIM may through the miR-30e-ATG5 modulating autophagy inhibit the proliferation of gastric cancer cells. PMID:27372603

  16. Treatment of gastric cancer

    PubMed Central

    Orditura, Michele; Galizia, Gennaro; Sforza, Vincenzo; Gambardella, Valentina; Fabozzi, Alessio; Laterza, Maria Maddalena; Andreozzi, Francesca; Ventriglia, Jole; Savastano, Beatrice; Mabilia, Andrea; Lieto, Eva; Ciardiello, Fortunato; De Vita, Ferdinando

    2014-01-01

    The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status PMID:24587643

  17. Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

    PubMed

    Jia, Yanfei; Sun, Haiji; Wu, Hongqiao; Zhang, Huilin; Zhang, Xiuping; Xiao, Dongjie; Ma, Xiaoli; Wang, Yunshan

    2016-01-01

    Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of α5-nAChR. To evaluate the hypothesis that α5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of α5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through α5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of α5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that α5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin. PMID:26909550

  18. Reduction of apoptosis by proanthocyanidin-induced autophagy in the human gastric cancer cell line MGC-803

    PubMed Central

    NIE, CHAO; ZHOU, JIE; QIN, XIAOKANG; SHI, XIANMING; ZENG, QINGQI; LIU, JIA; YAN, SHIHAI; ZHANG, LEI

    2016-01-01

    Proanthocyanidins are flavonoids that are widely present in the skin and seeds of various plants, with the highest content in grape seeds. Many experiments have shown that proanthocyanidins have antitumor activity both in vivo and in vitro. Autophagy and apoptosis of tumor cells induced by drugs are two of the major causes of tumor cell death. However, reports on the effect of autophagy induced by drugs in tumor cells are not consistent and suggest that autophagy can have synergistic or antagonistic effects with apoptosis. This research was aimed at investigating whether proanthocyanidins induced autophagy and apoptosis in human gastric cancer cell line MGC-803 cells and to identify the mechanism of proanthocyanidins action to further determine the effect of proanthocyanidins-induced autophagy on apoptosis. MTT assay was used to examine the proanthocyanidin cytotoxicity against human gastric cancer cell line MGC-803. Transmission electron microscopy and monodansylcadaverine (MDC) staining were used to detect autophagy. Annexin V APC/7-AAD double staining and Hoechst 33342/propidium iodide (PI) double staining were used to explore apoptosis. Western blotting was used to determine expression of proteins related to autophagy and apoptosis. Real-time quantitative PCR technology was used to determine the mRNA level of Beclin1 and BCL-2. The results showed that proanthocyanidins exhibit a significant inhibitory effect on the human gastric cancer cell line MGC-803 proliferation in vitro and simultaneously activate autophagy and apoptosis to promote cell death. Furthermore, when proanthocyanidin-induced autophagy is inhibited, apoptosis increases significantly, proanthocyanidins can be used together with autophagy inhibitors to enhance cytotoxicity. PMID:26572257

  19. Microbes Associated with Freshly Prepared Juices of Citrus and Carrots

    PubMed Central

    Aneja, Kamal Rai; Dhiman, Romika; Aggarwal, Neeraj Kumar; Kumar, Vikas; Kaur, Manpreeet

    2014-01-01

    Fruit juices are popular drinks as they contain antioxidants, vitamins, and minerals that are essential for human being and play important role in the prevention of heart diseases, cancer, and diabetes. They contain essential nutrients which support the growth of acid tolerant bacteria, yeasts, and moulds. In the present study, we have conducted a microbiological examination of freshly prepared juices (sweet lime, orange, and carrot) by serial dilution agar plate technique. A total of 30 juice samples were examined for their microbiological quality. Twenty-five microbial species including 9 bacterial isolates, 5 yeast isolates, and 11 mould isolates were isolated from juices. Yeasts and moulds were the main cause of spoilage of juices. Aspergillus flavus and Rhodotorula mucilaginosa were observed in the maximum number of juice samples. Among bacteria Bacillus cereus and Serratia were dominant. Escherichia coli and Staphylococcus aureus were detected in few samples. Candida sp., Curvularia, Colletotrichum, and Acetobacter were observed only in citrus juice samples. Alternaria, Aspergillus terreus, A. niger, Cladosporium, and Fusarium were also observed in tested juice samples. Some of the microorganisms detected in these juice samples can cause disease in human beings, so there is need for some guidelines that can improve the quality of fruit juices. PMID:26904628

  20. Oncogenic NanogP8 expression regulates cell proliferation and migration through the Akt/mTOR signaling pathway in human gastric cancer – SGC-7901cell line

    PubMed Central

    Jiang, Zheng; Liu, Yao; Wang, Chuan

    2016-01-01

    Background Although elevated expression of NanogP8 has been detected in many human tumor tissues, its role in gastric tumorigenesis remains unclear. Therefore, this study aimed to investigate the function and regulatory mechanism of NanogP8 in gastric cancer. Methods In this study, NanogP8 cDNA was amplified by real time polymerase chain reaction from the human gastric cancer cell line SGC-7901. The shRNA for RNA interference was established. The NanogP8, pAkt, Akt, pERK, ERK, p-mTOR, and mTOR proteins were detected by using the Western blot assay. Cell viability was evaluated by using the CCK-8 assay. Cell migration and invasion were also examined by using the transwell assay. Results The results indicated that the NanogP8 overexpression promoted proliferation and migration of SGC-7901 cell line, whereas its ablation exerted opposite effects. Interestingly, NanogP8 activated Akt, a key mediator of survival signals, and without affecting total Akt protein level. The NanogP8-increased gastric cell proliferation was downregulated by Akt inhibition. Our results further showed that increasing NanogP8 expression in human gastric cancer cells promoted cell proliferation by activating the AKT/mTOR pathway and further maintained gastric cell survival. Conclusion Our findings extend the knowledge regarding the oncogenic functions and proved that the NanogP8 regulates cell proliferation and migration by Akt/mTOR signaling pathway in human gastric cancer SGC-7901cell line. PMID:27563247

  1. RRR-α-tocopheryl succinate induces apoptosis in human gastric cancer cells via the NF-κB signaling pathway.

    PubMed

    Sun, Yanpei; Zhao, Yan; Hou, Liying; Zhang, Xuguang; Zhang, Zhihong; Wu, Kun

    2014-09-01

    To investigate the effects of the nuclear factor (NF)-κB signaling pathway on the induction of apoptosis by vitamin E succinate (RRR-α-tocopheryl succinate; VES) in human gastric carcinoma cells. Human gastric carcinoma SGC-7901 cells were treated with temperate concentrations of VES and pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Cell viability and apoptosis were respectively estimated by methylthiazol tetrazolium (MTT) assay and the Annexin V‑FITC method. Western blot analysis was used to evaluate the protein expressions of NF-κBp65 and Bcl-2 family members Bcl-2, Bax and cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP). The DNA-binding activity of NF-κBp65 was measured by electrophoretic mobility shift assay (EMSA). Reverse transcription and polymerase chain reaction (RT-PCR) was implemented to evaluate the transcription of inhibitor of apoptosis (IAP) genes. Apoptosis assessment showed that VES induces apoptotic cell death in human gastric carcinoma cells. In the following experiments, PDTC (100 µM) was used in cell treatment 2 h before VES. The decreased ratio of the nuclear and cytosolic NF-κBp65 protein level was induced by VES and PDTC reinforced this trend. PDTC treatment significantly enhanced the decrease of NF-κB-DNA binding activity induced by VES in human gastric SGC-7901. The decrease in protein expression of Bcl-2 as well as the increase in the protein expression of Bax were induced by VES treatment. The cleavage of caspase-9, caspase-3 and PARP was induced. There was no effect on the gene transcription of c-IAP-1, c-IAP-2, and x-linked IAP (XIAP) compared with the control group, whereas mRNA levels of survivin and the neuronal apoptosis inhibitory protein (NAIP) markedly decreased. Notably, pretreatment with PDTC reinforced all the above VES-induced effects. In conclusion, VES-induced apoptosis in SGC-7901 cells is accompanied by the inhibition of the NF-κB signaling pathway, including

  2. Fresh and Commercially Pasteurized Orange Juice: An Analysis of the Metabolism of Flavonoid Compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Orange juice is a rich source of flavonoids, mainly the flavanones hesperidin and narirutin, associated with health benefits in humans. The objective of this study was to analyze the uptake of flavonoids in humans after the consumption of two types of orange juice, fresh squeezed (fresh juice, FJ) a...

  3. Association between Helicobacter pylori hopQI genotypes and human gastric cancer risk.

    PubMed

    Kazemi, E; Kahrizi, D; Moradi, M T; Sohrabi, M; Amini, S; Mousavi, S A R; Yari, K

    2016-01-01

    The Helicobacter pylori use a number of mechanisms to survive in the stomach lumen and can lead to gastritis and reduction in stomach acid secretion. It has been found that the risk of developing gastric carcinoma is associated to heterogeneity of H. pylori virulence factors such as HopQ. The HopQ is one of the outer membrane proteins involved in bacterial adherence to gastric mucosa and has been suggested to also main role in the virulence of H. pylori. The purpose of the current study was to investigate the association between different H. pylori virulence hopQI (types I) genotyping and patients with gastroduodenal disorders. For this purpose 58 stomach biopsies of the patients with gastric cancer and 100 saliva samples from healthy and H. pylori infected individuals were collected and studied. Then genomic DNA was purified and PCR was done for desired gene via specific primers. The H. pylori infections were diagnosed using PCR for GlmM gene. Then frequencies of hopQI+ and hopQI- genotypes were determined in H. pylori infected cases. Statistical analysis showed that there were not significant differences between healthy and diseased ones for genotypes hopQI+ and hopQI-. Then the hopQI+ cannot be as a risk factor genotype for gastric cancer. PMID:26828979

  4. GASTRIC MOTOR DISTURBANCES IN PATIENTS WITH IDIOPATHIC RAPID GASTRIC EMPTYING

    PubMed Central

    Bharucha, Adil E.; Manduca, Armando; Lake, David S.; Fidler, Jeff; Edwards, Phillip; Grimm, Roger C.; Zinsmeister, Alan R.; Riederer, Stephen J.

    2011-01-01

    Background and Aims The mechanisms of “idiopathic” rapid gastric emptying, which is associated with functional dyspepsia and functional diarrhea, are not understood. Our hypotheses were that increased gastric motility and reduced postprandial gastric accommodation contribute to rapid gastric emptying. Methods Fasting and postprandial (300kCal nutrient meal) gastric volumes were measured by magnetic resonance imaging (MRI) in 20 healthy people and 17 with functional dyspepsia; 7 had normal and 10 had rapid gastric emptying. In 17 healthy people and patients, contractility was analyzed by spectral analysis of a time-series of gastric cross-sectional areas. Logistic regression models analyzed whether contractile parameters, fasting volume, and postprandial volume change could discriminate between health and patients with normal or rapid gastric emptying. Results While upper gastrointestinal symptoms were comparable, patients with rapid emptying had a higher (p = 0.002) body mass index (BMI) than normal gastric emptying. MRI visualized propagating contractions at ~ 3 cpm in healthy people and patients. Compared to controls (0.16 ± 0.02, Mean ± SEM), the amplitude of gastric contractions in the entire stomach was higher (OR 4.1, 95% CI 1.2–14.0) in patients with rapid (0.24 ± 0.03) but not normal gastric emptying (0.10 ± 0.03). Similar differences were observed in the distal stomach. However, the propagation velocity, fasting gastric volume, and the postprandial volume change were not significantly different between patients and controls. Conclusions MRI provides a noninvasive and refined assessment of gastric volumes and contractility in humans. Increased gastric contractility may contribute to rapid gastric emptying in functional dyspepsia. PMID:21470342

  5. An assessment of human gastric fluid composition as a function of PPI usage

    PubMed Central

    Foltz, Emily; Azad, Sassan; Everett, Mary Lou; Holzknecht, Zoie E.; Sanders, Nathan L.; Thompson, J. Will; Dubois, Laura G.; Parker, William; Keshavjee, Shaf; Palmer, Scott M.; Davis, R. Duane; Lin, Shu S.

    2015-01-01

    Abstract The standard of care for chronic gastro‐esophageal reflux disease (GERD), which affects up to 40% of the population, is the use of drugs such as proton pump inhibitors (PPIs) that block the production of stomach acid. Despite widespread use, the effects of PPIs on gastric fluid remain poorly characterized. In this study, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Various enzymatic and immunoassays as well as mass spectrometry were utilized to analyze the concentrations of bile, gastricsin, trypsin, and pepsin in the gastric fluid. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. In general, the concentrations of all analytes evaluated varied over several orders of magnitude, covering a minimum of a 2000‐fold range (gastricsin) and a maximum of a 1 × 106 –fold range (trypsin). Furthermore, the concentrations of various analytes were poorly correlated with one another in the samples. For example, trypsin and bile concentrations showed a significant (P < 0.0001) but not strong correlation (r = 0.54). Finally, direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid. These results further delineate the profound effects that PPI usage has on the physiology of the stomach. PMID:25626870

  6. Induction of peripheral lymph node addressin in human gastric mucosa infected by Helicobacter pylori

    PubMed Central

    Kobayashi, Motohiro; Mitoma, Junya; Nakamura, Naoshi; Katsuyama, Tsutomu; Nakayama, Jun; Fukuda, Minoru

    2004-01-01

    Helicobacter pylori infects over half the world's population and is a leading cause of peptic ulcer and gastric cancer. H. pylori infection results in chronic inflammation of the gastric mucosa, and progression of chronic inflammation leads to glandular atrophy and intestinal metaplasia. However, how this chronic inflammation is induced or maintained is not well known. Here, we show that chronic inflammation caused by H. pylori infection is highly correlated with de novo synthesis of peripheral lymph node addressin (PNAd) presented on high-endothelial venule (HEV)-like vessels. The number of HEV-like vessels dramatically increases as chronic inflammation progresses. We found that the PNAd is bound by L-selectin·IgM chimeric protein, and decorated by NCC-ST-439 antibody, which is suggested to recognize both nonsulfated and 6-sulfated sialyl Lewis X on core 2 branched O-glycans, and MECA-79 antibody, which reacts with 6-sulfo N-acetyllactosamine on extended core 1 O-glycans. These results indicate that PNAd on HEV-like vessels present in the gastric mucosa subsequent to H. pylori infection is similar to those on HEVs present in the secondary lymphoid organs, which are essential for lymphocyte circulation. Moreover, eradication of H. pylori is associated with the disappearance of HEV-like vessels in the gastric mucosa. By contrast, very few PNAd were found in the gastric mucosa of patients with chemical gastritis caused by nonsteroidal antiinflammatory drugs. These results strongly suggest that PNAd in HEV-like vessels plays a critical role in lymphocyte recruitment during chronic inflammation induced by H. pylori infection. PMID:15591109

  7. Modulation of microRNAs by ionizing radiation in human gastric cancer.

    PubMed

    He, Jinpeng; Hua, Junrui; Ding, Nan; Xu, Shuai; Sun, Rui; Zhou, Guangming; Xie, Xiaodong; Wang, Jufang

    2014-08-01

    Gastric cancer is one of the most common cancers in China. Although surgery is the primary therapeutic method, radiotherapy has become an integral part, particularly in the early and intermediate stages of gastric cancer. microRNAs (miRNAs) are involved in the regulation of diverse cellular processes in response to intrinsic and extrinsic stress. A change in miRNA expression profile has been identified in various types of tumor cells in response to radiation; however, there is no relevant information concerning gastric cancer. In the present study, we investigated the miRNA profiles of two clinical gastric cancer samples exposed to X‑rays using miRNA microarray. We found that 16 miRNAs were downregulated and 2 miRNAs were upregulated significantly in both irradiated samples when compared with the unirradiated samples. Decreases in the levels of miR‑300 and miR‑642 expression were confirmed by qRT‑PCR in more clinical samples and in cultured cell lines. We predicted the targets of the two miRNAs with TargetScan and classified all the candidate targets with Gene Ontology, which indicated that both miR‑300 and miR‑642 potentially regulate cellular radiation response by modulating apoptosis, cell cycle regulation and DNA damage and repair pathway-related genes. Cell cycle assay and immunofluorescence assay demonstrated that miR‑300 regulates radiation‑induced G2 cell cycle arrest and DNA damage repair. In conclusion, our findings indicate that ionizing radiation modulates the miRNA expression profile, and the changes in several specific miRNAs such as miR‑300 have the potential to be used in the treatment, diagnosis and prognosis of gastric cancer. PMID:24919435

  8. Properties of a potassium channel in cultured human gastric cells (HGT-1) possessing specific omeprazole binding sites.

    PubMed Central

    Sandle, G I; Fraser, G; Fogg, K; Warhurst, G

    1993-01-01

    The HGT-1 human gastric cell line is similar to acid secreting parietal cells in that it possesses H2 receptors, histamine sensitive adenyl cyclase, and Cl- channels, which are activated by histamine by a cyclic adenosine monophosphate (cAMP) dependent mechanism. To discover if HGT-1 cells have additional properties found in parietal cells, [3H]omeprazole and patch clamp recording techniques were used to evaluate specific omeprazole binding sites and K+ channels in the plasma membrane. HGT-1 cells exhibited [3H]omeprazole binding in the non-stimulated state, which increased 100% in the presence of 1 mM histamine. High conductance (about 155 pS) K+ channels were active spontaneously in 17% of cell attached or excised inside out patches in non-stimulated subconfluent HGT-1 cells. In inside out patches, channel activity increased fivefold during depolarisation, ion substitution experiments confirmed that the channels were highly selective for K+, and channel activity was almost abolished by removal of Ca2+ or addition of 5 mM Ba2+. In quiescent cell attached patches, 0.1 mM dibutyryl cAMP failed to activate K+ channels. In contrast, 6.7 microM A23187 (a Ca2+ ionophore) increased intracellular Ca2+ concentration from mean (SEM) 14 (3) nM to 248 (30) nM and activated K+ channels in 21% of patches. It is concluded that the plasma membrane of HGT-1 cells possesses (a) specific 3H-omeprazole binding sites, which may reflect the omeprazole sensitive H+,K(+)-ATPase present in gastric parietal cells; and (b) Ca(2+)-activated K+ channels, which may be located in the basolateral membrane of human gastric parietal cells and play a part in acid secretion triggered by Ca(2+)-mediated secretory agonists. PMID:8244097

  9. Nobiletin Induces Protective Autophagy Accompanied by ER-Stress Mediated Apoptosis in Human Gastric Cancer SNU-16 Cells.

    PubMed

    Moon, Jeong Yong; Cho, Somi Kim

    2016-01-01

    Nobiletin, a major component of citrus fruits, is a polymethoxyflavone derivative that exhibits anticancer activity against several forms of cancer, including SNU-16 human gastric cancer cells. To explore the nobiletin-induced cell death mechanism, we examined the changes in protein expression caused by nobiletin in human gastric cancer SNU-16 cells by means of two-dimensional gel electrophoresis (2-DGE), followed by peptide mass fingerprinting (PMF) analysis. Seventeen of 20 selected protein spots were successfully identified, including nine upregulated and eight downregulated proteins. In nobiletin-treated SNU-16 cells the glucose-regulated protein 78 kDa (GRP78) mRNA level was induced most significantly among six proteins related to cell survival and death. Western blot analysis was used to confirm the expression of GRP78 protein. We detected increases in the levels of the ER-stress related proteins inositol requiring enzyme 1 alpha (IRE1-α), activating transcription factor 4 (ATF-4), and C/EBP homology protein (CHOP), as well as GRP78, in response to nobiletin in SNU-16 cells. Furthermore, the ER stress-mediated apoptotic protein caspase-4 was proteolytically activated by nobiletin. Pretreatment with chloroquine, an autophagy inhibitor, strongly augmented apoptosis in SNU-16 cells, as evidenced by decreased cell viability, an increased number of sub-G1 phase cells and increased levels of cleaved PARP. Our results suggest that nobiletin-induced apoptosis in SNU-16 cells is mediated by pathways involving intracellular ER stress-mediated protective autophagy. Thus, the combination of nobiletin and an autophagy inhibitor could be a promising treatment for gastric cancer patients. PMID:27428937

  10. In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

    SciTech Connect

    Gunassekaran, G.R.; Kalpana Deepa Priya, D.; Gayathri, R.; Sakthisekaran, D.

    2011-08-12

    Highlights: {yields} Gossypol is a well known polyphenolic compound used for anticancer studies but we are the first to report that gossypol has antitumor effect on MNNG induced gastric cancer in experimental animal models. {yields} Our study shows that gossypol inhibits the proliferation of AGS (human gastric adenocarcinoma) cell line. {yields} In animal models, gossypol extends the survival of cancer bearing animals and also protects the cells from carcinogenic effect. {yields} So we suggest that gossypol would be a potential chemotherapeutic and chemopreventive agent for gastric cancer. -- Abstract: The present study has evaluated the chemopreventive effects of gossypol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C{sub 30}H{sub 30}O{sub 8}, is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in patients

  11. Cellular inhibitor of apoptosis protein 1 (cIAP1) stability contributes to YM155 resistance in human gastric cancer cells.

    PubMed

    Jung, Soo-A; Park, Yong-Man; Hong, Seung-Woo; Moon, Jai-Hee; Shin, Jae-Sik; Lee, Ha-Reum; Ha, Seung-Hee; Lee, Dae-Hee; Kim, Jeong Hee; Kim, Seung-Mi; Kim, Jeong Eun; Kim, Kyu-pyo; Hong, Yong Sang; Choi, Eun Kyung; Lee, Jung Shin; Jin, Dong-Hoon; Kim, TaeWon

    2015-04-17

    YM155, which blocks the expression of survivin, a member of the inhibitor of apoptosis (IAP) family, induces cell death in a variety of cancer types, including prostate, bladder, breast, leukemia, and non-small lung cancer. However, the mechanism underlying gastric cancer susceptibility and resistance to YM155 is yet to be specified. Here, we demonstrate that cIAP1 stability dictates resistance to YM155 in human gastric cancer cells. Treatment of human gastric cancer cells with YM155 differentially induced cell death dependent on the stability of cIAP1 as well as survivin. Transfection with cIAP1 expression plasmids decreased cell sensitivity to YM155, whereas knockdown of endogenous cIAP1 using RNA interference enhanced sensitivity to YM155. In addition, double knockdown of survivin and cIAP1 significantly induced cell death in the YM155-resistant cell line, MKN45. We also showed that YM155 induced autoubiquitination and proteasome-dependent degradation of cIAP1. Surprisingly, survivin affected the stability of cIAP1 through binding, contributing to cell sensitivity to YM155. Thus, our findings reveal that YM155 sensitizes human gastric cancer cells to apoptotic cell death by degrading cIAP1, and furthermore, cIAP1 in gastric cancer cells may act as a PD marker for YM155 treatment. PMID:25635055

  12. RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions.

    PubMed

    Broad, John; Takahashi, Nobuyuki; Tajimi, Masaomi; Sudo, Masaki; Góralczyk, Adam; Parampalli, Umesh; Mannur, Kesava; Yamamoto, Toshinori; Sanger, Gareth J

    2016-02-01

    The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically-mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ-00201894 0.1-30 μM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 μM this activity was usually prolonged. At higher concentrations (3-30 μM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 μM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying. PMID:26685754

  13. Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway.

    PubMed

    Wang, Lan; Ouyang, Fei; Liu, Xiaobo; Wu, Shu; Wu, Hong-Mei; Xu, Yuandong; Wang, Bin; Zhu, Jinrong; Xu, Xuehu; Zhang, Liang

    2016-01-26

    CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer. PMID:26565812

  14. Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway

    PubMed Central

    Wang, Lan; Ouyang, Fei; Liu, Xiaobo; Wu, Shu; Wu, Hong-mei; Xu, Yuandong; Wang, Bin; Zhu, Jinrong; Xu, Xuehu; Zhang, Liang

    2016-01-01

    CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer. PMID:26565812

  15. Grifola frondosa Glycoprotein GFG-3a Arrests S phase, Alters Proteome, and Induces Apoptosis in Human Gastric Cancer Cells.

    PubMed

    Cui, Fengjie; Zan, Xinyi; Li, Yunhong; Sun, Wenjing; Yang, Yan; Ping, Lifeng

    2016-01-01

    GFG-3a is a novel glycoprotein previously purified from the fermented mycelia of Grifola frondosa with novel sugar compositions and protein sequencing. The present study aims to investigate its effects on the cell cycle, differential proteins expression, and apoptosis of human gastric cancer SGC-7901 cells. Our findings revealed that GFG-3a induced the cell apoptosis and arrested cell cycle at S phase. GFG-3a treatment resulted in the differential expression of 21 proteins in SGC-7901 cells by upregulating 10 proteins including RBBP4 associated with cell cycle arrest and downregulating 11 proteins including RUVBL1, NPM, HSP90AB1, and GRP78 involved in apoptosis and stress response. qRT-PCR and Western blot analysis also suggested that GFG-3a could increase the expressions of Caspase-8/-3, p53, Bax, and Bad while decrease the expressions of Bcl2, Bcl-xl, PI3K, and Akt1. These results indicated that the stress response, p53-dependent mitochondrial-mediated, Caspase-8/-3-dependent, and PI3k/Akt pathways were involved in the GFG-3a-induced apoptosis process in SGC-7901 cells. These findings might provide a basis to prevent or treat human gastric cancer with GFG-3a and understand the tumor-inhibitory molecular mechanisms of mushroom glycoproteins. PMID:27040446

  16. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    PubMed

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer. PMID:27507203

  17. Xanthatin induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma MKN-45 cells.

    PubMed

    Zhang, Lei; Tao, Li; Ruan, Junshan; Li, Weidong; Wu, Yu; Yan, Linggeng; Zhang, Feng; Fan, Fangtian; Zheng, Shizhong; Wang, Aiyun; Lu, Yin

    2012-06-01

    Xanthatin, a natural bioactive compound of sesquiterpene lactones, was isolated and purified from air-dried aerial part of Xanthium sibiricum Patrin ex Widder. In the present study, we demonstrated the significant antiproliferative and proapoptotic effects of xanthatin on human gastric carcinoma MKN-45 cells. MTS assay showed that xanthatin produced obvious cytotoxicity in MKN-45 cells with IC50 values of 18.6, 9.3, and 3.9 µM for 12, 24, and 48 h, respectively. Results of flow cytometry analysis indicated that the antiproliferative activity induced by xanthatin might be executed via G2/M cell cycle arrest and proapoptosis in MKN-45 cells. Western blot analysis elucidated that: a) xanthatin downregulated expression of Chk1 and Chk2 and phosphorylation of CDC2, which are known as key G2/M transition regulators; b) xanthatin increased p53 activation, decreased the bcl-2/bax ratio and the levels of downstream procaspase-9 and procaspase-3, which are key regulators in the intrinsic apoptosis pathway; c) xanthatin blocked phosphorylation of NF-κB (p65 subunit) and of IκBα, which might contribute to its proapoptotic effects on MKN-45 cells. In conclusion, our results suggest that xanthatin may have therapeutic potential against human gastric carcinoma. PMID:22532019

  18. Protective Effect of Tropical Highland Blackberry Juice (Rubus adenotrichos Schltdl.) Against UVB-Mediated Damage in Human Epidermal Keratinocytes and in a Reconstituted Skin Equivalent Model

    PubMed Central

    Calvo-Castro, Laura; Syed, Deeba N.; Chamcheu, Jean C.; Vilela, Fernanda M. P.; Pérez, Ana M.; Vaillant, Fabrice; Rojas, Miguel; Mukhtar, Hasan

    2014-01-01

    Solar ultraviolet (UV) radiation, particularly its UVB (280–320 nm) spectrum, is the primary environmental stimulus leading to skin carcinogenesis. Several botanical species with antioxidant properties have shown photochemopreventive effects against UVB damage. Costa Rica’s tropical highland blackberry (Rubus adenotrichos) contains important levels of phenolic compounds, mainly ellagitannins and anthocyanins, with strong antioxidant properties. In this study, we examined the photochemopreventive effect of R. adenotrichos blackberry juice (BBJ) on UVB-mediated responses in human epidermal keratinocytes and in a three-dimensional (3D) reconstituted normal human skin equivalent (SE). Pretreatment (2 h) and posttreatment (24 h) of normal human epidermal keratinocytes (NHEKs) with BBJ reduced UVB (25 mJ cm−2)-mediated (1) cyclobutane pyrimidine dimers (CPDs) and (2) 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) formation. Furthermore, treatment of NHEKs with BBJ increased UVB-mediated (1) poly(ADP-ribose) polymerase cleavage and (2) activation of caspases 3, 8 and 9. Thus, BBJ seems to alleviate UVB-induced effects by reducing DNA damage and increasing apoptosis of damaged cells. To establish the in vivo significance of these findings to human skin, immunohistochemistry studies were performed in a 3D SE model, where BBJ was also found to decrease CPDs formation. These data suggest that BBJ may be developed as an agent to ameliorate UV-induced skin damage. PMID:23711186

  19. Protective effect of tropical highland blackberry juice (Rubus adenotrichos Schltdl.) against UVB-mediated damage in human epidermal keratinocytes and in a reconstituted skin equivalent model.

    PubMed

    Calvo-Castro, Laura; Syed, Deeba N; Chamcheu, Jean C; Vilela, Fernanda M P; Pérez, Ana M; Vaillant, Fabrice; Rojas, Miguel; Mukhtar, Hasan

    2013-01-01

    Solar ultraviolet (UV) radiation, particularly its UVB (280-320 nm) spectrum, is the primary environmental stimulus leading to skin carcinogenesis. Several botanical species with antioxidant properties have shown photochemopreventive effects against UVB damage. Costa Rica's tropical highland blackberry (Rubus adenotrichos) contains important levels of phenolic compounds, mainly ellagitannins and anthocyanins, with strong antioxidant properties. In this study, we examined the photochemopreventive effect of R. adenotrichos blackberry juice (BBJ) on UVB-mediated responses in human epidermal keratinocytes and in a three-dimensional (3D) reconstituted normal human skin equivalent (SE). Pretreatment (2 h) and posttreatment (24 h) of normal human epidermal keratinocytes (NHEKs) with BBJ reduced UVB (25 mJ cm(-2))-mediated (1) cyclobutane pyrimidine dimers (CPDs) and (2) 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation. Furthermore, treatment of NHEKs with BBJ increased UVB-mediated (1) poly(ADP-ribose) polymerase cleavage and (2) activation of caspases 3, 8 and 9. Thus, BBJ seems to alleviate UVB-induced effects by reducing DNA damage and increasing apoptosis of damaged cells. To establish the in vivo significance of these findings to human skin, immunohistochemistry studies were performed in a 3D SE model, where BBJ was also found to decrease CPDs formation. These data suggest that BBJ may be developed as an agent to ameliorate UV-induced skin damage. PMID:23711186

  20. Helicobacter pylori-infected MSCs acquire a pro-inflammatory phenotype and induce human gastric cancer migration by promoting EMT in gastric cancer cells

    PubMed Central

    ZHANG, QIANG; DING, JUAN; LIU, JINJUN; WANG, WEI; ZHANG, FENG; WANG, JUNHE; LI, YUYUN

    2016-01-01

    Accumulating clinical and experimental evidence has suggested that Helicobacter pylori (H. pylori) infection-associated gastric cancer (GC) is associated with high rates of mortality and serious health effects. The majority of patients succumb to H. pylori infection-associated GC due to metastasis. Mesenchymal stem cells (MSCs), which have multipotent differentiation potential, may be recruited into the tumor-associated stroma. MSCs are crucial components of the H. pylori infection-associated GC microenvironment, and may be critical for GC cell migration. In this study, an MSCs/H. pylori co-culture model was designed, and the effect of H. pylori-infected MSCs on the migration of GC cells was evaluated using a Transwell migration assay. H. pylori-infected MSC cytokine expression was evaluated using Luminex/ELISA. The expression of epithelial-mesenchymal transition (EMT) markers in the GC cells treated with supernatants from H. pylori-infected MSCs were detected by western blot analysis. The results demonstrated that the interaction between MSCs and H. pylori may induce GC cell migration, through secretion of a combination of cytokines that promote EMT in GC cells. The expression of phosphorylated forms of nuclear factor-κB (NF-κB) was observed to be increased in MSCs by H. pylori. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate blocked the effects of H. pylori-infected MSCs on SGC-7901 human stomach adenocarcinoma cell migration. Overall, the results of the present study suggest that H. pylori-infected MSCs acquire a pro-inflammatory phenotype through secretion of a combination of multiple cytokines, a number of which are NF-κB-dependent. These cytokines enhance H. pylori infection-associated GC cell migration by promoting EMT in GC cells. The results of the present study provide novel evidence for the modulatory effect of MSCs in the tumor microenvironment and provide insight into the significance of stromal cell involvement in GC progression

  1. Cloning and analysis of human gastric mucin cDNA reveals two types of conserved cysteine-rich domains.

    PubMed Central

    Klomp, L W; Van Rens, L; Strous, G J

    1995-01-01

    Human gastric mucin was isolated by successive CsCl-gradient ultracentrifugation in the presence of guanidinium hydrochloride to prevent degradation of the polypeptide moieties of the molecules. The amino acid sequence of a tryptic fragment of this molecule was identical to that of a tryptic fragment of tracheobronchial mucin. An oligonucleotide based on this sequence hybridized specifically to human stomach mRNA and was subsequently used to screen a human stomach lambda ZAPII cDNA library. The largest of 10 positive clones encoded 850 amino acid residues, including the tryptic fragment, with high amounts of threonine, serine and proline residues. Interestingly, cysteine accounted for almost 8% of the amino acid residues. The 3' part of the sequence was very similar but not identical to the 3' region of human tracheobronchial cDNA. No tandem repeated sequences were present and the deduced polypeptide sequence contained two potential N-linked glycosylation sites. Four cysteine-rich clusters were detected, one of which was apparently homologous to the D-domains present in other mucins and in von Willebrand factor. The arrangement of the cysteines in three other cysteine-rich clusters was conserved in the human gastric mucin cDNA in a similar fashion as in two domains in the MUC2 gene product. The cysteine-rich domains were separated by short stretches of non-repetitive amino acid residues with a very high content of threonine and serine residues. These data suggest that the encoded polypeptide of this clone may be involved in disulphide-bond-mediated oligomerization of the mucin, and provide new insights into the molecular organization of mammalian apomucins. Images Figure 1 PMID:8948439

  2. Effects of Orange Juice Formulation on Prebiotic Functionality Using an In Vitro Colonic Model System

    PubMed Central

    Costabile, Adele; Walton, Gemma E.; Tzortzis, George; Vulevic, Jelena; Charalampopoulos, Dimitris; Gibson, Glenn R.

    2015-01-01

    A three-stage continuous fermentative colonic model system was used to monitor in vitro the effect of different orange juice formulations on prebiotic activity. Three different juices with and without Bimuno, a GOS mixture containing galactooligosaccharides (B-GOS) were assessed in terms of their ability to induce a bifidogenic microbiota. The recipe development was based on incorporating 2.75g B-GOS into a 250 ml serving of juice (65°Brix of concentrate juice). Alongside the production of B-GOS juice, a control juice – orange juice without any additional Bimuno and a positive control juice, containing all the components of Bimuno (glucose, galactose and lactose) in the same relative proportions with the exception of B-GOS were developed. Ion Exchange Chromotography analysis was used to test the maintenance of bimuno components after the production process. Data showed that sterilisation had no significant effect on concentration of B-GOS and simple sugars. The three juice formulations were digested under conditions resembling the gastric and small intestinal environments. Main bacterial groups of the faecal microbiota were evaluated throughout the colonic model study using 16S rRNA-based fluorescence in situ hybridization (FISH). Potential effects of supplementation of the juices on microbial metabolism were studied measuring short chain fatty acids (SCFAs) using gas chromatography. Furthermore, B-GOS juices showed positive modulations of the microbiota composition and metabolic activity. In particular, numbers of faecal bifidobacteria and lactobacilli were significantly higher when B-GOS juice was fermented compared to controls. Furthermore, fermentation of B-GOS juice resulted in an increase in Roseburia subcluster and concomitantly increased butyrate production, which is of potential benefit to the host. In conclusion, this study has shown B-GOS within orange juice can have a beneficial effect on the fecal microbiota. PMID:25807417

  3. Effects of orange juice formulation on prebiotic functionality using an in vitro colonic model system.

    PubMed

    Costabile, Adele; Walton, Gemma E; Tzortzis, George; Vulevic, Jelena; Charalampopoulos, Dimitris; Gibson, Glenn R

    2015-01-01

    A three-stage continuous fermentative colonic model system was used to monitor in vitro the effect of different orange juice formulations on prebiotic activity. Three different juices with and without Bimuno, a GOS mixture containing galactooligosaccharides (B-GOS) were assessed in terms of their ability to induce a bifidogenic microbiota. The recipe development was based on incorporating 2.75g B-GOS into a 250 ml serving of juice (65°Brix of concentrate juice). Alongside the production of B-GOS juice, a control juice--orange juice without any additional Bimuno and a positive control juice, containing all the components of Bimuno (glucose, galactose and lactose) in the same relative proportions with the exception of B-GOS were developed. Ion Exchange Chromotography analysis was used to test the maintenance of bimuno components after the production process. Data showed that sterilisation had no significant effect on concentration of B-GOS and simple sugars. The three juice formulations were digested under conditions resembling the gastric and small intestinal environments. Main bacterial groups of the faecal microbiota were evaluated throughout the colonic model study using 16S rRNA-based fluorescence in situ hybridization (FISH). Potential effects of supplementation of the juices on microbial metabolism were studied measuring short chain fatty acids (SCFAs) using gas chromatography. Furthermore, B-GOS juices showed positive modulations of the microbiota composition and metabolic activity. In particular, numbers of faecal bifidobacteria and lactobacilli were significantly higher when B-GOS juice was fermented compared to controls. Furthermore, fermentation of B-GOS juice resulted in an increase in Roseburia subcluster and concomitantly increased butyrate production, which is of potential benefit to the host. In conclusion, this study has shown B-GOS within orange juice can have a beneficial effect on the fecal microbiota. PMID:25807417

  4. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    PubMed

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P<0.0001). Also, apoB was significantly increased after RGj consumption (149.0 ± 22.35 and 157.19 ± 18.60 mg/dl; P<0.002). But apoAI levels were not changed significantly before and after of RGj consumption (154.27 ± 21.55 and 155.35 ± 21.07 mg/dl; P>0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals. PMID:21633724

  5. [Research on Early Diagnosis of Gastric Cancer by the Surface Enhanced Raman Spectroscopy of Human Hemoglobin].

    PubMed

    Wang, Wei; Pan, Zhi-feng; Tang, Wei-yue; Li, Yun-tao; Fan, Chun-zhen

    2015-12-01

    Early diagnosis have great positive effect on the treatment of gastric cancer patients. Raman spectroscopy can provide a useful monitor for hemoglobin dynamics. Besides, Raman spectroscopy has notable advantages in the fields of abnormal hemoglobin diagnosis, hemoglobin oxygen saturation deter mination and blood methemoglobin analysis. In this paper, novel silver colloid was synthesized by microwave heated method. The surface enhanced Raman spectrums of hemoglobin from 11 normal persons and 20 gastric cancer patients are measured and analyzed in order to obtain spectrums which are high repeatability and characteristic peaks protruding. By analyzing the assignations of the SERS bands, it found that the content of asparagine, tyrosine and phenylalanine in the hemoglobin are significantly lower than healthy people. Discussing the structure of hemoglobin, when hemoglobin combines with oxygen, Fe²⁺ is in a low spin state, ionic radius shrinks and moves 0. 075 nm and fall into the pore in the middle of the heme porphyrin ring plane. This spatial variation affects F8His connected with the iron, will narrow the gap between the globin in the two strands of the helix, as a result, HC2 tyrosine pushed out of the void. Using this mechanism, the absorption peak of 1 560 cm⁻¹ confirmed that the tyrosine content in patients with gastric cancer was lower than that of normal people. Principal component analysis(PCA) is employed to get a three-dimensional scatter plot of PC scores for the health and cancer groups, and it can be learned that they are distributed in separate areas. By using the method of discriminate analysis, it is found that the diagnostic algorithm separates the two groups with sensitivity of 90.0% and diagnostic specificity of 90.9%, the overall diagnostic accuracy was 90.3%. The results from this exploratory study demonstrate that, SERS detection of oxyhemoglobin combined with multivariate analysis would be an effective method for early diagnosis of gastric

  6. Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway

    PubMed Central

    Kong, Gui-Mei; Tao, Wen-Hua; Diao, Ya-Li; Fang, Peng-Hua; Wang, Ji-Jun; Bo, Ping; Qian, Feng

    2016-01-01

    8695.7 ± 449.1 U/g). The expression of the Cyt C, Endo G, and AIF proteins in SGC-7901 cells was significantly higher than those in the control (P < 0.05), while the expression of the Smac/Diablo protein was significantly lower than the control group after melittin exposure (P < 0.01). Ac-DEVD-CHO did not, however, have any effect on the expression of caspase-8 and FAS in the SGC-7901 cells. CONCLUSION: Melittin can induce apoptosis of human gastric cancer (GC) cells through the mitochondria pathways, and it may be a potent agent in the treatment of human GC. PMID:27003995

  7. IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway

    SciTech Connect

    Kim, Jihye; Kim, Cherlhyun; Kim, Tae Sung; Bang, Sa Ik; Yang, Young; Park, Hyunjeong; Cho, Daeho . E-mail: cdhkor@sookmyung.ac.kr

    2006-06-16

    IL-18 is a pleiotropic cytokine that is produced by many cancer cells. A recent report suggested that IL-18 plays a key role in regulating the immune escape of melanoma and gastric cancer cells. Thrombospondin (TSP-1) is known to inhibit angiogenesis in several cancers but some studies have reported that it stimulates angiogenesis in some cancers such as gastric cancer. IL-18 and TSP-1 are related to tumor proliferation and metastasis. This study investigated the relationship between IL-18 and TSP-1 in gastric cancer. RT-PCR and ELISA showed that after the cells had been treated with IL-18, the level of TSP-1 mRNA expression and TSP-1 protein production by IL-18 increased in both a dose- and time-dependent manner. The cells were next treated with specific inhibitors in order to determine the signal pathway involved in IL-18-enhanced TSP-1 production. IL-18-enhanced TSP-1 expression was blocked by SP600125, a c-Jun N-terminal kinase (JNK) specific inhibitor. In addition, Western blot showed that IL-18 enhanced the expression of phosphorylated JNK. Overall, these results suggest that IL-18 plays a key role in TSP-1 expression involving JNK.

  8. Analysis of the Distribution of Mucins in Adult Human Gastric Mucosa and Its Functional Significance

    PubMed Central

    2016-01-01

    Introduction Mucins are complex composition of carbohydrates seen in the epithelial cells lining the gastrointestinal tract (GIT). Normal distribution of such mucins in different part of the GIT and its alteration in various inflammatory, benign and malignant lesions of GIT has aroused interest in the field of histochemistry. Aim By applying variety of histochemical techniques an attempt has been made to draw a map of mucin secretion by the different epithelial cell types in different parts of the stomach. Materials and Methods Fifty samples were taken each from different parts of the stomach like fundus, body and pylorus, from dissected fresh specimens (total of 150 specimens). Tissue samples were subjected for routine process and studied for histological and different histochemical staining. Results Mucin pattern in adult predominantly secretes neutral mucosubstances. Surface epithelium shows predominant neutral mucin while cardiac and gastric glands with foveolar cells show moderate amount. Sialomucin is present in a few cells of the surface epithelium, foveolar cells and in most of the mucous neck cells. Small amount of sialomucin and sulphomucin are found in surface epithelial foveolar cells while traces of sulphomucin are found in deep foveolar cells. Mucous neck cells secrete both sulphomucin and sialomucin. Conclusion Normal gastric mucosa adjacent to gastric ulcers and malignant tumours of stomach secretes mucins which differ histochemically and biochemically from that of normal. Early recognition of such changes could be useful in recognizing the different type of carcinomas and their prognosis. PMID:27042436

  9. Parallel gastric emptying of nonhydrolyzable fat and water after a solid-liquid meal in humans

    SciTech Connect

    Cortot, A.; Phillips, S.F.; Malagelada, J.R.

    1982-05-01

    Our aim was to examine the control of gastric emptying of the oil phase of a mixed solid and liquid meal. Previous studies had shown that liquid dietary fats normally leave the stomach at a slower rate than does water. We wished to determine whether the slower emptying of fats was due to the physical characteristics of food (lower density and greater viscosity than water), to retardation by duodenal feedback mechanisms, or whether both factors contributed. Thus, we quantified the emptying rates of water and sucrose polyester (a nonabsorbable analog of dietary fat) ingested by healthy volunteers as a mixed solid and liquid meal. Gastric emptying was quantified by an intubation-perfusion method incorporating an occlusive jejunal balloon to facilitate recovery. Four phase-specific, nonabsorbable markers were used. (14C(Sucrose octaoleate and polyethylene glycol were incorporated in the meal and traced the lipid and water phases, respectively; (3H)glycerol triether and phenolsulfonphthalein were used as duodenal recovery markers. Sucrose polyester (substituting for dietary fat) was emptied very rapidly, and at about the same rate as was water, in contrast to natural fat, which empties very slowly. Emptying of water was rapid and comparable to that observed after mixed meals containing natural fat. These results imply that gastric emptying of the oil phase is controlled by receptors sensitive to the hydrolytic products of fat digestion and that the slow emptying of dietary fat is not simply due to its lower density.

  10. Effects of ophiopogonin B on the proliferation and apoptosis of SGC-7901 human gastric cancer cells

    PubMed Central

    ZHANG, WEIYUE; ZHANG, QIAOYAN; JIANG, YIPING; LI, FENG; XIN, HAILIANG

    2016-01-01

    Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon japonicus, which is often used in traditional Chinese medicine to treat cancer. The present study aimed to investigate the antitumor activity of OP-B in gastric cancer. Cell Counting kit-8, flow cytometry with Annexin V-fluorescein isothiocyanate, Hoechst staining, mitochondrial membrane potential (MMP) detection, and reactive oxygen species (ROS) assay were used to detect the biological function of SGC-7901 gastric cancer cells. The results demonstrated that high concentrations of OP-B (5, 10 and 20 μmol/l) exerted potent antiproliferative effects on SGC-7901 cells in a dose-dependent manner. Furthermore, apoptotic rates were increased and cell morphology was altered following treatment with OP-B. In addition, OP-B-induced apoptosis of SGC-7901 cells was associated with loss of MMP and increased ROS generation. Western blotting indicated that treatment with OP-B increased the protein expression levels of caspase-3 and B-cell lymphoma 2 (Bcl-2)-associated X protein, whereas the expression levels of Bcl-2 and the phosphorylation levels of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases 1/2 were decreased. These results suggest that OP-B may be considered a potential inhibitor of gastric cancer progression, and may be used as an alternative compound for its treatment. PMID:27121658

  11. The effects of restraint on uptake of radioactive sulfate in the salivary and gastric secretions of rats with pyloric ligation

    NASA Technical Reports Server (NTRS)

    Chayvialle, J. A.; Lambert, R.; Ruet, D.

    1980-01-01

    The effects of restraint on the amount of nondialysable radioactive sulfate in the gastric wall and the gastric juice and saliva were investigated. It was found that restraint provokes a significant decrease in salivary radioactive sulfate. This, in turn, is responsible for the decrease of sulfate in the gastric contents observed under these conditions in rats with pyloric ligation. Esophageal ligation associated with this prevents passage of saliva and lowers the amount of radioactive sulfate in the gastric juice. Restraint causes then an increase in the amount of sulfate in the gastric juice, the value observed being very much lower than that of rats with a free esophagus. At the level of the gastric wall, the change observed during restraint does not reach a significant threshold.

  12. Effects of Aloe-emodin and Emodin on Proliferation of the MKN45 Human Gastric Cancer Cell Line.

    PubMed

    Chihara, Takeshi; Shimpo, Kan; Beppu, Hidehiko; Yamamoto, Naoki; Kaneko, Takaaki; Wakamatsu, Kazumasa; Sonoda, Shigeru

    2015-01-01

    Aloe-emodin (1, 8-dihydroxy-3-hydroxyl-methylanthraquinone; AE) and emodin (1,3,8-trihydroxy-6- methylanthraquinone; EM) are anthraquinone derivatives that have been detected in some medical plants and share similar anthraquinone structures. AE and EM have been shown to exhibit anticancer activities in various cancer cell lines; however, the inhibitory effects of these derivatives on the growth of cancer cells were previously reported to be different. Gastric cancer is the second most common cause of cancer cell death worldwide. In the present study, we examined the inhibitory effects of 0.05 mM AE and 0.05 mM EM on the proliferation of the MKN45 human gastric cancer cell line. The proliferation of MKN45 cells was significantly inhibited in AE- and EM-treated groups 24 h and 48 h after treatment. Furthermore, the inhibitory effects of EM were stronger than those of AE. The cell cycle of MKN45 cells were arrested in G0/G1 phase or G0/G1 and G2/M phases by AE and EM, respectively. However, an analysis of intracellular polyamine levels and DNA fragmentation revealed that the mechanisms underlying cell death following cell arrest induced by AE and EM differed. PMID:25987055

  13. New Alkyl Phloroglucinol Derivatives from Rhus trichocarpa Roots and Their Cytotoxic Effects on Human Gastric Adenocarcinoma AGS Cells.

    PubMed

    Lee, Ki Yong; Choi, Ji Hoon; Kim, Hyeon Woo; Yan, Xi-Tao; Shin, Hyeji; Jeon, Young Ho; Sung, Sang Hyun

    2016-05-01

    The phytochemical investigation of the roots of Rhus trichocarpa led to this isolation of five new alkyl phloroglucinol derivatives, characterized as (Z)-15-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol A, 1), (Z)-15-hydroxy-1-(2,6-dihydroxy-4-methoxyphenyl)-9-octadecen-1-one (named trichocarpol B, 2), (Z)-17-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol C, 3), (Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol D, 4), and (9Z,12Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9,12-octadecadien-1-one (named trichocarpol E, 5), together with a known compound, 4-(2,6-dihydroxy-4-methoxyphenyl)-4-oxobutanoic acid (6). In vitro cytotoxic activity of compounds 1-6 was evaluated in the human gastric adenocarcinoma AGS cell line and compounds 1-5 showed significant cytotoxicity. Our results indicate that R. trichocarpa, especially the alkyl phloroglucinol derivatives in it, is a good source of promising natural agents for the treatment of gastric cancer. PMID:26845711

  14. Inhibition of neutrophil elastase and metalloprotease-9 of human adenocarcinoma gastric cells by chamomile (Matricaria recutita L.) infusion.

    PubMed

    Bulgari, Michela; Sangiovanni, Enrico; Colombo, Elisa; Maschi, Omar; Caruso, Donatella; Bosisio, Enrica; Dell'Agli, Mario

    2012-12-01

    This study investigated whether the antiinflammatory effect of chamomile infusion at gastric level could be ascribed to the inhibition of metalloproteinase-9 and elastase. The infusions from capitula and sifted flowers (250-1500 µg/mL) and individual flavonoids (10 µM) were tested on phorbol 12-myristate 13-acetate-stimulated AGS cells and human neutrophil elastase. The results indicate that the antiinflammatory activity associated with chamomile infusions from both the capitula and sifted flowers is most likely due to the inhibition of neutrophil elastase and gastric metalloproteinase-9 activity and secretion; the inhibition occurring in a concentration dependent manner. The promoter activity was inhibited as well and the decrease of metalloproteinase-9 expression was found to be associated with the inhibition of NF-kB driven transcription. The results further indicate that the flavonoid-7-glycosides, major constituents of chamomile flowers, may be responsible for the antiinflammatory action of the chamomile infusion observed here. PMID:22407864

  15. Carnosine Inhibits the Proliferation of Human Gastric Cancer SGC-7901 Cells through Both of the Mitochondrial Respiration and Glycolysis Pathways

    PubMed Central

    Shen, Yao; Yang, Jianbo; Li, Juan; Shi, Xiaojie; Ouyang, Li; Tian, Yueyang; Lu, Jianxin

    2014-01-01

    Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy. PMID:25115854

  16. HPLC-ESI-MS ANALYSIS OF FURANOCOUMARINS IN GRAPEFRUIT JUICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The furanocoumarins in grapefruit juice inhibit intestinal and liver cytochrome P450 3A4 (CYP3A4) and are responsible for the effects in humans caused by grapefruit juice consumption on the metabolism of certain prescription drugs. A number of the (furano)coumarins that occur in the highest concen...

  17. 21 CFR 156.145 - Tomato juice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Tomato juice. 156.145 Section 156.145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN..., seeds, and other coarse or hard substances, but contains finely divided insoluble solids from the...

  18. Soy protein isolate does not affect ellagitannin bioavailability and urolithin formation when mixed with pomegranate juice in humans.

    PubMed

    Yang, Jieping; Lee, Rupo; Henning, Susanne M; Thames, Gail; Hsu, Mark; ManLam, Hei; Heber, David; Li, Zhaoping

    2016-03-01

    We investigated the effect of mixing soy protein isolate and pomegranate juice (PJ) on the bioavailability and metabolism of ellagitannins (ETs) in healthy volunteers. Eighteen healthy volunteers consumed PJ alone or PJ premixed with soy protein isolate (PJSP). The concentration of plasma ellagic acid (EA) and urine urolithins was measured. There was no significant difference in plasma EA over a 6-h period between the two interventions. While the maximum concentration of plasma EA after PJSP consumption was slightly but significantly lower than after PJ consumption, EA remained in the plasma longer with an elimination half-life t1/2E at 1.36±0.59 versus 1.06±0.47h for PJSP and PJ consumption, respectively. Urinary urolithin A, B and C was not significantly different between the two interventions. In conclusion, premixing soy protein isolate and PJ did not affect the bioavailability or the metabolism of pomegranate ETs in healthy volunteers. PMID:26471685

  19. Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia

    PubMed Central

    Asano, Teita; Aida, Shuji; Suemasu, Shintaro; Tahara, Kayoko; Tanaka, Ken-ichiro; Mizushima, Tohru

    2015-01-01

    Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here. PMID:26620883

  20. Combined derivatization and high-performance liquid chromatography with fluorescence and ultraviolet detection for simultaneous analysis of octreotide and gabexate mesylate metabolite in human pancreatic juice samples.

    PubMed

    Carlucci, Giuseppe; Selvaggi, Federico; Sulpizio, Sara; Bassi, Claudio; Carlucci, Maura; Cotellese, Roberto; Ferrone, Vincenzo; Innocenti, Paolo; Locatelli, Marcello

    2015-06-01

    A simple and sensitive method based on the combination of derivatization and high-performance liquid chromatography with ultraviolet and fluorimetric detection was developed for the simultaneous determination of octreotide and gabexate mesylate metabolite in human pancreatic juice samples. Parameters of the derivatization procedure affecting extraction efficiency were optimized. The developed method was validated according to the International Conference on Harmonization guidelines. The calibration curves were linear over a range of 0.1-15 µg/mL for octreotide and 0.20-15 µg/mL for gabexate mesylate metabolite. Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The limits of detection were 0.025 and 0.05, respectively, for octreotide and gabexate mesylate metabolite. This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-FL) method for the simultaneous analysis of octreotide and gabexate mesylate metabolite in pancreatic juice by protein precipitation using zinc sulfate-methanol-acetonitrile containing the derivatizing reagent, 4-fluoro-7-nitro-[2,1,3]-benzoxadiazole (NBD-F). Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The method was validated over the concentration ranges 0.1-15 and 0.2-15 µg/mL for octreotide and gabexate mesylate metabolite, respectively, in human pancreatic juice. Biphalin and methyl-p-hydroxybenzoate were used as the internal standards. This method was successfully utilized to support clinical studies in humans. The results from assay validations show that the method is selective, sensitive and robust. The limit

  1. Drug marker absorption in relation to pellet size, gastric motility and viscous meals in humans

    NASA Technical Reports Server (NTRS)

    Rhie, J. K.; Hayashi, Y.; Welage, L. S.; Frens, J.; Wald, R. J.; Barnett, J. L.; Amidon, G. E.; Putcha, L.; Amidon, G. L.

    1998-01-01

    PURPOSE: The objective of this study was to evaluate drug marker absorption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets as a function of viscosity and the underlying gastric motility. METHODS: Twelve subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated pellets were concurrently administered with a viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneously measured with antral manometry and compared to time events in the plasma profiles of the drug markers. RESULTS: Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetaminophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all viscosity levels, however, less variability was observed with the 4000 cP meal. Specifically, the onset of absorption from the of 3.6 mm pellets correlated with the onset of Phase II fasted state contractions (r = 0.929, p < 0.01). CONCLUSIONS: The timeframe of drug marker absorption and the onset of motility events were not altered within the range of viscosities evaluated. Rather, the differences in drug marker profiles from the non-digestible solids were most likely the result of the interaction between viscosity and motility influencing antral flow dynamics. The administration of the two sizes of pellets and a viscous caloric meal with subsequent monitoring of drug marker profiles is useful as a reference to assess the influence of motility patterns on the absorption profile of orally administered agents.

  2. Dietary fibers affect viscosity of solutions and simulated human gastric and small intestinal digesta.

    PubMed

    Dikeman, Cheryl L; Murphy, Michael R; Fahey, George C

    2006-04-01

    Two experiments were conducted to determine the viscosities of both soluble and insoluble dietary fibers. In Expt. 1, corn bran, defatted rice bran, guar gum, gum xanthan, oat bran, psyllium, soy hulls, stabilized rice bran, wheat bran, wood cellulose, and 2 methylcellulose controls (Ticacel 42, Ticacel 43) were hydrated in water overnight at 0.5, 1, 1.5, or 2% concentrations. In Expt. 2, guar gum, oat bran, psyllium, rice bran, wheat bran, and wood cellulose were subjected to a 2-stage in vitro gastric and small intestinal digestion simulation model. Viscosity was measured every 2 and 3 h during gastric and small intestinal simulation, respectively. Viscosities in both experiments were measured at multiple shear rates. Viscosities of all fiber solutions were concentration- and shear rate-dependent. Rice brans, soy hulls, and wood cellulose had the lowest viscosities, whereas guar gum, psyllium, and xanthan gum had the highest viscosities, regardless of concentration. During gastric simulation, viscosity was higher (P < 0.05) at 4 h than at 0 h for guar gum, psyllium, rice bran, and wheat bran. During small intestinal simulation, viscosities were higher (P < 0.05) between 3 and 9 h compared with 18 h for guar gum, oat bran, and rice bran. Guar gum, psyllium, and oat bran exhibited viscous characteristics throughout small intestinal simulation, indicating potential for these fibers to elicit blood glucose and lipid attenuation. Wheat and rice brans and wood cellulose did not exhibit viscous characteristics throughout small intestinal digestion; thus, they may be beneficial for laxation. PMID:16549450

  3. Novel epidermal growth factor receptor pathway mediates release of human β-defensin 3 from Helicobacter pylori-infected gastric epithelial cells.

    PubMed

    Muhammad, Jibran S; Zaidi, Syed F; Zhou, Yue; Sakurai, Hiroaki; Sugiyama, Toshiro

    2016-04-01

    Persistent Helicobacter pylori (H. pylori) infection in hostile gastric mucosa can result in gastric diseases. Helicobacter pylori induces to express antimicrobial peptides from gastric epithelial cells, especially human β-defensin 3 (hBD3), as an innate immune response, and this expression of hBD3 is mediated by epidermal growth factor receptor (EGFR) activation. In this study, we found that phosphorylation of a serine residue of EGFR via transforming growth factor β-activated kinase-1 (TAK1), and subsequent p38α activation is essential for H. pylori-induced hBD3 release from gastric epithelial cells. We showed that this pathway was dependent on H. pylori type IV secretion system and was independent of H. pylori-derived CagA or peptidoglycan. H. pylori infection induced phosphorylation of serine residue of EGFR, and this phosphorylation was followed by internalization of EGFR; consequently, hBD3 was released at an early phase of the infection. In the presence of TAK1 or p38α inhibitors, synthesis of hBD3 was completely inhibited. Similar results were observed in EGFR-, TAK1- or p38α-knockdown cells. However, NOD1 knockdown in gastric epithelial cells did not inhibit hBD3 induction. Our study has firstly demonstrated that this novel EGFR activating pathway functioned to induce hBD3 at an early phase of H. pylori infection. PMID:26733497

  4. Constitutive hypophosphorylation of extracellular signal-regulated kinases-1/2 and down-regulation of c-Jun in human gastric adenocarcinoma

    SciTech Connect

    Wu, William Ka Kei; Sung, Joseph Joe Yiu; Yu Le; Li Zhijie; Chu, Kent Man; Cho, C.H.

    2008-08-22

    Hyperphosphorylation of extracellular signal-regulated protein kinases-1/2 (ERK1/2) is known to promote cancer cell proliferation. We therefore investigated the constitutive phosphorylation levels of ERK1/2 and the expression of its downstream targets c-Fos, c-Jun, and cyclooxygenase-2 (COX-2) in biopsied human gastric cancer tissues. Results showed that ERK1/2 phosphorylation and c-Jun expression were significantly lowered in gastric cancer compared with the non-cancer adjacent tissues. The expression of c-Fos, however, was not altered while COX-2 was significantly up-regulated. To conclude, we demonstrate that hypophosphorylation of ERK1/2 may occur in gastric cancer. Such discovery may have implication in the application of pathway-directed therapy for this malignant disease.

  5. Circadian Rhythm Genes CLOCK and PER3 Polymorphisms and Morning Gastric Motility in Humans

    PubMed Central

    Yamaguchi, Mitsue; Kotani, Kazuhiko; Tsuzaki, Kokoro; Takagi, Ayaka; Motokubota, Naoko; Komai, Naho; Sakane, Naoki; Moritani, Toshio; Nagai, Narumi

    2015-01-01

    Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut. PMID:25775462

  6. Effect of Helicobacter pylori on NFKB1, p38α and TNF-α mRNA expression levels in human gastric mucosa

    PubMed Central

    SULZBACH DE OLIVEIRA, HENRIQUE SULZBACH; BIOLCHI, VANDERLEI; RICHARDT MEDEIROS, HELOUISE RICHARDT; BIZERRA GANDOR JANTSCH, DAIANE BIZERRA GANDOR; KNABBEN DE OLIVEIRA BECKER DELVING, LUCIANA KNABBEN; RECKZIEGEL, ROBERTO; GOETTERT, MÁRCIA INÊS; BRUM, ILMA SIMONI; POZZOBON, ADRIANE

    2016-01-01

    Helicobacter pylori infects ~50% of the world population, causing chronic gastritis and other forms of cellular damage. The present study assessed the influence of H. pylori on the mRNA expression levels of nuclear factor-κB1 (NFKB1), p38α and tumor necrosis factor-α (TNF-α) in human gastric mucosa in a southern Brazilian population. Human gastric tissue was collected by upper endoscopy and H. pylori diagnosis was performed using a rapid urease test and histological analysis. Total RNA was extracted and purified for subsequent cDNA synthesis and analysis by quantitative polymerase chain reaction (qPCR). The gastric tissue samples were divided into four groups as follows: Normal, inactive chronic gastritis, active chronic gastritis and intestinal metaplasia. The SDHA gene was classified as the most stable when compared with ACTB, GAPDH, B2M and HPRT1 genes, and was therefore selected as the reference gene for qPCR data normalization. TNF-α mRNA expression was significantly higher in samples that were positive for H. pylori and with active chronic gastritis. However, no difference was detected in the mRNA expression levels of NFKB1 and p38α between the groups. The present study concluded that the presence of H. pylori is associated with TNF-α upregulation in human gastric mucosa, but had no effect on NFKB1 and p38α mRNA expression levels. PMID:27284322

  7. [Solubilization, purification and molecular characterization of H2 histamine receptor from human tumoral gastric cells HGT-1].

    PubMed

    Reyl-Desmars, F; Cherifi, Y; Le Romancer, M; Pigeon, C; Le Roux, S; Lewin, M J

    1991-01-01

    This communication reports the solubilization, the purification and the molecular characterization of the H2-histamine receptor from the cell line HGT-1 derived from a human gastric cancer. The receptor has been solubilized by Triton X100 and purified by gel filtration onto Sephacryl, affinity-chromatography (Sepharose-famotidine) and high performance liquid chromatography (HPLC). The purified receptor specifically bound the H2 selective ligand 3H-methyltiotidine with a kD of 160 nM (vs 50 nM for the intact HGT-1 cell) and a maximal binding capacity of 14,000 pmol/mg protein which represents a 12,170-fold enrichment and a degree of purity of 98%. It is a glycoprotein of 70 kDa molecular mass containing N-acetylglucosamine residues. PMID:1904297

  8. Overexpression of fatty acid synthase predicts a poor prognosis for human gastric cancer

    PubMed Central

    DUAN, JIANGMAN; SUN, LI; HUANG, HONGXIANG; WU, ZHENZHEN; WANG, LIN; LIAO, WANGJUN

    2016-01-01

    Fatty acid synthase (FASN), a lipogenic multi-enzyme complex, is reported to be overexpressed in various types of of tumor tissues and serves an important role in tumor development and progression. However, the expression of FASN and its possible role in gastric cancer (GC) remains to be defined. In the present study, FASN expression in a group sample of 167 GC tissues was detected by immunohistochemistry and its correlation with clinicopathological features was analyzed. By clinical analysis, it was identified that FASN overexpression was positively correlated with the overall survival [P=0.008; hazard ratio (HR), 4.412; 95% confidence interval (CI), 1.463–13.305] and recurrence rate (P=0.014; HR, 1.705; 95% CI, 1.116–2.606) in patients with GC. In addition, expression of the FASN protein in GC tissues was correlated with age (P=0.032), clinical stage (P<0.001), gastric wall invasion (P=0.014), lymph node metastasis (P<0.001) and distant metastasis (P<0.001), however not with gender (P>0.05). In addition, FASN was observed to be overexpressed in GC tissues at an mRNA and protein level, compared with the adjacent non-cancerous tissues (P<0.05). Taken together, it was suggested that FASN was closely associated with GC metastasis and survival, which further provided evidence that FASN may be a promising prognostic biomarker for patients with GC. PMID:26936091

  9. [The influence of aging on autonomic nervous system activity and gastric myoelectric activity in humans].

    PubMed

    Thor, P J; Kolasińska-Kloch, W; Pitala, A; Janik, A; Kopp, B; Sibiga, W

    1999-01-01

    The study was performed on 84 healthy volunteers (33 women, 52 men) of age 20-71 years with no history of the circulatory or gastrointestinal system disease. The gastric myoelectrical activity (EGG) was recorded with the cutaneous electrodes--electrogastrography Synectics (Sweden). The activity of the cardiac autonomic nervous system was measured by HRV (heart rate variability) recorded with EGG and computer assisted programme Proster (Poland). Subject were divided into 5 groups according to the decade of age (20-70). Percentage of basal electrical rhythm (BER) dysrhythmias increased (1.9 +/- 0.5% vs 21.1 +/- 3.2% in fasting and 2.4 +/- 1.2% vs 24.6 +/- 5% postprandially but decrease of the EGG amplitude after the meal was observed (270 +/- 20% vs 90 +/- 7%) in youngest and oldest group respectively. With the ageing the cardiac sympathetic and parasympathetic activity (LF and HF) decreased in first and last group respectively. In the forth decade in man and women the sympathetic activity system prevalence expressed by the LF/HF rate increased (1.09 +/- 0.2 vs. 2.14 +/- 0.5) (p < 0.05). The results of our study suggest the deleterious influence of the ageing on the of autonomic system activity as shown by changes in HRV and dysrhythmia of the gastric slow waves in EGG. PMID:10909474

  10. Applications of microencapsulated Bifidobacterium longum with Eleutherine americana in fresh milk tofu and pineapple juice.

    PubMed

    Phoem, Atchara N; Chanthachum, Suphitchaya; Voravuthikunchai, Supayang P

    2015-04-01

    Bifidobacterium longum was microencapsulated by extrusion technique and added in fresh milk tofu and pineapple juice. Microencapsulation of B. longum with Eleutherine americana extract, oligosaccharides extract, and commercial fructo-oligosaccharides was assessed for the bacterial survival after sequential exposure to simulated gastric and intestinal juices, and refrigeration storage. Microencapsulated B. longum with the extract and oligosaccharides extract in the food products showed better survival than free cells under adverse conditions. Sensory analysis demonstrated that the products containing co-encapsulated bacterial cells were more acceptable by consumers than free cells. Pineapple juice prepared with co-encapsulated cells had lower values for over acidification, compared with the juice with free cells added. This work suggested that microencapsulated B. longum with E. americana could enhance functional properties of fresh milk tofu and pineapple juice. PMID:25854832

  11. Applications of Microencapsulated Bifidobacterium Longum with Eleutherine Americana in Fresh Milk Tofu and Pineapple Juice

    PubMed Central

    Phoem, Atchara N.; Chanthachum, Suphitchaya; Voravuthikunchai, Supayang P.

    2015-01-01

    Bifidobacterium longum was microencapsulated by extrusion technique and added in fresh milk tofu and pineapple juice. Microencapsulation of B. longum with Eleutherine americana extract, oligosaccharides extract, and commercial fructo-oligosaccharides was assessed for the bacterial survival after sequential exposure to simulated gastric and intestinal juices, and refrigeration storage. Microencapsulated B. longum with the extract and oligosaccharides extract in the food products showed better survival than free cells under adverse conditions. Sensory analysis demonstrated that the products containing co-encapsulated bacterial cells were more acceptable by consumers than free cells. Pineapple juice prepared with co-encapsulated cells had lower values for over acidification, compared with the juice with free cells added. This work suggested that microencapsulated B. longum with E. americana could enhance functional properties of fresh milk tofu and pineapple juice. PMID:25854832

  12. Superior antitumor activity of trastuzumab combined with capecitabine plus oxaliplatin in a human epidermal growth factor receptor 2-positive human gastric cancer xenograft model

    PubMed Central

    HARADA, SUGURU; YANAGISAWA, MIEKO; KANEKO, SAORI; YOROZU, KEIGO; YAMAMOTO, KANAME; MORIYA, YOICHIRO; HARADA, NAOKI

    2015-01-01

    In the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction cancer, it has been reported that the combination of trastuzumab with capecitabine plus cisplatin, or with 5-fluorouracil (5-FU) plus cisplatin, significantly increased overall survival compared with chemotherapy alone (ToGA trial). In addition, adjuvant therapy with capecitabine plus oxaliplatin (XELOX) improved the survival of patients who received curative D2 gastrectomy (CLASSIC trial). However, the efficacy of the combination of trastuzumab with XELOX for patients with HER2-positive gastric cancer remains unknown. The aim of this study, was to investigate the efficacy of the combination of trastuzumab with XELOX in a HER2-positive human gastric cancer xenograft model. Combination treatment with these three agents (trastuzumab 20 mg/kg, capecitabine 359 mg/kg and oxaliplatin 10 mg/kg), was found to exhibit a significantly stronger antitumor activity in NCI-N87 xenografts compared with either trastuzumab or XELOX alone. In this model, treatment with trastuzumab alone or trastuzumab plus oxaliplatin enhanced the expression of thymidine phosphorylase (TP), a key enzyme in the generation of 5-FU from capecitabine in tumor tissues. In in vitro experiments, trastuzumab induced TP mRNA expression in NCI-N87 cells. In addition, NCI-N87 cells co-cultured with the natural killer (NK) cell line CD16(158V)/NK-92 exhibited increased expression of TP mRNA. When NCI-N87 cells were cultured with CD16(158V)/NK-92 cells in the presence of trastuzumab, the mRNA expression of cytokines reported to have the ability to induce TP was upregulated in tumor cells. Furthermore, a medium conditioned by CD16(158V)/NK-92 cells also upregulated the expression of TP mRNA in NCI-N87 cells. These results suggest that trastuzumab promotes TP expression, either by acting directly on NCI-N87 cells, or indirectly via a mechanism that includes trastuzumab-mediated interactions

  13. Stable gastric pentadecapeptide BPC 157-NO-system relation.

    PubMed

    Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Aralica, Gorana; Stupnisek, Mirjana; Suran, Jelena; Barisic, Ivan; Dzidic, Senka; Vrcic, Hrvoje; Sebecic, Bozidar

    2014-01-01

    We reviewed stable gastric pentadecapeptide BPC 157-NO-system-relation, its close participation in Moncada's (maintained vascular integrity, platelets control) homeostatic healing response of NO-system to injury. Namely, BPC 157's particular healing effect also affects all events after vascular integrity loss (dependent on circumstances, it reduces either thrombosis (abdominal aorta anastomosis) or bleeding/thrombocytopenia (amputation, heparin, warfarin, aspirin)) and in a series of different injurious models, acute and chronic, BPC 157 consistently advances healing after severe injuries in various tissues spontaneously unable to heal; stimulates egr-1 and naB2 genes; exhibits high safety (LD1 not achieved)). Hypothesis, that BPC 157 (since formed constitutively in the gastric mucosa, stable in human gastric juice, along with significance of NO-synthase and the basal formation of NO in stomach mucosa, greater than that seen in other tissues) exhibits a general, effective competing both with L-arginine analogues (i. e., L-NAME) and L-arginine, and that this has some physiologic importance (NO-generation), later, practically supports its beneficial effects illustrating BPC 157 and NOsystem mutual (with L-NAME/L-arginine; alone and together) relations in (i) gastric mucosa and mucosal protection, following alcohol lesions, in cytoprotection course, NO-generation, and blood pressure regulation; (ii) alcohol acute/chronic intoxication, and withdrawal; (iii) cardiovascular disturbances, chronic heart failure, pulmonary hypertension, and arrhythmias; (iv) disturbances after hypokalemia and hyperkalemia, and potassium-cell membrane dysfunction; and finally, in (v) complex healing failure, proved by the fistulas healing, colocutaneous and esophagocutaneous. However, how this advantage of modulating NO-system (i. e., particular effect on eNOS gene), may be practically translated into an enhanced clinical performance remains to be determined. PMID:23755725

  14. Euphol from Euphorbia tirucalli selectively inhibits human gastric cancer cell growth through the induction of ERK1/2-mediated apoptosis.

    PubMed

    Lin, Ming-Wei; Lin, An-Shen; Wu, Deng-Chyang; Wang, Sophie S W; Chang, Fang-Rong; Wu, Yang-Chang; Huang, Yaw-Bin

    2012-12-01

    Gastric cancer is one of the most common malignancies worldwide, and the main cause of cancer-related death in Asia. The present study assessed the anticancer effects of euphol, a triterpene alcohol with anti-inflammatory and antiviral activities on human gastric cancer cells. Euphol showed higher cytotoxicity activity against human gastric CS12 cancer cells than against noncancer CSN cells. In addition, it up-regulated the pro-apoptotic protein BAX and down-regulated the prosurvival protein Bcl-2, causing mitochondrial dysfunction, possibly by caspase-3 activation. The anti-proliferative effects of euphol were associated with the increased p27(kip1) levels and decreased cyclin B1 levels. Inhibition of ERK1/2 activation by PD98059 reversed euphol-induced pro-apoptotic protein expression and cell death. Taken together, these findings suggest that euphol selectively induced gastric cancer cells apoptosis by modulation of ERK signaling, and could thus be of value for cancer therapy. PMID:22634261

  15. Grapefruit Juice and Statins.

    PubMed

    Lee, Jonathan W; Morris, Joan K; Wald, Nicholas J

    2016-01-01

    We determined the validity of current medical advice to avoid grapefruit juice consumption while taking 3 widely used statins. A daily glass of grapefruit juice increases blood levels of simvastatin and lovastatin by about 260% if taken at the same time (about 90% if taken 12 hours apart), and atorvastatin by about 80% (whenever taken). Simvastatin 40 mg, lovastatin 40 mg, and atorvastatin 10 mg daily reduce low-density lipoprotein (LDL) cholesterol levels in a 60-year-old man with an LDL cholesterol of 4.8 mmol/L by 37%, reducing ischemic heart disease risk by 61%. When simvastatin or lovastatin are taken at the same time as grapefruit juice, the estimated reduction in LDL cholesterol is 48%, and in heart disease is 70%. If the juice is taken 12 hours before these statins, the reductions are, respectively, 43% and 66%, and for atorvastatin, 42% and 66%. The increased rhabdomyolysis risk from grapefruit juice consumption due to the increased effective statin dose is minimal compared with the greater effect in preventing heart disease. Grapefruit juice should not be contraindicated in people taking statins. PMID:26299317

  16. Antioxidant activity of pomegranate juice reduces emphysematous changes and injury secondary to cigarette smoke in an animal model and human alveolar cells

    PubMed Central

    Husari, Ahmad; Hashem, Yasmine; Bitar, Hala; Dbaibo, Ghassan; Zaatari, Ghazi; El Sabban, Marwan

    2016-01-01

    Background Cigarette smoke (CS) increases oxidative stress (OS) in the lungs. Pomegranate juice (PJ) possesses potent antioxidant activities, attributed to its polyphenols. This study investigates the effects of PJ on the damaging effects of CS in an animal model and on cultured human alveolar cells (A549). Methods Male C57BL/6J mice were divided into the following groups: Control, CS, CS + PJ, and PJ. Acute CS exposure was for 3 days, while chronic exposure was for 1 and 3 months (5 days of exposure/week). PJ groups received daily 80 μmol/kg via bottle, while other groups received distilled water. At the end of the experiments, different parameters were studied: 1) expression levels of inflammatory markers, 2) apoptosis, 3) OS, and 4) histopathological changes. In vitro, A549 cells were pretreated for 48 hours with either PJ (0.5 μM) or vehicle. Cells were then exposed to increasing concentrations of CS extracted from collected filters. Cell viability was assessed by counting of live and dead cells with trypan blue staining. Results Acutely, a significant increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression, apoptosis, and OS was noted in CS when compared to Control. PJ significantly attenuated the expression of inflammatory mediators, apoptosis, and OS. Chronically (at 1 and 3 months), increased expression of TNF-α was observed, and lung sections demonstrated emphysematous changes when compared to Control. PJ supplementation to CS animals attenuated the increased expression of TNF-α and normalized lung cytoarchitecture. At the cellular level, CS extract reduced cellular proliferation and triggered cellular death. Pretreatment with PJ attenuated the damaging effects of CS extract on cultured human alveolar cells. Conclusion The expression of inflammatory mediators associated with CS exposure and the emphysematous changes noted with chronic CS exposure were reduced with PJ supplementation. In vitro, PJ attenuated the damaging

  17. Effects of recombinant human endostatin on the expression of vascular endothelial growth factor in human gastric cancer cell line MGC-803

    PubMed Central

    WANG, YU-BIN; LIU, JUN-HONG; SONG, ZONG-MIN

    2013-01-01

    The present study aimed to explore the effects of recombinant human endostatin, endostar (ES), on the expression of vascular endothelial growth factor (VEGF) in the human gastric cancer cell line MGC-803. The expression of VEGF protein in MGC-803 cells was examined using immunohistochemistry. Subsequent to treatment with various concentrations of ES, the mRNA and VEGF protein expressions were determined in MGC-803 cells. A high level of VEGF protein expression was detected in MGC-803 cells. Subsequent to ES treatment, the mRNA and VEGF protein expressions were significantly decreased in MGC-803 cells (all P<0.05). In conclusion, ES is likely to inhibit the VEGF expression in MGC-803 cells. PMID:24648897

  18. A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter

    PubMed Central

    2014-01-01

    Background Gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. Vaccinia viral therapy has had promising therapeutic potential for various cancers and has a great safety profile. We investigated the therapeutic efficacy of a novel genetically-engineered vaccinia virus carrying the human sodium iodide symporter (hNIS) gene, GLV-1 h153, on gastric cancers and its potential utility for imaging with 99mTc pertechnetate scintigraphy and 124I positron emission tomography (PET). Methods GLV-1 h153 was tested against five human gastric cancer cell lines using cytotoxicity and standard viral plaque assays. In vivo, subcutaneous flank tumors were generated in nude mice with human gastric cancer cells, MKN-74. Tumors were subsequently injected with either GLV-1 h153 or PBS and followed for tumor growth. 99mTc pertechnetate scintigraphy and 124I microPET imaging were performed. Results GFP expression, a surrogate for viral infectivity, confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1, GLV-1 h153 achieved > 90% cytotoxicity in MNK-74, OCUM-2MD3, and AGS over 9 days, and >70% cytotoxicity in MNK- 45 and TMK-1. In vivo, GLV-1 h153 was effective in treating xenografts (p < 0.001) after 2 weeks of treatment. GLV-1 h153-infected tumors were readily imaged by 99mTc pertechnetate scintigraphy and 124I microPET imaging 2 days after treatment. Conclusions GLV-1 h153 is an effective oncolytic virus expressing the hNIS protein that can efficiently regress gastric tumors and allow deep-tissue imaging. These data encourages its continued investigation in clinical settings. PMID:24383569

  19. Role of the IL-11/STAT3 signaling pathway in human chronic atrophic gastritis and gastric cancer.

    PubMed

    Wang, D Q; Ding, X P; Yin, S; Mao, Y D

    2016-01-01

    The expression of interleukin-11 (IL-11) and its products STAT3 and phospho-STAT3 (p-STAT3) in patients with chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), and gastric cancer (GC) may provide insight into the diagnostic role of the IL-11/STAT3 signaling pathway in GC. Gastric mucosa specimens and serum samples were collected from 90 patients with CSG, CAG, and GC (30/group). The expression of IL-11, STAT3, and p-STAT3 was detected via immunohistochemistry and western blot. Additionally, serum levels of IL-11 were measured by enzyme-linked immunosorbent assay. For IL-11, 60% stained positive in CAG and 83.3% stained positive in GC, which were both higher than the value observed for CSG (33.3%). Moreover, the percent positive for IL-11 in GC was higher than that in CAG (P < 0.05). The percent positive for STAT3 in CAG (80%) and GC (83.3%) was higher than that in CSG (53.3%) (P < 0.05). Compared with CSG (36.7%), the percent positive for p-STAT3 in CAG (63.3%) and GC (86.7%) was also significantly higher. STAT3 expression was similar in GC and CAG, which was significantly higher than that in CSG. Expectedly, p-STAT3 expression gradually increased from CSG to CAG to GC. Furthermore, p-STAT3 levels were higher in GC tissues than in CAG (P < 0.01). Intriguingly, serum IL-11 levels gradually increased from CSG to CAG to GC, which coincided with disease severity. Together, these results suggest that the IL-11/STAT3 signaling pathway plays a critical role in human CAG, and may provide new targets to prevent and treat GC. PMID:27173233

  20. Suppressive effects of an ethanol extract of Gleditsia sinensis thorns on human SNU-5 gastric cancer cells.

    PubMed

    Lee, Se-Jung; Ryu, Dong Hee; Jang, Lee Chan; Cho, Seok-Cheol; Kim, Wun-Jae; Moon, Sung-Kwon

    2013-04-01

    The thorns of Gleditsia sinensis are a traditional Oriental medicine used for the treatment of swelling, suppuration, carbuncle and skin diseases. In the present study, we identified a novel molecular mechanism by which an ethanol extract of Gleditsia sinensis thorns (EEGS) inhibits the growth of the SNU-5 human gastric cancer cell line. EEGS treatment inhibited cell growth and was associated with G1 phase cell cycle arrest at a concentration of 400 µg/ml (IC50) in SNU-5 cells. Treatment with EEGS also stimulated p21WAF1 expression, which significantly decreased the expression of cyclins and cyclin-dependent kinases (CDKs). Further study suggested that p38 MAP kinase pathways may be involved in the inhibition of cell proliferation through p21WAF1‑dependent G1 phase cell cycle arrest in EEGS-treated cells. In addition, NF-κB and AP-1 transcription factor binding sites were identified as the cis-elements for tumor necrosis factor-α (TNF-α)-induced matrix metalloproteinase-9 (MMP-9) expression in SNU-5 cells, as determined by gel-shift assay. Treatment of cells with EEGS suppressed MMP-9 expression induced by TNF-α via a decrease in the binding activity of both NF-κB and AP-1 motifs. These data demonstrate that EEGS-mediated inhibition of cell growth appears to involve the activation of p38 MAP kinase, subsequently leading to the induction of p21WAF1 and the downregulation of cyclin D1/CDK4 and cyclin E/CDK2 complexes. Moreover, EEGS strongly inhibited TNF-α-induced MMP-9 expression by impeding the DNA binding activity of NF-κB and AP-1. Overall, these results provide a potential mechanism for EEGS in the treatment of gastric cancer. PMID:23381601

  1. Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26

    PubMed Central

    NISHIKAWA, SHIMPEI; KONNO, MASAMITSU; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; KANO, YOSHIHIRO; FUKUSUMI, TAKAHITO; SATOH, TAROH; TAKIGUCHI, SHUJI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

    2015-01-01

    Cancer tissue is maintained by relatively small populations of cancer stem cells (CSCs), which are involved in chemotherapy resistance, recurrence and metastasis. As tumor tissues are comprised of various cells, studies of human clinical samples are important for the characterization of CSCs. In the present study, an expression profiling study was performed in which an anti-cell surface marker antibody-based array platform, a flow cytometry-based cell separation technique and a tumorigenicity analysis in immunodeficient animals were utilized. These approaches revealed that the markers cluster of differentiation (CD)44 and CD26 facilitated the fractionation of surgically resected human gastric cancer (GC) cells into the following subset populations with distinct tumorigenic potentials: Highly tumorigenic CD26+CD44+ cells (6/6 mice formed tumors), moderately tumorigenic CD26+CD44− cells (5/6 mice formed tumors), and weakly or non-tumorigenic CD26−CD44− cells (2/6 mice formed tumors). Furthermore, exposure to 5-fluorouracil significantly increased the proportion of CD26+ cells in vitro. The present study demonstrated that the combined expression of CD26 and CD44 presents a potential marker of human GC stem cells. PMID:26137071

  2. 21 CFR 156.145 - Tomato juice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... prevent spoilage. (2) Labeling. (i) The name of the food is: (a) “Tomato juice” if it is prepared from... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Tomato juice. 156.145 Section 156.145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR...

  3. NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations

    PubMed Central

    PARK, EUNJU; PARK, JINAH; HAN, SAE-WON; IM, SEOCK-AH; KIM, TAE-YOU; OH, DO-YOUN; BANG, YUNG-JUE

    2012-01-01

    Aberrations of Phosphoinositide 3-kinase (PI3K)/AKT signaling are frequently observed in many types of cancer, promoting its emergence as a promising target for cancer treatment. PI3K can become activated by various pathways, one of which includes RAS. RAS can not only directly activate the PI3K/AKT pathway via binding to p110 of PI3K, but also regulates mTOR via ERK or RSK independently of the PI3K/AKT pathway. Thus, actively mutated RAS can constitutively activate PI3K signaling. Additionally, in RAS tumorigenic transformation, signal transducer and activator of transcription 3 (STAT3) has been known also to be required. In this study, we examined the efficacy of NVP-BKM120, a pan-class I PI3K inhibitor in human gastric cancer cells and hypothesized that the combined inhibition of PI3K and STAT3 would be synergistic in KRAS mutant gastric cancer cells. NVP-BKM120 demonstrated anti-proliferative activity in 11 human gastric cancer cell lines by decreasing mTOR downstream signaling. But NVP-BKM120 treatment increased p-AKT by subsequent abrogation of feedback inhibition by stabilizing insulin receptor substrate-1. In KRAS mutant gastric cancer cells, either p-ERK or p-STAT3 was also increased upon treatment of NVP-BKM120. The synergistic efficacy study demonstrated that dual PI3K and STAT3 blockade showed a synergism in cells harboring mutated KRAS by inducing apoptosis. The synergistic effect was not seen in KRAS wild-type cells. Together, these findings suggest for the first time that the dual inhibition of PI3K and STAT3 signaling may be an effective therapeutic strategy for KRAS mutant gastric cancer patients. PMID:22159814

  4. MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells

    PubMed Central

    Xia, Jianling; Zhou, Rui; Wu, Zhenzhen; Zhao, Yang; Shi, Min

    2016-01-01

    The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is unclear how MACC1 activity is regulated in GC. In this study, we demonstrated that ACh acts via M3Rs to promote GC cell invasion and migration as well as expression of several markers of epithelial-mesenchymal transition (EMT). The M3R antagonist darifenacin inhibited GC cell activity in both the presence and absence of exogenous ACh, suggesting GC cells secrete endogenous ACh, which then acts in an autocrine fashion to promote GC cell migration/invasion. ACh up-regulated MACC1 in GC cells, and MACC1 knockdown using siRNA attenuated the effects of ACh on GC cells. AMP-activated protein kinase (AMPK) served as an intermediate signal between ACh and MACC1. These findings suggest that ACh acts via a M3R/AMPK/MACC1 signaling pathway to promote GC cell invasion/migration, which provides insight into the mechanisms underlying GC growth and metastasis and may shed light on new targets for GC treatment. PMID:26919111

  5. Candidate microRNA Biomarkers in Human Gastric Cancer: A Systematic Review and Validation Study

    PubMed Central

    Kong, Xuan; Wang, Zhen-Hua; Chen, Hao-Yan; Xu, Jie; Fang, Jing-Yuan

    2013-01-01

    Gastric cancer (GC) remains a major cause of morbidity and mortality worldwide and there is therefore a clear need to search for more sensitive early diagnostic biomarkers. We performed a systematic review of eight published miRNA profiling studies that compared GC tissues with adjacent noncancerous tissues. A miRNA ranking system was used that took the frequency of comparisons, direction of differential expression and total sample size into consideration. We identified five miRNAs that were most consistently reported to be upregulated (miR-21, miR-106b, miR-17, miR-18a and miR-20a) and two miRNAs that were downregulated (miR-378 and miR-638). Six of these were further validated in 32 paired sets of GC and adjacent noncancerous tissue samples using real-time PCR. MiR-21, miR-106b, miR-17, miR-18a and miR-20a were confirmed to be upregulatedin GC tissues, while the expression of miR-378 was decreased. Moreover, we found a significant association between expression levels of miR-21, miR-106b, miR-17, miR-18a and miR-20a and clinicopathological features of GC. These miRNAs may be used for diagnostic and/or prognostic biomarkers for GC and therefore warrant further investigation. PMID:24040025

  6. Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells.

    PubMed

    Reis, Filipa S; Lima, Raquel T; Morales, Patricia; Ferreira, Isabel C F R; Vasconcelos, M Helena

    2015-01-01

    Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was not known if it induces autophagy or decreases the autophagic flux. The treatment of a gastric adenocarcinoma cell line (AGS) with the mushroom extract increased the formation of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular levels of LC3-II were also increased, and the cellular levels of p62 decreased, confirming that the extract affects cellular autophagy. Treating the cells with the extract together with lysossomal protease inhibitors, the cellular levels of LC3-II and p62 increased. The results obtained proved that, in AGS cells, the methanolic extract of G. lucidum causes an induction of autophagy, rather than a reduction in the autophagic flux. To our knowledge, this is the first study proving that statement. PMID:26426001

  7. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer

    NASA Astrophysics Data System (ADS)

    Yang, Zhe; Luo, Huiyan; Cao, Zhong; Chen, Ya; Gao, Jinbiao; Li, Yingqin; Jiang, Qing; Xu, Ruihua; Liu, Jie

    2016-06-01

    Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44.Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor

  8. Simplified miniaturized ultrasound-assisted matrix solid phase dispersion extraction and high performance liquid chromatographic determination of seven flavonoids in citrus fruit juice and human fluid samples: hesperetin and naringenin as biomarkers.

    PubMed

    Barfi, Behruz; Asghari, Alireza; Rajabi, Maryam; Barfi, Azadeh; Saeidi, Iman

    2013-10-11

    In the present study, for the first time, a simplified miniaturized ultrasound-assisted matrix solid-phase dispersion (SM-USA-MSPD) method with a different application for liquid matrices was developed to extract different flavonoids (hesperidin, diosmin, eriocitrin, narirutin, naringin, hesperetin and naringenin) from citrus fruit juice and human fluid samples prior to their determination using high performance liquid chromatography (HPLC). Different effective parameters were studied and under the optimum conditions (including sample volume: 150μL; solid phase: silica-based C18, 200mg; eluting solvent: methanol, 500μL; pH: 4; and sonication: 6min; at room temperature), limits of detection and limits of quantification were ranged from 23.3 to 46.8ngmL(-1) and 74.8 to 141.5ngmL(-1), respectively. Once optimized, analytical performance of the method was studied in terms of linearity (0.074-198.5μgmL(-1), r(2)>0.991), accuracy (recovery=84.6-101.5%), and precision (repeatability: intra-day precision<5.9%, and inter-day precision<7.2%). At the end, SM-USA-MSPD method was successfully applied to estimate the levels of hesperetin and naringenin in plasma and urinary excretion -after ingestion of orange, grapefruit and lime juices- and the obtained results confirmed that these compounds could be used as good biomarkers of citrus fruit juice intake. PMID:24011420

  9. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer.

    PubMed

    Yang, Zhe; Luo, Huiyan; Cao, Zhong; Chen, Ya; Gao, Jinbiao; Li, Yingqin; Jiang, Qing; Xu, Ruihua; Liu, Jie

    2016-06-01

    Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44. PMID:27203688

  10. A C21-Steroidal Glycoside Isolated from the Roots of Cynanchum auriculatum Induces Cell Cycle Arrest and Apoptosis in Human Gastric Cancer SGC-7901 Cells

    PubMed Central

    Wang, Yi-Qi; Zhang, Shui-Juan; Lu, Hong; Yang, Bo; Ye, Liang-Fei; Zhang, Ru-Song

    2013-01-01

    Caudatin 3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside (CGII) is one of the C21-steroidal glycosides isolated from the roots of Cynanchum auriculatum ROYLE ex WIGHT. This study aimed to determine the cell growth, cell proliferation, and apoptotic cell death of human gastric cancer cells after CGII treatment. MTT assay was used to determine cell growth; fluorescence-activated cell sorting analysis was used to evaluate cell cycle distribution and apoptotic cell death. Immunoblotting was applied for measuring the expression of proteins involved in the cell cycle progression. The activities of caspase-3, -8, and -9 were detected by colorimetric caspase activity assays. CGII inhibited cell growth of human gastric cancer SGC-7901 cells in a concentration- and time-dependent manner. Treatment of SGC-7901 cells with CGII resulted in G1 phase cell cycle arrest, accompanied with decreased expression of cyclin D1 and cyclin-dependent kinases 4 and 6. CGII induced cell apoptosis and activated caspase-3, caspase-8, and caspase-9. In contrast, pan-caspase inhibitor z-VAD-fmk partially abolished the CGII-induced growth inhibition of SGC-7901 cells. In conclusion, CGII inhibits cell growth of human gastric cancer cells by inducing G1 phase cell cycle arrest and caspase-dependent apoptosis cascades. PMID:24454488

  11. Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products.

    PubMed

    Manu, Kanjoormana A; Shanmugam, Muthu K; Li, Feng; Chen, Luxi; Siveen, Kodappully Sivaraman; Ahn, Kwang Seok; Kumar, Alan Prem; Sethi, Gautam

    2014-03-01

    Chemoresistance remains a major problem in the treatment of gastric cancer patients. Hence, novel pharmacological agents that can overcome drug resistance are urgently required. Whether simvastatin can sensitize the gastric cancer to the antitumor effects of capecitabine in vitro and in vivo was investigated. The effect of simvastatin on the proliferation of gastric cancer cells was examined by mitochondrial dye-uptake 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis by esterase staining, NF-κB activation by DNA binding assay, and protein expression by western blot analysis. The effect of simvastatin on the tumor growth in xenograft mouse model of human gastric cancer was also examined. Simvastatin suppressed the proliferation of gastric cancer cells, enhanced the apoptotic effects of capecitabine, suppressed the constitutive activation of NF-κB, and abrogated the expression of cyclooxygenase-2 (COX-2), cyclin D1, Bcl-2, survivin, CXC motif receptor 4, and MMP-9 proteins. In a xenograft mouse model, we observed that the administration of simvastatin alone (5 mg/kg body weight, intraperitoneal thrice/week) significantly suppressed the growth of the tumor and this effect was further potentiated by capecitabine treatment. As compared to the vehicle control, simvastatin also suppressed the expression of NF-κB-regulated gene products such as cyclin D1, COX-2, ICAM-1, MMP-9, survivin, Bcl-xL, and XIAP in tumor tissues. Overall, our results demonstrate that simvastatin can enhance the effects of capecitabine through suppression of NF-κB-regulated markers of proliferation, invasion, angiogenesis, and metastasis. PMID:24233024

  12. Melatonin downregulates nuclear receptor RZR/RORγ expression causing growth-inhibitory and anti-angiogenesis activity in human gastric cancer cells in vitro and in vivo

    PubMed Central

    Wang, Ri-Xiong; Liu, Hui; Xu, Li; Zhang, Hui; Zhou, Rui-Xiang

    2016-01-01

    An adequate supply of oxygen and nutrients, derived from the formation of novel blood vessels, is critical for the growth and expansion of tumor cells. It has been demonstrated that melatonin (MLT) exhibits marked in vitro and in vivo oncostatic activities. The primary purpose of the present study was to evaluate the in vitro and in vivo antitumor activity of MLT on the growth and angiogenesis of gastric cancer cells, and explore the underlying molecular mechanisms. The present results revealed that MLT inhibited the growth of gastric cancer SGC-7901 cells in a dose- and time-dependent manner. In addition, the present study demonstrated that low concentrations (0.01, 0.1 and 1 mM) of MLT had no clear effect on vascular endothelial growth factor (VEGF) secretion, whereas a high concentration (3 mM) of MLT suppressed VEGF secretion in SGC-7901 cells. Notably, administration of MLT caused suppression of gastric cancer growth and blockade of tumor angiogenesis in tumor-bearing nude mice. Furthermore, MLT treatment reduced the expression of the MLT nuclear receptor RZR/RORγ, SUMO-specific protease 1, hypoxia-inducible factor-1α and VEGF at transcriptional and translational levels within gastric cancer cells during tumorigenesis. In conclusion, MLT nuclear receptor RZR/RORγ may be of great importance in the MLT mediated anti-angiogenesis and growth-inhibitory effect in gastric cancer cells. Since RZR/RORγ is overexpressed in multiple human cancers, MLT may be a promising agent for the treatment of cancers. PMID:27446366

  13. AURKA regulates JAK2-STAT3 activity in human gastric and esophageal cancers.

    PubMed

    Katsha, Ahmed; Arras, Janet; Soutto, Mohammed; Belkhiri, Abbes; El-Rifai, Wael

    2014-12-01

    Aurora kinase A is a frequently amplified and overexpressed gene in upper gastrointestinal adenocarcinomas (UGCs). Using in vitro cell models of UGCs, we investigated whether AURKA can regulate Signal Transducer and Activator of Transcription 3 (STAT3). Our data indicate that overexpression of AURKA in FLO-1 and AGS cells increase STAT3 phosphorylation at the Tyr705 site, whereas AURKA genetic depletion by siRNA results in decreased phosphorylation levels of STAT3 in FLO-1 and MKN45 cells. Immunofluorescence analysis showed that AURKA overexpression enhanced STAT3 nuclear translocation while AURKA genetic knockdown reduced the nuclear translocation of STAT3 in AGS and FLO-1 cells, respectively. Using a luciferase reporter assay, we demonstrated that AURKA expression induces transcriptional activity of STAT3. Pharmacological inhibition of AURKA by MLN8237 reduced STAT3 phosphorylation along with down-regulation of STAT3 pro-survival targets, BCL2 and MCL1. Moreover, by using clonogenic cells survival assay, we showed that MLN8237 single dose treatment reduced the ability of FLO-1 and AGS cells to form colonies. Additional experiments utilizing cell models of overexpression and knockdown of AURKA indicated that STAT3 upstream non-receptor tyrosine kinase Janus kinase 2 (JAK2) is mediating the effect of AURKA on STAT3. The inhibition of JAK2 using JAK2-specific inhibitor AZD1480 or siRNA knockdown, in presence of AURKA overexpression, abrogated the AURKA-mediated STAT3 activation. These results confirm that the AURKA-JAK2 axis is the main mechanism by which AURKA regulates STAT3 activity. In conclusion, we report, for the first time, that AURKA promotes STAT3 activity through regulating the expression and phosphorylation levels of JAK2. This highlights the importance of targeting AURKA as a therapeutic approach to treat gastric and esophageal cancers. PMID:24953013

  14. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery.

    PubMed

    Albers, Peter H; Bojsen-Møller, Kirstine N; Dirksen, Carsten; Serup, Annette K; Kristensen, Dorte E; Frystyk, Jan; Clausen, Trine R; Kiens, Bente; Richter, Erik A; Madsbad, Sten; Wojtaszewski, Jørgen F P

    2015-09-01

    Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose-tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 wk and 3 and 12 mo after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 mo postsurgery when major weight loss was evident and occurred concomitantly with alterations in plasma adiponectin and in protein expression/signaling in peripheral tissues. In skeletal muscle, protein expression of GLUT4, phosphorylated levels of TBC1D4, as well as insulin-induced changes in phosphorylation of Akt and glycogen synthase activity were enhanced 12 mo postsurgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4, and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC, as well as insulin-induced changes in phosphorylation of Akt and TBC1D4, were enhanced 12 mo postsurgery. Adipose tissue from glucose-tolerant subjects was the most responsive to RYGB compared with type 2 diabetic patients, whereas changes in skeletal muscle were largely similar in these two groups. In conclusion, an improved molecular insulin-sensitive phenotype of skeletal muscle and adipose tissue appears to contribute to the improved whole body insulin action following a substantial weight loss after RYGB. PMID:26062634

  15. Large-scale characterization of DNA methylation changes in human gastric carcinomas with and without metastasis

    PubMed Central

    Liu, Zhaojun; Zhang, Jun; Gao, Yanhong; Pei, Lirong; Zhou, Jing; Gu, Liankun; Zhang, Lianhai; Zhu, Budong; Hattori, Naoko; Ji, Jiafu; Yuasa, Yasuhito; Kim, Wooho; Ushijima, Toshikazu; Shi, Huidong; Deng, Dajun

    2014-01-01

    Purpose Metastasis is the leading cause of death for gastric carcinoma (GC). An epigenetic biomarker panel for predicting GC metastasis could have significant clinical impact on the care of GC patients. The main purpose of this study is to characterize the methylation differences between GCs with and without metastasis. Experimental Design Genome-wide DNA methylation profiles between 4 metastatic and 4 non-metastatic GCs and their surgical margins (SM) were analyzed using methylated-CpG island amplification with microarray. The methylation states of 73 candidate genes were further analyzed in GC patients in a discovery cohort (n=108) using DHPLC, bisulfite-sequencing, and MethyLight. The predictive values of potential metastasis-methylation biomarkers were validated in GC patient cohorts in China (n=330), Japan (n=129), and Korea (n=153). Results The GC genome showed significantly higher proportions of hypomethylation in the promoter and exon-1 regions, as well as increased hypermethylation of intragenic fragments when compared to SMs. Significant differential methylation was validated in the CGIs of 15 genes (Ps<0.05) and confirmed using bisulfite-sequencing. These genes included BMP3, BNIP3, CDKN2A, ECEL1, ELK1, GFRA1, HOXD10, KCNH1, PSMD10, PTPRT, SIGIRR, SRF, TBX5, TFPI2, and ZNF382. Methylation changes of GFRA1, SRF and ZNF382 resulted in up- or down-regulation of their transcription. Most importantly, the prevalence of GFRA1, SRF, and ZNF382 methylation alterations was consistently and coordinately associated with GC metastasis and the patients’ overall survival throughout discovery and validation cohorts in China, Japan and Korea. Conclusion Methylation changes of GFRA1, SRF, and ZNF382 may be a potential biomarker set for prediction of GC metastasis. PMID:25009298

  16. Gastric suction

    MedlinePlus

    ... al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila) . 2013;51(3); 140-146. ... 2012:chap 49. Zeringe M, Fowler GC. Gastrointesinal decontamination. In: Pfenninger JL, Fowler GC, eds. Pfenninger & Fowler's ...

  17. Gastric Banding

    MedlinePlus

    ... gastric banding before deciding to have the procedure. Advertisements for a device or procedure may not include ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  18. Gastric culture

    MedlinePlus

    ... test or procedure preparation (3 to 6 years) School age test or procedure preparation (6 to 12 ... immune system. The final results of the gastric culture test may take several weeks. Your provider will ...

  19. Evaluation of the change in sphingolipids in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 treated with arsenic trioxide.

    PubMed

    Zou, Jianhua; Ma, Xiaoqiong; Zhang, Guangji; Shen, Li; Zhou, Liting; Yu, Yu; Zhu, Fanfan; Chen, Zhe

    2015-11-01

    Arsenic trioxide (As2O3) has been found to display anticancer activity against many types of tumors and has been developed into an anticancer drug in clinical treatments. Sphingolipids are membrane lipids that participate in many signal transduction pathways. In this paper, the changes in sphingolipids of the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803 treated with arsenic trioxide were investigated using an HPLC-ESI-MS/MS method. Analytes were separated by an XBridge BEH C8 column used for Cer, HexCer, LacCer and SM chromatographic separation, and a Capcell PAK MG II C18 column was used for Sph, dhSph, S1P and dhS1P chromatographic separation and gradient elution with acetonitrile-water containing 0.1% formic acid as a mobile phase. A tandem mass spectrometer QTrap in SRM mode was employed in combination with RPLC as a detector for quantitative analysis. The ceramide/sphingolipid internal standard (IS) mixture was used to quantify the levels of sphingolipids. The distributions of sphingolipids were found to be different in the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803. Ceramide (Cer), hexosylceramide (HexCer) and dihexosylceramide (Hex2Cer) levels in U266 cell line are higher than those in MGC-803 cell line. Additionally, sphingomyelin (SM), sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (dhS1P) levels in the MGC-803 cell line are higher than those in the U266 cell line. When treated with arsenic trioxide (1-5μM iAs(III)(As(III) ions)), the levels of Hex2Cer in the human multiple myeloma cell line U266 decreased, and the levels of S1P and dhS1P in the human gastric cancer cell line MGC-803 decreased. The decrease of Hex2Cer, S1P and dhS1P in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 were observed when the concentration of iAs(III) is 1.0μM. Therefore, arsenic trioxide exhibits anti-cancer activity by altering the sphingolipid pathway in the

  20. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157.

    PubMed

    Sikiric, P; Seiwerth, S; Rucman, R; Turkovic, B; Rokotov, D S; Brcic, L; Sever, M; Klicek, R; Radic, B; Drmic, D; Ilic, S; Kolenc, D; Stambolija, V; Zoricic, Z; Vrcic, H; Sebecic, B

    2012-01-01

    Stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419) may be the new drug stable in human gastric juice, effective both in the upper and lower GI tract, and free of side effects. BPC 157, in addition to an antiulcer effect efficient in therapy of inflammatory bowel disease (IBD) (PL 14736) so far only tested in clinical phase II, has a very safe profile, and exhibited a particular wound healing effect. It also has shown to interact with the NO-system, providing endothelium protection and angiogenic effect, even in severely impaired conditions (i.e., it stimulated expression of early growth response 1 gene responsible for cytokine and growth factor generation and early extracellular matrix (collagen) formation (but also its repressor nerve growth factor 1-A binding protein-2)), important to counteract severe complications of advanced and poorly controlled IBD. Hopefully, the lessons from animal studies, particularly advanced intestinal anastomosis healing, reversed short bowel syndrome and fistula healing indicate BPC 157's high significance in further IBD therapy. Also, this supportive evidence (i.e., no toxic effect, limit test negative, LD1 not achieved, no side effect in trials) may counteract the problems commonly exercised in the use of peptidergic agents, particularly those used on a long-term basis. PMID:22300085

  1. Fermentation Rates of Grape Juice

    PubMed Central

    Ough, C. S.; Kunkee, R. E.

    1968-01-01

    Microbiological analysis showed that juices from white grapes had less biotin than juices from red grapes. The biotin content of the juices of some varieties was significantly different from that of other varieties. We did not note any regional effects on the biotin content of the juices. Biotin content of the Cabernet Sauvignon grapes increased significantly with maturity, whereas the biotin content of a white variety did not. The biotin content, with the total nitrogen, can be used to estimate indirectly the yeast growth potential and hence to predict the fermentation rate of the juice. About 84% of the rate variation can be accounted for by the calculated regression equations. PMID:16349801

  2. Determination of amygdalin in apple seeds, fresh apples and processed apple juices.

    PubMed

    Bolarinwa, Islamiyat F; Orfila, Caroline; Morgan, Michael R A

    2015-03-01

    Cyanogenic glycosides are natural plant toxicants. Action by endogenous plant enzymes can release hydrogen cyanide causing potential toxicity issues for animals including humans. We have quantified amygdalin in seeds from different apple varieties, determined the effects of processing on the amygdalin content of apple juice and quantified amygdalin in commercially-available apple juices. Amygdalin contents of seeds from fifteen varieties of apples ranged from 1 mg g(-1) to 4 mg g(-1). The amygdalin content of commercially-available apple juice was low, ranging from 0.01 to 0.04 mg ml(-1) for pressed apple juice and 0.001-0.007 mg ml(-1) for long-life apple juice. Processing led to juice with low amygdalin content, ranging from 0.01 mg ml(-1) to 0.08 mg ml(-1). The results presented show that the amygdalin contents of commercially-available apple juices are unlikely to present health problems to consumers. PMID:25306368

  3. Ethanolic extract of Tulipa edulis Bak induces apoptosis in SGC-7901 human gastric carcinoma cells via the mitochondrial signaling pathway

    PubMed Central

    LIN, RUHUI; LI, ZUANFANG; LIN, JIUMAO; YE, JINXIA; CAI, QIAOYAN; CHEN, LIDIAN; PENG, JUN

    2015-01-01

    Tulipa edulis Bak (TEB) is an active ingredient in various traditional Chinese medicine compounds and is commonly used to treat swelling and redness, remove toxicity and eliminate stagnation, as well as to prevent and treat certain cancer types. However, the underlying molecular mechanism of the anticancer activity of TEB remains unclear. The aim of the current study was to investigate the effect and underlying mechanism of the ethanolic extract of TEB (EETEB) on SGC-7901 human gastric carcinoma cells. An MTT assay was performed to analyze cell viability. In addition, transmission electron microscopy, an Annexin V/fluorescein isothiocyanate assay, a JC-1 assay and laser scanning confocal microscopy with DAPI staining were used to determine the rate of apoptosis. Furthermore, reverse transcription-polymerase chain reaction and western blot analysis were used to detect the expression levels of the apoptosis gene and protein. EETEB was identified to inhibit the growth of SGC-7901 cells in a dose-dependent manner and induce changes in cell morphology. At the molecular level, EETEB induced SGC-7901 cell DNA fragmentation, loss of plasma membrane and asymmetrical collapse of the mitochondrial membrane potential, while it increased the expression of pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein and reduced expression of anti-apoptotic Bcl-2. Thus, the results of the current study revealed that the application of EETEB may inhibit the growth of the SGC-7901 cells due to mitochondria-mediated apoptosis. PMID:26622854

  4. Effect of hyperthermic CO2-treated dendritic cell-derived exosomes on the human gastric cancer AGS cell line

    PubMed Central

    WANG, JINLIN; WANG, ZHIYONG; MO, YANXIA; ZENG, ZHAOHUI; WEI, PEI; LI, TAO

    2015-01-01

    The aim of the present study was to determine the antitumor effects of hyperthermic CO2 (HT-CO2)-treated dendritic cell (DC)-derived exosomes (Dex) on human gastric cancer AGS cells. Mouse-derived DCs were incubated in HT-CO2 at 43°C for 4 h. The exosomes in the cell culture supernatant were then isolated. Cell proliferation was analyzed using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was observed using flow cytometry, Hoechst 33258 staining and the analysis of caspase-3 activity. In addition, the proliferation of tumor cells was evaluated in xenotransplant nude mice. HT-CO2 markedly inhibited cell proliferation, as assessed by the CCK-8 assay, and also induced apoptosis in a time-dependent manner, as demonstrated by Annexin V/propidium iodide flow cytometry, caspase-3 activity and morphological analysis using Hoechst fluorescent dye. It was also revealed that HT-CO2-treated Dex decreased the expression of heat shock protein 70 and inhibited tumor growth in nude mice. In conclusion, HT-CO2 exerted an efficacious immune-enhancing effect on DCs. These findings may provide a novel strategy for the elimination of free cancer cells during laparoscopic resection. However, the potential cellular mechanisms underlying this process require further investigation. PMID:26170979

  5. In vitro analysis of the role of the mitochondrial apoptosis pathway in CSBE therapy against human gastric cancer

    PubMed Central

    JI, YU-BIN; YU, LEI

    2015-01-01

    The caper plant (Capparis spinosa L.) was a common Uyghur folk medicine, and is a member of the Capparidaceae family. In a previous study, the n-butanol extract of C. spinosa L. (CSBE) was demonstrated to exert anti-tumor activity; however, the underlying mechanism is currently not understood. The present study aimed to elucidate the mechanism underlying the CSBE-induced mitochondrial apoptotic pathway, in order to investigate the anti-tumor effects of this plant extract. CSBE-induced apoptosis of the SGC-7901 human gastric cancer cell line was observed, and alterations in the expression levels and localization of initiators, markers, and executors of the mitochondrial apoptosis pathway were analyzed. Following treatment of SGC-7901 cells with CBSE, proliferation was inhibited and apoptosis was induced; and these effects were associated with mitochondrial membrane potential disruption, cytochrome c release into the cytoplasm, and caspase-9 and caspase-3 activation. CSBE may have induced SGC-7901 cell apoptosis by upregulating the expression of B-cell lymphoma-2 (BCL-2)-associated X protein, and downregulating the expression of BCL-2. The results of the present study suggested that CSBE may induce SGC-7901 cell apoptosis via activation of the mitochondrial apoptosis pathway. PMID:26668648

  6. Correlation of particle properties with cytotoxicity and cellular uptake of hydroxyapatite nanoparticles in human gastric cancer cells.

    PubMed

    Cui, Xinhui; Liang, Tong; Liu, Changsheng; Yuan, Yuan; Qian, Jiangchao

    2016-10-01

    Three types of hydroxyapatite nanoparticles (HAPNs) were synthesized employing a sonochemistry-assisted microwave method by changing microwave power (from 200 to 300W) or using calcination treatment: L200 (200W, lyophilization), L300 (300W, lyophilization) and C200 (200W, lyophilization & calcination). Their physiochemical properties were characterized and correlated with cytotoxicity to human gastric cancer cells (MGC80-3). The major differences among these HAPN preparations were their size and specific surface area, with the L200 showing a smaller size and higher specific surface area. Although all HAPNs inhibited cell proliferation and induced apoptosis of cancer cells, L200 exhibited the greatest toxicity. All types of HAPNs were internalized through energy-dependent pathways, but the L200 nanoparticles were more efficiently uptaken by MGC80-3 cells. Inhibitor studies with dynasore and methyl-β-cyclodextrin suggested that caveolae-mediated endocytosis and, to a much lesser extent, clathrin-mediated endocytosis, were involved in cellular uptake of the various preparations, whereas the inhibition of endocytosis was more obvious for L200. Using fluorescein isothiocyanate-labeled HAPNs and laser-scanning confocal microscopy, we found that all forms of nanoparticles were present in the cytoplasm, and some L200 HAPNs were even found within nuclei. Treatment with all HAPN preparations led to the increase in the intracellular calcium level with the highest level detected for L200. PMID:27287142

  7. The effect of two nucleoside antitumor drugs on the proliferation and DNA methylation of human gastric cancer cells

    PubMed Central

    CHEN, XIU-LI; WANG, FENG-MEI; LI, JIA-JIA; HE, XIAO-YING; LIU, XI-YU; MA, LI-BING

    2015-01-01

    Fluorouracil (5-Fu) and 5-azacitidine (5-aza) are two types of nucleoside analog, which have been widely applied in the treatment of several types of cancer. However, the effect of these two types of drug on the proliferation and DNA methylation of cancer cells has not been compared in a single study. In the present study, in vitro cultured human gastric cancer cells (hGCCs) were treated with various concentrations of 5-Fu and 5-aza, and cell counting, MTT assay and methyl-sensitive amplified polymorphism were used to evaluate the resulting levels of proliferation and DNA methylation of hGCCs. The results revealed that the two drugs were able to inhibit the proliferation of hGCCs, but that the effect of 5-aza was weaker than that of 5-Fu. However, 5-aza decreased the level of DNA methylation in hGCCs, whereas 5-Fu did not alter DNA methylation. These results indicated that 5-Fu was able to more efficiently inhibit the proliferation of hGCCs than 5-aza, and that this difference may be due to differences in the anticancer mechanism of these two types of drug. PMID:26622775

  8. Apoptosis induced by farrerol in human gastric cancer SGC-7901 cells through the mitochondrial-mediated pathway.

    PubMed

    Liu, Enli; Liang, Taigang; Wang, Xiaojian; Ban, Shurong; Han, Lingge; Li, Qingshan

    2015-09-01

    Farrerol, a typical flavanone isolated from the Chinese medicinal plant Rhododendron dauricum L., has been found to show various biological activities. However, to the best of our knowledge, its inhibitory actions against cancer cells have not been reported as yet. Therefore, the present study aimed to investigate the cytotoxic and apoptotic effects of farrerol on human gastric cancer SGC-7901 cells. Farrerol showed a 50% inhibition of SGC-7901 cell growth at a concentration of 40.4 μmol/l for 24 h according to MTT assays. The cell morphology results indicated that SGC-7901 cells treated with farrerol showed several features of apoptotic cell death, which was also confirmed by the Annexin-V FITC/PI double-staining assay. Further studies showed that farrerol treatment induced the attenuation of mitochondrial membrane potential, accompanied by the release of Cyt-c and the activation of caspase-9 and caspase-3. Furthermore, farrerol decreased the gene expression of Bcl-2, whereas the gene expression level of Bax was found to increase after farrerol treatment. These combined results indicated that farrerol can induce apoptosis through a mitochondrial-mediated pathway. PMID:26061993

  9. JWA reverses cisplatin resistance via the CK2—XRCC1 pathway in human gastric cancer cells

    PubMed Central

    Xu, W; Chen, Q; Wang, Q; Sun, Y; Wang, S; Li, A; Xu, S; Røe, O D; Wang, M; Zhang, R; Yang, L; Zhou, J

    2014-01-01

    Gastric cancer is the third most common malignancy in China, with a median 5-year survival of only 20%. Cisplatin has been used in first-line cancer treatment for several types of cancer including gastric cancer. However, patients are often primary resistant or develop acquired resistance resulting in relapse of the cancer and reduced survival. Recently, we demonstrated that the reduced expression of base excision repair protein XRCC1 and its upstream regulator JWA in gastric cancerous tissues correlated with a significant survival benefit of adjuvant first-line platinum-based chemotherapy as well as XRCC1 playing an important role in the DNA repair of cisplatin-resistant gastric cancer cells. In the present study, we demonstrated the role of JWA in cisplatin-induced DNA lesions and aquired cisplatin resistance in five cell-culture models: gastric epithelial cells GES-1, cisplatin-sensitive gastric cancer cell lines BGC823 and SGC7901, and the cisplatin-resistant gastric cancer cell lines BGC823/DDP and SGC7901/DDP. Our results indicated that JWA is required for DNA repair following cisplatin-induced double-strand breaks (DSBs) via XRCC1 in normal gastric epithelial cells. However, in gastric cancer cells, JWA enhanced cisplatin-induced cell death through regulation of DNA damage-induced apoptosis. The protein expression of JWA was significantly decreased in cisplatin-resistant cells and contributed to cisplatin resistance. Interestingly, as JWA upregulated XRCC1 expression in normal cells, JWA downregulated XRCC1 expression through promoting the degradation of XRCC1 in cisplatin-resistant gastric cancer cells. Furthermore, the negative regulation of JWA to XRCC1 was blocked due to the mutation of 518S/519T/523T residues of XRCC1, and indicating that the CK2 activated 518S/519T/523T phosphorylation is a key point in the regulation of JWA to XRCC1. In conclusion, we report for the first time that JWA regulated cisplatin-induced DNA damage and apoptosis through the

  10. Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells.

    PubMed

    Wang, Ri-Xiong; Liu, Hui; Xu, Li; Zhang, Hui; Zhou, Rui-Xiang

    2015-11-01

    The melatonin nuclear receptor is an orphan member of the nuclear receptor superfamily RZR/ROR, which consists of three subtypes (α, β and γ), suggesting that immunomodulatory and antitumor effects through the intracellular action of melatonin depend on nuclear signaling. In the present study, the biological mechanisms of melatonin were elucidated in association with the RZR/RORγ pathway in SGC-7901 human gastric cancer cells under hypoxia. Melatonin suppressed the activity of RZR/RORγ and SUMO-specific protease 1 (SENP1) signaling pathway, which is essential for stabilization of hypoxia‑inducible factor-1α (HIF‑1α) during hypoxia. Furthermore, melatonin inhibited the stability of HIF-1α in a time- and conce-ntration-dependent manner in SGC-7901 human gastric cancer cells during hypoxia. Consistently, siRNA-RZR/RORγ effectively blocked the expression of SENP1, HIF-1α and vascular endothelial growth factor (VEGF) production in SGC-7901 cells under hypoxia, suggesting the role of nuclear receptor RZR/RORγ in melatonin-inhibited HIF-1α and VEGF accumulation. Moreover, siRNA RZR/RORγ obviously antagonized to inhibit the action of the gastric cancer cell proliferation by melatonin. Our findings suggest that melatonin suppresses HIF-1α accumulation and VEGF generation via inhibition of melatonin nuclear receptor RZR/RORγ in SGC-7901 cells under hypoxia. PMID:26330273

  11. Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins.

    PubMed

    Girennavar, B; Jayaprakasha, G K; Patil, B S

    2007-10-01

    The cytochrome P450 enzyme family is the most abundant and responsible for the metabolism of more than 60% of currently marketed drugs and is considered central in many clinically important drug interactions. Seven different grapefruit and pummelo juices as well as 5 furocoumarins isolated from grapefruit juice were evaluated at different concentration on cytochrome P450 3A4 (CYP3A4), cytochrome P450 2C9 (CYP2C9), and cytochrome P450 2D6 (CYP2D6) isoenzyme activity. Grapefruit and pummelo juices were found to be potent inhibitors of cytochrome CYP3A4 and CYP2C9 isoenzymes at 25% concentration, while CYP2D6 is inhibited significantly low at all the tested concentration of juices (P < 0.05). Among the 5 furocoumarins tested, the inhibitory potency was in the order of paradisin A > dihydroxybergamottin > bergamottin > bergaptol > geranylcoumarin at 0.1 microM to 0.1 mM concentrations. The IC(50) value was lowest for paradisin A for CYP3A4 with 0.11 microM followed by DHB for CYP2C9 with 1.58 microM. PMID:17995595

  12. IDENTIFICATION AND URINARY EXCRETION OF METABOLITES OF 5-(HYDROXYMETHYL)-2-FURFURAL (HMF) IN HUMAN SUBJECTS FOLLOWING CONSUMPTION OF DRIED PLUMS OR DRIED PLUM JUICE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    5-(hydroxymethyl)-2-Furfural (HMF) is a major breakdown product occurring in solutions with high concentrations of fructose and glucose and is present in many fruit juices, in heat-sterilized parental solutions, and in baby cereals. The objective of this study was to characterize and identify for th...

  13. The effect of Aloe vera A. Berger (Liliaceae) on gastric acid secretion and acute gastric mucosal injury in rats.

    PubMed

    Yusuf, Sadiq; Agunu, Abdulkarim; Diana, Mshelia

    2004-07-01

    The effect of varying doses of ethanol extract of Aloe vera (Liliaceae) on acute gastric mucosal lesions induced by 0.6 M HCl and acid output was studied in the pylorus ligated and lumen perfuse rats, respectively. Acid secretion was determined by titration of the collected gastric juice to pH 7.0. Intraperitoneal injection of Aloe vera, dose dependently inhibited gastric acid secretion. The plant was more active as a gastroprotective agent at lower concentration against mucosal injury induced by 0.6 M HCl. In conclusion, Aloe vera is endowed with gastric acid anti-secretory activity and could protect the gastric mucosa at low concentrations against injurious agents. PMID:15182901

  14. Enhanced exposure of phosphatidylserine in human gastric carcinoma cells overexpressing the half-size ABC transporter BCRP (ABCG2).

    PubMed Central

    Woehlecke, Holger; Pohl, Antje; Alder-Baerens, Nele; Lage, Hermann; Herrmann, Andreas

    2003-01-01

    Members of the ABC (ATP-binding cassette) transporter super-family are emerging to be involved in lipid transport. In the present study, we studied the organization of phospholipids in the plasma membrane of EPG85-257 human gastric carcinoma cells overexpressing BCRP (breast cancer resistance protein, ABCG-2), a half-size transporter belonging to the ABCG subfamily. A significantly increased plasma membrane association of the PS (phosphatidylserine)-binding probe FITC-Annexin V in comparison with control cells was observed. Treatment of BCRP -overexpressing cells with the inhibitor Tryprostatin A decreased FITC-Annexin V binding almost to the control level. This suggests an enhanced exposure of PS in BCRP -overexpressing cells, which is dependent on functional BCRP. A role of BCRP in the transverse distribution of lipids in the plasma membrane is supported by the increased outward transport of the lipid analogue C6- N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-PS in BCRP -overexpressing EPG85-257 cells and MCF-7 human breast cancer cells. As shown for BCRP -overexpressing EPG85-257 cells, enhanced outward redistribution of the lipid analogue is inhibited by Tryprostatin A as well as by reduction of BCRP expression on transfection with an anti- BCRP -ribozyme. We also observed an enhanced outward transport of C6- N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-phosphatidylcholine in BCRP -overexpressing EPG85-257 cells, suggesting that the influence of BCRP on transverse lipid organization is not highly specific. PMID:12946267

  15. Expression of sphingosine kinase gene in the interactions between human gastric carcinoma cell and vascular endothelial cell

    PubMed Central

    Ren, Juan; Dong, Lei; Xu, Cang-Bao; Pan, Bo-Rong

    2002-01-01

    AIM: To study the interactions between human gastric carcinoma cell (HGCC) and human vascular endothelial cell (HVEC), and if the expression of sphingosine kinase (SPK) gene was involved in these interactions. METHODS: The specific inhibitor to SPK, dimethyl sphingosine (DMS), was added acting on HGCC and HVEC, then the cell proliferation was measured by MTT. The conditioned mediums (CMs) of HGCC and HVEC were prepared. The CM of one kind of cell was added to the other kind of cell, and the cell proliferation was measured by MTT. After the action of CM, the cellular expression of SPK gene in mRNA level was detected with in situ hybridization (ISH). RESULTS: DMS could almost completely inhibit the proliferation of HGCC and HVEC. The growth inhibitory rates could amount to 97.21%, 83.42%, respectively (P < 0.01). The CM of HGCC could stimulate the growth of HVEC (2.70 ± 0.01, P < 0.01) while the CM of HVEC could inhibit the growth of HGCC (52.97% ± 0.01%, P < 0.01). There was no significant change in the mRNA level of SPK gene in one kind of cell after the action of the CM of the other kind of cell. CONCLUSION: SPK plays a key role in regulating the proliferation of HGCC and HVEC. There exist complicated interactions between HGCC and HVEC. HGCC can significantly stimulate the growth of HVEC while HVEC can significantly inhibit the growth of HGCC. The expression of SPK gene is not involved in the interactions. PMID:12174364

  16. Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery.

    PubMed

    Sterl, Karin; Wang, Songyan; Oestricker, Lauren; Wallendorf, Michael J; Patterson, Bruce W; Reeds, Dominic N; Wice, Burton M

    2016-08-01

    Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of enteroendocrine cells located in the proximal small intestine. Many effects of Xen are mediated by neurotensin receptor-1 on neurons. In healthy humans with normal glucose tolerance (NGT), Xen administration causes diarrhea and inhibits postprandial glucagon-like peptide-1 (GLP-1) release but not insulin secretion. This study determines (i) if Xen has similar effects in humans with Roux-en-Y gastric bypass (RYGB) and (ii) whether neural pathways potentially mediate effects of Xen on glucose homeostasis. Eight females with RYGB and no history of type 2 diabetes received infusions with 0, 4 or 12pmol Xen/kg/min with liquid meals on separate occasions. Plasma glucose and gastrointestinal hormone levels were measured and insulin secretion rates calculated. Pancreatic polypeptide and neuropeptide Y levels were surrogate markers for parasympathetic input to islets and sympathetic tone, respectively. Responses were compared to those in well-matched non-surgical participants with NGT from our earlier study. Xen similarly increased pancreatic polypeptide and neuropeptide Y responses in patients with and without RYGB. In contrast, the ability of Xen to inhibit GLP-1 release and cause diarrhea was severely blunted in patients with RYGB. With RYGB, Xen had no statistically significant effect on glucose, insulin secretory, GLP-1, glucose-dependent insulinotropic peptide, and glucagon responses. However, insulin and glucose-dependent insulinotropic peptide secretion preceded GLP-1 release suggesting circulating GLP-1 does not mediate exaggerated insulin release after RYGB. Thus, Xen has unmasked neural circuits to the distal gut that inhibit GLP-1 secretion, cause diarrhea, and are altered by RYGB. PMID:27288245

  17. Allicin induces apoptosis of the MGC-803 human gastric carcinoma cell line through the p38 mitogen-activated protein kinase/caspase-3 signaling pathway.

    PubMed

    Zhang, Xuecheng; Zhu, Yong; Duan, Wei; Feng, Chen; He, Xuan

    2015-04-01

    Gastric cancer is one of the most common forms of malignant tumor, and the development of anti‑gastric cancer drugs with minimal toxicity is of clinical importance. Allicin is extracted from Allium sativum (garlic). Recent research, including clinical experiments, has shown that garlic has anticancer and tumor suppressive effects. The present study aimed to investigate the effects of allicin on the MGC‑803 human gastric carcinoma cell line, and to further explore the possible mechanisms of its tumor suppressor effects. The effects of allicin on the MGC‑803 cells were initially examined using an 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Hoechst staining was also used, in order to demonstrate the impact of allicin on MGC‑803 cell apoptosis. In addition, western blot analysis was performed to determine the abnormal expression levels of apoptosis‑associated proteins, following the treatment of MGC‑803 cells with allicin. Western blotting was also used to investigate the specific mechanisms underlying allicin‑induced apoptosis of MGC‑803 cells. The rate of MGC‑803 apoptosis was significantly increased, when the concentration and treatment time of allicin were increased. Hoechst staining detected an enhanced rate of apoptosis, and enhanced expression levels of cleaved caspase 3 were determined by western blotting. Notably, the protein expression levels of p38 were increased when the MGC‑803 cells were treated with allicin. The results of the present study suggest that allicin may inhibit the proliferation and induce the apoptosis of MGC‑803 human gastric carcinoma cells, and this may partially be achieved through the enhanced expression of p38 and cleaved caspase 3. PMID:25523417

  18. Gastric Emptying in the Elderly.

    PubMed

    Soenen, Stijn; Rayner, Chris K; Horowitz, Michael; Jones, Karen L

    2015-08-01

    Aging is characterized by a diminished homeostatic regulation of physiologic functions, including slowing of gastric emptying. Gastric and small intestinal motor and humoral mechanisms in humans are complex and highly variable: ingested food is stored, mixed with digestive enzymes, ground into small particles, and delivered as a liquefied form into the duodenum at a rate allowing efficient digestion and absorption. In healthy aging, motor function is well preserved whereas deficits in sensory function are more apparent. The effects of aging on gastric emptying are relevant to the absorption of oral medications and the regulation of appetite, postprandial glycemia, and blood pressure. PMID:26195094

  19. Use of lectin microarray to differentiate gastric cancer from gastric ulcer

    PubMed Central

    Huang, Wei-Li; Li, Yang-Guang; Lv, Yong-Chen; Guan, Xiao-Hui; Ji, Hui-Fan; Chi, Bao-Rong

    2014-01-01

    AIM: To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer. METHODS: Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed. Protein was extracted from the frozen tissues and stored. The lectins were dissolved in buffer, and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized. The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block. Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval. Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody. The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray, and then validated by lectin histochemistry. Data are presented as mean ± SD for the indicated number of independent experiments. RESULTS: The glycosylation level of gastric cancer was significantly higher than that in ulcer. In gastric cancer, most of the lectin binders showed positive signals and the intensity of the signals was stronger, whereas the opposite was the case for ulcers. Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin. For MPL and VVA, all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer, especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma. GalNAc bound to MPL showed a significant increase. A statistically significant association between MPL and gastric cancer was observed. As with MPL, there were significant differences in VVA staining between gastric cancer and ulcer. CONCLUSION: Lectin microarray can differentiate the different

  20. Immunotherapy in gastric cancer

    PubMed Central

    Matsueda, Satoko; Graham, David Y

    2014-01-01

    Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright. PMID:24587645

  1. Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway

    PubMed Central

    Yang, Zhi-Ping; Zhao, Yan; Huang, Fang; Chen, Jie; Yao, Ya-Hong; Li, Jun; Wu, Xiao-Nan

    2015-01-01

    AIM: To investigate the anti-tumor effects of equol in gastric cancer cells and the underlying molecular mechanisms. METHODS: MGC-803 cells were employed for in vitro experiments in this study. Cells were treated with control (vehicle, 0.1% DMSO) or equol under specified dose titration or time courses. Cell viability was examined by MTS assay, and the levels of Ki67 were determined by qPCR and immunofluorescent assay. Changes in cell cycle distribution and apoptosis rate were detected by flow cytometry. The mRNA expression of cyclin E1 and P21WAF1 was determined by qPCR. The protein levels of cell cycle regulators, PARP and Caspase-3 cleavage, and the phosphorylation of Akt were examined by Western blot. In addition, to characterize the role of elevated Akt activation in the anti-tumor effect exerted by equol, Ly294002, a PI3K/AKT pathway inhibitor, was used to pretreat MGC-803 cells. RESULTS: Equol (5, 10, 20, 40, or 80 μmol/L) inhibited viability of MGC-803 cells in a dose- and time-dependent manner after treatment for 24, 36, or 48 h (P < 0.05 for all). Equol also decreased the mRNA (P < 0.05 for 12 and 24 h treatment) and protein levels of Ki67. Equol treatment significantly induced G0/G1 cell cycle arrest (P < 0.05), with the percentages of G0/G1 cells of 32.23% ± 3.62%, 36.31% ± 0.24%, 45.58% ± 2.29%, and 65.10% ± 2.04% for equol (0, 10, 20, or 30 μmol/L) treatment, respectively, accompanied by a significant decrease of CDK2/4 (P < 0.05 for 24 and 48 h treatment) and Cyclin D1/Cyclin E1 (P < 0.05), and an increased level of P21WAF1 (P < 0.05). A marked increase of apoptosis was observed, with the percentages of apoptotic cells of 5.01% ± 0.91%, 14.57% ± 0.99%, 37.40% ± 0.58%, and 38.46% ± 2.01% for equol (0, 5, 10, or 20 μmol/L) treatment, respectively, accompanied by increased levels of cleaved PARP and caspase-3. In addition, we found that equol treatment increased P-Akt (Ser473 and Thr308) at 12 and 24 h compared to vehicle-treated control

  2. 21 CFR 146.185 - Pineapple juice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Pineapple juice. 146.185 Section 146.185 Food and....185 Pineapple juice. (a) Identity. (1) Pineapple juice is the juice, intended for direct consumption..., ripe pineapple (Ananas comosus L. Merrill). The juice may have been concentrated and...

  3. 21 CFR 146.185 - Pineapple juice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Pineapple juice. 146.185 Section 146.185 Food and....185 Pineapple juice. (a) Identity. (1) Pineapple juice is the juice, intended for direct consumption..., ripe pineapple (Ananas comosus L. Merrill). The juice may have been concentrated and...

  4. 21 CFR 146.185 - Pineapple juice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Pineapple juice. 146.185 Section 146.185 Food and....185 Pineapple juice. (a) Identity. (1) Pineapple juice is the juice, intended for direct consumption..., ripe pineapple (Ananas comosus L. Merrill). The juice may have been concentrated and...

  5. 21 CFR 146.185 - Pineapple juice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Pineapple juice. 146.185 Section 146.185 Food and....185 Pineapple juice. (a) Identity. (1) Pineapple juice is the juice, intended for direct consumption..., ripe pineapple (Ananas comosus L. Merrill). The juice may have been concentrated and...

  6. 21 CFR 146.185 - Pineapple juice.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Pineapple juice. 146.185 Section 146.185 Food and....185 Pineapple juice. (a) Identity. (1) Pineapple juice is the juice, intended for direct consumption..., ripe pineapple (Ananas comosus L. Merrill). The juice may have been concentrated and...

  7. Tumor Heterogeneity in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer Assessed by CT Texture Analysis: Association with Survival after Trastuzumab Treatment

    PubMed Central

    Yoon, Sung Hyun; Lee, Yoon Jin; Park, Jihoon; Kim, Jin Won; Lee, Hye Seung; Kim, Bohyoung

    2016-01-01

    Background Image texture analysis is a noninvasive technique for quantifying intratumoral heterogeneity, with derived texture features reported to be closely related to the treatment outcome of tumors. Gastric cancer is one of the most common tumors and the third leading cause of cancer-related deaths worldwide. Although trastuzumab is associated with a survival gain among patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, optimal patient selection is challenging. The purpose of this study was to determine whether CT texture features of HER2-positive gastric cancer were related to the survival rate after trastuzumab treatment. Methods and Findings Patients diagnosed with HER2-positive advanced gastric cancer from February 2007 to August 2014 were retrospectively selected. Using in-house built software, histogram features (kurtosis and skewness) and gray-level co-occurrence matrices (GLCM) features (angular second moment [ASM], contrast, entropy, variance, and correlation) were derived from the CT images of HER2-positive advanced gastric cancer in 26 patients. All the patients were followed up for more than 6 months, with no confirmed deaths. The patients were dichotomized into a good and poor survival group based on cutoff points of overall survival of 12 months. A receiver-operating characteristics (ROC) analysis was performed to test the ability of each texture parameter to identify the good survival group. Kaplan–Meier curves for patients above and below each threshold were constructed. Using a threshold of >265.8480 for contrast, >488.3150 for variance, and ≤0.1319×10−3. for correlation, all of the area under the ROC curves showed fair accuracy (>0.7). Kaplan–Meier analysis showed statistically significant survival difference between two groups according to optimal cutoff values of contrast, variance, correlation and ASM. However, as this study had a small number of patients, a further study with a larger

  8. Nitrosation of Nigerian medicinal plant preparations under 'chemical' and 'simulated' gastric conditions.

    PubMed

    Atawodi, S E; Lamorde, A G; Spiegelhalder, B; Preussmann, R

    1995-01-01

    Preparations of some tropical plants of medicinal importance, collected from the savannah vegetational belt of Nigeria, were nitrosated and analysed for volatile N-nitrosamines formed under chemical and simulated gastric conditions. N-Nitrosamines were determined on a Thermal Energy Analyser following gas chromatographic separation. Mean concentrations of N-nitrosodimethylamine (NDMA) in the range of 7 to 58 ppb and N-nitrosodiethylamine (NDEA) in the range of 23 to 26 ppb were formed in 31 and 7%, respectively, of the preparations using artificial gastric juice (simulated gastric condition). Under chemically optimal conditions, relatively high levels of NDMA (72-2008 ppb), NDEA (23-1528 ppb) and N-nitrosopyrrolidine (20-405 ppb) were formed in 100, 75 and 32% of the preparations, respectively; N-nitrosomethylethylamine, N-nitrosodibutylamine and N-nitrosomorpholine were formed in fewer preparations. These findings suggest that the endogenous formation of N-nitroso compounds from precursors present in medicinal plants might be another source of human exposure to environmental carcinogens in Nigeria and other developing countries. PMID:7821876

  9. Expression of human epidermal growth factor receptor 2 in primary and paired parenchymal recurrent and/or metastatic sites of gastric cancer.

    PubMed

    Shibata, Ryosuke; Nimura, Satoshi; Hashimoto, Tatsuya; Miyake, Toru; Takeno, Shinsuke; Hoshino, Seiichiro; Nabeshima, Kazuki; Yamashita, Yuichi

    2014-09-01

    Human epidermal growth factor receptor 2 (HER2) status has been evaluated at the primary site of gastric cancer when planning trastuzumab therapy against recurrent or metastatic lesions, since tissue sampling is uncommon in recurrent or metastatic lesions. This study retrospectively investigated the concordance of HER2 expression between primary and metastatic/recurrent lesions in order to confirm sensitivity to trastuzumab. The subjects comprised 37 patients with gastric adenocarcinoma who underwent tissue biopsy or surgical resection of the primary sites and 49 paired synchronous or metachronous metastatic sites (excluding lymph nodes) at the Fukuoka University Hospital between January, 1998 and September, 2012. All the samples were evaluated for HER2 status at the invasive front by immunohistochemistry (IHC). The HER2 positivity rate of the primary sites was ~16% and the concordance ratio of the IHC results between primary and paired metastatic sites was ~97%. No discordant cases regarding HER2 status were found among metachronous interventions for metastatic lesions. Only one patient exhibited conversion from a HER2-negative status in all the portions of the primary site to a positive status in a metastatic site. In conclusion, a high concordance ratio for HER2 status was observed between primary and paired metastatic lesions. Thus, employing trastuzumab therapy against metastatic or recurrent gastric cancer based on the HER2 status of the primary lesion appears to be an acceptable approach. PMID:25054041

  10. Quantitative ultrastructural analysis of the human parietal cell during acid inhibition and increase of gastric potential difference by glucagon.

    PubMed Central

    Ivey, K J; Tarnawski, A; Sherman, D; Krause, W J; Ackman, K; Burks, M; Hewett, J

    1980-01-01

    Glucagon inhibits gastric acid secretion and increases the negativity of gastric mucosal potential difference (PD) in man. To test the hypothesis that the increased negativity of PD after glucagon in man could be due to decreased parietal cell canalicular membrane area, a quantitative ultrastructural analysis was carried out. Four healthy volunteers with normal gastric mucosa were submitted to biopsy before and 20 minutes after intravenous injection of 2 mg glucagon (G). This time corresponded with the maximal change in PD and a decrease in gastric acid secretion. Canalicular and tubulovesicular membrane area of 80 parietal cells (40 cells before glucagon and 40 cells after glucagon) were quantified by the Loud morphometric method. After glucagon, the oxyntic cell canalicular membrane area was reduced by one-fourth (P less than 0.05), while tubulovesicular membrane area showed an increase (P less than 0.05) at the same time. The decrease in the area of parietal cell canalicular membrane caused by glucagon may in part be responsible for increased negativity of the gastric PD caused by this hormone. Images Fig. 2 PMID:7364316

  11. Other Helicobacters and gastric microbiota.

    PubMed

    De Witte, Chloë; Schulz, Christian; Smet, Annemieke; Malfertheiner, Peter; Haesebrouck, Freddy

    2016-09-01

    This article aimed to review the literature from 2015 dealing with gastric and enterohepatic non-Helicobacter pylori Helicobacter species (NHPH). A summary of the gastric microbiota interactions with H. pylori is also presented. An extensive number of studies were published during the last year and have led to a better understanding of the pathogenesis of infections with NHPH. These infections are increasingly reported in human patients, including infections with H. cinaedi, mainly characterized by severe bacteremia. Whole-genome sequencing appears to be the most reliable technique for identification of NHPH at species level. Presence of NHPH in laboratory animals may influence the outcome of experiments, making screening and eradication desirable. Vaccination based on UreB proteins or bacterial lysate with CCR4 antagonists as well as oral glutathione supplementation may be promising strategies to dampen the pathogenic effects associated with gastric NHPH infections. Several virulent factors such as outer membrane proteins, phospholipase C-gamma 2, Bak protein, and nickel-binding proteins are associated with colonization of the gastric mucosae and development of gastritis. The development of high-throughput sequencing has led to new insights in the gastric microbiota composition and its interaction with H. pylori. Alterations in the gastric microbiota caused by the pH-increasing effect of a H. pylori infection may increase the risk for gastric cancer. PMID:27531542

  12. Nicotinic Receptor Subtypes Mediating Relaxation of the Normal Human Clasp and Sling Fibers of the Upper Gastric Sphincter

    PubMed Central

    Ruggieri, Michael R.; Braverman, Alan S.; Vegesna, Anil K.; Miller, Larry S.

    2014-01-01

    Background Proper function of the gastroesophageal high pressure zone is essential for the integrity of the antireflux barrier. Mechanisms include tonic contractions as well as the decreased tone during transient lower esophageal sphincter relaxations. Methods We characterized the pharmacology of nicotinic receptors mediating relaxations of the human upper gastric sphincter (clasp and sling fibers) using currently available subtype selective nicotinic antagonists in tissue from organ transplant donors. Donors with either a history of gastroesophageal reflux disease or histologic evidence of Barrett’s esophagus were excluded. Clasp and sling muscle fiber strips were used for one of three paradigms. For paradigm 1, each strip was exposed to carbachol, washed, exposed to nicotinic antagonists then re-exposed to carbachol. In paradigm 2, strips were exposed to a near maximally effective bethanechol concentration then nicotine was added. Strips then were washed, exposed to nicotinic antagonists then re-exposed to bethanechol followed by nicotine. In paradigm 3, strips were exposed to bethanechol then choline or cytisine. Key Results 100 µM methyllycaconitine has no inhibitory effects on relaxations, eliminating homomeric α7 subtypes. Subtypes composed of α4β2 subunits are also eliminated because choline acts as an agonist and dihydro-beta-erythroidine is ineffective. Conclusions & Inferences Because mecamylamine blocks the relaxations and both choline and cytisine act as agonists in both clasp and sling fibers, the nicotinic receptor subtypes responsible for these relaxations could be composed of α3β4β2, α2β4 or α4β4 subunits. PMID:24827539

  13. Differential cytotoxic responses to low- and high-dose photodynamic therapy in human gastric and bladder cancer cells.

    PubMed

    Yoo, Je-Ok; Lim, Young-Cheol; Kim, Young-Myeong; Ha, Kwon-Soo

    2011-10-01

    Here, we present differential cytotoxic responses to two different doses of photodynamic therapies (PDTs; low-dose PDT [LDP] and high-dose PDT [HDP]) using a chlorin-based photosensitizer, DH-II-24, in human gastric and bladder cancer cells. Fluorescence-activated cell sorting analysis using Annexin V and propidium iodide (PI) showed that LDP induced apoptotic cell death, whereas HDP predominantly caused necrotic cell death. The differential cytotoxic responses to the two PDTs were further confirmed by a DiOC(6) and PI double-staining assay via confocal microscopy. LDP, but not HDP, activated caspase-3, which was inhibited by Z-VAD, Trolox, and BAPTA-AM. LDP and HDP demonstrated opposite effects on intracellular reactive oxygen species (ROS)/Ca(2+) signals; LDP stimulated intracellular ROS production, contributing to a transient increase of intracellular Ca(2+) , whereas HDP induced a massive and prolonged elevation of intracellular Ca(2+) responsible for the transient production of intracellular ROS. In addition, the two PDTs also increased in situ transglutaminase 2 (TG2) activity, with a higher stimulation by HDP, and this increase in activity was prevented by Trolox, BAPTA-AM, and TG2-siRNA. LDP-induced apoptotic cell death was strongly inhibited by Trolox and TG2-siRNA and moderately suppressed by BAPTA-AM. However, HDP-mediated necrotic cell death was partially inhibited by BAPTA-AM but not by TG2-siRNA. Thus, these results demonstrate that LDP and HDP induced apoptotic and necrotic cell death by differential signaling mechanisms involving intracellular Ca(2+) , ROS, and TG2. PMID:21678478

  14. Lipid peroxidation and coupled vitamin oxidation in simulated and human gastric fluid inhibited by dietary polyphenols: health implications.

    PubMed

    Gorelik, Shlomit; Lapidot, Tair; Shaham, Inbal; Granit, Rina; Ligumsky, Moshe; Kohen, Ron; Kanner, Joseph

    2005-05-01

    The Western diet contains large quantities of oxidized lipids, because a large proportion of the food in the diet is consumed in a fried, heated, processed, or stored form. We investigated the reaction that could occur in the acidic pH of the stomach and accelerate the generation of lipid hydroperoxides and cooxidation of dietary vitamins. To estimate the oxygen content in the stomach after food consumption, oxygen released from masticated bread (20 g) into deoxygenated water (100 mL) was measured. Under these conditions, the oxygen concentration rose by 250 microM and reached a full oxygen saturation. The present study demonstrated that heated red meat homogenized in human gastric fluid, at pH 3.0, generated hydroperoxides and malondialdehyde. The cross-reaction between free radicals produced during this reaction cooxidized vitamin E, beta-carotene, and vitamin C. Both lipid peroxidation and cooxidation of vitamin E and beta-carotene were inhibited at pH 3.0 by red wine polyphenols. Ascorbic acid (44 mg) at a concentration that represented the amount that could be ingested during a meal inhibited lipid peroxidation only slightly. Red wine polyphenols failed to prevent ascorbic acid oxidation significantly but, in conjunction with ascorbic acid, did inhibit lipid peroxidation. In the presence of catechin, a well-known polyphenol found in red wine, ascorbic acid at pH 3.0 works in a synergistic manner preventing lipid peroxidation and beta-carotene cooxidation. The present data may explain the major benefits to our health and the crucial role of consuming food products rich in dietary antioxidants such as fruits, vegetables, red wines, or green tea during the meal. PMID:15853378

  15. Effect of deoxycholic acid on Ca2+ movement, cell viability and apoptosis in human gastric cancer cells.

    PubMed

    Chien, Jau-Min; Chou, Chiang-Ting; Liang, Wei-Zhe; Cheng, Jin-Shiung; Chang, Hong-Tai; Tseng, Hui-Wen; Kuo, Soong-Yu; Kuo, Chun-Chi; Chen, Fu-An; Shieh, Pochuen; Ho, Chin-Man; Lin, Jia-Rong; Kuo, Daih-Huang; Jan, Chung-Ren

    2015-02-01

    Deoxycholic acid (DOA) is one of the secondary bile acids used as a mild detergent for the isolation of membrane associated proteins. This study examined whether the secondary bile acid, DOA, altered Ca(2+) movement, cell viability and apoptosis in SCM1 human gastric cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i. DOA-evoked [Ca(2+)]i rises concentration dependently. The response was reduced by removing extracellular Ca(2+). DOA-evoked Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (nifedipine, econazole and SKF96365), the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA) and the PKC inhibitor GF109203X. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) abolished DOA-evoked [Ca(2+)]i rises. Conversely, treatment with DOA abolished TG-evoked [Ca(2+)]i rises. Inhibition of phospholipase C with U73122 abolished DOA-evoked [Ca(2+)]i rises. At 100-500 μM, DOA decreased cell viability, which was not changed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). DOA between 100 and 300 μM also induced apoptosis. Collectively, in SCM1 cells, DOA-induced [Ca(2+)]i rises by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. DOA also caused Ca(2+)-independent apoptosis. PMID:25406855

  16. (-)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells.

    PubMed

    Xie, Jianhui; Lin, Zhixiu; Xian, Yanfang; Kong, Songzhi; Lai, Zhengquan; Ip, Siupo; Chen, Haiming; Guo, Huizhen; Su, Zuqing; Yang, Xiaobo; Xu, Yang; Su, Ziren

    2016-06-01

    (-)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions. PMID:27017292

  17. Identification of Novel Changes in Human Skeletal Muscle Proteome After Roux-en-Y Gastric Bypass Surgery.

    PubMed

    Campbell, Latoya E; Langlais, Paul R; Day, Samantha E; Coletta, Richard L; Benjamin, Tonya R; De Filippis, Elena Anna; Madura, James A; Mandarino, Lawrence J; Roust, Lori R; Coletta, Dawn K

    2016-09-01

    The mechanisms of metabolic improvements after Roux-en-Y gastric bypass (RYGB) surgery are not entirely clear. Therefore, the aim of our study was to investigate the role of obesity and RYGB on the human skeletal muscle proteome. Basal muscle biopsies were obtained from seven obese (BMI >40 kg/m(2)) female subjects (45.1 ± 3.6 years) pre- and 3 months post-RYGB, and euglycemic-hyperinsulinemic clamps were used to assess insulin sensitivity. Four age-matched (48.5 ± 4.7 years) lean (BMI <25 kg/m(2)) females served as control subjects. We performed quantitative mass spectrometry and microarray analyses on protein and RNA isolated from the muscle biopsies. Significant improvements in fasting plasma glucose (104.2 ± 7.8 vs. 86.7 ± 3.1 mg/dL) and BMI (42.1 ± 2.2 vs. 35.3 ± 1.8 kg/m(2)) were demonstrated in the pre- versus post-RYGB, both P < 0.05. Proteomic analysis identified 2,877 quantifiable proteins. Of these, 395 proteins were significantly altered in obesity before surgery, and 280 proteins differed significantly post-RYGB. Post-RYGB, 49 proteins were returned to normal levels after surgery. KEGG pathway analysis revealed a decreased abundance in ribosomal and oxidative phosphorylation proteins in obesity, and a normalization of ribosomal proteins post-RYGB. The transcriptomic data confirmed the normalization of the ribosomal proteins. Our results provide evidence that obesity and RYGB have a dynamic effect on the skeletal muscle proteome. PMID:27207528

  18. Reversal of cisplatin-induced delay in gastric emptying in rats by ginger (Zingiber officinale).

    PubMed

    Sharma, S S; Gupta, Y K

    1998-08-01

    Cisplatin causes nausea, vomiting and inhibition of gastric emptying. We have demonstrated the antiemetic effect of the acetone and ethanolic extract of ginger (Zingiber officinale, Roscoe, Zingiberacae) against cisplatin-induced emesis in dogs. In the present study, the acetone and 50% ethanolic extract of ginger in the doses of 100, 200 and 500 mg/kg (p.o.) and ginger juice, in the doses of 2 and 4 ml/kg, were investigated against cisplatin effect on gastric emptying in rats. All three ginger preparations significantly reversed cisplatin-induced delay in gastric emptying. The ginger juice and acetone extract were more effective than the 50% ethanolic extract. The reversal produced by the ginger acetone extract was similar to that caused by the 5-HT3 receptor antagonist ondansetron; however, ginger juice produced better reversal than ondansetron. Therefore, ginger, an antiemetic for cancer chemotherapy, may also be useful in improving the gastrointestinal side effects of cancer chemotherapy. PMID:9720611

  19. 13-acetoxysarcocrassolide induces apoptosis on human gastric carcinoma cells through mitochondria-related apoptotic pathways: p38/JNK activation and PI3K/AKT suppression.

    PubMed

    Su, Ching-Chyuan; Chen, Jeff Yi-Fu; Din, Zhong-Hao; Su, Jui-Hsin; Yang, Zih-Yan; Chen, Yi-Jen; Wang, Robert Y L; Wu, Yu-Jen

    2014-10-01

    13-acetoxysarcocrassolide (13-AC), an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells) gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ΔΨm, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor) and SP600125 (a JNK-specific inhibitor) led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways. PMID:25342459

  20. Diversity of the Gastric Microbiota in Thoroughbred Racehorses Having Gastric Ulcer.

    PubMed

    Dong, Hee-Jin; Ho, Hungwui; Hwang, Hyeshin; Kim, Yongbaek; Han, Janet; Lee, Inhyung; Cho, Seongbeom

    2016-04-28

    Equine gastric ulcer syndrome is one of the most frequently reported diseases in thoroughbred racehorses. Although several risk factors for the development of gastric ulcers have been widely studied, investigation of microbiological factors has been limited. In this study, the presence of Helicobacter spp. and the gastric microbial communities of thoroughbred racehorses having mild to severe gastric ulcers were investigated. Although Helicobacter spp. were not detected using culture and PCR techniques from 52 gastric biopsies and 52 fecal samples, the genomic sequences of H. pylori and H. ganmani were detected using nextgeneration sequencing techniques from 2 out of 10 representative gastric samples. The gastric microbiota of horses was mainly composed of Firmicutes (50.0%), Proteobacteria (18.7%), Bacteroidetes (14.4%), and Actinobacteria (9.7%), but the proportion of each phylum varied among samples. There was no major difference in microbial composition among samples having mild to severe gastric ulcers. Using phylogenetic analysis, three distinct clusters were observed, and one cluster differed from the other two clusters in the frequency of feeding, amount of water consumption, and type of bedding. To the best of our knowledge, this is the first study to investigate the gastric microbiota of thoroughbred racehorses having gastric ulcer and to evaluate the microbial diversity in relation to the severity of gastric ulcer and management factors. This study is important for further exploration of the gastric microbiota in racehorses and is ultimately applicable to improving animal and human health. PMID:26809803

  1. Identification of miRNomes in human stomach and gastric carcinoma reveals miR-133b/a-3p as therapeutic target for gastric cancer.

    PubMed

    Liu, Yanfang; Zhang, Xin; Zhang, Yujing; Hu, Zunqi; Yang, Dejun; Wang, Changming; Guo, Meng; Cai, Qingping

    2015-12-01

    Gastric cancer (GC) is the fourth most frequent malignant disease and the second leading cause of cancer mortality worldwide, but the molecular mechanisms underlying this clinically heterogeneous disease are complex and remain far from completely understood. Accumulating evidence suggests that abnormal microRNA (miRNA) expression is involved in tumorigenesis. However, their accurate expression pattern, function, and mechanism in GC remain unclear. Here, a heatmap analysis of the miRNomes was performed across TCGA datasets and the expression of miR-133 family was found to be consistently downregulated in GC. This result was confirmed in two GC cell lines and 20 pairs of primary GC tissues, and further study demonstrated that the downregulation of miR-133 was mainly mediated by histone modification within its promoter region. Importantly, restoration of miR-133b/a-3p expression could suppress GC cell proliferation and promote cell apoptosis by targeting anti-apoptotic molecules Mcl-1 and Bcl-xL. Consistent with in vitro results, reintroducing of miR-133b/a-3p expression significantly delayed tumor formation and reduced tumor size of GC cells in xenograft nude mice. And the inverse relationship between miR-133b/a-3p and its targets was verified in xenograft mice. Taken together, our findings suggest that miR-133b/a-3p acts as a tumor suppressor in GC by directly targeting Mcl-1 and Bcl-xL. Revealing novel mechanism for oncogene inhibition by miRNA-mediated pathways offers new avenues for GC treatment. PMID:26276722

  2. Models of gastric emptying.

    PubMed Central

    Stubbs, D F

    1977-01-01

    Some empirical and theoretical models of the emptying behaviour of the stomach are presented. The laws of Laplace, Hooke, and Poisseuille are used to derive a new model of gastric emptying. Published data on humans are used to test the model and evaluate empirical constants. It is shown that for meals with an initial volume of larger than or equal to 300 ml, the reciprocal of the cube root of the volume of meal remaining is proportional to the time the meal is in the stomach.For meals of initial volume of less than 300 ml the equation has to be corrected for the fact that the 'resting volume' of gastric contents is about 28 ml. The more exact formula is given in the text. As this model invokes no neural or hormonal factors, it is suggested that the gastric emptying response to the volume of a meal does not depend on these factors. The gastric emptying response to the composition of the meal does depend on such factors and a recent model of this process is used to evaluate an empirical constant. PMID:856678

  3. No difference in fecal levels of bacteria or short chain fatty acids in humans, when consuming fruit juice beverages containing fruit fiber, fruit polyphenols, and their combination.

    PubMed

    Wallace, Alison J; Eady, Sarah L; Hunter, Denise C; Skinner, Margot A; Huffman, Lee; Ansell, Juliet; Blatchford, Paul; Wohlers, Mark; Herath, Thanuja D; Hedderley, Duncan; Rosendale, Douglas; Stoklosinski, Halina; McGhie, Tony; Sun-Waterhouse, Dongxiao; Redman, Claire

    2015-01-01

    This study examined the effect of a Boysenberry beverage (750 mg polyphenols), an apple fiber beverage (7.5 g dietary fiber), and a Boysenberry plus apple fiber beverage (750 mg polyphenols plus 7.5 g dietary fiber) on gut health. Twenty-five individuals completed the study. The study was a placebo-controlled crossover study, where every individual consumed 1 of the 4 treatments in turn. Each treatment phase was 4-week long and was followed by a 2-week washout period. The trial beverages were 350 g taken in 2 doses every day (ie, 175 mL taken twice daily). The hypothesis for the study was that the combination of polyphenols and fiber would have a greater benefit on gut health than the placebo product or the fiber or polyphenols on their own. There were no differences in fecal levels of total bacteria, Bacteroides-Prevotella-Porphyromonas group, Bifidobacteriumspecies, Clostridium perfringens, or Lactobacillus species among any of the treatment groups. Fecal short chain fatty acid concentrations did not vary among treatment groups, although prostaglandin E2 concentrations were higher after consumption of the Boysenberry juice beverage. No significant differences were found in quantitative measures of gut health between the Boysenberry juice beverage, the apple fiber beverage, the Boysenberry juice plus apple fiber beverage, and the placebo beverage. PMID:25530011

  4. Inductions of Caspase-, MAPK- and ROS-dependent Apoptosis and Chemotherapeutic Effects Caused by an Ethanol Extract of Scutellaria barbata D. Don in Human Gastric Adenocarcinom Cells

    PubMed Central

    Shim, Ji Hwan; Gim, Huijin; Lee, Soojin

    2016-01-01

    Objectives: The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line). Methods: The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated. Results: ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti-proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin. Conclusion: ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria- , caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS-dependent pathway. PMID:27386146

  5. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells

    SciTech Connect

    Yi, Ho-Keun; Kim, Sun-Young; Hwang, Pyoung-Han; Kim, Chan-Young; Yang, Doo-Hyun; Oh, Youngman; Lee, Dae-Yeol . E-mail: leedy@chonbuk.ac.kr

    2005-05-13

    PTEN is a tumor suppressor gene that is frequently mutated or deleted in a variety of human cancers including human gastric cancer. PTEN functions primarily as a lipid phosphatase and plays a key role in the regulation of the PI3 kinase/Akt pathway, thereby modulating cell proliferation and cell survival. On the other hand, the IGF system plays an important role in cell proliferation and cell survival via the PI3 kinase/Akt and MAP kinase pathways in many cancer cells. To characterize the impact of PTEN on the IGF-IGFR-IGFBP axis in gastric cancer, we overexpressed PTEN using an adenovirus gene transfer system in human gastric adenocarcinoma cells, SNU-484 and SNU-663, which lack PTEN. Overexpression of PTEN inhibited serum-induced as well as IGF-I-induced cell proliferation as compared to control cells. PTEN overexpression resulted in a significant decrease in the expression of IGF-I, -II, and IGF-IR. Interestingly, amongst the six IGFBPs, only IGFBP-3 was upregulated by PTEN, whereas IGFBP-4 and -6 were reduced. The IGFBP-3 promoter activity assay and Western immunoblotting demonstrate that PTEN regulates IGFBP-3 at the transcriptional level. In addition, the PI3 kinase inhibitor, LY294002, upregulates IGFBP-3 expression but downregulates IGF-I and IGF-II, indicating that PTEN controls IGFBP-3 and IGFs by an Akt-dependent pathway. These findings suggest that PTEN may inhibit antiapoptotic IGF actions not only by blocking the IGF-IGFR-induced Akt activity, but also by regulating expression of components of the IGF system, in particular, upregulation of IGFBP-3, which is known to exert antiproliferative effects through IGF-dependent and IGF-independent mechanisms in cancer cells.

  6. Genetically engineered Newcastle disease virus expressing human interferon-λ1 induces apoptosis in gastric adenocarcinoma cells and modulates the Th1/Th2 immune response.

    PubMed

    Bu, Xuefeng; Li, Mi; Zhao, Yinghai; Liu, Sha; Wang, Mubin; Ge, Jinying; Bu, Zhigao; Yan, Yulan

    2016-09-01

    Interferon-λ1 (IFN-λ1), a recently discovered cytokine of the type III IFN family, was found to be a therapeutic alternative to type I IFN in terms of tumors. Using reverse genetics technique, we generated a recombinant Newcastle disease virus (NDV) LaSota strains named as human IFN‑λ1 recombinant adenovirus (rL-hIFN-λ1) containing human IFN-λ1 gene and further evaluated the expressing of IFN-λ1 in human gastric adenocarcinoma cell line SGC-7901 after infected with rL-hIFN-λ1 by using western blot analysis, RT-PCR and immunofluorescence analyses. IFN-λl specific receptor IFNLR1 was detected on several gastric tumor cell lines including SGC-7901 and AGS and on PBMCs.The expression of the IFN-λ1 proteins reached a high level detected in the supernatant harvested 24 h after the infection of tumor cells. The proliferation changes of SGC infected with rL-hIFN-λ1 was significantly inhibited compared with NDV-infected group. Apoptosis was significantly induced by rL-hIFN-λ1 in gastric cancer cells compared with NDV virus tested by TUNEL assay, western blot analysis and Annexin V flow cytometry. Due to the high dose of IFN-λ1 expressed by the rL-hIFN-λ1-infected tumor cells, the immune study showed that rL-hIFN-λ1 increased IFN-γ production [the T helper cell subtype 1 (Th1) response] and inhibited interleukin (IL)-13 production [the T helper cell subtype 2 (Th2) response] to change the Th1/Th2 response of tumor microenvironment which inhibited tumor growth. This study aims at building recombinant NDV rL-hIFN-λ1 as an efficient antitumor agent. PMID:27430534

  7. [Formation of volatile carcinogenic N-nitroso compounds from drugs under simulated human gastric conditions].

    PubMed

    Ziebarth, D

    1985-01-01

    41 commercial drugs approved for peroral application in the GDR, whose active agents contain N,N-dialkylamino groups in their chemical structures, have been investigated under simulated conditions of the human stomach. With the drugs containing aminophenazone, amitriptyline, doxycycline and oxytetracycline as active agents N-nitrosodimethylamine is formed as a result of nitrosation reactions. With the drugs containing clomiphene++, disulfiram, probenecid and a diethylamine-containing liquid hypnoticum, there occurred N-nitrosodiethylamine. In no case N-nitrosodi-n-propylamine or N-nitrosopiperidine were detectable. The isolated active agents amitriptyline, clomiphene++ and probenecid themselves proved not to be nitrosatable. The positive findings with these drugs were caused by not yet identified nitrosatable contaminants of these drugs. The quantitative determination of volatile N-nitroso compounds was done upon steam distillation by means of gas chromatograph and chemiluminescence detector. PMID:4062492

  8. [Gastric Acid].

    PubMed

    Ruíz Chávez, R

    1996-01-01

    Gastric acid, a product of parietal cells secretion, full fills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressive lyactivated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms. PMID:12165790

  9. Influence of orange juice in the levels and in the genotoxicity of iron and copper.

    PubMed

    Franke, Silvia Isabel Rech; Prá, Daniel; Giulian, Raquel; Dias, Johnny Ferraz; Yoneama, Maria Lúcia; da Silva, Juliana; Erdtmann, Bernardo; Henriques, João Antonio Pêgas

    2006-03-01

    World consumption of natural juices is increasing as a consequence of the human search for a healthier life. The juice production industry, especially for orange juice, is expanding in several countries and particularly in Brazil. Despite scientific data reporting beneficial properties derived from juice consumption, some components of juices have been identified as mutagenic or carcinogenic. Carcinogenic or genotoxic effects may be mediated by the interaction of juice components with transition metals or by sub-products of juice auto-oxidation. In this study, the mutagenic potential of orange juice and two metallic agents used in dietary supplementation, FeSO(4) and CuSO(4), were investigated using the comet assay in mouse blood cells (in vivo). Both metal compounds were genotoxic for eukaryotic cells after 24h treatment at the doses used. Significant damage repair was observed after 48h of treatment with the same compounds. Orange juice had a modulating effect on the action of metallic sulfates. In the case of iron treatment, the presence of the orange juice had a preventive, but not restorative, effect. On the other hand, in the case of copper treatment, the effects were both preventive and restorative. PIXE (particle induced X-ray emission) analysis indicated a positive correlation between DNA damage and the hepatic levels of iron and a negative correlation between whole blood copper and DNA damage. A negative correlation between hepatic iron and whole blood copper content was also seen in the treatment with both ferrous and cupric sulfates. PMID:16263202

  10. Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to promote invasive and metastatic potentials of human gastric cancer

    PubMed Central

    Guo, Zheng-Jun; Yang, Lang; Qian, Feng; Wang, Yan-Xia; Yu, Xi; Ji, Cheng-Dong; Cui, Wei; Xiang, Dong-Fang; Zhang, Xia; Zhang, Peng; Wang, Ji Ming; Cui, You-Hong; Bian, Xiu-Wu

    2016-01-01

    Runt-related transcription factor 2 (RUNX2) is a regulator of embryogenesis and development, but has also been implicated in the progression of certain human cancer. This study aimed to elucidate the role of RUNX2 in the invasive and metastatic potentials of human gastric cancer (GC) and the underlying mechanisms. We found that the levels of RUNX2 expression in gastric cancer tissues were correlated with the differentiation degrees, invasion depth and lymph node metastasis. COX regression analysis indicated that RUNX2 was an independent prognostic indicator for GC patients. RUNX2 significantly increased the migration and invasion ability of GC cells in vitro and enhanced the invasion and metastatic potential of GC cells in an orthotopic GC model of nude mice. Mechanistically, RUNX2 directly bound to the promoter region of the gene coding for the chemokine receptor CXCR4 to enhance its transcription. CXCR4 knockdown or treatment with AMD3100, a CXCR4 inhibitor, attenuated RUNX2-promoted invasion and metastasis. These results demonstrate that RUNX2 promotes the invasion and metastasis of human GC by transcriptionally up-regulating the chemokine receptor CXCR4. Therefore, the RUNX2-CXCR4 axis is a potential therapeutic target for GC. PMID:27007162

  11. Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas.

    PubMed

    Byun, Do-Sun; Cho, Kyucheol; Ryu, Byung-Kyu; Lee, Min-Goo; Kang, Min-Ju; Kim, Hak-Ryul; Chi, Sung-Gil

    2003-11-01

    events in gastric tumorigenesis. Collectively, our study suggests that epigenetic silencing of XAF1 by aberrant promoter methylation may contribute to the malignant progression of human gastric tumors. PMID:14612497

  12. Acute effect of oral sensation of sweetness on celiac artery blood flow and gastric myoelectrical activity in humans.

    PubMed

    Eguchi, Kohei; Kashima, Hideaki; Yokota, Akiko; Miura, Kohei; Yamaoka Endo, Masako; Hirano, Harutoyo; Tsuji, Toshio; Fukuba, Yoshiyuki

    2016-05-01

    Little is known about the effect of sweet taste stimulus on gastrointestinal motility and splanchnic blood flow. We examined whether gastric myoelectrical activity and/or celiac artery blood flow (CABF), which perfuses the stomach, are increased following an oral sensation of sweetness. After overnight fasting, 11 subjects rested for 5min and sipped, but not swallowed, one of four solutions for 1min. The fluid was then spat out, and subjects remained at rest for a further 10min. Fluids were approximately 15ml of three glucose solutions (4, 16, or 48%) or distilled water. Subjects completed trials with all four solutions in a randomized order. During each trial, gastric myoelectrical activity and CABF were continuously measured using electrogastrography and pulsed Doppler ultrasonography, respectively. None of the four solutions affected gastric myoelectrical activity. CABF was significantly increased after oral stimuli by all three glucose solutions, but not by water. There were no significant differences in the increments in CABF among the three glucose solutions. These results suggest that a sweet taste stimulus above a certain level of intensity acutely increases CABF during cephalic phase, without augmentation of gastric myoelectrical activity. PMID:26987409

  13. Fruit juice inhibition of uptake transport: a new type of food–drug interaction

    PubMed Central

    Bailey, David G

    2010-01-01

    A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume–effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice. PMID:21039758

  14. L-arginine/nitric oxide pathway modulates gastric motility and gallbladder emptying induced by erythromycin and liquid meal in humans.

    PubMed

    Fiorucci, S; Distrutti, E; Quintieri, A; Sarpi, L; Spirchez, Z; Gulla, N; Morelli, A

    1995-06-01

    There is recent evidence that nitric oxide, a soluble gas produced from L-arginine, is released by the smooth muscle cells and neurons of the gastrointestinal tract where it exerts a myorelaxive action. However, little is known about the effects nitric oxide has on gastric and gallbladder motility during the inter- and postprandial phases in man. We therefore investigated the effects 200 mg/kg/hr L-arginine exerts on the gastric and gallbladder motility induced by 2 mg/kg erythromycin or a liquid meal in 21 subjects in a double-blind, placebo-controlled study. Gastric and gallbladder emptying were evaluated by sonography. Fasting antral motility was expressed as antral motility index (MI). In fasting subjects, L-arginine administration determined a threefold increase in plasma nitrite concentrations. Administration of erythromycin caused a significant rise in the antral MI, which was inhibited by L-arginine (P < 0.05). Ingestion of a liquid meal also significantly increased antral MI, but it returned to basal values 90 min after the end of the meal. Although L-arginine administration caused a significant reduction in the antral MI (P < 0.05), it did not inhibit gastric emptying. L-Arginine provoked an approximately 40% increase in basal gallbladder volume, completely blocked erythromycin-induced emptying, and partially, but significantly, prevented the emptying induced by a liquid meal (P < 0.01). Our study suggests that nitric oxide may be implicated in the physiological modulation of gastric and gallbladder motility during the inter- and postprandial phases in man. PMID:7781462

  15. What gastric cancer proteomic studies show about gastric carcinogenesis?

    PubMed

    Leal, Mariana Ferreira; Wisnieski, Fernanda; de Oliveira Gigek, Carolina; do Santos, Leonardo Caires; Calcagno, Danielle Queiroz; Burbano, Rommel Rodriguez; Smith, Marilia Cardoso

    2016-08-01

    Gastric cancer is a complex, heterogeneous, and multistep disease. Over the past decades, several studies have aimed to determine the molecular factors that lead to gastric cancer development and progression. After completing the human genome sequencing, proteomic technologies have presented rapid progress. Differently from the relative static state of genome, the cell proteome is dynamic and changes in pathologic conditions. Proteomic approaches have been used to determine proteome profiles and identify differentially expressed proteins between groups of samples, such as neoplastic and nonneoplastic samples or between samples of different cancer subtypes or stages. Therefore, proteomic technologies are a useful tool toward improving the knowledge of gastric cancer molecular pathogenesis and the understanding of tumor heterogeneity. This review aimed to summarize the proteins or protein families that are frequently identified by using high-throughput screening methods and which thus may have a key role in gastric carcinogenesis. The increased knowledge of gastric carcinogenesis will clearly help in the development of new anticancer treatments. Although the studies are still in their infancy, the reviewed proteins may be useful for gastric cancer diagnosis, prognosis, and patient management. PMID:27126070

  16. Purification of a histamine H3 receptor negatively coupled to phosphoinositide turnover in the human gastric cell line HGT1.

    PubMed

    Cherifi, Y; Pigeon, C; Le Romancer, M; Bado, A; Reyl-Desmars, F; Lewin, M J

    1992-12-15

    The histamine H3 receptor agonist (R)alpha-methylhistamine (MeHA) inhibited, in a nanomolar range, basal and carbachol-stimulated inositol phosphate formation in the human gastric tumoral cell line HGT1-clone 6. The inhibition was reversed by micromolar concentrations of the histamine H3 receptor antagonist thioperamide and was sensitive to cholera or pertussis toxin treatment. Using [3H]N alpha-MeHA as specific tracer, high affinity binding sites were demonstrated with a Bmax of 54 +/- 3 fmol/mg of protein and a KD of either 0.61 +/- 0.04 or 2.2 +/- 0.4 nM, in the absence or presence of 50 microM GTP[gamma]S, respectively. The binding sites were solubilized by Triton X-100 and prepurified by gel chromatography. They were separated from the histamine H2 receptor sites by filtration through Sepharose-famotidine and finally retained on Sepharose-thioperamide. The purified sites concentrated in one single silver-stained protein band of 70 kDa in SDS-polyacrylamide gel electrophoresis. They specifically bound [3H]N alpha-MeHA with a KD of 1.6 +/- 0.1 nM and a Bmax of 12,000 +/- 750 pmol/mg of protein. This corresponds to a 90,225-fold purification over cell lysate and a purity degree of 84%. Binding was competitively displaced by N alpha-MeHA (IC50 = 5.8 +/- 0.7 nM), (R) alpha-MeHA (IC50 = 9 +/- 1 nM), and thioperamide (IC50 = 85 +/- 10 nM), but not by famotidine (H2 antagonist) or by mepyramine (H1 antagonist). These findings provide the first evidence for solubilization, purification, and molecular mass characterization of the histamine H3 receptor protein and for the negative coupling of this receptor phosphatidylinositol turnover through a so far unidentified G protein. PMID:1334091

  17. Gastric Carcinoids

    PubMed Central

    Borch, Kurt; Ahrén, Bo; Ahlman, Håkan; Falkmer, Sture; Granérus, Göran; Grimelius, Lars

    2005-01-01

    Objective: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. Background: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. Methods: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. Results: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. Conclusion: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids. PMID:15973103

  18. Development of a gastric retentive system as a sustained-release formulation of pranlukast hydrate and its subsequent in vivo verification in human studies.

    PubMed

    Sugihara, Hikaru; Matsui, Yuji; Takeuchi, Hirofumi; Wilding, Ian; Connor, Alyson; Abe, Kazuya; Nishiura, Akio

    2014-03-12

    Pranlukast hydrate was demonstrated in a human site-of-absorption study to have extremely poor absorption properties in the lower gastrointestinal tract. The ratios of AUC0-24 in the distal small bowel and colon compared to stomach delivery were approximately 1/7 and 1/70, respectively. As a consequence, a gastroretentive double-layered tablet formulation (gastric swelling system; GSS), consisting of a swelling layer and a drug release layer, was developed for once-daily dosing. To study the gastric retention of the optimized GSS, an in vivo gamma scintigraphic study was carried out in nine healthy volunteers. The transit profiles demonstrated that the GSS was retained in the stomach for more than 10h. The plasma profile was prolonged, especially following administration after an evening meal. The human data validated the design concept and suggest that GSS could be a promising approach for the development of sustained-release formulation for drugs with a limited absorption window in the upper small bowel. PMID:24316098

  19. Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway.

    PubMed

    Jing, Xiaoping; Cheng, Weiwei; Wang, Shiying; Li, Pin; He, Li

    2016-01-01

    Resveratrol is a polyphenolic compound that is extracted from Polygonum cuspidatum and is used in traditional Chinese medicine. Previous data have shown that resveratrol inhibits the growth of human gastric cancer. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and trypan blue assays showed that resveratrol significantly decreased the survival rate of MGC803 cells in a concentration- and time-dependent manner. Our flow cytometric analysis showed that resveratrol treatment arrested the cells at the G0/G1 phase of the cell cycle. Furthermore, western blotting demonstrated that resveratrol decreased the protein expression of phospho-glycogen synthase kinase 3β (p-GSK3β), cyclin D1, phospho-phosphatase and tensin homologue (p-PTEN), phospho-phosphatidylinositol 3'-OH kinase (p-PI3K), and phospho-protein kinase B (p-PKB/Akt). We also found that resveratrol inhibited the progression of the cell cycle in MGC803 cells by repressing p-PI3K and p-Akt expression. Meanwhile, resveratrol did not decrease the phosphorylation level of Akt when the PTEN gene expression was knocked down by an siRNA in the MGC803 cells. Taken together, these results suggest that resveratrol induced cell cycle arrest in human gastric cancer MGC803 cells by regulating the PTEN/PI3K/Akt signaling pathway. PMID:26530632

  20. Cochinchina momordica seed extract induces apoptosis and cell cycle arrest in human gastric cancer cells via PARP and p53 signal pathways.

    PubMed

    Liu, Hong-Rui; Meng, Lin-Yi; Lin, Zhi-Yan; Shen, Yang; Yu, Yun-Qiu; Zhu, Yi-Zhun

    2012-01-01

    Cochinchina momordica seed is the dried ripe seed of Momordica cochinchinensis (Lour.) Spreng, which is a kind of fruit and consumed for dietary as well as medicinal uses. In this study, using the human SGC7901 and MKN-28 gastric cancer cell lines, we explored the anticancer activity of the extract from cochinchina momordica seed (ECMS). ECMS inhibited significantly the survival rates of SGC7901 and MKN-28 cells in concentration- and time-dependent manners by MTT assay. The typical apoptotic morphological changes were observed by Hoechst 33258 dye assay after SGC7901 and MKN-28 cells were treated with ECMS for 48 h. Flow cytometry analysis revealed that ECMS-treatment blocked the cells at the S phase of cell cycle. Furthermore, the protein expression levels of poly (ADP-ribose) polymerase (PARP) and Bcl-2 were downregulated notably by ECMS-treatment, whereas those of Fas/Fas-associated death domain, p53, and Bax were upregulated in SGC7901 cells. ECMS dramatically enhanced the enzymatic activities of caspase-3 and caspase-9 whilst slightly increased caspase-8 activity. Taken together, this study demonstrated that ECMS exerted cytotoxic activities via PARP and p53 signal pathways in the human gastric cancer cells. PMID:23020228

  1. Effect of lapachol, a naphthaquinone isolated from Tectona grandis, on experimental peptic ulcer and gastric secretion.

    PubMed

    Goel, R K; Pathak, N K; Biswas, M; Pandey, V B; Sanyal, A K

    1987-02-01

    Lapachol, a naphthaquinone isolated from the roots of Tectona grandis given at a dose of 5 mg kg-1 p.o. twice daily for 3 days was found to have an anti-ulcerogenic effect on subsequently induced experimental gastric and duodenal ulcers in rats and guinea-pigs. Its action appears to be associated with an effect on the protein content of gastric juice, and it reversed aspirin-induced changes in peptic activity, protein and sialic acid. PMID:2882001

  2. 27 CFR 24.237 - Spirits added to juice or concentrated fruit juice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... concentrated fruit juice. 24.237 Section 24.237 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... concentrated fruit juice. Juice or concentrated fruit juice to which spirits have been added may not have an alcohol content exceeding 24 percent by volume. Although not considered to be wine, juice or...

  3. 27 CFR 24.237 - Spirits added to juice or concentrated fruit juice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... concentrated fruit juice. 24.237 Section 24.237 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... concentrated fruit juice. Juice or concentrated fruit juice to which spirits have been added may not have an alcohol content exceeding 24 percent by volume. Although not considered to be wine, juice or...

  4. 27 CFR 24.237 - Spirits added to juice or concentrated fruit juice.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... concentrated fruit juice. 24.237 Section 24.237 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... concentrated fruit juice. Juice or concentrated fruit juice to which spirits have been added may not have an... fruit juice to which spirits have been added will be included in the appropriate tax class of any...

  5. 27 CFR 24.237 - Spirits added to juice or concentrated fruit juice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... concentrated fruit juice. 24.237 Section 24.237 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... concentrated fruit juice. Juice or concentrated fruit juice to which spirits have been added may not have an... fruit juice to which spirits have been added will be included in the appropriate tax class of any...

  6. 27 CFR 24.237 - Spirits added to juice or concentrated fruit juice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... concentrated fruit juice. 24.237 Section 24.237 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... concentrated fruit juice. Juice or concentrated fruit juice to which spirits have been added may not have an... fruit juice to which spirits have been added will be included in the appropriate tax class of any...

  7. Bioavailability of Anthocyanins from Purple Carrot Juice: Effects of Acylation and Plant Matrix

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bioavailability of anthocyanins from juiced purple carrots was investigated through a human feeding study. Ten healthy adults consumed three doses of purple carrot juice, and bioavailability was assessed by appearance of anthocyanins in plasma for 8 hours after the dose. Doses were 50 mL, 150 mL, ...

  8. 21 CFR 146.114 - Lemon juice.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Lemon juice. 146.114 Section 146.114 Food and....114 Lemon juice. (a) Identity—(1) Description. Lemon juice is the unfermented juice, obtained by mechanical process, from sound, mature lemons (Citrus limon (L.) Burm. f.), from which seeds...

  9. 21 CFR 146.114 - Lemon juice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Lemon juice. 146.114 Section 146.114 Food and....114 Lemon juice. (a) Identity—(1) Description. Lemon juice is the unfermented juice, obtained by mechanical process, from sound, mature lemons (Citrus limon (L.) Burm. f.), from which seeds...

  10. 21 CFR 146.114 - Lemon juice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Lemon juice. 146.114 Section 146.114 Food and....114 Lemon juice. (a) Identity—(1) Description. Lemon juice is the unfermented juice, obtained by mechanical process, from sound, mature lemons (Citrus limon (L.) Burm. f.), from which seeds...

  11. 21 CFR 146.114 - Lemon juice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Lemon juice. 146.114 Section 146.114 Food and....114 Lemon juice. (a) Identity—(1) Description. Lemon juice is the unfermented juice, obtained by mechanical process, from sound, mature lemons (Citrus limon (L.) Burm. f.), from which seeds...

  12. 21 CFR 146.114 - Lemon juice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Lemon juice. 146.114 Section 146.114 Food and....114 Lemon juice. (a) Identity—(1) Description. Lemon juice is the unfermented juice, obtained by mechanical process, from sound, mature lemons (Citrus limon (L.) Burm. f.), from which seeds...

  13. 21 CFR 73.250 - Fruit juice.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Fruit juice. 73.250 Section 73.250 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.250 Fruit juice. (a) Identity. (1) The color additive fruit juice is prepared either by expressing the juice from mature varieties of fresh, edible fruits, or...

  14. 21 CFR 73.250 - Fruit juice.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Fruit juice. 73.250 Section 73.250 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.250 Fruit juice. (a) Identity. (1) The color additive fruit juice is prepared either by expressing the juice from mature varieties of fresh, edible fruits, or...

  15. 21 CFR 73.250 - Fruit juice.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Fruit juice. 73.250 Section 73.250 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.250 Fruit juice. (a) Identity. (1) The color additive fruit juice is prepared either by expressing the juice from mature varieties of fresh, edible fruits, or...

  16. 21 CFR 73.250 - Fruit juice.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Fruit juice. 73.250 Section 73.250 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.250 Fruit juice. (a) Identity. (1) The color additive fruit juice is prepared either by expressing the juice from mature varieties of fresh, edible fruits, or...

  17. 21 CFR 73.250 - Fruit juice.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Fruit juice. 73.250 Section 73.250 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.250 Fruit juice. (a) Identity. (1) The color additive fruit juice is prepared either by expressing the juice from mature varieties of fresh, edible fruits, or...

  18. Effects of ophiopogonin B on the proliferation and apoptosis of SGC‑7901 human gastric cancer cells.

    PubMed

    Zhang, Weiyue; Zhang, Qiaoyan; Jiang, Yiping; Li, Feng; Xin, Hailiang

    2016-06-01

    Ophiopogonin B (OP‑B) is a bioactive component of Radix Ophiopogon japonicus, which is often used in traditional Chinese medicine to treat cancer. The present study aimed to investigate the antitumor activity of OP‑B in gastric cancer. Cell Counting kit‑8, flow cytometry with Annexin V‑fluorescein isothiocyanate, Hoechst staining, mitochondrial membrane potential (MMP) detection, and reactive oxygen species (ROS) assay were used to detect the biological function of SGC‑7901 gastric cancer cells. The results demonstrated that high concentrations of OP‑B (5, 10 and 20 µmol/l) exerted potent antiproliferative effects on SGC‑7901 cells in a dose‑dependent manner. Furthermore, apoptotic rates were increased and cell morphology was altered following treatment with OP‑B. In addition, OP‑B‑induced apoptosis of SGC‑7901 cells was associated with loss of MMP and increased ROS generation. Western blotting indicated that treatment with OP‑B increased the protein expression levels of caspase‑3 and B‑cell lymphoma 2 (Bcl‑2)‑associated X protein, whereas the expression levels of Bcl‑2 and the phosphorylation levels of extracellular signal‑regulated kinases 1/2 and c‑Jun N‑terminal kinases 1/2 were decreased. These results suggest that OP‑B may be considered a potential inhibitor of gastric cancer progression, and may be used as an alternative compound for its treatment. PMID:27121658

  19. Helicobacter pylori alters the distribution of ZO-1 and p120ctn in primary human gastric epithelial cells.

    PubMed

    Krueger, Sabine; Hundertmark, Tanja; Kuester, Doerthe; Kalinski, Thomas; Peitz, Ulrich; Roessner, Albert

    2007-01-01

    Helicobacter pylori infection is related to the development of diverse gastric pathologies, possibly by affecting epithelial junctional complexes that define cell polarity and play an essential role in transepithelial transport and cell-cell adhesion. Using primary gastric epithelial cell cultures, effects of H. pylori on the expression and localization of tight/adherence junction proteins and the resulting morphological changes and migratory capabilities were studied under in vivo-like conditions. Gastric epithelial cells were isolated from biopsies or gastrectomies and maintained in Quantum286 on collagen I-coated culture dishes or cover-slips. Cell cultures were characterized and further analyzed by western blot and immunofluorescent staining for ZO-1, p120ctn, and H. pylori CagA. Morphological changes and migratory response were monitored by time-lapse digital image microscopy. ZO-1 and p120ctn protein expression levels remain unaffected by H. pylori infection. Immunocytochemistry on H. pylori-infected primary cell monolayers focally showed disruption of intercellular ZO-1 staining and accumulation of ZO-1 in small vesicles. H. pylori infection recruited non-phosphorylated p120ctn to perinuclear vesicles. The fraction of phosphorylated p120ctn increased and could be detected in the nucleus, at the cell membrane, and at the leading edge of migrating cells. These alterations, triggered by H. pylori infection, are associated with an elongation phenotype and increased migration. PMID:17509776

  20. Stage-specific Dietary Factors Associated with the Correa Multistep and Multifactorial Process of Human Gastric Carcinogenesis.

    PubMed

    Hsiung, Hui-Yin; Fann, Jean Ching-Yuan; Yen, Amy Ming-Fang; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Ku, Tsung-Ho; Liu, Tzeng-Ying; Chen, Hsiu-Hsi; Lin, Ming-Wei

    2016-01-01

    We assessed how individual dietary intakes act at different points in the chain of sequential stage of the Correa model in an area of Taiwan with high incidence of gastric cancer (GC). Using data on 2,201 participants in a two-stage screening for gastric neoplasia with pepsinogen test, we identified 154 superficial gastritis (SG), 32 atrophic gastritis (AG), 117 intestinal metaplasia (IM), and 22 GC. Effects of individual item-based and construct-based dietary variables aggregated by factor analysis on each stage of gastric neoplasm were assessed. Based on 1,211 subjects with complete information on serological test and dietary questionnaire, SG was associated with positive quartile trend for the intake of meat (trend test P = 0.0014) and the intake of fruits and leafy vegetables (trend test P = 0.0177), but with the negative trend for the intake of shrimp sauce (trend test P = 0.039). A significant positive association was noted between milk and AG (trend test P = 0.014) and IM (P = 0.0087). A positive association between seafood and IM was noted (P = 0.011). Frequent leafy vegetable intake based on individual item was inversely associated with GC (P = 0.0084), whereas frequent intake of meat showed a high positive association (P<0.001). Stage-specific dietary factors underpinning the Correa model were identified. PMID:27042805

  1. Gastric infarction following gastric bypass surgery

    PubMed Central

    Do, Patrick H; Kang, Young S; Cahill, Peter

    2016-01-01

    Gastric infarction is an extremely rare occurrence owing to the stomach’s extensive vascular supply. We report an unusual case of gastric infarction following gastric bypass surgery. We describe the imaging findings and discuss possible causes of this condition. PMID:27200168

  2. MiR-148a Functions as a Tumor Suppressor by Targeting CCK-BR via Inactivating STAT3 and Akt in Human Gastric Cancer

    PubMed Central

    Su, Liping; Li, Jianfang; Yu, Yingyan; Gu, Qinlong; Yan, Min; Zhu, Zhenggang; Liu, Bingya

    2016-01-01

    MicroRNAs (miRNAs) have been widely accepted as a class of gene expression regulators which post-translationally regulate protein expression. These small noncoding RNAs have been proved closely involved in the modulation of various pathobiological processes in cancer. In this research, we demonstrated that miR-148a expression was significantly down-regulated in gastric cancer tissues in comparison with the matched normal mucosal tissues, and its expression was statistically associated with lymph node metastasis. Ectopic expression of miR-148a inhibited tumor cell proliferation and migration in vitro, and inhibited tumor formation in vivo. Subsequently, we identified cholecystokinin B receptor (CCK-BR) as a direct target of miR-148a using western blot and luciferase activity assay. More importantly, siRNA-induced knockdown of CCK-BR elicited similar anti-oncogenic effects (decreased proliferation and migration) as those induced by enforced miR-148a expression. We also found that miR-148a-mediated anti-cancer effects are dependent on the inhibition of STAT3 and Akt activation, which subsequently regulates the pathways involved in cell proliferation and migration. Taken together, our results suggest that miR-148a serves as a tumor suppressor in human gastric carcinogenesis by targeting CCK-BR via inactivating STAT3 and Akt. PMID:27518872

  3. RAPID HEALING OF PEPTIC ULCERS IN PATIENTS RECEIVING FRESH CABBAGE JUICE

    PubMed Central

    Cheney, Garnett

    1949-01-01

    Thirteen patients with peptic ulcer were treated with fresh cabbage juice, which, experiments have indicated, contains an antipeptic ulcer factor. This factor (vitamin U) prevents the development of histamin-induced peptic ulcers in guinea pigs. The average crater healing time for seven of these patients who had duodenal ulcer was only 10.4 days, while the average time as reported in the literature, in 62 patients treated by standard therapy, was 37 days. The average crater healing time for six patients with gastric ulcer treated with cabbage juice was only 7.3 days, compared with 42 days, as reported in the literature, for six patients treated by standard therapy. The rapid healing of peptic ulcers observed radiologically and gastroscopically in 13 patients treated with fresh cabbage juice indicates that the anti-peptic ulcer dietary factor may play an important role in the genesis of peptic ulcer in man. ImagesFigure 2.Figure 3. PMID:18104715

  4. High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT

    PubMed Central

    Zhang, Jia; Yan, Yan; Yang, Ya; Wang, Li; Li, Min; Wang, Jizhao; Liu, Xu; Duan, Xiaoyi; Wang, Jiansheng

    2016-01-01

    Abstract Tumor-associated macrophages (TAMs) are associated with poor prognosis in numerous human cancers and play important roles in tumor progression. Epithelial-mesenchymal transition (EMT) contributes to invasion and metastasis in cancer. However, the associations between TAMs and EMT are not clear in gastric cancer (GC). The present study was designed to investigate the effects of TAMs on EMT in human GC. TAMs marker CD68 and EMT-related proteins were detected by immunohistochemistry (IHC) in human GC tissues and their clinical significance were evaluated. A high level of infiltration of TAMs was associated with aggressive characteristics of tumor and an independent poor prognostic factor in human GC tissues. Infiltration of TAMs was also associated with EMT-related proteins in human GC tissues. Our findings suggest that the high level of infiltration TAMs was associated with aggressive features of GC and is an independent poor prognostic factor in GC patients. TAMs are associated with EMT induction in human GC tissues. The level of TAMs infiltration may be used as a prognostic factor and even a therapeutic target in GC. PMID:26871785

  5. High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT.

    PubMed

    Zhang, Jia; Yan, Yan; Yang, Ya; Wang, Li; Li, Min; Wang, Jizhao; Liu, Xu; Duan, Xiaoyi; Wang, Jiansheng

    2016-02-01

    Tumor-associated macrophages (TAMs) are associated with poor prognosis in numerous human cancers and play important roles in tumor progression. Epithelial-mesenchymal transition (EMT) contributes to invasion and metastasis in cancer. However, the associations between TAMs and EMT are not clear in gastric cancer (GC). The present study was designed to investigate the effects of TAMs on EMT in human GC.TAMs marker CD68 and EMT-related proteins were detected by immunohistochemistry (IHC) in human GC tissues and their clinical significance were evaluated.A high level of infiltration of TAMs was associated with aggressive characteristics of tumor and an independent poor prognostic factor in human GC tissues. Infiltration of TAMs was also associated with EMT-related proteins in human GC tissues.Our findings suggest that the high level of infiltration TAMs was associated with aggressive features of GC and is an independent poor prognostic factor in GC patients. TAMs are associated with EMT induction in human GC tissues. The level of TAMs infiltration may be used as a prognostic factor and even a therapeutic target in GC. PMID:26871785

  6. The long non-coding RNA H19-derived miR-675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1

    SciTech Connect

    Zhuang, Ming; Gao, Wen; Xu, Jing; Wang, Ping; Shu, Yongqian

    2014-06-06

    Graphical abstract: - Highlights: • H19 regulates gastric cancer cell proliferation phenotype via miR-675. • MiR-675 modulates cell proliferation of gastric cancer cells by targeting tumor suppressor RUNX1. • The H19/miR-675/RUNX1 axis plays an important role in the tumorigenesis of gastric cancer. - Abstract: The lncRNA H19 has been recently shown to be upregulated and play important roles in gastric cancer tumorigenesis. However, the precise molecular mechanism of H19 and its mature product miR-675 in the carcinogenesis of gastric cancer remains unclear. In this study, we found that miR-675 was positively expressed with H19 and was a pivotal mediator in H19-induced gastric cancer cell growth promotion. Subsequently, the tumor suppressor Runt Domain Transcription Factor1 (RUNX1) was confirmed to be a direct target of miR-675 using a luciferase reporter assay and Western blotting analyses. A series of rescue assays indicated that RUNX1 mediated H19/miR-67-induced gastric cancer cell phenotypic changes. Moreover, the inverse relationship between the expression of RUNX1 and H19/miR-675 was also revealed in gastric cancer tissues and gastric cancer cell lines. Taken together, our study demonstrated that the novel pathway H19/miR-675/RUNX1 regulates gastric cancer development and may serve as a potential target for gastric cancer therapy.

  7. Identification of the Residue in Human CYP3A4 That Is Covalently Modified by Bergamottin and the Reactive Intermediate That Contributes to the Grapefruit Juice Effect

    PubMed Central

    Lin, Hsia-lien; Kenaan, Cesar

    2012-01-01

    Previous studies have demonstrated that bergamottin (BG), a component of grapefruit juice, is a mechanism-based inactivator of CYP3A4 and contributes, in part, to the grapefruit juice-drug interaction. Although the covalent binding of [14C]BG to the CYP3A4 apoprotein has been demonstrated by SDS-polyacrylamide gel electrophoresis, the identity of the modified amino acid residue and the reactive intermediate species of BG responsible for the inactivation have not been reported. In the present study, we show that inactivation of CYP3A4 by BG results in formation of a modified apoprotein-3A4 and a GSH conjugate, both exhibiting mass increases of 388 Da, which corresponds to the mass of 6′,7′-dihydroxybergamottin (DHBG), a metabolite of BG, plus one oxygen atom. To identify the adducted residue, BG-inactivated 3A4 was digested with trypsin, and the digests were then analyzed by liquid chromatography-tandem mass spectrometry (MS/MS). A mass shift of 388 Da was used for the SEQUEST database search, which revealed a mass increase of 388 Da for the peptide with the sequence 272LQLMIDSQNSK282, and MS/MS analysis of the adducted peptide demonstrated that Gln273 is the residue modified. Mutagenesis studies showed that the Gln273 to Val mutant was resistant to inactivation by BG and DHBG and did not generate two of the major metabolites of BG formed by 3A4 wild type. In conclusion, we have determined that the reactive intermediate, oxygenated DHBG, covalently binds to Gln273 and thereby contributes to the mechanism-based inactivation of CYP3A4 by BG. PMID:22344702

  8. Effect of inhibitors of Na+/H+-exchange and gastric H+/K+ ATPase on cell volume, intracellular pH and migration of human polymorphonuclear leucocytes

    PubMed Central

    Ritter, M; Schratzberger, P; Rossmann, H; Wöll, E; Seiler, K; Seidler, U; Reinisch, N; Kähler, C M; Zwierzina, H; Lang, H J; Lang, F; Paulmichl, M; Wiedermann, C J

    1998-01-01

    Stimulation of chemotaxis of human polymorphonuclear leucocytes (PMNs) with the chemoattractive peptide fMLP (N-formyl-Met-Leu-Phe) is paralleled by profound morphological and metabolic alterations like changes of intracellular pH (pHi) and cell shape. The present study was performed to investigate the interrelation of cell volume (CV) regulatory ion transport, pHi and migration of fMLP stimulated PMNs.Addition of fMLP to PMNs stimulated directed migration in Boyden chamber assays and was accompanied by rapid initial intracellular acidification and cell swelling.Inhibition of the Na+/H+ exchanger suppressed fMLP stimulated cell migration, accelerated the intracellular acidification and inhibited the fMLP-induced cell swelling.Step omission of extracellular Na+ caused intracellular acidification, which was accelerated by subsequent addition of gastric H+/K+ ATPase inhibitor SCH 28080, or by omission of extracellular K+ ions. In addition Na+ removal caused cell swelling, which was further enhanced by fMLP.H+/K+ATPase inhibitors omeprazole and SCH 28080 inhibited stimulated migration and blunted the fMLP-induced increase in CV.Increasing extracellular osmolarity by addition of mannitol to the extracellular solution caused cell shrinkage followed by regulatory volume increase, partially due to activation of the Na+/H+ exchanger. In fMLP-stimulated cells the CV increase was counteracted by simultaneous addition of mannitol. Under these conditions the fMLP stimulated migration was inhibited.The antibacterial activity of PMNs was not modified by Hoe 694 or omeprazole.Western analysis with a monoclonal anti gastric H+/K+ATPase β-subunit antibody detected a glycosylated 35 kD core protein in lysates of mouse and human gastric mucosa as well as in human PMNs.The results indicate that fMLP leads to cell swelling of PMNs due to activation of the Na+/H+ exchanger and a K+-dependent H+-extruding mechanism, presumably an H+/K+ ATPase. Inhibition of these ion transporters

  9. Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway

    PubMed Central

    Li, Jing; Shen, Lin; Lu, Fu-rong; Qin, You; Chen, Rui; Li, Jia; Li, Yan; Zhan, Han-zi; He, Yuan-qiao

    2012-01-01

    Aim: To investigate the effects and underlying mechanisms of plumbagin, a naphthoquinone derived from medicinal plant Plumbago zeylanica, on human gastric cancer (GC) cells. Methods: Human gastric cancer cell lines SGC-7901, MKN-28, and AGS were used. The cell viability was examined using CCK-8 viability assay. Cell proliferation rate was determined using both clonogenic assay and EdU incorporation assay. Apoptosis was detected via Annexin V/propidium iodide double-labeled flow cytometry. Western blotting was used to assess the expression of both NF-κB-regulated gene products and TNF-α-induced activation of p65, IκBα, and IKK. The intracellular location of NF-κB p65 was detected using confocal microscopy. Results: Plumbagin (2.5–40 μmol/L) concentration-dependently reduced the viability of the GC cells. The IC50 value of plumbagin in SGC-7901, MKN-28, and AGS cells was 19.12, 13.64, and 10.12 μmol/L, respectively. The compound (5–20 μmol/L) concentration-dependently induced apoptosis of SGC-7901 cells, and potentiated the sensitivity of SGC-7901 cells to chemotherapeutic agents TNF-αand cisplatin. The compound (10 μmol/L) downregulated the expression of NF-κB-regulated gene products, including IAP1, XIAP, Bcl-2, Bcl-xL, tumor factor (TF), and VEGF. In addition to inhibition of NF-κB p65 nuclear translocation, the compound also suppressed TNF-α-induced phosphorylation of p65 and IKK, and the degradation of IκBα. Conclusion: Plumbagin inhibits cell growth and potentiates apoptosis in human GC cells through the NF-κB pathway. PMID:22231395

  10. Determination of Zinc(II) Ions Released into Artificial Digestive Juices from Culinary-Medicinal Button Mushroom, Agaricus bisporus (Agaricomycetidae), Biomass of In Vitro Cultures Using an Anodic Stripping Voltammetry Method.

    PubMed

    Kala, Katarzyna; Muszynska, Bozena; Zajac, Magdalena; Krezalek, Remigiusz; Opoka, Wlodzimierz

    2016-01-01

    Zinc is one of those microelements that are essential for the proper functioning of the human body and must be supplemented in our food at a daily dose of 15 mg. It is well known that mushrooms accumulate elements; thus, in order to determine the extent of accumulation and the level of zinc released from mushrooms, in vitro cultures of Agaricus bisporus were established. The cultures were run on a modified Oddoux medium (a control culture) as well as on the same medium with the addition of zinc hydroaspartate (100 and 200 mg/L) and zinc sulfate (87.23 and 174.47 mg/L). These compounds were chosen to help estimate which form, organic or inorganic, results in a better assimilation of zinc(II) ions by biomass. As the next step, the level of zinc(II) ions released from the lyophilized biomass of in vitro cultures to the digestive juices, under thermal conditions of the human body (37°C), was determined. For this purpose, artificial digestive juices, imitating the composition of human digestive juices, were used. For determination of zinc(II) ions in the digestive tract, an anodic stripping voltammetry method was employed. The amount of zinc released into artificial saliva over 1 minute varied from 0.15 mg/100 g d.w. in the control culture to 2.35 mg/100 g d.w. in the biomass in the medium to which 200 mg/L zinc hydroaspartate had been added. Values were higher in gastric juice and depended on incubation time (2.66 to 30.63 mg/100 g d.w.). In intestinal juice, the highest value of the released zinc grew to 24.20 mg/100 g d.w. (biomass of A. bisporus in vitro cultures in medium with the addition of 200 mg/L zinc hydroaspartate). Total average amount of zinc released into artificial digestive juices was the highest (56.26 mg/100 g d.w.) from A. bisporus biomass of in vitro cultures in the medium to which 200 mg/L zinc hydroaspartate had been added. PMID:27279537

  11. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.

    PubMed

    Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Vrcic, Hrvoje; Sebecic, Bozidar

    2011-01-01

    Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, safe in inflammatory bowel disease clinical trials (GEPPPGKPADDAGLV, M.W. 1419, PL 14736) and wound healing, stable in human gastric juice and has no reported toxicity. We focused on BPC 157 as a therapy in peridontitis, esophagus, stomach, duodenum, intestine, liver and pancreas lesions. Particularly, it has a prominent effect on alcohol-lesions (i.e., acute, chronic) and NSAIDs-lesions (interestingly, BPC 157 both prevents and reverses adjuvant arthritis). In rat esophagitis and failed function of both lower esophageal sphincter (LES) and pyloric sphincters (PS), BPC 157 increased pressure in both sphincters till normal and reduced esophagitis. However, in healthy rats, it may decrease (PS) or increase (LES) the pressure in sphincters. It has strong angiogenic potential, it acts protectively on endothelium, prevents and reverses thrombus formation after abdominal aorta anastomosis, affects many central disturbances (i.e., dopamine and 5-HT system), the NO-system (either L-arginine and L-NAME effects), endothelin, acts as a free radical scavenger (counteracting CCl4-, paracetamol-, diclofenac-injuries) and exhibits neuroprotective properties. BPC 157 successfully heals the intestinal anastomosis, gastrocutaneous, duodenocutaneous and colocutaneous fistulas in rats, as well as interacting with the NO-system. Interestingly, the fistula closure was achieved even when the BPC 157 therapy was postponed for one month. In short-bowel syndrome escalating throughout 4 weeks, the constant weight gain above preoperative values started immediately with peroral and parental BPC 157 therapy and the villus height, crypth depth and muscle thickness (inner (circular) muscular layer) additionally increased. Thus, BPC 157 may improve gastrointestinal tract therapy. PMID:21548867

  12. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157.

    PubMed

    Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Aralica, Gorana; Safic, Hana; Suran, Jelena; Rak, Davor; Dzidic, Senka; Vrcic, Hrvoje; Sebecic, Bozidar

    2013-01-01

    Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, stable in human gastric juice, with no toxicity being reported. Recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and antiplatelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Robert's cytoprotection and BPC 157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAIDs use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (μg, ng/kg) in parenteral or peroral regimens. PMID:22950504

  13. 21 CFR 101.30 - Percentage juice declaration for foods purporting to be beverages that contain fruit or vegetable...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Percentage juice declaration for foods purporting to be beverages that contain fruit or vegetable juice. 101.30 Section 101.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION FOOD LABELING Specific Food Labeling...

  14. Protective effect of hydrogen sulfide against cold restraint stress-induced gastric mucosal injury in rats.

    PubMed

    Aboubakr, Esam M; Taye, Ashraf; El-Moselhy, Mohamed A; Hassan, Magdy K

    2013-12-01

    Hydrogen sulfide (H2S) is an endogenous gaseous mediator plays a potential role in modulating gastric inflammatory responses. However, its putative protective role remains to be defined. The present study aimed to evaluate role of the exogenously released and endogenously synthesized H2S in cold restraint stress (CRS)-induced oxidative gastric damage in rats. Rats were restrained, and maintained at 4 °C for 3 h. The H2S donor, sodium hydrosulfide (NaHS) (60 μmol/kg) was injected intraperitoneally (i.p.) before CRS. Our results revealed that NaHS pretreatment significantly attenuated ulcer index, free and total acid output, and pepsin activity in gastric juice along with decreased gastric mucosal carbonyl content and reactive oxygen species production. This was accompanied by increased gastric juice pH and mucin concentration in addition to restoring the deficits in the gastric reduced glutathione, catalase as well as superoxide dismutase enzyme activities. NaHS pretreatment markedly reduced the serum level of tumor necrosis factor (TNF-α) and myeloperoxidase activity compared to CRS-non-treated. Moreover, NaHS preadministration significantly abrogated the inflammatory and the deleterious responses of gastric mucosa in CRS. The protective effects of H2S were confirmed by gastric histopathological examination. However, pretreatment with the H2S-synthesizing enzyme, cystathionine-gamma-lyase inhibitor, beta-cyano-L-alanine (50 mg/kg, i.p.) reversed the gastroprotection afforded by the endogenous H2S. Collectively, our results suggest that H2S can protect rat gastric mucosa against CRS-induced gastric ulceration possibly through mechanisms that involve anti-oxidant and anti-inflammatory actions alongside enhancement of gastric mucosal barrier and reduction in acid secretory parameters. PMID:23812778

  15. Primary Gastric Chorioadenocarcinoma.

    PubMed

    Baraka, Bahaaeldin A; Al Kharusi, Suad S; Al Bahrani, Bassim J; Bhathagar, Gunmala

    2016-09-01

    Primary gastric chorioadenocarcinoma (PGC) is a rare and rapidly invasive tumor. Choriocarcinoma is usually known to be of endometrial origin and gestational; however, it has been reported in other extragenital organs, such as the gall bladder, prostate, lung, liver, and the gastrointestinal tract. Human chorionic gonadotropin related neoplasms of the stomach are seldom discussed in the literature. We report a case of PGC in a 56-year-old man treated with a standard non-gestational choriocarcinoma chemotherapy regimen, EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), with a complete response and good tolerability. PMID:27602194

  16. Primary Gastric Chorioadenocarcinoma

    PubMed Central

    Baraka, Bahaaeldin A.; Al Kharusi, Suad S.; Al Bahrani, Bassim J.; Bhathagar, Gunmala

    2016-01-01

    Primary gastric chorioadenocarcinoma (PGC) is a rare and rapidly invasive tumor. Choriocarcinoma is usually known to be of endometrial origin and gestational; however, it has been reported in other extragenital organs, such as the gall bladder, prostate, lung, liver, and the gastrointestinal tract. Human chorionic gonadotropin related neoplasms of the stomach are seldom discussed in the literature. We report a case of PGC in a 56-year-old man treated with a standard non-gestational choriocarcinoma chemotherapy regimen, EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), with a complete response and good tolerability. PMID:27602194

  17. Curcumin induced human gastric cancer BGC-823 cells apoptosis by ROS-mediated ASK1-MKK4-JNK stress signaling pathway.

    PubMed

    Liang, Tao; Zhang, Xiaojian; Xue, Wenhua; Zhao, Songfeng; Zhang, Xiang; Pei, Jianying

    2014-01-01

    The signaling mediated by stress-activated MAP kinases (MAPK), c-Jun N-terminal kinase (JNK) has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS) production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion) significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells. PMID:25198898

  18. Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway

    PubMed Central

    Liang, Tao; Zhang, Xiaojian; Xue, Wenhua; Zhao, Songfeng; Zhang, Xiang; Pei, Jianying

    2014-01-01

    The signaling mediated by stress-activated MAP kinases (MAPK), c-Jun N-terminal kinase (JNK) has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS) production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion) significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells. PMID:25198898

  19. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    2016-01-01

    Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer. PMID:27573782

  20. The Effect of Docetaxel (Taxotere®) on Human Gastric Cancer Cells Exhibiting Low-Dose Radiation Hypersensitivity

    PubMed Central

    Balcer-Kubiczek, Elizabeth K.; Attarpour, Mona; Wang, Jian Z.; Regine, William F.

    2008-01-01

    Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells in the G2/M phase of the cell cycle. Some previous studies suggested that HRS might result from the abrogation of the early G2 checkpoint arrest. First we tested whether HRS occurs in gastric cancer—derived cells, and whether pre-treatment of cells with low docetaxel concentrations can enhance the magnitude of HRS in gastric cancer cells. The results demonstrated HRS at ~0.3 Gy and the synergy between 0.3 Gy and docetaxel (3 nM for 24 h), and the additivity of other drug/dose combinations. The synergistic effect was associated with a significant docetaxel-induced G2 accumulation. Next, we evaluated in time-course experiments ATM kinase activity and proteins associated with the induction and maintenance of the early G2 checkpoint. The results of multi-immunoblot analysis demonstrate that HRS does not correlate with the ATM-dependent early G2 checkpoint arrest. We speculate that G2 checkpoint adaptation, a phenomenon associated with a prolonged cell cycle arrest, might be involved in HRS. Our results also suggest a new approach for the improvement the effectiveness of docetaxel-based radiotherapy using low doses per fraction. PMID:21892291

  1. Inhibition of peritoneal metastasis of human gastric cancer cells by dextran sulphate through the reduction in HIF-1α and ITGβ1 expression

    PubMed Central

    XU, YUANYI; JIN, XIU; HUANG, YUNNING; DONG, JIANDA; WANG, HONGHONG; WANG, XIAOFEI; CAO, XIANGMEI

    2016-01-01

    The aim of the present study was to investigate the effects of dextran sulphate (DS) on HIF-1α and integrin β1 (ITGβ1) expression in human gastric cancer cells, the correlation between HIF-1α and ITGβ1 expression and the influence of DS on the peritoneal metastasis of human gastric cancer cells. In in vitro experiments, BGC-823 cells in the experimental and control groups were administered DS and PBS, respectively, and exposed to hypoxic conditions for different periods. Immunocytochemistry, western blot and RT-PCR analyses were used to evaluate HIF-1α and ITGβ1 expression levels. In in vivo experiments, an animal model was established by injecting BGC-823 cells into nude mice. The experimental and control groups received DS and PBS injections, respectively. The mice were euthanized at different times, and the number of tumor nodules in the celiac implantation was recorded. Immunohistochemistry, RT-PCR and western blot analyses were used to detect HIF-1α and ITGβ1 expression in the tumor nodules of the greater omentum. The in vitro and in vivo results revealed that HIF-1α and ITGβ1 expression levels in the experimental group were significantly lower than those in the control group (P<0.05), and the expression levels of these factors were positively correlated with each other. The number of tumor nodules in the in vivo experiments was notably less in the experimental group than that noted in the control group (P<0.01). In conclusion, DS may act through inhibition of HIF-1α expression, which decreased ITGβ1 expression, consequently reducing tumor metastasis. PMID:27004522

  2. Transport of Zinc Oxide Nanoparticles in a Simulated Gastric Environment

    NASA Astrophysics Data System (ADS)

    Mayfield, Ryan T.

    Recent years have seen a growing interest in the use of many types of nano sized materials in the consumer sector. Potential uses include encapsulation of nutrients, providing antimicrobial activity, altering texture, or changing bioavailability of nutrients. Engineered nanoparticles (ENP) possess properties that are different than larger particles made of the same constituents. Properties such as solubility, aggregation state, and toxicity can all be changed as a function of size. The gastric environment is an important area for study of engineered nanoparticles because of the varied physical, chemical, and enzymatic processes that are prevalent there. These all have the potential to alter those properties of ENP that make them different from their bulk counterparts. The Human Gastric Simulator (HGS) is an advanced in vitro model that can be used to study many facets of digestion. The HGS consists of a plastic lining that acts as the stomach cavity with two sets of U-shaped arms on belts that provide the physical forces needed to replicate peristalsis. Altering the position of the arms or changing the speed of the motor which powers them allows one to tightly hone and replicate varied digestive conditions. Gastric juice, consisting of salts, enzymes, and acid levels which replicate physiological conditions, is introduced to the cavity at a controllable rate. The release of digested food from the lumen of simulated stomach is controlled by a peristaltic pump. The goal of the HGS is to accurately and repeatedly simulate human digestion. This study focused on introducing foods spiked with zinc oxide ENP and bulk zinc oxide into the HGS and then monitoring how the concentration of each changed at two locations in the HGS over a two hour period. The two locations chosen were the highest point in the lumen of the stomach, which represented the fundus, and a point just beyond the equivalent of the pylorus, which represented the antrum of the stomach. These points were

  3. Deacidification of cranberry juice by electrodialysis with bipolar membranes.

    PubMed

    Rozoy, Elodie; Boudesocque, Leslie; Bazinet, Laurent

    2015-01-21

    Cranberry is recognized for its many benefits on human health; however, its high acidity may be a limiting factor for its consumption. This study aimed to investigate the deacidification of cranberry juice using a two simultaneous step electrodialysis with bipolar membranes (EDBM) process. In step 1 (deacidification), during the 6 h treatment, the pH of the juice increased from 2.47 to 2.71 and a deacidification rate of 22.84% was obtained, whereas in step 2 (pH lowering) the pH of juice 2 was almost stable. Citric, quinic, and malic acid were extracted with a maximum of 25% and were mainly transferred to the KCl 2 fraction. A significant loss of anthocyanins in juice 2 (step 2) was observed, due to their oxidation by oxygen incorporated by the centrifugal pump. This also affected its coloration. The first step of the EDBM process was successful for cranberry juice deacidification and could be improved by increasing the number of membranes stacked. PMID:25537500

  4. Helicobacter pylori infection and gastric cancer.

    PubMed

    Sugiyama, Toshiro; Asaka, Masahiro

    2004-09-01

    Helicobacter pylori infection has an association with histological gastritis, gastric atrophy, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma in the stomach. Gastric cancer occurs in only a minority of infected individuals, however. Such clinical diversities are caused by variations of H. pylori pathogenicity, host susceptibility, environmental factors, and interactions of these factors. By three prospective epidemiological studies, the International Agency for Research on Cancer, World Health Organization (IARC/WHO) concluded in 1994 that H. pylori had a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. In addition, the Mongolian gerbil model with or without low-dose chemical carcinogens demonstrated that H. pylori infection could develop into gastric cancer. The experimental studies have elucidated that virulence factors of H. pylori have an interaction with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster and codes the type IV secretion machinery system, forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird morphology, growth factor-like effect. The other gene products are probably translocated into target cells and accelerate cellular proliferation and apoptosis. Understanding the molecular mechanism of the interaction between H. pylori and gastric epithelial cells will provide us with a new strategy for effective prevention of the development of gastric cancer induced by H. pylori infection. PMID:15449106

  5. Volunteer stratification is more relevant than technological treatment in orange juice flavanone bioavailability.

    PubMed

    Tomás-Navarro, María; Vallejo, Fernando; Sentandreu, Enrique; Navarro, Jose L; Tomás-Barberán, Francisco A

    2014-01-01

    The effect of two technological treatments on orange juice flavanone bioavailability in humans was assessed. Processing affected flavanone solubility and particle size of the cloud. Volunteers were stratified in high, medium, and low urinary excretion capabilities. Flavanones from high-pressure homogenized juice showed better absorption than those of conventional pasteurized juice in high excretors. These differences were not observed in medium and low excretors. High flavanone excretors took advantage of the high-pressure homogenization juice attributes (smaller cloud particle size) and showed an improved absorption/excretion. Stratification of the individuals by their excretion capability is more relevant than technological treatments in terms of flavanone bioavailability. This stratification should be considered in clinical studies with citrus juices and extracts as it could explain the large interindividual variability that is often observed. PMID:24344926

  6. Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

    SciTech Connect

    Batzri, S.; Catravas, G.

    1988-11-01

    We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig.

  7. Exploring the physiologic role of human gastroesophageal reflux by analyzing time‐series data from 24‐h gastric and esophageal pH recordings

    PubMed Central

    Lu, Luo; Mu, John C.; Sloan, Sheldon; Miner, Philip B.; Gardner, Jerry D.

    2014-01-01

    Abstract Our previous finding of a fractal pattern for gastric pH and esophageal pH plus the statistical association of sequential pH values for up to 2 h led to our hypothesis that the fractal pattern encodes information regarding gastric acidity and that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity by influencing gastric secretion of acid or bicarbonate. Under our hypothesis values of gastric pH should provide information regarding values of esophageal pH and vice versa. We used vector autoregression, a theory‐free set of inter‐related linear regressions used to measure relationships that can change over time, to analyze data from 24‐h recordings of gastric pH and esophageal pH. We found that in pH records from normal subjects, as well as from subjects with gastroesophageal reflux disease alone and after treatment with a proton pump inhibitor, gastric pH values provided important information regarding subsequent values of esophageal pH and values of esophageal pH provided important information regarding subsequent values of gastric pH. The ability of gastric pH and esophageal pH to provide information regarding subsequent values of each other was reduced in subjects with gastroesophageal reflux disease compared to normal subjects. Our findings are consistent with the hypothesis that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity, and that this ability is impaired in subjects with gastroesophageal reflux disease. PMID:25347850

  8. Effect of blending Huanglongbing (HLB) disease affected orange juice with juice from healthy oranges on flavor quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Huanglongbing, or citrus greening disease, has been a concern for the citrus industry as it progressively damages and ultimately kills citrus trees. While this disease does not affect human health, it is associated with bitter off-flavor for orange juice. The objective of this study was to determine...

  9. Characterization of molecular structural changes in pectin during juice cloud destabilization in frozen concentrated orange juice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pectin comprises one of the major components of cloud material in citrus juices. Juice cloud is a complex mixture of polysaccharides, proteins and lower molecular weight compounds that are responsible for the turbid appearance of citrus juices. The stability of juice cloud depends on a number of fac...

  10. How Much Cranberry Juice Is in Cranberry-Apple Juice? A General Chemistry Spectrophotometric Experiment

    ERIC Educational Resources Information Center

    Edionwe, Etinosa; Villarreal, John R.; Smith, K. Christopher

    2011-01-01

    A laboratory experiment that spectrophotometrically determines the percent of cranberry juice in cranberry-apple juice is described. The experiment involves recording an absorption spectrum of cranberry juice to determine the wavelength of maximum absorption, generating a calibration curve, and measuring the absorbance of cranberry-apple juice.…

  11. Bovine lactoferrin digested with human gastrointestinal enzymes inhibits replication of human echovirus 5 in cell culture.

    PubMed

    Furlund, Camilla B; Kristoffersen, Anja B; Devold, Tove G; Vegarud, Gerd E; Jonassen, Christine M

    2012-07-01

    Many infant formulas are enriched with lactoferrin (Lf) because of its claimed beneficial effects on health. Native bovine Lf (bLf) is known to inhibit in vitro replication of human enteroviruses, a group of pathogenic viruses that replicate in the gut as their primary infection site. On the basis of a model digestion and human gastrointestinal enzymes, we hypothesized that bLf could retain its antiviral properties against enterovirus in the gastrointestinal tract, either as an intact protein or through bioactive peptide fragments released by digestive enzymes. To test our hypothesis, bLf was digested with human gastric juice and duodenal juice in a 2-step in vitro digestion model. Two gastric pH levels and reduction conditions were used to simulate physiological conditions in adults and infants. The antiviral activity of native bLf and of the digested fractions was studied on echovirus 5 in vitro, using various assay conditions, addressing several mechanisms for replication inhibition. Both native and digested bLf fractions revealed a significant inhibitory effect, when added before or simultaneously with the virus onto the cells. Furthermore, a significant stronger sustained antiviral effect was observed when bLf was fully digested in the gastric phase with fast pH reduction to 2.5, compared with native bLf, suggesting the release of antiviral peptides from bLf during the human digestion process. In conclusion, this study demonstrates that bLf may have a role in the prevention of human gastrointestinal virus infection under physiological conditions and that food containing bLf may protect against infection in vivo. PMID:22901558

  12. Bioactive properties of commercialised pomegranate (Punica granatum) juice: antioxidant, antiproliferative and enzyme inhibiting activities.

    PubMed

    Les, Francisco; Prieto, Jose M; Arbonés-Mainar, Jose Miguel; Valero, Marta Sofía; López, Víctor

    2015-06-01

    Pomegranate juice and related products have long been used either in traditional medicine or as nutritional supplements claiming beneficial effects. Although there are several studies on this food plant, only a few studies have been performed with pomegranate juice or marketed products. The aim of this work is to evaluate the antioxidant effects of pomegranate juice on cellular models using hydrogen peroxide as an oxidizing agent or DPPH and superoxide radicals in cell free systems. The antiproliferative effects of the juice were measured on HeLa and PC-3 cells by the MTT assay and pharmacologically relevant enzymes (cyclooxygenases, xanthine oxidase, acetylcholinesterase and monoamine oxidase A) were selected for enzymatic inhibition assays. Pomegranate juice showed significant protective effects against hydrogen peroxide induced toxicity in the Artemia salina and HepG2 models; these effects may be attributed to radical scavenging properties of pomegranate as the juice was able to reduce DPPH and superoxide radicals. Moderate antiproliferative activities in HeLa and PC-3 cancer cells were observed. However, pomegranate juice was also able to inhibit COX-2 and MAO-A enzymes. This study reveals some mechanisms by which pomegranate juice may have interesting and beneficial effects in human health. PMID:26030005

  13. Detection thresholds for 2-isopropyl-3-methoxypyrazine in Concord and Niagara grape juice.

    PubMed

    Pickering, G J; Karthik, A; Inglis, D; Sears, M; Ker, K

    2008-08-01

    2-isopropyl-3-methoxypyrazine (IPMP) is the compound responsible for the off-flavor known as ladybug taint, which occurs when Harmnonia axyridis beetles become incorporated with the grapes during juice processing. It is also an important grape-derived component of juice flavor in some varieties. The main objective of this study was to determine the orthonasal (ON) and retronasal (RN) detection thresholds for IPMP in juice. The ASTM E679 ascending forced choice method of limits was used to determine detection thresholds for 26 individuals in Concord and Niagara juices. Group best estimate thresholds (BETs) averaged 0.93 ng/L and were 50% and 21% higher in Concord than in Niagara juices for ON and RN evaluation, respectively. Group BETs for IPMP (ng/L) for Concord were ON: 1.11; RN: 1.02 and for Niagara were ON: 0.74; RN: 0.84. Variation in individual detection thresholds was observed, although familiarity with ladybug taint was not associated with individual threshold values. We conclude that humans are very sensitive to IPMP in juice, and that detection thresholds are more strongly influenced by grape variety than evaluation mode. These results may assist juice producers in establishing tolerance levels for IPMP in juice affected by ladybug taint or derived from grapes of suboptimal ripeness. PMID:19241569

  14. Major furocoumarins in grapefruit juice I: levels and urinary metabolite(s).

    PubMed

    Messer, Anastasia; Nieborowski, Anna; Strasser, Christian; Lohr, Christiane; Schrenk, Dieter

    2011-12-01

    Furocoumarins are phototoxic and photogenotoxic natural plant constituents occurring in cosmetics, food and drugs. Grapefruit juice is considered as a major dietary source of furocoumarins although few is known about the variability of furocoumarins in grapefruit juice. We analyzed the major furocoumarins in eight commercial grapefruit juices and in freshly prepared juices made from pink grapefruit obtained from German retailers. Bergaptol was the major furocoumarin in commercial juices, followed by bergamottin and 6',7'-dihydroxy-bergamottin (DHB), whereas an inverse picture (DHB>bergamottin>bergaptol) was obtained in freshly prepared juices. Results from different batches of a single brand of commercial juice, purchased over a period of 7 months, revealed a variability of about 50% for the individual furocoumarins and the sum. In a study with healthy volunteers, consumption of 900 ml commercial grapefruit juice (containing 12.5mg bergaptol, 6.9 mg bergamottin, and 0.6 mg DHB) resulted in an average urinary excretion of 0.36 mg free plus 13.23 mg conjugated bergaptol within 6h. Other furocoumarins were not found in urine. Thus, other grapefruit furocoumarins were obviously converted in the human body, at least in part, into bergaptol excreted in urine, since the excreted amount of bergaptol exceeded the consumed one. PMID:21945416

  15. Role of pomegranate and citrus fruit juices in colon cancer prevention

    PubMed Central

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko

    2014-01-01

    Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Recent studies prove that though chemotherapeutic agents are being used for the treatment of colon cancer, they become non-effective when the cancer progresses to an invasive stage. Since consumption of certain dietary agents has been linked with various cancers, fruit juices have been investigated for their consistently protective effect against colon cancer. The unique biochemical composition of fruit juices is responsible for their anticancer properties. In this review, the chemo-preventive effect of fruit juices such as pomegranate and citrus juices against colon cancer are discussed. For this purpose, the bioavailability, in vitro and in vivo effects of these fruit juices on colorectal cancer are highlighted. Moreover, there is a scarcity of studies involving human trials to estimate the preventive nature of these juices against colon cancer. This review will support the need for more preclinical tests with these crude juices and their constituents in different colorectal cancer cell lines and also some epidemiological studies in order to have a better understanding and promote pomegranate and citrus juices as crusaders against colon cancer. PMID:24782614

  16. The effect of aloe emodin-encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells.

    PubMed

    Li, Kai-Ting; Duan, Qin-Qin; Chen, Qing; He, Juan-Wen; Tian, Si; Lin, Hai-Dan; Gao, Qing; Bai, Ding-Qun

    2016-02-01

    Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)-encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE-encapsulated nanoliposomes (nano-AE) were prepared by reverse evaporation method. Electron microscopy and nano-ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase-3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH-DA staining. Outcomes demonstrated that the nano-AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r-caspase-3 was transfected had higher protein expression of the caspase-3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano-AE-mediated PDT in an energy-dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm(2) ). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano-AE PDT group had quadrupled in SGC-7901 cells as early as 1 h after PDT, while it is similar to the group of nano-AE transfection and PDT. Nano-AE-mediated r-caspase-3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human

  17. DAG/PKCδ and IP3/Ca2+/CaMK IIβ Operate in Parallel to Each Other in PLCγ1-Driven Cell Proliferation and Migration of Human Gastric Adenocarcinoma Cells, through Akt/mTOR/S6 Pathway

    PubMed Central

    Dai, Lianzhi; Zhuang, Luhua; Zhang, Bingchang; Wang, Fen; Chen, Xiaolei; Xia, Chun; Zhang, Bing

    2015-01-01

    Phosphoinositide specific phospholipase Cγ (PLCγ) activates diacylglycerol (DAG)/protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)/Ca2+/calmodulin-dependent protein kinase II (CaMK II) axes to regulate import events in some cancer cells, including gastric adenocarcinoma cells. However, whether DAG/PKCδ and IP3/Ca2+/CaMK IIβ axes are simultaneously involved in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells and the underlying mechanism are not elucidated. Here, we investigated the role of DAG/PKCδ or CaMK IIβ in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells, using the BGC-823 cell line. The results indicated that the inhibition of PKCδ and CaMK IIβ could block cell proliferation and migration of BGC-823 cells as well as the effect of inhibiting PLCγ1, including the decrease of cell viability, the increase of apoptotic index, the down-regulation of matrix metalloproteinase (MMP) 9 expression level, and the decrease of cell migration rate. Both DAG/PKCδ and CaMK IIβ triggered protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/S6 pathway to regulate protein synthesis. The data indicate that DAG/PKCδ and IP3/Ca2+/CaMK IIβ operate in parallel to each other in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells through Akt/mTOR/S6 pathway, with important implication for validating PLCγ1 as a molecular biomarker in early gastric cancer diagnosis and disease surveillance. PMID:26633375

  18. Biphasic nature of gastric emptying.

    PubMed

    Siegel, J A; Urbain, J L; Adler, L P; Charkes, N D; Maurer, A H; Krevsky, B; Knight, L C; Fisher, R S; Malmud, L S

    1988-01-01

    The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the lag phase or the emptying rate of solids and liquids. We have evaluated the ability of a modified power exponential function to define the emptying parameters of two different solid meals. Dual labelled meals were administered to 24 normal volunteers. The subjects received meals consisting of either Tc-99m in vivo labelled chicken liver or Tc-99m-egg, which have different densities, and In-111-DTPA in water. The emptying curves were biphasic in nature. For solids, this represented an initial delay in emptying or lag phase followed by an equilibrium emptying phase characterised by a constant rate of emptying. The curves were analysed using a modified power exponential function of the form y(t) = 1-(1-e-kt)beta, where y(t) is the fractional meal retention at time t, k is the gastric emptying rate in min-1, and beta is the extrapolated y-intercept from the terminal portion of the curve. The length of the lag phase and half-emptying time increased with solid food density (31 +/- 8 min and 77.6 +/- 11.2 min for egg and 62 +/- 16 min and 94.1 +/- 14.2 min for chicken liver, respectively). After the lag phase, both solids had similar emptying rates, and these rates were identical to those of the liquids. In vitro experiments indicated that the egg meal disintegrated much more rapidly than the chicken liver under mechanical agitation in gastric juice, lending further support to the hypothesis that the initial lag in emptying of solid food is due to the processing of food into particles small enough to pass the pylorus. We conclude that the modified power exponential model permits characterisation of the biphasic

  19. Prevention of chemically induced urinary bladder cancers by naproxen: protocols to reduce gastric toxicity in humans do not alter preventive efficacy.

    PubMed

    Lubet, Ronald A; Scheiman, James M; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M Margaret; Boring, Daniel L; Steele, Vernon E; Grubbs, Clinton J

    2015-04-01

    The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2-specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder-specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN-treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN -: treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in palpable cancers in 27%, 22%, 19%, and 96% of rats (P < 0.01). Short-term naproxen treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols that should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials. PMID:25762530

  20. Essential role of Her3 in two signaling transduction patterns: Her2/Her3 and MET/Her3 in proliferation of human gastric cancer.

    PubMed

    Yun, Chen; Gang, Li; Rongmin, Gu; Xu, Wen; Xuezhi, Ming; Huanqiu, Chen

    2015-12-01

    Various receptor tyrosine kinase (RTK) pathways were verified in many cancers including gastric cancer (GC), We sought to investigate the expression of RTKs including Her2, Her3, and Met and their transduction patterns in human GC. Over-expression of Her2, Her3, and c-Met in human GC was verified by immunohistochemistry leading to constitutive activation of RTK signaling pathways. Combined RTKs expression was valuable indicators for poor prognosis of GC patients. Using ErbB2 specific inhibitor Lapatinib and c-Met specific inhibitor PHA-665752, we further demonstrated that this constitutive activation of RTK signaling is necessary for the survival of GC cells. However, various RTK pattern: Her3/Her2 and Met/Her3 were verified in the transduction growth stimulus from outside via both AKT and MAPK signaling. Moreover, the essential roles of Her3 in both two heterodimers were obtained which showed significantly attenuated growth effect due to Her3 knockdown both in vitro and in vivo. In conclusion, various molecular transduction patterns: Her2/Her3 and Met/Her3 were verified in human GC, and Her3 could serve as a potential target in GC treatment. PMID:25400108

  1. Apoptosis induction by glycoprotein isolated from Laminaria japonica is associated with down-regulation of telomerase activity and prostaglandin E2 synthesis in AGS human gastric cancer cells.

    PubMed

    Han, Min Ho; Kim, Gi Young; Moon, Sung-Kwon; Kim, Wun-Jae; Nam, Taek-Jeong; Choi, Yung Hyun

    2011-02-01

    Glycoprotein isolated from Laminaria japonica (LJGP) is known to exhibit significant cytotoxic activity against human cancer cells; however, the mechanisms of its cytoxicity are poorly understood. In this study, we investigated further possible mechanisms by which LJGP exerts its anti-cancer action in cultured human gastric carcinoma AGS cells. LJGP treatment of AGS cells resulted in inhibition of growth and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay, fluorescence microscopy, and flow cytometry analysis. The increase in apoptosis was associated with up-regulation of pro-apoptotic Bax expression, down-regulation of anti-apoptotic Bcl-2 and IAP family members, and activation of caspase-3 and -9. LJGP treatment markedly down-regulated the activity of telomerase and expression of human telomerase reverse transcriptase, a main determinant of telomerase enzymatic activity, with inhibition of Sp1 and c-Myc expression in a concentration-dependent manner. Furthermore, LJGP treatment also caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. These results provide important new insights into the possible molecular mechanisms of the anti-cancer activity of LJGP. PMID:21132266

  2. Stomach (Gastric) Cancer Screening

    MedlinePlus

    ... Treatment Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a ...

  3. Isoprenaline Induces Periostin Expression in Gastric Cancer

    PubMed Central

    Liu, Guo-Xiao; Xi, Hong-Qing; Sun, Xiao-Yan; Geng, Zhi-Jun; Yang, Shao-Wei; Lu, Yan-Jie

    2016-01-01

    Purpose Periostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression. Materials and Methods Normal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting. Results Periostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of α-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress-related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. Conclusion These findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. PMID:26996552

  4. Quantitative Assessment of Citric Acid in Lemon Juice, Lime Juice, and Commercially-Available Fruit Juice Products

    PubMed Central

    PENNISTON, KRISTINA L.; NAKADA, STEPHEN Y.; HOLMES, ROSS P.; ASSIMOS, DEAN G.

    2009-01-01

    Background and Purpose Knowledge of the citric acid content of beverages may be useful in nutrition therapy for calcium urolithiasis, especially among patients with hypocitraturia. Citrate is a naturally-occurring inhibitor of urinary crystallization; achieving therapeutic urinary citrate concentration is one clinical target in the medical management of calcium urolithiasis. When provided as fluids, beverages containing citric acid add to the total volume of urine, reducing its saturation of calcium and other crystals, and may enhance urinary citrate excretion. Information on the citric acid content of fruit juices and commercially-available formulations is not widely known. We evaluated the citric acid concentration of various fruit juices. Materials and Methods The citric acid content of 21 commercially-available juices and juice concentrates and the juice of three types of fruits was analyzed using ion chromatography. Results Lemon juice and lime juice are rich sources of citric acid, containing 1.44 and 1.38 g/oz, respectively. Lemon and lime juice concentrates contain 1.10 and 1.06 g/oz, respectively. The citric acid content of commercially available lemonade and other juice products varies widely, ranging from 0.03 to 0.22 g/oz. Conclusions Lemon and lime juice, both from the fresh fruit and from juice concentrates, provide more citric acid per liter than ready-to-consume grapefruit juice, ready-to-consume orange juice, and orange juice squeezed from the fruit. Ready-to-consume lemonade formulations and those requiring mixing with water contain ≤6 times the citric acid, on an ounce-for-ounce basis, of lemon and lime juice. PMID:18290732

  5. Ghrelin and gastric acid secretion

    PubMed Central

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-induced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion. PMID:19009648

  6. Cranberry Juice for Urinary Tract Infection?

    MedlinePlus

    ... medlineplus/news/fullstory_157466.html Cranberry Juice for Urinary Tract Infection? Specialist says grocery-store varieties aren't strong ... popular belief, cranberry juice does not cure a urinary tract infection, a doctor says. Many people drink cranberry juice ...

  7. Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model

    PubMed Central

    Moser, Sydney; Lim, Jongbin; Chegeni, Mohammad; Wightman, JoLynne D.; Hamaker, Bruce R.; Ferruzzi, Mario G.

    2016-01-01

    While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and α-glucosidase (6.2%–11.5% inhibition; p < 0.05). Separately, all GJ extracts (10–100 µM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%–38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%–15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%–38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal. PMID:27399765

  8. Garlic (Allium sativum) Fresh Juice Induces Apoptosis in Human Oral Squamous Cell Carcinoma: The Involvement of Caspase-3, Bax and Bcl-2

    PubMed Central

    Farhadi, Farrokh; Jahanpour, Salar; Hazem, Kameliya; Aghbali, Amirala; Baradran, Behzad; Vahid Pakdel, Seyyed Mahdi

    2015-01-01

    Background and aims. There is no report on the apoptotic impact of Allium sativum L.(Garlic) on the oral squamous cell carcinoma (KB); hence, this study was designed to survey the apoptotic effects of garlic fresh juice (GFJ) on the KB cells. Materials and methods. MTTassay (MicrocultureTetrazolium Assay) was carried out to evaluate the cytotoxicity of GFJ on KB cells. Furthermore, TUNEL(Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling)and DNA fragmentation tests were performed to determine if GFJ is able to induce apoptosis in KB cells. Also a standard kit was used to assess caspase-3 activity in KB cells. Also western blotting was employed to evaluate the effect of GFJ on Bax:Bcl-2 ratio. Results. Significant cytotoxic effects were observed for the minimum used concentration (1μg/mL) as calculated to be 77.97±2.3% for 24 h and 818±3.1% for 36h of incubation (P < 0.001). Furthermore, TUNEL and DNA fragmentation tests corroborated the apoptosis inducing activity of GFJ. Consistently, after treating KB cells with GFJ(1μg/mL), caspase-3 activity and Bax:Bcl-2 ratio were raised by 7.3±0.6 and (P <0.001) folds, respectively. Conclusion. The results of this study advanced that GFJ induces apoptosis in the KB cells through increasing caspase-3 activity and Bax:Bcl2 ratio which could be attributed to its organo-sulfurcomponents. PMID:26889365

  9. Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model.

    PubMed

    Moser, Sydney; Lim, Jongbin; Chegeni, Mohammad; Wightman, JoLynne D; Hamaker, Bruce R; Ferruzzi, Mario G

    2016-01-01

    While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and α-glucosidase (6.2%-11.5% inhibition; p < 0.05). Separately, all GJ extracts (10-100 µM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%-38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%-15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%-38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal. PMID:27399765

  10. Garlic ((Allium sativum)) Fresh Juice Induces Apoptosis in Human Oral Squamous Cell Carcinoma: The Involvement of Caspase-3, Bax and Bcl-2.

    PubMed

    Farhadi, Farrokh; Jahanpour, Salar; Hazem, Kameliya; Aghbali, Amirala; Baradran, Behzad; Vahid Pakdel, Seyyed Mahdi

    2015-01-01

    Background and aims. There is no report on the apoptotic impact of Allium sativum L.(Garlic) on the oral squamous cell carcinoma (KB); hence, this study was designed to survey the apoptotic effects of garlic fresh juice (GFJ) on the KB cells. Materials and methods. MTTassay (MicrocultureTetrazolium Assay) was carried out to evaluate the cytotoxicity of GFJ on KB cells. Furthermore, TUNEL(Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling)and DNA fragmentation tests were performed to determine if GFJ is able to induce apoptosis in KB cells. Also a standard kit was used to assess caspase-3 activity in KB cells. Also western blotting was employed to evaluate the effect of GFJ on Bax:Bcl-2 ratio. Results. Significant cytotoxic effects were observed for the minimum used concentration (1μg/mL) as calculated to be 77.97±2.3% for 24 h and 818±3.1% for 36h of incubation (P < 0.001). Furthermore, TUNEL and DNA fragmentation tests corroborated the apoptosis inducing activity of GFJ. Consistently, after treating KB cells with GFJ(1μg/mL), caspase-3 activity and Bax:Bcl-2 ratio were raised by 7.3±0.6 and (P <0.001) folds, respectively. Conclusion. The results of this study advanced that GFJ induces apoptosis in the KB cells through increasing caspase-3 activity and Bax:Bcl2 ratio which could be attributed to its organo-sulfurcomponents. PMID:26889365

  11. Survival of salmonellae in pasteurized, refrigerated calcium-fortified orange juice.

    PubMed

    Sharma, M; Beuchat, L R; Doyle, M P; Chen, J

    2001-09-01

    Studies were done to determine the survival of salmonellae in orange juice as affected by fortification with calcium. Four brands of commercially pasteurized orange juice fortified with calcium (350 mg/240-ml serving) and nonfortified juice were inoculated separately with three types of inocula: strains of Salmonella Muenchen (inoculum 1), serotypes of human and animal origin (inoculum 2), and isolates from raw produce- and juice-associated outbreaks (inoculum 3). Juice inoculated with populations of 6.6 to 7.0 log10 CFU of Salmonella per ml was held at 4 degrees C for up to 32 days. The number of cells of inoculum 1 that survived in juice fortified with calcium lactate/tricalcium phosphate (CaL/TCP) was significantly lower (P < or = 0.05) (2.80 log10 CFU/ml) than in nonfortified juice (3.50 log10 CFU/ml) after 32 days' storage. Death of salmonellae in inocula 1 and 2 was less in juice fortified with TCP (3.21 and 3.33 log10 CFU/ml, respectively) than in the nonfortified juice (3.75 and 4.15 log10 CFU/ml, respectively). During the 32-day storage period, populations in inocula 1 and 3 showed significantly less inactivation (2.62 and 3.12 log10 CFU/ml, respectively) in juice fortified with calcium citrate (CC) than in nonfortified juice (3.14 and 3.60 log10 CFU/ml, respectively). There were no significant differences in the survival of Salmonella in juice fortified with calcium citrate malate (CCM) and nonfortified juice. Polymerase chain reaction (PCR) typing of randomly selected Salmonella colonies revealed that Salmonella Heidelberg in inoculum 2 and Salmonella Baildon and Salmonella Poona in inoculum 3 were the most prevalent at the end of the 32-day storage period at 4 degrees C, suggesting that serotypes selected for use in inocula differed in tolerance to acidic environments. This study reveals that the form of calcium used to fortify orange juice may affect the survival of Salmonella. PMID:11563503

  12. miR-20a induces cisplatin resistance of a human gastric cancer cell line via targeting CYLD.

    PubMed

    Zhu, Mingxia; Zhou, Xin; Du, Yiping; Huang, Zebo; Zhu, Jun; Xu, Jing; Cheng, Gongming; Shu, Yongqian; Liu, Ping; Zhu, Wei; Wang, Tongshan

    2016-08-01

    The dysregulation of microRNAs (miRNAs) has been demonstrated to contribute to drug resistance of cancer cells, and sustained nuclear factor (NF)κB activation is also pivotal in tumor resistance to chemotherapy. In the present study, an essential role for miRNA (miR)-20a was identified in the regulation of gastric cancer (GC) chemoresistance. The expression level of miR‑20a was assayed by reverse transcription‑quantitative polymerase chain reaction. Additionally, 3-(4,5-dimethylthiazol-2‑yl)-2,5-diphenyltetrazolium bromide was used to detect the drug‑resistance phenotype changes of cancer cells associated with upregulation or downregulation of miR‑20a. Protein expression levelss were measured by western blotting and immunohistochemistry. Flow cytometry was used to detect cisplatin‑induced apoptosis. It was found that miR‑20a was markedly upregulated in GC plasma and tissue samples. Additionally, miR‑20a was upregulated in GC plasma and tissues from patients with cisplatin (DDP) resistance, and in the DPP‑resistant gastric cancer cell line (SGC7901/DDP). The expression of miR‑20a was inversely correlated with the expression of cylindromatosis (CYLD). Subsequently, the assessment of luciferase activity verified that CYLD was a direct target gene of miR‑20a. Treatment with miR‑20a inhibitor increased the protein expression of CYLD, downregulated the expression levels of p65, livin and survivin, and led to a higher proportion of apoptotic cells in the SGC7901/DDP cells. By contrast, ectopic expression of miR‑20a significantly repressed the expression of CYLD, upregulated the expression levels of p65, livin and survivin, and resulted in a decrease in the apoptosis induced by DDP in the SGC7901 cells. Taken together, the results of the present study suggested that miR‑20a directly repressed the expression of CYLD, leading to activation of the NFκB pathway and the downstream targets, livin and survivin, which potentially induced GC

  13. The warfarin–cranberry juice interaction revisited: A systematic in vitro–in vivo evaluation

    PubMed Central

    Ngo, Ngoc; Brantley, Scott J; Carrizosa, Daniel R; Kashuba, Angela DM; Dees, E Claire; Kroll, David J; Oberlies, Nicholas H; Paine, Mary F

    2010-01-01

    Background Cranberry products have been implicated in several case reports to enhance the anticoagulant effect of warfarin. The mechanism could involve inhibition of the hepatic CYP2C9-mediated metabolic clearance of warfarin by components in cranberry. Because dietary/natural substances vary substantially in bioactive ingredient composition, multiple cranberry products were evaluated in vitro before testing this hypothesis in vivo. Methods The inhibitory effects of five types of cranberry juices were compared with those of water on CYP2C9 activity (S-warfarin 7-hydroxylation) in human liver microsomes (HLM). The most potent juice was compared with water on S/R-warfarin pharmacokinetics in 16 healthy participants given a single dose of warfarin 10 mg. Results Only one juice inhibited S-warfarin 7-hydroxylation in HLM in a concentration-dependent manner (P < 0.05), from 20% to >95% at 0.05% to 0.5% juice (v/v), respectively. However, this juice had no effect on the geometric mean AUC0–∞ and terminal half-life of S/R-warfarin in human subjects. Conclusions A cranberry juice that inhibited warfarin metabolism in HLM had no effect on warfarin clearance in healthy participants. The lack of an in vitro–in vivo concordance likely reflects the fact that the site of warfarin metabolism (liver) is remote from the site of exposure to the inhibitory components in the cranberry juice (intestine). PMID:20865058

  14. Carotenoid bioaccessibility in pulp and fresh juice from carotenoid-rich sweet oranges and mandarins.

    PubMed

    Rodrigo, María Jesús; Cilla, Antonio; Barberá, Reyes; Zacarías, Lorenzo

    2015-06-01

    Citrus fruits are a good source of carotenoids for the human diet; however, comparative studies of carotenoids in different citrus food matrices are scarce. In this work the concentration and bioaccessibility of carotenoids in sweet oranges and mandarins with marked differences in carotenoid composition were evaluated in pulp and compared to those in fresh juice. The pulp and juice of the red-fleshed Cara Cara sweet orange variety was highly rich in carotenes (mainly lycopene and phytoene) compared to standard Navel orange, while β-cryptoxanthin and phytoene predominated in mandarins. Total carotenoid content in the pulp of the ordinary Navel orange and in the red-fleshed Cara Cara orange, as well as in the Clementine mandarin were higher than in the corresponding juices, although individual carotenoids were differentially affected by juice preparation. Bioaccessibility of the bioactive carotenoids (the ones described to be absorbed by humans) was greater in both pulp and juice of the carotenoid-rich Cara Cara orange compared to the Navel orange while increasing levels of β-cryptoxanthin were detected in the bioaccessible fractions of pulp and juice of mandarins postharvest stored at 12 °C compared to freshly-harvested fruits. Overall, results indicated that higher soluble bioactive carotenoids from citrus fruits and, consequently, potential nutritional and health benefits are obtained by the consumption of pulp with respect to fresh juice. PMID:25996796

  15. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects.

    PubMed

    Park, Soo-Jin; Yeo, Chang-Woo; Shim, Eon-Jeong; Kim, Hyunmi; Liu, Kwang-Hyeon; Shin, Jae-Gook; Shon, Ji-Hong

    2016-08-01

    Previous in vitro and in vivo investigations reported controversial results for the inhibitory potential of pomegranate on Cytochrome P450 (CYP) 3A activity. This study evaluated the effect of pomegranate juice on the disposition of simvastatin, a CYP3A4 substrate, and simvastatin acid, its active metabolite, compared with grapefruit juice in healthy subjects. A single oral pharmacokinetic study of 40 mg simvastatin was conducted as a three-way crossover (control, pomegranate, and grapefruit juices) in 12 healthy male subjects. The subjects took pomegranate or grapefruit juice three times per day for 3 days (900 mL/day) and on the third day, the pharmacokinetic study was executed. Blood samples were collected to 24 h post-dose and the pharmacokinetic parameters of simvastatin and simvastatin acid were compared among the study periods. In the period of grapefruit juice, the mean C max and AUCinf of simvastatin [the geometric mean ratio (90 % CI) 15.6 (11.6-21.0) and 9.1 (6.0-13.7)] were increased significantly when compared with the control period, whereas they were not significantly different in the period of pomegranate juice [C max and AUCinf 1.20 (0.89-1.62) and 1.29 (0.85-1.94)]. The mean C max and AUCinf of simvastatin acid were increased significantly after intake of grapefruit juice, but not pomegranate juice. These results suggest that pomegranate juice affects little on the disposition of simvastatin in humans. Pomegranate juice does not seem to have a clinically relevant inhibitory potential on CYP3A4 activity. PMID:25720525

  16. Malignant transformation of human gastric epithelium cells via reactive oxygen species production and Wnt/β-catenin pathway activation following 40-week exposure to ochratoxin A.

    PubMed

    Jia, Xin; Cui, Jinfeng; Meng, Xinxing; Xing, Lingxiao; Shen, Haitao; Wang, Juan; Liu, Jing; Wang, Yuan; Lian, Weiguang; Zhang, Xianghong

    2016-03-01

    Ochratoxin A (OTA), one of the most abundant food-contaminating mycotoxins, is a possible carcinogenic to humans. We previously demonstrated that OTA treatment induced oxidative damage in human gastric epithelium cells (GES-1) in vitro. In this study, we found that long-term OTA treatment could result in increased proliferation, migration, and invasion abilities of GES-1 cells and induce anchorage-independent growth of cells in soft agar. Inoculation of OTA-treated GES-1 cells resulted in the formation of tumor xenografts in Balb/c nude mice in vivo, confirming that long-term OTA treatment can induce the malignant transformation of GES-1 cells. In addition, we found that long-term OTA treatment induced oxidative stress and activated the Wnt/β-catenin pathway, including the nuclear transition of β-catenin and the upregulation of the downstream molecules of the pathway. Finally, pretreatment with the antioxidant N-acetyl-L-cysteine (NAC) inhibited ROS formation and activation of the Wnt pathway in OTA-transformed GES-1 cells, which decreased the tumor formation abilities of these cells after inoculation in nude mice. These findings suggest that long-term OTA exposure induces the malignant transformation of GES-1 cells via intracellular ROS production and activation of the Wnt/β-catenin signaling pathway. PMID:26721203

  17. Bioactive potential of Vitis labrusca L. grape juices from the Southern Region of Brazil: phenolic and elemental composition and effect on lipid peroxidation in healthy subjects.

    PubMed

    Toaldo, Isabela Maia; Cruz, Fernanda Alves; Alves, Tatiana de Lima; de Gois, Jefferson Santos; Borges, Daniel L G; Cunha, Heloisa Pamplona; da Silva, Edson Luiz; Bordignon-Luiz, Marilde T

    2015-04-15

    Grapes are rich in polyphenols with biologically active properties. Although the bioactive potential of grape constituents are frequently reported, the effects of Brazilian Vitis labrusca L. grape juices ingestion have not been demonstrated in humans. This study identified the phenolic and elemental composition of red and white grape juices and the effect of organic and conventional red grape juice consumption on lipid peroxidation in healthy individuals. Concentrations of anthocyanins, flavanols and phenolic acids and the in vitro antioxidant activity were significantly higher in the organic juice. The macro-elements K, Ca, Na and Mg were the most abundant minerals in all juices. The acute consumption of red grape juices promoted significant decrease of lipid peroxides in serum and TBARS levels in plasma. It is concluded that red V. labrusca L. grape juices produced in Southern Brazil showed lipid peroxidation inhibition abilities in healthy subjects, regardless of the cultivation system. PMID:25466055

  18. Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination

    PubMed Central

    Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

    2016-01-01

    Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination. PMID:26934957

  19. Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR using synthetic DNA fragments.

    PubMed Central

    Furuta, T; Kaneko, E; Suzuki, M; Arai, H; Futami, H

    1996-01-01

    Helicobacter pylori is closely related to upper gastrointestinal diseases, and the precise evaluation of H. pylori infection is necessary for the treatment of these diseases. The aim of the present study was to establish a method for the quantitative detection of H. pylori. We applied a competitive PCR method using various amounts of synthetic DNA fragments containing the same primer-binding and a subset of the same template sequences as the target competing for primer binding and amplification in order to quantify H. pylori in gastric mucus. The results obtained by this method were compared with the results of histological examination, the rapid urease test, bacterial culture, the [13C]urea breath test, and urea and ammonia measurements in gastric juice. As the quantity of H. pylori in gastric mucus increased, the rates of positivity of histological examination, the rapid urease test, and bacterial culture increased. The quantity of H. pylori in gastric mucus was also significantly correlated with the results of the [13C]urea breath test and was negatively correlated with the urea/ammonia ratio in gastric juice. The competitive PCR method provides an objective measure of the quantity of H. pylori and makes it possible to distinguish true negatives from false negatives due to incomplete PCR and true positives from false positives due to contamination. This method is very useful for the precise evaluation of gastric H. pylori infection. PMID:8880492

  20. Fentanyl inhibits the progression of human gastric carcinoma MGC-803 cells by modulating NF-κB-dependent gene expression in vivo

    PubMed Central

    HE, GUODONG; LI, LI; GUAN, ENJIAN; CHEN, JING; QIN, YI; XIE, YUBO

    2016-01-01

    Fentanyl is widely used to treat acute and chronic pain. Previous in vitro studies by the present authors demonstrated that fentanyl inhibits the progression of the MGC-803 human gastric carcinoma cell line by affecting apoptosis-related genes, including nuclear factor-kappa B (NF-κB) and phosphatase and tensin homolog. In the present study, the effects of fentanyl on NF-κB-dependent gene expression were investigated in vivo. Nude mice were inoculated with an MGC-803 cell suspension, and mice that developed subcutaneous tumors measuring >1.0×1.0 cm were selected for study. Mice were administered intraperitoneal injections of fentanyl (0.05 mg/kg, group F1; 0.1 mg/kg, group F2; 0.2 mg/kg, group F3; and 0.4 mg/kg, group F4) for 14 consecutive days. Non-fentanyl-treated mice (group C) and normal saline-treated mice (group N) served as the control groups. Tumor growth was monitored by calculating the time-shift of the growth curve. Morphological changes were also observed using microscopy. The expression of NF-κB, B-cell lymphoma-2 (Bcl-2), B-cell associated X protein (Bax), vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) in the subcutaneous tumor tissue was also analyzed by reverse transcription-polymerase chain reaction and western blot analysis, and confirmed using immunohistochemistry. The relative tumor volumes of groups F1, F2, F3 and F4 were significantly reduced compared with groups C and N. Furthermore, subcutaneous tumor cells exhibited nuclear swelling, chromatin condensation, reduced chromatin and nuclear fragmentation in the F1, F2, F3 and F4 groups. The number of NF-κB+, Bcl-2+, VEGF-A+ and MMP-9+ subcutaneous tumor cells was reduced, whereas the number of Bax+ cells was increased in the F1, F2, F3 and F4 groups. Additionally, in these groups, tumor expression of NF-κB, Bcl-2, VEGF-A and MMP-9 transcripts and proteins was downregulated, while Bax messenger RNA and protein expression levels were upregulated. The

  1. Cashew juice containing prebiotic oligosaccharides.

    PubMed

    da Silva, Isabel Moreira; Rabelo, Maria Cristiane; Rodrigues, Sueli

    2014-09-01

    The enzyme dextransucrase in a medium containing sucrose and an acceptor as substrate synthesizes prebiotics oligosaccharides. The cashew apple juice works as a source of acceptors because it is rich in glucose and fructose (enzyme acceptors). The use of cashew apple juice becomes interesting because it aims at harnessing the peduncle of the cashew that is wasted during the nut processing, which is the product of greater economic expression. The production of dextransucrase enzyme was done by fermentative process by inoculating the bacterium Leuconostoc mesenteroides NRRL B512F into a culture medium containing sucrose as the only carbon source. Thus, the aim of this work was the production of prebiotic oligosaccharides by enzymatic process with addition of the dextransucrase enzyme to the clarified cashew apple juice. Dextran yield was favored by the combination of low concentrations of sucrose and reducing sugars. The formation of oligosaccharides was favored by increasing the concentration of reducing sugars and by the combination of high concentrations of sucrose and reducing sugars, the highest concentration of oligosaccharides obtained was 104.73 g/L and the qualitative analysis showed that at concentrations of 25 g/L and 75 g/L of sucrose and reducing sugar, respectively, it is possible to obtain oligosaccharides of degree of polymerization up to 12. The juice containing prebiotic oligosaccharide is a potential new functional beverage. PMID:25190866

  2. Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence.

    PubMed

    Srinivas, Nuggehally R

    2013-12-01

    The area of fruit juice-drug interaction has received wide attention with numerous scientific and clinical investigations performed and reported for scores of drugs metabolized by CYP3A4/CYP2C9. While grapefruit juice has been extensively studied with respect to its drug-drug interaction potential, numerous other fruit juices such as cranberry juice, orange juice, grape juice, pineapple juice and pomegranate juice have also been investigated for its potential to show drug-drug interaction of any clinical relevance. This review focuses on establishing any relevance for clinical drug-drug interaction potential with pomegranate juice, which has been shown to produce therapeutic benefits over a wide range of disease areas. The review collates and evaluates relevant published in vitro, preclinical and clinical evidence of the potential of pomegranate juice to be a perpetrator in drug-drug interactions mediated by CYP3A4 and CYP2C9. In vitro and animal pharmacokinetic data support the possibility of CYP3A4/CYP2C9 inhibition by pomegranate juice; however, the human relevance for drug-drug interaction was not established based on the limited case studies. PMID:23673492

  3. Do calories or osmolality determine gastric emptying

    SciTech Connect

    Shafer, R.B.; Levine, A.S.; Marlette, J.M.; Morley, J.E.

    1984-01-01

    Recent animal studies suggest that gastric emptying is dependent on the caloric and osmotic content of the ingested food. These studies have involved intubation with infusion of liquid meals into the stomach. Scintigraphic methods, which are non-invasive and do not alter normal physiology, are now available for precise quantitation of gastric emptying. To study the role of calories and osmolality on gastric emptying, the authors employed a standardized /sup 99m/Tc-scrambled egg meal washed with 50 cc tap water in 10 normal human volunteers. A variety of simple and complex sugars, non-absorbable complex carbohydrate (polycose), medium chain fatty acid (MCFA) and gluten were dissolved in water and ingested with the test meal. Each subject acted as his own control. Coefficient of variation in control tests in each subject 12 weeks apart was 9.9%. Results showed that incremental glucose (25-66 gm) produced a linear increase in gastric emptying (T/2 control 50 +- 3, 25 gm 60 +- 3, 50 gm 79 +- 3 and 66 gm 102 +- 3 minutes). 25 gm fructose (T/2 59 +- 3 minutes) and 25 gm polycose (T/2 59 +- 3 minutes) had similar effects to glucose. 25 gm sucrose and 25 gm gluten did not significantly differ from controls. MCFA had an effect similar to 50 gm glucose - suggesting that calories are important in gastric emptying. However, 25 gm xylose markedly prolonged gastric emptying to 80 +- 5 minutes. The rank order for osmolality for substances tested MCFA = gluten < polycose < polycose < fructose < sucrose = glucose < xylose defined no relationship to gastric emptying. The authors' results suggest that neither calories nor osmolality alone determine gastric emptying. A specific food does not necessarily have the same effect on gastric emptying in different individuals.

  4. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism.

    PubMed

    Patti, Mary-Elizabeth; Houten, Sander M; Bianco, Antonio C; Bernier, Raquel; Larsen, P Reed; Holst, Jens J; Badman, Michael K; Maratos-Flier, Eleftheria; Mun, Edward C; Pihlajamaki, Jussi; Auwerx, Johan; Goldfine, Allison B

    2009-09-01

    The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 +/- 4.84 micromol/l) than in both overweight (3.59 +/- 1.95, P = 0.005, Ov) and severely obese (3.86 +/- 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P < 0.05). Total bile acids were inversely correlated with 2-h post-meal glucose (r = -0.59, P < 0.003) and fasting triglycerides (r = -0.40, P = 0.05), and positively correlated with adiponectin (r = -0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = -0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB. PMID:19360006

  5. Gastric protein hydrolysis of raw and roasted almonds in the growing pig.

    PubMed

    Bornhorst, Gail M; Drechsler, Krista C; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J; Singh, R Paul

    2016-11-15

    Gastric protein hydrolysis may influence gastric emptying rate and subsequent protein digestibility in the small intestine. This study examined the gastric hydrolysis of dietary protein from raw and roasted almonds in the growing pig as a model for the adult human. The gastric hydrolysis of almond proteins was quantified by performing tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent image analysis. There was an interaction between digestion time, stomach region, and almond type for gastric protein hydrolysis (p<0.05). Gastric emptying rate of protein was a significant (p<0.05) covariate in the gastric protein hydrolysis. In general, greater gastric protein hydrolysis was observed in raw almonds (compared to roasted almonds), hypothesized to be related to structural changes in almond proteins during roasting. Greater gastric protein hydrolysis was observed in the distal stomach (compared to the proximal stomach), likely related to the lower pH in the distal stomach. PMID:27283660

  6. Assessment of physicochemical characteristics and hygienic practices along the value chain of raw fruit juice vended in Dar es Salaam City, Tanzania.

    PubMed

    Nonga, Hezron E; Simforian, Edeltruds A; Ndabikunze, Bernadette K

    2014-10-01

    Fresh fruit juice is an essential component of human diet and there is considerable evidence of health and nutritional benefits. However, nature of the fruits used in juicing and unhygienic processes in the value chain may cause poor quality of juice. This cross- sectional study was conducted to assess physicochemical characteristics and hygienic practices along the value chain of raw fruit juice vended in Dar es Salaam, Tanzania. A total of 90 juice vendors were interviewed. Ninety juice samples were collected and analysed for physicochemical quality. The pH of juices ranged between 2.7 and 6.4, acidity 0.01% and 1.3% and, total soluble solids ranged between -1.5 and 18.04 °Brix. Most juices (67.8%) had -Brix levels below Codex recommended values classified as weak and watery. Juices were made of mango, passion, tamarind, sugar cane and mixture of these fruits sourced from open markets in the city. Water for washing of fruits and dilution of juices was from deep wells (53.3%) and taps (46.7%). About one third (37.8%) of the juice vendors didn't wash the fruits before juicing and 44.4% didn't boil water for juice dilution. Juice extraction was done by kitchen blenders, boiling in water and squeezing by simple machines. Juice pasteurization was not done. The majority of vendors (78.9%) stored juices in plastic buckets and juice was sold in glass cups, reused plastic bottles and disposable cups. Vending sites were restaurants, bus stands and along roadsides. The majority of premises (78.9%) were in unhygienic condition that likely encouraged or introduced contaminants to the juices. It is concluded that, the overall handling, preparation practices and physicochemical quality of raw fruit juices vended in Dare es Salaam City are poor. The government should educate the vendors on food safety and hygiene as well as enforcing regular monitoring of the quality of street fruit juices. PMID:26891516

  7. Antioxidant and antiproliferative activity of chokeberry juice phenolics during in vitro simulated digestion in the presence of food matrix.

    PubMed

    Stanisavljević, Nemanja; Samardžić, Jelena; Janković, Teodora; Šavikin, Katarina; Mojsin, Marija; Topalović, Vladanka; Stevanović, Milena

    2015-05-15

    Chokeberry juice was subjected to in vitro gastric digestion in the presence of food matrix in order to determine the changes in polyphenol content and antioxidant activity. Addition of food matrix immediately decreased the total phenolic content, anthocyanin content, DPPH scavenging activity as well as total reducing power by 36%, 90%, 45% and 44%, respectively. After in vitro digestion, total phenolic content, anthocyanin content and reducing power are slightly elevated, but they are still lower than in initial non-digested juice. The effect of digested juice on Caco-2 cells proliferation was also studied, and the reduction of proliferative rate by approximately 25% was determined. Our results suggested that although a large proportion of chokeberry phenolics undergo transformation during digestion they are still potent as antioxidant and antiproliferative agents. PMID:25577114

  8. Alanine with the Precipitate of Tomato Juice Administered to Rats Enhances the Reduction in Blood Ethanol Levels

    PubMed Central

    Oshima, Shunji; Shiiya, Sachie; Tokumaru, Yoshimi; Kanda, Tomomasa

    2015-01-01

    Delay in gastric emptying (GE) lowers the blood ethanol concentration (BEC) after alcohol administration. We previously demonstrated that water-insoluble fractions, mainly comprising dietary fiber derived from many types of botanical foods, possessed the ability to absorb ethanol-containing aqueous solutions. Furthermore, there was a significant correlation between the absorption of ethanol and lowering of BEC because of delay in GE. Here we identified dietary nutrients that synergize with the water-insoluble fraction of tomatoes to lower BEC in rats. Consequently, unlike tomato juice without alanine, tomato juice with 5.0% alanine decreased BEC depending on the delay in GE and mediated the ethanol-induced decrease in the spontaneous motor activity (an indicator of drunkenness). Our findings indicate that the synergism between tomato juice and alanine to reduce the absorption of ethanol was attributable to the effect of alanine on precipitates such as the water-insoluble fraction of tomatoes. PMID:26713162

  9. Alanine with the Precipitate of Tomato Juice Administered to Rats Enhances the Reduction in Blood Ethanol Levels.

    PubMed

    Oshima, Shunji; Shiiya, Sachie; Tokumaru, Yoshimi; Kanda, Tomomasa

    2015-01-01

    Delay in gastric emptying (GE) lowers the blood ethanol concentration (BEC) after alcohol administration. We previously demonstrated that water-insoluble fractions, mainly comprising dietary fiber derived from many types of botanical foods, possessed the ability to absorb ethanol-containing aqueous solutions. Furthermore, there was a significant correlation between the absorption of ethanol and lowering of BEC because of delay in GE. Here we identified dietary nutrients that synergize with the water-insoluble fraction of tomatoes to lower BEC in rats. Consequently, unlike tomato juice without alanine, tomato juice with 5.0% alanine decreased BEC depending on the delay in GE and mediated the ethanol-induced decrease in the spontaneous motor activity (an indicator of drunkenness). Our findings indicate that the synergism between tomato juice and alanine to reduce the absorption of ethanol was attributable to the effect of alanine on precipitates such as the water-insoluble fraction of tomatoes. PMID:26713162

  10. 21 CFR 146.152 - Orange juice with preservative.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Orange juice with preservative. 146.152 Section... Fruit Juices and Beverages § 146.152 Orange juice with preservative. (a) Orange juice with preservative... of orange juice for manufacturing as provided for in § 146.151, except that a preservative is...

  11. 21 CFR 146.152 - Orange juice with preservative.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Orange juice with preservative. 146.152 Section... Fruit Juices and Beverages § 146.152 Orange juice with preservative. (a) Orange juice with preservative... of orange juice for manufacturing as provided for in § 146.151, except that a preservative is...

  12. 21 CFR 146.152 - Orange juice with preservative.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Orange juice with preservative. 146.152 Section... Fruit Juices and Beverages § 146.152 Orange juice with preservative. (a) Orange juice with preservative... of orange juice for manufacturing as provided for in § 146.151, except that a preservative is...

  13. 21 CFR 146.152 - Orange juice with preservative.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Orange juice with preservative. 146.152 Section... Fruit Juices and Beverages § 146.152 Orange juice with preservative. (a) Orange juice with preservative... of orange juice for manufacturing as provided for in § 146.151, except that a preservative is...

  14. 21 CFR 146.152 - Orange juice with preservative.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Orange juice with preservative. 146.152 Section... Fruit Juices and Beverages § 146.152 Orange juice with preservative. (a) Orange juice with preservative... of orange juice for manufacturing as provided for in § 146.151, except that a preservative is...

  15. Insights regarding sensory evaluation of bitterness development in citrus juice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Delayed bitterness is a well-known phenomenon in citrus juice and has a negative impact on juice quality. Bitterness results when the tasteless limonoic acid A-ring lactone (LARL) in juice is converted to the bitter compound limonin after juicing. Citrus varieties that produce juice that becomes bit...

  16. Effect of Korean pear (Pyruspyrifolia cv. Shingo) juice on hangover severity following alcohol consumption.

    PubMed

    Lee, Ho-Sun; Isse, Toyohi; Kawamoto, Toshihiro; Baik, Hyun Wook; Park, Jong Y; Yang, Mihi

    2013-08-01

    Korean pear has been used as a traditional prophylactic agent for alcohol hangover. However, its mechanism was not investigated in human yet. Therefore, we performed a randomized single blind crossover trial with 14 healthy young men to examine effects of Korean pear juice on alcohol hangover. All subjects consumed 540 ml of spirits (alcohol conc. 20.1 v/v%) after 30 min from the intervention, i.e. placebo or Korean pear juice treatment. Blood and urine specimens were collected in time-courses (9 time-points for 15 h after alcohol consumption). The total and average of hangover severity were alleviated to 16% and 21% by Korean pear juice at 15 h after the alcohol consumption, respectively (ps<0.05). Particularly, 'trouble concentrating' was significantly improved by the pear juice treatment (p<0.05). Impaired memory, and sensitivity to light and sound were significantly improved by Korean pear juice among the subjects with ALDH2*1/*1 or ALDH2*1/*2 genotypes (ps<0.05) but not in the subjects with ALDH2*2/*2 genotype. In addition, the pear juice treatment lowered levels of blood alcohol (p<0.01). Therefore, Korean pear juice may alleviate alcohol-hangover and its detoxification of alcohol seems to be modified by the genetic variation of ALDH2. PMID:23587660

  17. Identification and characterization of a dipeptidyl peptidase IV inhibitor from aronia juice

    SciTech Connect

    Kozuka, Miyuki; Yamane, Takuya; Nakano, Yoshihisa; Nakagaki, Takenori; Ohkubo, Iwao; Ariga, Hiroyoshi

    2015-09-25

    Aronia berries have many potential effects on health, including an antioxidant effect, effect for antimutagenesis, hepatoprotection and cardioprotection, an antidiabetic effect and inhibition of cancer cell proliferation. Previous human studies have shown that aronia juice may be useful for treatment of obesity disorders. In this study, we found that aronia juice has an inhibitory effect against dipeptidyl peptidase IV (DPP IV) (EC 3.4.14.5). DPP IV is a peptidase that cleaves the N-terminal region of incretins such as glucagon-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Inactivation of incretins by DPP IV induces reduction of insulin secretion. Furthermore, we identified that cyanidin 3, 5-diglucoside as the DPP IV inhibitor in aronia juice. DPP IV was inhibited more strongly by cyanidin 3, 5-diglucoside than by cyanidin and cyanidin 3-glucoside. The results suggest that DPP IV is inhibited by cyanidin 3, 5-diglucoside present in aronia juice. The antidiabetic effect of aronia juice may be mediated through DPP IV inhibition by cyanidin 3, 5-diglucoside. - Highlights: • DPP IV activity is inhibited by aronia juice. • DPP IV inhibitor is cyanidin 3, 5-diglucoside in aronia juice. • DPP IV is inhibited by cyanidin 3, 5-diglucoside more than cyanidin and cyanidin 3-glucoside.

  18. Supplementation of an orange juice with dietary proteins to prevent enamel and dentin erosion.

    PubMed

    Ferreira, Stella S; Scaramucci, Tais; Hara, Anderson T; Aoki, Idalina V; Sobral, Maria Angela Pita

    2015-01-01

    Protein supplementation may be an alternative to reduce the erosive potential of acidic drinks. The aim of this in vitro study was to evaluate the erosive potential of an orange juice modified by dietary proteins. A commercially available orange juice was added 0.2 g/L casein, 2.0 g/L ovalbumin and their combination. The juice with no additives and a commercially available calcium-modified juice were used as negative and positive controls, respectively. Human enamel and dentin specimens (n=11) were tested in an erosion-remineralization cycling model. Enamel was analyzed by surface microhardness and profilometry, whilst dentin by profilometry only. Statistical analyses were performed using one-way ANOVA followed by Tukey's test (p<0.05). Calcium-modified juice showed the lowest erosive potential for both analyses (p<0.05). For enamel, the protein-added groups did not differ from each other (p>0.05) and showed significantly lower enamel loss compared to negative control (p<0.05). Regarding surface microhardness, casein showed the highest values compared to negative control (p<0.05). For dentin, none of the protein-added groups showed lower values of surface loss compared to negative control (p>0.05). In conclusion, for enamel the protein-modified orange juices presented reduced erosion of enamel, with casein showing a trend for better protection. For dentin, no reduction in the erosive potential was observed for the tested protein-modified orange juices. PMID:26200150

  19. HUHS1015 induces necroptosis and caspase-independent apoptosis of MKN28 human gastric cancer cells in association with AMID accumulation in the nucleus.

    PubMed

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nishizaki, Tomoyuki

    2015-01-01

    The newly synthesized naftopidil analogue HUHS1015 reduced viability of MKN28 and MKN45 human gastric cancer cells in a concentration (0.3-100 μM)-dependent manner, with the potential greater than that for naftopidil. In the cell cycle analysis, HUHS1015 significantly increased the proportion at the subG1 phase of cell cycling in MKN28 cells. In the flow cytometry using propidium iodide (PI) and annexin V, HUHS1015 significantly increased the populations of PI-positive/annexin V-negative and PI-positive/annexin V-positive MKN28 cells, corresponding to primary necrosis and late apoptosis/secondary necrosis, respectively. HUHS1015-induced MKN28 cell death was attenuated by the necroptosis inhibitor Nec-1. In the enzymatic caspase assay, caspase-3, -4, -8, and -9 were not sufficiently activated by HUHS1015. HUHS1015 increased nuclear localization of apoptosis-inducing factor-homologous mitochondrion-associated inducer of death (AMID), without affecting expression of the AMID mRNA and protein in MKN28 cells. HUHS1015 caused nuclear fragmentation and condensation in MKN28 cells treated with HUHS1015. Taken together, these results of the present study indicate that HUHS1015 induces both necroptosis and caspase-independent apoptosis of MKN28 cells, possibly the latter effect being due to AMID accumulation in the nucleus. PMID:25244912

  20. Scopadulciol, Isolated from Scoparia dulcis, Induces β-Catenin Degradation and Overcomes Tumor Necrosis Factor-Related Apoptosis Ligand Resistance in AGS Human Gastric Adenocarcinoma Cells.

    PubMed

    Fuentes, Rolly G; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2015-04-24

    Scopadulciol (1), a scopadulan-type diterpenoid, was isolated from Scoparia dulcis along with three other compounds (2-4) by an activity-guided approach using the TCF reporter (TOP) luciferase-based assay system. A fluorometric microculture cytotoxicity assay (FMCA) revealed that compound 1 was cytotoxic to AGS human gastric adenocarcinoma cells. The treatment of AGS cells with 1 decreased β-catenin levels and also inhibited its nuclear localization. The pretreatment of AGS cells with a proteasome inhibitor, either MG132 or epoxomicin, protected against the degradation of β-catenin induced by 1. The 1-induced degradation of β-catenin was also abrogated in the presence of pifithrin-α, an inhibitor of p53 transcriptional activity. Compound 1 inhibited TOP activity in AGS cells and downregulated the protein levels of cyclin D1, c-myc, and survivin. Compound 1 also sensitized AGS cells to tumor necrosis factor-related apoptosis ligand (TRAIL)-induced apoptosis by increasing the levels of the death receptors, DR4 and DR5, and decreasing the level of the antiapoptotic protein Bcl-2. Collectively, our results demonstrated that 1 induced the p53- and proteasome-dependent degradation of β-catenin, which resulted in the inhibition of TCF/β-catenin transcription in AGS cells. Furthermore, 1 enhanced apoptosis in TRAIL-resistant AGS when combined with TRAIL. PMID:25793965

  1. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway.

    PubMed

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. PMID:27163639

  2. Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression.

    PubMed

    Tang, Bo; Xie, Rui; Qin, Yong; Xiao, Yu-Feng; Yong, Xin; Zheng, Lei; Dong, Hui; Yang, Shi-Ming

    2016-03-01

    Human telomerase reverse transcriptase (hTERT) is a central regulator of multiple hallmarks of tumors. However, the potential roles of hTERT in tumor invasion and metastasis and the underlying molecular mechanisms remain poorly understood. Here, we found that the expression of hTERT in gastric cancer (GC) was significantly associated with an advanced TNM stage, lymphatic metastasis. Survival analysis identified hTERT as an independent prognostic factor for survival of GC patients. hTERT promoted the invasion and metastasis of GC cells by binding to c-Myc and recruiting the complex to heparanase promoter to upregulate heparanase expression. In addition, our data demonstrated that hTERT activated Wnt/β-catenin signaling to promote c-Myc expression which could in turn activate hTERT transcription and expression, suggesting a positive feedback regulation in GC progression. Consistently, c-Myc and heparanase expression was positively correlated with hTERT levels, and was also an independent predictor of metastasis and survival. Collectively, our data provide a novel molecular mechanism for hTERT in promotion of GC invasion and metastasis, and highlight the molecular etiology and clinical significance of hTERT in GC progression. Targeting hTERT may represent a new therapeutic strategy to improve therapy and survival of GC patients. PMID:26689987

  3. Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression

    PubMed Central

    Tang, Bo; Xie, Rui; Qin, Yong; Xiao, Yu-Feng; Yong, Xin; Zheng, Lei; Dong, Hui; Yang, Shi-Ming

    2016-01-01

    Human telomerase reverse transcriptase (hTERT) is a central regulator of multiple hallmarks of tumors. However, the potential roles of hTERT in tumor invasion and metastasis and the underlying molecular mechanisms remain poorly understood. Here, we found that the expression of hTERT in gastric cancer (GC) was significantly associated with an advanced TNM stage, lymphatic metastasis. Survival analysis identified hTERT as an independent prognostic factor for survival of GC patients. hTERT promoted the invasion and metastasis of GC cells by binding to c-Myc and recruiting the complex to heparanase promoter to upregulate heparanase expression. In addition, our data demonstrated that hTERT activated Wnt/β-catenin signaling to promote c-Myc expression which could in turn activate hTERT transcription and expression, suggesting a positive feedback regulation in GC progression. Consistently, c-Myc and heparanase expression was positively correlated with hTERT levels, and was also an independent predictor of metastasis and survival. Collectively, our data provide a novel molecular mechanism for hTERT in promotion of GC invasion and metastasis, and highlight the molecular etiology and clinical significance of hTERT in GC progression. Targeting hTERT may represent a new therapeutic strategy to improve therapy and survival of GC patients. PMID:26689987

  4. Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells.

    PubMed

    Takahashi, Katsuyuki; Tanaka, Masako; Yashiro, Masakazu; Matsumoto, Masaki; Ohtsuka, Asuka; Nakayama, Keiichi I; Izumi, Yasukatsu; Nagayama, Katsuya; Miura, Katsuyuki; Iwao, Hiroshi; Shiota, Masayuki

    2016-08-01

    Heat shock protein 72 (Hsp72) is a molecular chaperone that assists in the folding of nascent polypeptides and in the refolding of denatured proteins. In many cancers, Hsp72 is constitutively expressed at elevated levels, which can result in enhanced stress tolerance. Similarly, following treatment with anticancer drugs, Hsp72 binds to denatured proteins that may be essential for survival. We therefore hypothesized that Hsp72 client proteins may play a crucial role in drug resistance. Here, we aimed to identify proteins that are critical for oxaliplatin (OXA) resistance by analyzing human gastric cancer cell lines, as well as OXA-resistant cells via a mass spectrometry-based proteomic approach combined with affinity purification using anti-Hsp72 antibodies. Stromal cell-derived factor 2 (SDF-2) was identified as an Hsp72 client protein unique to OCUM-2M/OXA cells. SDF-2 was overexpressed in OXA-resistant cells and SDF-2 silencing promoted the apoptotic effects of OXA. Furthermore, Hsp72 prevented SDF-2 degradation in a chaperone activity-dependent manner. Together, our data demonstrate that Hsp72 protected SDF-2 to avoid OXA-induced cell death. We propose that inhibition of SDF-2 may comprise a novel therapeutic strategy to counteract OXA-resistant cancers. PMID:27157913

  5. Low Circulating Adropin Concentrations with Obesity and Aging Correlate with Risk Factors for Metabolic Disease and Increase after Gastric Bypass Surgery in Humans

    PubMed Central

    Tam, Charmaine S.; Stanhope, Kimber L.; Wolfe, Bruce M.; Ali, Mohamed R.; O'Keeffe, Majella; St-Onge, Marie-Pierre; Ravussin, Eric

    2012-01-01

    Context: Mouse studies suggest that adropin, a peptide hormone, is required for metabolic homeostasis and prevention of obesity-associated insulin resistance. Whether obesity and insulin resistance are associated with low plasma adropin levels in humans is not known. Objectives: Our objective was to investigate the hypothesis that obesity and indicators of insulin resistance are associated with low adropin levels and determine whether weight loss regulates adropin levels. Design and Participants: Plasma was obtained from 85 female [age 21–67 yr, body mass index (BMI) 19.4–71.5 kg/m2] and 45 male (age 18–70 yr, BMI 19.1–62.6 kg/m2) volunteers for other clinical studies. The impact of Roux-en-Y gastric bypass was investigated in 19 obese females (BMI 37–65 kg/m2) using samples collected at baseline and 1–12 months after surgery. Results: Adropin levels correlate negatively with BMI (r = −0.335, P < 0.001) and age (r = −0.263, P=0.003). Age-adjusted adropin levels are higher in males [4.1 ng/ml; 95% confidence interval (CI) = 3.6–4.6 ng/ml] than females (3.0 ng/ml; 95% CI = 2.6–3.4 ng/ml) (P = 0.001). In all subjects, lower age-adjusted adropin levels were observed in overweight (3.3 ng/ml; 95% CI = 2.8–3.8 ng/ml, P = 0.033) and obese (2.7 ng/ml; 95% CI = 2.1–3.3 ng/ml, P = 0.001) compared with healthy-weight