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Sample records for adapted human gastric

  1. Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

    Konturek, J W; Dembinski, A; Stoll, R; Domschke, W; Konturek, S J

    1994-01-01

    The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth. PMID:7959223

  2. DBGC: A Database of Human Gastric Cancer.

    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.

  3. [Role of animal gastric Helicobacter species in human gastric pathology].

    Pozdeev, O K; Pozdeeva, A O; Pozdnyak, A O; Saifutdinov, R G

    2015-01-01

    Animal Helicobacter species other than Helicobacter pylori are also able to cause human gastritis, gastric ulcers, and MALT lymphomas. Animal Helicobacter species are presented with typical spiral fastidious microorganisms colonizing the gastric mucosa of different animals. Bacteria initially received their provisional name Helicobacter heilmannii, and out of them at least five species colonizing the gastric mucosa of pigs, cats, and dogs were isolated later on. A high proportion of these diseases are shown to be zoonotic. Transmission of pathogens occurs by contact. The factors of bacterial pathogenicity remain little studied.

  4. A Changing Gastric Environment Leads to Adaptation of Lipopolysaccharide Variants in Helicobacter pylori Populations during Colonization

    Nilsson, Christina; Björkholm, Britta; Normark, Staffan; Engstrand, Lars

    2009-01-01

    The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG) with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS) decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over time. Moreover, the isolates demonstrated considerable diversity in the levels of glycosylation and in the sizes of fucosylated O-antigen chains both within and between individuals. Thus our data suggest that different LPS variants exist in the colonizing H. pylori population, which can adapt to changes in the gastric environment and provide a means to regulate the inflammatory response of the host during disease progression. PMID:19517017

  5. A changing gastric environment leads to adaptation of lipopolysaccharide variants in Helicobacter pylori populations during colonization.

    Anna Skoglund

    Full Text Available The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarcinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over time. Moreover, the isolates demonstrated considerable diversity in the levels of glycosylation and in the sizes of fucosylated O-antigen chains both within and between individuals. Thus our data suggest that different LPS variants exist in the colonizing H. pylori population, which can adapt to changes in the gastric environment and provide a means to regulate the inflammatory response of the host during disease progression.

  6. A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

    Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

    2015-08-01

    At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid-Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post-explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13-52 h, as compared to normal cells, which had a doubling time of 20-53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin-secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer.

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

    Bimczok, Diane; John Y. Kao; 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 res...

  8. Comparative proteomics analysis of human gastric cancer

    Wei Li; Jian-Fang Li; Ying Qu; Xue-Hua Chen; Jian-Min Qin; Qin-Long Gu; Min Yan; Zheng-Gang Zhu; Bing-Ya Liu

    2008-01-01

    AIM: To isolate and identify differentially expressed proteins between cancer and normal tissues of gastric cancer by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).METHODS: Soluble fraction proteins of gastric cancer tissues and paired normal tissues were separated by 2-DE.The differentially expressed proteins were selected and identified by MALDI-TOF-MS and database search.RESULTS: 2-DE profiles with high resolution and reproducibility were obtained.Twenty-three protein spots were excised from sliver staining gel and digested in gel by trypsin,in which fifteen protein spots were identified successfully.Among the identified proteins,there were ten over-expressed and five under-expressed proteins in stomach cancer tissues compared with normal tissues.CONCLUSION: In this study,the well-resolved,reproducible 2-DE patterns of human gastric cancer tissue and paired normal tissue were established and optimized and certain differentially-expressed proteins were identified.The combined use of 2-DE and MS provides an effective approach to screen for potential tumor markers.

  9. Role of gastric blood flow, neutrophil infiltration, and mucosal cell proliferation in gastric adaptation to aspirin in the rat.

    Konturek, S J; Brzozowski, T; Stachura, J; Dembinski, A; Majka, J

    1994-01-01

    Gastric mucosa exhibits the ability to adapt to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated doses of acidified aspirin in rats with intact or resected salivary glands and with intact or suppressed synthase of nitric oxide. A single oral dose of aspirin produced a dose dependent increase in gastric lesions accompanied by considerable blood neutrophilia and mucosal neutrophil infiltration, significant reduction in gastric blood flow, and almost complete suppression of biosynthesis of prostaglandins. After rechallenge with aspirin, the mucosal damage became smaller and progressively declined with repeated aspirin insults. Gastric adaptation to aspirin was accompanied by a significant rise in gastric blood flow, reduction in both blood neutrophilia and mucosal neutrophil infiltration, and a remarkable increase in mucosal cell regeneration and mucosal content of epidermal growth factor. Salivectomy, which reduced the mucosal content of epidermal growth factor, aggravated the initial mucosal damage induced by the first exposure to acidified aspirin but did not prevent the adaptation of this mucosa to repeated aspirin insults. Pretreatment with NG-nitro-L-arginine (L-NNA), a specific inhibitor of nitric oxide synthase, eliminated the hyperaemic response to repeated aspirin but did not abolish the development of adaptation to aspirin showing that the maintenance of the gastric blood flow plays little part in this adaptation. In conclusion, the stomach adapts readily to repeated aspirin insults and this is accompanied by a considerable reduction in blood neutrophilia and the severity of neutrophil infiltration and by an extensive proliferation of mucosal cells possibly involving epidermal growth factor. PMID:7525421

  10. Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

    Meier, Juris J; Goetze, Oliver; Anstipp, Jens;

    2004-01-01

    . Gastric emptying was calculated from the (13)CO(2) exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA...... and one-way ANOVA. During the infusion, GIP rose to steady-state concentrations of 159 +/- 15 pmol/l for total and 34 +/- 4 pmol/l for intact GIP (P

  11. Detection and location of Helicobacter pylori in human gastric carcinomas

    Yun-Lian Tang; Run-Liang Gan; Bi-Hua Dong; Ri-Chen Jiang; Rong-Jun Tang

    2005-01-01

    AIM: To define the infection status of Helicobacter pylori in 109 patients with gastric cancers and Hpylorilocalization in gastric carcinoma tissues in South China.METHODS: The incidence of Hpyloriinfection in gastric carcinomas was estimated by polymerase chain reaction (PCR), simultaneously; both morphological features and the localization of H pylori in gastric carcinomas were demonstrated by Warthin-Starry (WS) staining. The relationships between Hpylori infection and the clinicalpathologic factors of gastric carcinomas were analyzed by software SPSS10.0.RESULTS: Hpyloriwas found in 42 (39.03%) and 58(53.21%) cases of 109 patients with gastric carcinomas by PCRand WS, respectively. H pyloriinfection rate detected in gastric carcinomas by WS was higher than that by PCR (x2 = 9.735,P<0.005<0.01). WS stain showed that H pylori existed in the gastric antrum mucus, mucosal gland of normal tissues adjacent to gastric carcinomas and the gland, mucus pool of cancer tissues. The positive rate of H pyloriin normal tissues adjacent to carcinomas was higher than that in cancer tissues (x2 = 15.750, P<0.005<0.01). No significant differences in age, sex, site,histological types and lymph node metastasis were found between H pylorFpositive gastric carcinomas and H pylorinegative cases by both methods, but there were statistically significant differences of H pylori positive rate between early and advanced stage of gastric carcinomas (x2=4.548or 5.922, P = 0.033 or 0.015<0.05).CONCLUSION: These results suggested that H pylori infection might play a certain role in the early stage of carcinogenesis of human gastric mucosa epithelia.

  12. Coexpression of cholecystokinin-B/gastrin receptor and gastrin gene in human gastric tissues and gastric cancer cell line

    Jian-Jiang Zhou; Man-Ling Chen; Qun-Zhou Zhang; Jian-Kun Hu; Wen-Ling Wang

    2004-01-01

    AIM: To compare the expression patterns of cholecystokininB (CCK-B)/gastrin receptor genes in matched human gastric carcinoma and adjacent non-neoplastic mucosa of patients with gastric cancer, inflammatory gastric mucosa from patients with gastritis, normal stomachs from 2 autopsied patients and a gastric carcinoma cell line (SGC-7901), and to explore their relationship with progression to malignancy of human gastric carcinomas.METHODS: RT-PCR and sequencing were employed to detect the mRNA expression levels of CCK-B receptor and gastrin gene in specimens from 30 patients with gastric carcinoma and healthy bordering non-cancerous mucosa, 10 gastritis patients and normal stomachs from 2 autopsied patients as well as SGC-7901. The results were semi-quantified by normalizing it to the mRNA level of β-actin gene using Lab Image software. The sequences were analyzed by BLAST program. RESULTS: CCK-B receptor transcripts were detected in all of human gastric tissues in this study, including normal, inflammatory and malignant tissues and SGC-7901. However, the expression levels of CCK-B receptor in normal gastric tissues were higher than those in other groups (P<0.05),and its expressions did not correlate with the differentiation and metastasis of gastric cancer (P>0.05). On the other hand, gastrin mRNA was detected in SGC-7901 and in specimens obtained from gastric cancer patients (22/30) but not in other gastric tissues, and its expression was highly correlated with the metastases of gastric cancer (P<0.05). CONCLUSION: Human gastric carcinomas and gastric cancer cell line SGC-7901 cells coexpress CCK-B receptor and gastrin mRNA. Gastrin/CCK-B receptor autocrine or paracrine pathway may possibly play an important role in the progression of gastric cancer.

  13. Biological role of β-arrestin1 in human gastric cancer BGC-823 cells

    王旭

    2012-01-01

    Objective To investigate the effects of β-arrestin1 on proliferation,migration,invasion and apoptosis of human gastric cancer BGC-823 cell line. Methods The expression of β-arrestin1 in human gastric epithelial cell line GES, human gastric cancer cell line BGC-823, MKN-28 and SGC-7901 was detected

  14. Chestnut extract induces apoptosis in AGS human gastric cancer cells.

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

    2011-06-01

    In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with 200 µg/mL CPE for 24 hr. CPE at various concentrations (0-200 µg/mL) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPE exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

  15. An Anticancer Role of Hydrogen Sulfide in Human Gastric Cancer Cells

    Li Zhang

    2015-01-01

    Full Text Available Hydrogen sulfide (H2S can be synthesized in mammalian cells by cystathionine γ-lyase (CSE and/or cystathionine β-synthase (CBS. Both CSE and CBS are expressed in rat gastric tissues but their role in human gastric neoplasia has been unclear. The aims of the present study were to detect CSE and CBS proteins in human gastric cancer and determine the effect of exogenous NaHS on the proliferation of gastric cancer cells. We found that both CSE and CBS proteins were expressed in human gastric cancer cells and upregulated in human gastric carcinoma mucosa compared with those in noncancerous gastric samples. NaHS induced apoptosis of gastric cancer cells by regulating apoptosis related proteins. Also, NaHS inhibited cancer cell migration and invasion. An antigastric cancer role of H2S is thus indicated.

  16. Comparative Study on Cancer Cell Apoptosis between Gastric and Intestinal-type Human Gastric Carcinoma

    2006-01-01

    Apoptosis of cancer cells between the gastric and intestinal-type human gastric carcinoma were compared in terms of the expression of oncogene MDM2 and CD68, the histological types, the infiltration depth, and lymph node metastasis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was employed to stain apoptotic cells.Histochemical method(AB-PAS) was applied to stain mucus that is neutral or acidic in nature. Immunohistochemical method (SABC) was used to detect expression of MDM2 and CD6. The results showed that the mean apoptosis index (AI) of total 48 cases was 8.60±2.60. AI in the 30 intestinal type cases was significantly higher than that in the 18 gastric type cases (t=4.67, P<0.01). In the 30intestinal type cases, the spontaneous apoptosis index of MDM2 negative cases was significantly higher than that of the positive cases (t=7.16, P<0.01). And in the 18 gastric type cases, the same result was found. (t=11.39, P<0.01). The MDM2 positive ratio in gastric type cases was higher than that in intestinal type cases (x2=4.68, P<0.05). There is no significant difference in AI between cases of lymph node metastasis and non-metastasis cases in intestinal type cases (t=0.26, P>0.05). But in the gastric type cases, a significant difference existed (t=5.87, P<0.01). A significant difference in lymph node metastasis ratio was found between the two gastric carcinoma types (x2=4.48, P<0.05).The CD68 expression ratio in the 30 intestinal type cases was much lower than that in the 18 gastric type cases (t=4.29, P<0.01). AI of 25 MDM2-positive cases was much lower than that of the 23MDM2-negative cases (t=7.80, P<0.01). CD68 positive ratio in the 25 MDM2-negative cases was much lower than that in the 23 negative cases. The difference was statistically significant (t=10.90,P<0.01). Except for few cells scattering within the cancer nest, most CD68 positive cells infiltrated in the interstitium around the cancer

  17. Human thrombin for the treatment of gastric and ectopic varices

    Norma C McAvoy; John N Plevris; Peter C Hayes

    2012-01-01

    AIM:To evaluate the efficacy of human thrombin in the treatment of bleeding gastric and ectopic varices.METHODS:Retrospective observational study in a Tertiary Referral Centre.Between January 1999-October 2005,we identified 37 patients who were endoscopically treated with human thrombin injection therapy for bleeding gastric and ectopic varices.Patient details including age,gender and aetiology of liver disease/ segmental portal hypertension were documented.The thrombin was obtained from the Scottish National Blood Transfusion Service and prepared to give a solution of 250 IU/mL which was injected via a standard injection needle.All patient case notes were reviewed and the total dose of thrombin given along with the number of endoscopy sessions was recorded.Initial haemostasis rates,rebleeding rates and mortality were catalogued along with the incidence of any immediate complications which could be attributable to the thrombin therapy.The duration of follow up was also listed.The study was conducted according to the United Kingdom research ethics guidelines.RESULTS:Thirty-seven patients were included.33 patients (89%) had thrombin (250 U/mL) for gastric varices,2 (5.4%) for duodenal varices,1 for rectal varices and 1 for gastric and rectal varices.(1) Gastric varices,an average of 15.2 mL of thrombin was used per patient.Re-bleeding occurred in 4 patients (10.8%),managed in 2 by a transjugular intrahepatic portosystemic shunt (TIPSS) (one unsuccessfully who died) and in other 2 by a distal splenorenal shunt; (2) Duodenal varices (or type 2 isolated gastric varices),an average of 12.5 mL was used per patient over 2-3 endoscopy sessions.Re-bleeding occurred in one patient,which was treated by TIPSS; and (3) Rectal varices,an average of 18.3 mL was used per patient over 3 endoscopy sessions.No re-bleeding occurred in this group.CONCLUSION:Human thrombin is a safe,easy to use and effective therapeutic option to control haemorrhage from gastric and ectopic varices.

  18. Accumulation of hypericin in human gastric tumors

    Melnik, Ivan S.; Dets, Sergiy M.; Rusina, Tatyana V.; Denisov, Nikolay A.; Braun, Evgeniy M.; Kikot, Vladimir O.; Chernyj, Vyacheslav A.

    1996-04-01

    Hypericin has been studied as a novel natural photosensitizer for PDT. It has been extracted from plants (St.-John's-wort). Oral administration (10% alcohol solution in a dose 2 mg/kg b.w.) was applied for 15 patients with gastric cancers 18 - 48 h before surgery. Normal and cancerous tissue samples were resected and underwent fluorescence analysis 1 - 2 h after resection. Tissue fluorescence was excited by He-Cd (20 mW, 442 nm) and Ar laser beams (100 mW, 488 nm) and registered from 510 to 725 nm. In tissue hypericin has maximum fluorescence peak at 603 nm for both excitation wavelengths. Fluorescence intensity ratio I603/I503 chosen as a criterion for tissue classification was varied from 1.6 to 3.2 (mean 2.5) for adenocarcinoma under He-Cd excitation whereas Ar laser excitation gave from 2.5 up to 4.2 (mean 3.5). Normal tissue had this ratio from 0.48 to 0.65 (mean 0.55) and from 0.53 to 0.75 (mean 3.5) for He-Cd and Ar laser excitation, respectively. No side effects were observed in patients during 6 month follow-up.

  19. Human Gastric Mucosal Hydrophobicity Does dot Decrease with Helicobacter Pylori Infection or Chronological Age

    Mohammed S Al-Marhoon

    2005-01-01

    Full Text Available BACKGROUND AND AIMS: Infection with cytotoxin-associated gene A (cagA Helicobacter pylori is associated with severe gastric diseases. Previous studies in humans have reported a decreased gastric hydrophobicity with H pylori infection. The aim of the present study was to differentiate between the effect of cagA+ and cagA- strains on gastric mucus hydrophobicity.

  20. Elevated levels of adaption in Helicobacter pylori genomes from Japan; a link to higher incidences of gastric cancer?

    Soto-Girón, Maria Juliana; Ospina, Oscar E; Massey, Steven Edward

    2015-03-18

    Helicobacter pylori is a bacterium that lives in the human stomach and is a major risk factor for gastric cancer and ulcers. H.pylori is host dependent and has been carried with human populations around the world after their departure from Africa. We wished to investigate how H.pylori has coevolved with its host during that time, focusing on strains from Japanese and European populations, given that gastric cancer incidence is high in Japanese populations, while low in European. A positive selection analysis of eight H.pylori genomes was conducted, using maximum likelihood based pairwise comparisons in order to maximize the number of strain-specific genes included in the study. Using the genic Ka/Ks ratio, comparisons of four Japanese H.pylori genomes suggests 25-34 genes under positive selection, while four European H.pylori genomes suggests 16-21 genes; few of the genes identified were in common between lineages. Of the identified genes which were annotated, 38% possessed homologs associated with pathogenicity and / or host adaptation, consistent with their involvement in a coevolutionary 'arms race' with the host. Given the efficacy of identifying host interaction factors de novo, in the absence of functionally annotated homologs our evolutionary approach may have value in identifying novel genes which H.pylori employs to interact with the human gut environment. In addition, the larger number of genes inferred as being under positive selection in Japanese strains compared to European implies a stronger overall adaptive pressure, potentially resulting from an elevated immune response which may be linked to increased inflammation, an initial stage in the development of gastric cancer.

  1. Human gut microbiota in obesity and after gastric bypass.

    Zhang, Husen; DiBaise, John K; Zuccolo, Andrea; Kudrna, Dave; Braidotti, Michele; Yu, Yeisoo; Parameswaran, Prathap; Crowell, Michael D; Wing, Rod; Rittmann, Bruce E; Krajmalnik-Brown, Rosa

    2009-02-17

    Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H(2)-producing bacteria with relatively high numbers of H(2)-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H(2) transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.

  2. Malabsorption and intestinal adaptation after one anastomosis gastric bypass compared with Roux-en-Y gastric bypass in rats.

    Cavin, Jean-Baptiste; Voitellier, Eglantine; Cluzeaud, Françoise; Kapel, Nathalie; Marmuse, Jean-Pierre; Chevallier, Jean-Marc; Msika, Simon; Bado, André; Le Gall, Maude

    2016-09-01

    The technically easier one-anastomosis (mini) gastric bypass (MGB) is associated with similar metabolic improvements and weight loss as the Roux-en-Y gastric bypass (RYGB). However, MGB is controversial and suspected to result in greater malabsorption than RYGB. In this study, we compared macronutrient absorption and intestinal adaptation after MGB or RYGB in rats. Body weight and food intake were monitored and glucose tolerance tests were performed in rats subjected to MGB, RYGB, or sham surgery. Carbohydrate, protein, and lipid absorption was determined by fecal analyses. Intestinal remodeling was evaluated by histology and immunohistochemistry. Peptide and amino acid transporter mRNA levels were measured in the remodeled intestinal mucosa and those of anorexigenic and orexigenic peptides in the hypothalamus. The MGB and RYGB surgeries both resulted in a reduction of body weight and an improvement of glucose tolerance relative to sham rats. Hypothalamic orexigenic neuropeptide gene expression was higher in MGB rats than in RYGB or sham rats. Fecal losses of calories and proteins were greater after MGB than RYGB or sham surgery. Intestinal hyperplasia occurred after MGB and RYGB with increased jejunum diameter, higher villi, and deeper crypts than in sham rats. Peptidase and peptide or amino acid transporter genes were overexpressed in jejunal mucosa from MGB rats but not RYGB rats. In rats, MGB led to greater protein malabsorption and energy loss than RYGB. This malabsorption was not compensated by intestinal overgrowth and increased expression of peptide transporters in the jejunum.

  3. Expression of ATP7B in human gastric cardiac carcinomas in comparison with distal gastric carcinomas

    Da-Long Wu; Hui-Xing Yi; Feng-Ying Sui; Xiao-Hong Jiang; Xiao-Ming Jiang; Ying-Ying Zhao

    2006-01-01

    AIM: To analyze expression of ATP7B in gastric cardiac adenocarcinomas, its clinicopathologic significance, in comparison with distal gastric adenocarcinomas.METHODS: Immunohistochemical avidin-biotin peroxidase complex method was applied to detect the expression of ATP7B in 49 cases of cardiac carcinomas,the corresponding adjacent non-neoplastic epithelium and 55 cases of distal gastric carcinomas.RESULTS: The proportion of ATP7B positive samples in gastric cardiac carcinomas (51.0%, 25 of 49) was significantly higher than that in the corresponding adjacent non-neoplastic epithelium (22.4%, 11 of 49)(P = 0.003). ATP7B expression in poorly differentiated gastric cardiac carcinomas was significantly higher than that in well/moderately differentiated gastric cardiac carcinomas (P = 0.030). ATP7B expression in gastric cardiac carcinomas was independent of age, tumor size, nodal stage and metastasis status. ATP7B protein was detected in 30.9% (17/55 cases) of distal gastric carcinomas, markedly lower than that in gastric cardiac carcinomas (P = 0.037).CONCLUSION: ATP7B protein is frequently overexpressed in gastric cardiac carcinomas, and correlated with the differentiation of cardiac carcinoma. ATP7B expression in gastric cardiac carcinomas is significantly higher than that in distal gastric carcinomas, which might partially explain the difference of chemotherapy response and prognosis between these two gastric carcinomas.

  4. Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities

    Pedersen, Pernille Barbre; Vilmann, Peter; Bar-Shalom, Daniel

    2013-01-01

    be considered important during development of gastric simulated media. Further, the activity of the HGL is active even under fasted gastric conditions and might contribute to the digestion and emulsification of lipid-based drug delivery systems in the entire gastrointestinal tract. HGL should therefore...... be considered in gastric evaluation of lipid-based drug delivery systems....

  5. Expression of nitric oxide synthase in human gastric carcinoma and its relation to p53, PCNA

    Yong-Zhong Wang; You-Qing Cao; Jian-Nong Wu; Miao Chen; Xiao-Ying Cha

    2005-01-01

    AIM: To investigate the expression of NOS in gastric carcinoma, and to explore the relationship between the expression of nitric oxide synthases (NOS) and p53, PCNA,pathological features and clinical staging of gastric cancer.METHODS: The activity of NOS protein was investigated in 85 samples of human gastric carcinoma and 25 samples of normal gastric mucosal tissue by biochemical assay. We then examined the expression of NOS, p53, PCNA in 85 samples of human gastric cancer was examined by immunohistochemistry, and NOS mRNA expression in 85 gastric cancer tissue specimens by in situ hybridization.RESULTS: Biochemical assay showed that the activity of NOS was significantly higher in gastric carcinoma than in normal gastric mucosal tissues (t = 0.4161, P<0.01).Immunohistochemistry revealed that endothelial nitric oxide synthase (eNOS) expressed in all samples of normal gastric mucosa, but only 6 cases of 85 gastric cancer specimens showed weak positive immunohistochemical reactions to eNOS (20%). Inducible nitric oxide synthase (iNOS) was expressed strongly in human gastric carcinoma (81.2%). In situ hybridization analysis showed that iNOS mRNA expression was significantly stronger than eNOS mRNA expression in gastric cancer tissue (x2 = 10.23, P<0.01). The expression of iNOS in gastric cancer was associated with differentiation, clinical stages or lymph node metastases (r= 0.3426, P<0.05). However,iNOS expression did not correlate with histological classifications and morphological types. The expression of iNOS was significantly correlated with p53 or PCNA expression (r = 0.3612, P<0.05). The expression of neuronal nitric oxide synthase (nNOS) was not examined by immunohistochemistry and in situ hybridization in gastric cancer specimens and normal gastric mucosa.CONCLUSION: In human gastric cancer, there is an enhanced expression of iNOS, but not of eNOS. NOS promotes the proliferation of tumor cells and plays an important role in gastric cancer spread

  6. Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma

    Ming-Dong Zhao; Xue-Mei Hu; Dian-Jing Sun; Qun Zhang; Yu-Hao Zhang; Wei Meng

    2005-01-01

    AIM: To study the effect of IGF-1/IGF-1R and gastrin/ CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma. METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation.RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumorfree tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues. CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.

  7. Effect of sialoadenectomy and synthetic human urogastrone on healing of chronic gastric ulcers in rats

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands...... delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined...... administration of synthetic human EGF/URO and cimetidine further increased healing of gastric ulcers compared with administration of each substance. Neither synthetic human EGF/URO, nor removal of the submandibular glands had any influence on gastric acid secretion. This study showed that the submandibular...

  8. Apoptosis mechanisms of human gastric cancer cell line MKN-45 infected with human mutant p27

    Jin-Shui Zhu; Long Wang; Guo-Qiang Cheng; Qin Li; Zu-Ming Zhu; Li Zhu

    2005-01-01

    AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection efficiency reached 100%. After 18 h of infection, we observed an apoptotic hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was significantly higher in the Ad-p27mt group (89.4±3.12%)compared to the control group (3.12±0.13%, P < 0.01).CONCLUSION: Human mutant p27 can induce apoptosis of the human gastric cancer cells in vitro.

  9. CD147 Expression in Human Gastric Cancer Is Associated with Tumor Recurrence and Prognosis

    Dake Chu; Shaojun Zhu; Jipeng Li; Gang Ji; Weizhong Wang; Guosheng Wu; Jianyong Zheng

    2014-01-01

    CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site o...

  10. Multidrug resistance reversal in human gastric carcinoma cells by neferine

    Jian-Guo Cao; Xiao-Qing Tang; Shu-Hong Shi

    2004-01-01

    AIM: To investigate the reversal effect of neferine on multidrug resistance in human gastric carcinoma cell line.METHODS: Cells of a human gastric cancer cells line, SGC7901,and its vincristine (VCR) -resistant variant, SGC7901/VCR,were cultivated with or without neferine and/or VCR. The cytotoxic effect of VCR was evaluated by the MTT assay. Cell apoptosis induced by VCR was determined by flow cytometry (FCM). The expression of P-glycoprotein (P-gp) and a multidrug-resistance-associated protein (MRP) in cells was examined by immunofluorescence and FCM.RESULTS: Neferine at the concentration from 2.5 μmol/L to 10 μmol/L had no cytotoxicity to SGC7901 cells, and its variant SGC7901/VCR cells. The IC50 of VCR against SGC7901 and SGC7901/VCR cells was 0.059 μg/mL and 2.32 μg/mL,respectively, indicating that SGC7901/VCR cells were 39 times more resistant to VCR than its parent SGC7 901 cells. After treatment with neferine at concentrations of 2.5, 5 and 10 μmol/L, the IC50 of VCR to SGC7901/VCR cell line decreased to 0.340, 0.128 and 0.053 μg/mL, respectively,thus, increased the chemosensitivity by 6.8-, 18.1- and 43.8-fold, respectively. SGC7901/VCR cells were apoptosis resistant to VCR. Neferine (2.5, 5 and 10 μmol/L) promoted the VCR-induced apoptosis of SGC7901/VCR cells in a dosedependent manner. The expressions of P-gp and MRP were strongly positive in SGC7901/VCR cells, which were significantly down-regulated after treatment with neferine (10 μmol/L)for 24 h.CONCLUSION: Neferine reverses multidrug resistance of human gastric carcinoma SGC7901/VCR cells, which may be associated with the down-regulations of P-gp and MRP expression in SGC701/VCR cells.

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

    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.

  12. INTERACTIONS BETWEEN THE HUMAN GASTRIC CARCINOMA CELL AND THE HUMAN VASCULAR ENDOTHELIAL CELL

    2001-01-01

    Objective To definite the interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the establishment and maintenance of the tumor vascular system and the tumor hematogenous metastasis.Methods We prepared the conditioned mediums of each cell so as to study the effect of the conditioned medium on itself or others by MTT colorimetry. The comprehensive effect of interactions between two cells was determined by stratified transfilter co-culture or direct contact co-culture.Results The conditioned medium of human gastric carcinoma cell can stimulate the proliferation of the human vascular endothelial cell, but the CM of HVEC can inhibit the growth of HGCC. Both kinds of cells can inhibit the growth of itself. The ultimate comprehensive effect of the interactions between two kinds of cells was increase of total cell numbers.Conclusion There exist the complicated interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the tumor angiogenesis and the tumor hematogenous metastasis. The ultimate comprehensive effect of the interactions is increase of total cells numbers and tumor volume.

  13. Immune Homeostasis of Human Gastric Mucosa in Helicobacter pylori Infection.

    Reva, I V; Yamamoto, T; Vershinina, S S; Reva, G V

    2015-05-01

    We present the results of electron microscopic, microbiological, immunohistochemical, and molecular genetic studies of gastric biopsy specimens taken for diagnostic purposes according by clinical indications during examination of patients with gastrointestinal pathology. Immune homeostasis of the gastric mucosa against the background of infection with various pathogen strains of Helicobacter pylori was studied in patients of different age groups with peptic ulcer, gastritis, metaplasia, and cancer. Some peculiarities of Helicobacter pylori contamination in the gastric mucosa were demonstrated. Immune homeostasis of the gastric mucosa in different pathologies was analyzed depending on the Helicobacter pylori genotype.

  14. Tnhibitory effect of Fuzheng Yiliuyin in combination with chemotherapeutics on human gastric carcinoma cell strain

    Yi Liu; Rui Wang; Gen-Quan Qiu; Ke-Jun Nan; Xi-Cai Sun

    2006-01-01

    AIM: To study the inhibitory effects of Fuzheng Yiliuyin (Decoction for Suppressing Tumors by Strengthening the Body Resistance) in combination with chemotherapeutics on human gastric carcinoma cell strain.METHODS: Fuzheng Yiliuyin (ZY) combined with various kinds of chemotherapeutics was put into two kinds of cultivated human gastric carcinoma cell strains,then its inhibitory effects on human gastric carcinoma cell strains were determind by the MTT method. Flow cytometer was used to assay the apoptosis rate, and the ultrastructure of gastric carcinoma cells was observed under transmission electron microscope.RESULTS: Obvious apoptosis was seen in gastric carcinoma cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic inhibition effects on the cultivated gastric carcinoma cells, but the effects were different on various cell strains. The inhibitory effects of ZY could be strengthened by cytotoxic action and apoptosis. ZY combined with fluorouracil, etoposide and cisplatin (EFP) chemotherapeutics had better inhibitory effects on SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better inhibitory effects than other drugs on MGC-803.CONCLUSION: ZY induces apoptosis and inhibits the growth of gastric carcinoma cells. ZY has the synergistic function of chemotherapeutics.

  15. Methionine-dependence and combination chemotherapy on human gastric cancer cells in vitro

    Wei-Xin Cao; Jing-Min Ou; Xu-Feng Fei; Zheng-Gang Zhu; Hao-Ran Yin; Min Yan; Yan-Zhen Lin

    2002-01-01

    AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial calls in vitro can grow normally in a rnethionine (Met) depleted environment, i.e.Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells.lMETHODS: Fresh human gastric cancer and mucosal tissueswere managed to form monocellular suspensions, whichwere then cultured in the Met-free but homocysteine-containing ( MetHcy+ ) medium, with differentchemotherapeutic drugs. The proliferation of the cells wasexamined by cell counter, flow cytometry (FCM) andmicrocytotoxicity assay (MTT).RESULTS: The growth of human primary gastric cancer cellsin Met Hcy+ was suppressed, manifested by the decrease oftotal cell counts [1.46±0.42 ( x 109@L-1) in Met-Hcy+ vs .64±0.44 ( x l09@L-1) in Met+ Hcy, P<0.01], the decline inthe percentage of G0G1 phase cells (0.69±0.24 in Met-Hey+vs 0.80±0.18 in Met+ Hcy, P<0.01) and the increase of Scells(0.24±0.20inMet-Hcy+ vs 0.17 ± 0.16 in Met+ Hcy-, P< 0.01); however, gastric mucusal cells grew normally. IfMet-Hcy+ medium was used in combination withchemotherapeutic drugs, the number of surviving gastriccancer cells dropped significantly.CONCLUSION: Human primary gastric cancer cells in vitroare Met-dependent; however, gastric mucosal cells have notshown the same characteristica. Met- Hcy+ environment maystrengthen the killing effect of chemotherapy on humanprimary gastric cancer cells.

  16. Synchrotron-radiation phase-contrast imaging of human stomach and gastric cancer: in vitro studies.

    Tang, Lei; Li, Gang; Sun, Ying-Shi; Li, Jie; Zhang, Xiao-Peng

    2012-05-01

    The electron density resolution of synchrotron-radiation phase-contrast imaging (SR-PCI) is 1000 times higher than that of conventional X-ray absorption imaging in light elements, through which high-resolution X-ray imaging of biological soft tissue can be achieved. For biological soft tissue, SR-PCI can give better imaging contrast than conventional X-ray absorption imaging. In this study, human resected stomach and gastric cancer were investigated using in-line holography and diffraction enhanced imaging at beamline 4W1A of the Beijing Synchrotron Radiation Facility. It was possible to depict gastric pits, measuring 50-70 µm, gastric grooves and tiny blood vessels in the submucosa layer by SR-PCI. The fine structure of a cancerous ulcer was displayed clearly on imaging the mucosa. The delamination of the gastric wall and infiltration of cancer in the submucosa layer were also demonstrated on cross-sectional imaging. In conclusion, SR-PCI can demonstrate the subtle structures of stomach and gastric cancer that cannot be detected by conventional X-ray absorption imaging, which prompt the X-ray diagnosis of gastric disease to the level of the gastric pit, and has the potential to provide new methods for the imageology of gastric cancer.

  17. 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.

    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 χ(2) 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 (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.

  18. GAGE12 mediates human gastric carcinoma growth and metastasis.

    Lee, Eun Kyung; Song, Kyung-A; Chae, Ji-Hye; Kim, Kyoung-Mee; Kim, Seok-Hyung; Kang, Myung-Soo

    2015-05-15

    The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes.

  19. Changes of multiple genes in human gastric carcinomas

    2001-01-01

    Objective: To investigate the mutual relation of the changesamong multiple genes in human gastric carcinomas (GC). Methods: By means of software package about social science (SPSS) and statistics analysis system (SAS), the mutual relation of the expression of oncogenes (p21, p185) and tumor suppressor genes (RB, p53, p16, nm23) in 78 GC is discussed. Results: There existed correlations among some genes, i.e., p21 and p185, RB and p16, p16 and p53 as well as p16 and nm23; It is relatively uncommon that the carcinogenesis of GC simultaneously related to more changes of multiple genes; The inactivation of p16 gene was independent factor to predict the metastasis of lymphaden, the mutation of p53 gene and the inactivation of p16 gene were independent factors to predict the invasive depth. Conclusion: There are not only the changes of multiple genes including oncogenes activation and tumor suppressor genes inactivation, but also they may play an important role in carcinogenesis of GC through mutual cooperation. The inactivation of p16 gene is one of the most useful index to predict the prognosis of patient with GC.

  20. Effects of methylation status of caspase-8 promoter on antitumor activity of TRAIL to human gastric cancer cells

    ZHANG Ru-gang; FANG Dian-chun; YANG Liu-qin; LUO Yuan-gang

    2004-01-01

    Objective: To study the effects of the methylation status of caspase-8 promoter on the antitumor activity of TRAIL to the human gastric cancer cells. Methods: The methylation of caspase-8 was measured with methylation specific PCR (MSP) and the antitomor capability of TRAIL to human gastric cancer cells was determined with MTT. Results: No methylation of caspase-8 in the human gastric cancer cells was found. The sensitivity of 5 lines of gastric cancer cells to the antitumor activity of TRAIL was different. The administration of the demethylation agent 5-Aza-2'-deoxycytidine ( 5-AzaCdR) increased the sensitivity of gastric cancer cells to TRAIL but did not change the methylation status of caspase-8 promoter in gastric cancer cells. Conclusion: 5-Aza-CdR increases the sensitivity of most of gastric cancer cells to TRAIL but caspase-8 is not involved in the antitumor activity of TRAIL.

  1. Apoptosis of human primary gastric carcinoma cells induced by genistein

    Hai-Bo Zhou; Juan-Juan Chen; Wen-Xia Wang; Jian-Ting Cai; Qin Du

    2004-01-01

    AIM: To investigate the apoptosis in primary gastric cancer cells induced by genistein, and the relationship between this apoptosis and expression of bcl-2 and bax.METHODS: MTT assay was used to determine the cell growth inhibitory rate in vitro. Transmission electron microscope and TUNEL staining were used to quantitatively and qualitatively detect the apoptosis of primary gastric cancer cells before and after genistein treatment. Immunohistochemical staining and RT-PCR were used to detect the expression of apoptosisassociated genes bcl-2 and bax.RESULTS: Genistein inhibited the growth of primary gastric cancer cells in dose-and time-dependent manner. Genistein induced primary gastric cancer cells to undergo apoptosis with typically apoptotic characteristics. TUNEL assay showed that after the treatment of primary gastric cancer cells with genistein for 24 to 96 h, the apoptotic rates of primary gastric cancer cells increased time-dependently. Immunohistochemical staining showed that after the treatment of primary gastric cancer cells with genistein for 24 to 96 h, the positivity rates of Bcl-2 proteins were apparently reduced with time and the positivity rates of Bax proteins were apparently increased with time. After exposed to genistein at 20 μmol/L for 24,48, 72 and 96 respectively, the density of bcl-2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time.CONCLUSION: Genistein is able to induce the apoptosis in primary gastric cancer cells. This apoptosis may be mediated by down-regulating the apoptosis- associated bcl-2 gene and up-regulating the expression of apoptosis-associated bax gene.

  2. Cyclooxygenase 2,pS2,inducible nitric oxide synthase and transforming growth factor alpha in gastric adaptation to stress

    Shi-Nan Nie; Hai-Chen Sun; Xue-Hao Wu; Xiao-Ming Qian

    2004-01-01

    AIM: To determine the role of mucosal gene expression of cyclooxygenase 2 (COX-2), pS2 (belongs to trefoil peptides),inducible nitric oxide synthase (iNOS) and transforming growth factor alpha (TGFα) in gastric adaptation to water immersion and restraint stress (WRS) in rats.METHODS: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 d. Gastric mucosal blood flow (GMBF) was measured by laser Doppler fiowmeter3. The extent of gastric mucosal lesions were evaluated grossly and histologically and expressions of COX-2, pS2,iNOS and TGFα were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot.RESULTS: The damage to the surface of gastric epithelium with focal areas of deep haemorrhagic necrosis was induced by repeated WRS.The adaptative cytoprotection against stress was developed with activation of cell proliferation in the neck regions of gastric glands. The ulcer index (UI) in groups Ⅱ, Ⅲ and Ⅳ was markedly reduced as compared with group Ⅰ (Ⅰ: 47.23±1.20; Ⅳ: 10.39±1.18,P<0.01). GMBF significantly decreased after first exposure to WRS with an adaptive increasement of GMBF in experimental groups after repetitive challenges with WRS. After the 4th WRS,the value of GMBF almost restored to normal level (Ⅰ:321.87±8.85; Ⅳ: 455.95±11.81,P<0.01). First WRS significantly decreased the expression of pS2 and significantly increased the expressions of COX-2, iNOS and TGFα. After repeated WRS, pS2 and TGFα expressions gradually increased (pS2: Ⅰ: 0.37±0.02; Ⅳ: 0.77±0.01; TGFα: Ⅰ:0.86±0.01; Ⅳ: 0.93±0.03, P<0.05) with a decrease in the expressions of COX-2 and iNOS (COX-2: Ⅰ: 0.45±0.02; Ⅳ:0.22±0.01; iNOS: Ⅰ: 0.93±0.01; Ⅳ: 0.56±0.01, P<0.01).Expressions of pS2, COX-2, iNOS and TGFα showed regular changes with a good relationship among them.CONCLUSION: Gastric adaptation to WRS injury involves enhanced cell proliferation, increased expression of pS2 and

  3. Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.

    Zhi Xu

    Full Text Available Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7% in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.

  4. CD147 expression in human gastric cancer is associated with tumor recurrence and prognosis.

    Dake Chu

    Full Text Available CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site or Lauren classification. Kaplan-Meier analysis confirmed that CD147 was associated with disease-free and overall survival in patients with gastric cancer; i.e., patients with positive CD147 staining tend to have worse disease-free and overall survival. Moreover, Cox's proportional hazards analysis demonstrated that CD147 was an independent marker of disease-free and overall survival for patients with gastric cancer. These results confirm the association of CD147 with gastric cancer invasion and metastasis and prove that CD147 might be an indicator of tumor recurrence and prognosis in gastric cancer.

  5. The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells.

    Hütz, Katharina; Mejías-Luque, Raquel; Farsakova, Katarina; Ogris, Manfred; Krebs, Stefan; Anton, Martina; Vieth, Michael; Schüller, Ulrich; Schneider, Marlon R; Blum, Helmut; Wagner, Ernst; Jung, Andreas; Gerhard, Markus

    2014-04-01

    Gastric cancer (GC) is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with Helicobacter pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker SOX2 has been observed in stomach cancer. However, the role of SOX2 in gastric tumors has not been well established to date. To elucidate the role of SOX2 in gastric tumorigenesis, SOX2 transcriptional activity was blocked in AZ-521 cells. Interestingly, inhibition of SOX2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of SOX2 also reduced the tumorigenic potential of AZ-521 cells in vivo. In addition, correlation of SOX2 expression and proliferation was observed in a subset of human gastric tumors. Finally, target genes of SOX2 were for the first time identified by RNA microarray in GC cells. Taken together, the results presented here indicate that SOX2 controls several aspects related to GC development and progression by regulating the expression of members of important signaling pathways. These findings could provide new therapeutic options for a subset of GCs exhibiting SOX2 deregulation.

  6. CD147 expression in human gastric cancer is associated with tumor recurrence and prognosis.

    Chu, Dake; Zhu, Shaojun; Li, Jipeng; Ji, Gang; Wang, Weizhong; Wu, Guosheng; Zheng, Jianyong

    2014-01-01

    CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site or Lauren classification. Kaplan-Meier analysis confirmed that CD147 was associated with disease-free and overall survival in patients with gastric cancer; i.e., patients with positive CD147 staining tend to have worse disease-free and overall survival. Moreover, Cox's proportional hazards analysis demonstrated that CD147 was an independent marker of disease-free and overall survival for patients with gastric cancer. These results confirm the association of CD147 with gastric cancer invasion and metastasis and prove that CD147 might be an indicator of tumor recurrence and prognosis in gastric cancer.

  7. Do sensory neurons mediate adaptive cytoprotection of gastric mucosa against bile acid injury?

    Mercer, D W; Ritchie, W P; Dempsey, D T

    1992-01-01

    Pretreatment with the mild irritant 1 mmol acidified taurocholate protects the gastric mucosa from the injury induced by the subsequent application of 5 mmol acidified taurocholate, a phenomenon referred to as "adaptive cytoprotection." How this occurs remains an enigma. The purpose of this study was to investigate the role of sensory neurons and mucus secretion in this phenomenon. Prior to injury with 5 mmol acidified taurocholate (pH 1.2), the stomachs of six groups of rats were subjected to the following protocol. Two groups were topically pretreated with either saline or the mild irritant 1 mmol acidified taurocholate. Two other groups received the topical anesthetic 1% lidocaine prior to pretreatment with either saline or 1 mmol acidified taurocholate. The last two groups got the mucolytic agent 10% N-acetylcysteine (NAC) after pretreatment with either saline or 1 mmol acidified taurocholate. Injury was assessed by measuring net transmucosal ion fluxes, luminal appearance of deoxyribonucleic acid (DNA), and gross and histologic injury. Pretreatment with the mild irritant 1 mmol acidified taurocholate significantly decreased bile acid-induced luminal ion fluxes and DNA accumulation, suggesting mucosal protection (corroborated by gross and histologic injury analysis). This effect was negated by lidocaine but not by NAC. Thus, it appears that sensory neurons, and not increased mucus secretion, play a critical role in adaptive cytoprotection.

  8. Human Adaptation to the Computer.

    1986-09-01

    8217"’ TECHNOSTRESS " 5 5’..,:. VI I. CONCLUSIONS-------------------------59 -- LIST OF REFERENCES-------------------------61 BI BLI OGRAPHY...computer has not developed. Instead, what has developed is a "modern disease of adaptation" called " technostress ," a phrase coined by Brod. Craig...34 technostress ." Managers (according to Brod) have been implementing computers in ways that contribute directly to this stress: [Ref. 3:p. 38) 1. They

  9. Effect of staurosporine on cycle of human gastric cancer cells

    Min-Wen Ha; Ke-Zuo Hou; Yun-Peng Liu; Yuan Yuan

    2004-01-01

    AIM: To study the effect of staurosporine (ST) on the cell cycle of human gastriccancer cell lines MGC803 and SGC7901.METHODS: Cell proliferation was evaluated by trypan blue dye exclusion method. Apoptotic morphology was observed under a transmission electron microscope. Changes of cell cycle and apoptotic peaks of cells were determined by flow cytometry. Expression of p21WAFI gene was examined using immunohistochemistry and RT-PCR.RESULTS: The growth of MGC803 and SGC7901 cells was inhibited by ST. The inhibitory concentrations against 50% cells (IC50) at 24 h and 48 h were 54 ng/ml and 23 ng/ml for MlGC803, and 61 ng/ml and 37 ng/ml for SGC7901. Typical apoptotic bodies and apoptotic peaks were observed 24 hafter cells were treated wth ST at a concentration of 200ng/ml. The percentage of cells at G0/G1 phase was decreased and that of cells at G2/M was increased significantly in the group treated wth ST at the concentrations of 40ng/ml,60 ng/ml, 100 ng/ml for 24 h, compared with the control group (P<0.01). The expression levels of p21WAFI gene in both MGC803 and SGC7901 cells were markedly up-regulated after treatment with ST.CONCLUSION: ST can cause arrest of gastric cancer cells at G2/M phase, which may be one of the mechanisms that inhibit cell proliferation and cause apoptosis in these cells.Effect of ST on cells at G2/M phase may be attributed to the up-regulattion of p21WAFI gene.

  10. Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

    Hu Song

    2012-01-01

    Full Text Available Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA. Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1 and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

  11. Molecular cross-talk between Helicobacter pylori and human gastric mucosa

    Vittorio Ricci; Marco Romano; Patrice Boquet

    2011-01-01

    Helicobacter pylori (H. pylori ) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently. A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host, but confers a risk for serious diseases including gastric cancer. During its long coexistence with humans, H. pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and inflammation, as well as immune effector activity. The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H. pylori /human gastric mucosa interaction (and its pathological sequelae), which is the result of millennia of co-evolution of, and thus of reciprocal knowledge between, the pathogen and its human host.

  12. TELOMERASE ACTIVITY IN HUMAN GASTRIC AND COLORECTAL CANCER AND SURROUNDING TISSUES

    CHEN Wen; ZHANG Qiao; WAN De-sen; CUN Ling-yun; WU Cheng-qiu; PAN Zhi-zhong

    1999-01-01

    Objective: To study the telomerase activities in human gastric and colorectal tumors. Methods: The telomerase activity was assayed by the telomeric repeat amplification protocol (TRAP) technique. Forty human tumor samples including 9 colonic, 20 rectal and 11gastric carcinomas and their surrounding tissues were used for the detection. Results: Thirty-six out of 40human tumor samples exhibited telomerase activity regardless of the stages or the differentiation of the tumors. However, only 1 out of 39 tumor surrounding tissues showed telomerase activity. Conclusion: Telomerase may be a good diagnosis biomarker for tumor detection.

  13. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

    Liu Jun

    2004-07-01

    Full Text Available Abstract Background BAK (Bcl-2 homologous antagonist/killer is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Methods Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53 and MKN-28 (mutant-type p53. RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. Results BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45, or in p53 mutant-type (MKN-28 gastric cancer cells. Conclusions The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies.

  14. Significance of expression of heat shock protein90α in human gastric cancer

    Dong-Sheng Zuo; Jie Dai; Ai-Hua Bo; Jie Fan; Xiu-Ying Xiao

    2003-01-01

    AIM: To evaluate the significance of hsp90α expression in human gastric cancer tissues.METHODS: Immunohistochemical staining was used in clinical specimens from 33 cases of gastric cancer and 33 cases of gastritis with rabbit anti-human hsp90α multi-clonal antibody in order to explore the relationship between the expression of hsp90α in gastric carcinoma tissue and gastritis tissue as well as in mucous membrane adjacent to cancer and lymph node metastasis.RESULTS: Hsp90α was detected in 88 % of gastric carcinoma cases and 55 % of gastritis cases. The hsp90α positive rate in gastric cancer group was significantly higher than that in gastritis group (P<0.01, P=0.005). The hsp90α positive rate in gastric cancer and in mucous membrane adjacent to cancer was 88 % and 55 % respectively (P<0.01,P=0.005). The hsp90α positive rate in lymph node metastasis group and non-lymph node metastasis group was 100 % and 60 %respectively, and a significant correlation between hsp90α expression and lymph node metastasis was shown (P<0.01,P=0.005).CONCLUSION: The hsp90α expression rate in gastric cancer group was significantly higher than that in gastritis group as well as that in the group of mucous membrane adjacent to cancer. The hsp90α expression in lymphatic node metastasis group was higher than that in non-lymphatic node metastasis group. The results indicate that increased hsp90α expression has a close relationship with occurrence and lymph node metastasis of gastric cancer.

  15. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection

    Bartfeld, Sina; Bayram, Tülay; van de Wetering, Marc; Huch, Meritxell; Begthel, Harry; Kujala, Pekka; Vries, Robert; Peters, Peter J; Clevers, Hans

    2015-01-01

    BACKGROUND & AIMS: We previously established long-term, 3-dimensional culture of organoids from mouse tissues (intestine, stomach, pancreas, and liver) and human intestine and pancreas. Here we describe conditions required for long-term 3-dimensional culture of human gastric stem cells. The technolo

  16. Paclitaxel induces apoptosis in human gastric carcinoma cells

    Hai-Bo Zhou; Ju-Ren Zhu

    2003-01-01

    AIM: To investigate the apoptosis in gastric cancer cells induced by paclitaxel, and the relation between this apoptosis and expression of Bcl-2 and Bax.METHODS: In in vitro experiments, MTT assay was used to determine the cell growth inhibitory rate. Transmission electron microscope and TUNEL staining method were used to quantitatively and qualitively detect the apoptosis status of gastric cancer cell line SGC-7901 before and after the paditaxel treatment. Immunohistochemical staining was used to detect the expression of apoptosis-regulated gene Bcl-2and Bax.RESULTS: Paclitaxel inhibited the growth of gastric cancer cell line SGC-7901 in a dose-and time-dependent manner.Paclitaxel induced SGC-7901 cells to undergo apoptosis with typically apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation and apoptotic body formation. Paclitaxel could reduce the expression of apoptosis-regulated gene Bcl-2, and improve the expression of apoptosis-regulated gene Bax.CONCLUSION: Paclitaxel is able to induce the apoptosis in gastric cancer. This apoptosis may be mediated by downexpression of apoptosis-regulated gene Bcl-2 and upexpression of apoptosis-regulated gene Bax.

  17. An adaptive paradigm for human space settlement

    Smith, Cameron M.

    2016-02-01

    Because permanent space settlement will be multigenerational it will have to be viable on ecological timescales so far unfamiliar to those planning space exploration. Long-term viability will require evolutionary and adaptive planning. Adaptations in the natural world provide many lessons for such planning, but implementing these lessons will require a new, evolutionary paradigm for envisioning and carrying out Earth-independent space settlement. I describe some of these adaptive lessons and propose some cognitive shifts required to implement them in a genuinely evolutionary approach to human space settlement.

  18. Isolation and bioinformatics analysis of differentially methylated genomic fragments in human gastric cancer

    Ai-Jun Liao; Qi Su; Xun Wang; Bin Zeng; Wei Shi

    2008-01-01

    AIM:To isolate and analyze the DNA sequences which are methylated differentially between gastric cancer and normal gastric mucosa.METHODS:The differentially methylated DNA sequences between gastric cancer and normal gastric mucosa were isolated by methylation-sensitive representational difference analysis (MS-RDA).Similarities between the separated fragments and the human genomic DNA were analyzed with Basic Local Alignment Search Tool (BLAST).RESULTS:Three differentially methylated DNA sequences were obtained,two of which have been accepted by GenBank.The accession numbers are AY887106 and AY887107.AY887107 was highly similar to the 11th exon of LOC440683 (98%),3'end of LOC440887 (99%),and promoter and exon regions of DRD5 (94%).AY887106 was consistent (98%) with a CpG island in ribosomal RNA isolated from colorectal cancer by Minoru Toyota in 1999.CONCLUSION:The methylation degree is different between gastric cancer and normal gastric mucosa.The differentially methylated DNA sequences can be isolated effectively by MS-RDA.

  19. Real-time determination of human telomerase reverse transcriptase mRNA in gastric cancer

    Li-Hua Hu; Feng-Hua Chen; Yi-Rong Li; Lin Wang

    2004-01-01

    AIM: To set up a real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay,to detect human telomerase reverse transcriptase (hTERT)messenger RNA in gastric carcinomas, and to evaluate quantitative determination of hTERT mRNA in the diagnostic value of gastric carcinomas, and to analyze the correlation between the expression level of hTERT mRNA and dinicopathological parameters in patients with gastric cancer.METHODS: A real-time quantitative RT-PCR (RQ-PCR)based on TaqMan fluorescence methodoloogy and the LightCyder system was used to quantify the full range of hTERT mRNA copy numbers in 35 samples of gastric carcinomas and corresponding adjacent non-cancerous tissues. The normalized hTERT (NhTERT) was standardized by quantifying the number of GAPDH transcripts as internal control and expressed as 100× (hTERT/GAPDH) ratio. Variables were analyzed by the Student's t-test, χ2 test and Fisher's exact test.RESULTS: NhTERT from gastric carcinomas and corresponding adjacent non-cancerous tissues was 6.27±0.89 and 0.93±0.18,respectively (t= 12.76, P<0.001). There was no significant association between gastric cancer hTERT mRNA expression level and patient's age, gender, tumor size, location and stage (pTNM), but a significant correlation was found between hTERT mRNA expression level in gastric carcinomas and the degree of differentiation.CONCLUSION: Quantitative determination of hTERT mRNA by RQ-PCR is a rapid and sensitive method. hTERT might be a potential biomarker for the early detection of gastric cancer.

  20. MTA1 promotes proliferation and invasion in human gastric cancer cells

    Yao Y

    2015-07-01

    Full Text Available Yuan Yao,1 Shuting Feng,1 Mingming Xiao,2 Yan Li,1 Li Yang,1 Jiao Gong1 1Digestive System Department, 2Department of Pathology, The People’s Hospital of Liaoning Province, Shenyang, Liaoning, People’s Republic of China Abstract: Although metastasis-associated protein 1 (MTA1 has been widely li­nked to tumor metastasis, the relevant mechanisms remain to be elucidated, especially in gastric cancer. The aim of this study was to examine whether the MTA1 gene is associated with the process of proliferation and invasion by regulating several molecular targets in gastric cancer. MTA1 expression in 61 gastric cancer tissue and adjacent noncancerous tissues was analyzed by immunohistochemistry. The prognostic value of MTA1 for overall survival and disease-free survival was determined by Kaplan–Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. Furthermore, overexpression of MTA1 in SGC7901 and BGC823 cells promoted cell cycle progression, cell adhesion, and cell invasion. Our study found that MTA1 is overexpressed in gastric cancers, which contributes to malignant cell growth by facilitating cell cycle progression through upregulation of cyclin D1 and accelerates the migration and invasion of human gastric cancer cells by regulating expression of fibronectin and MMP2/MMP9. Taken together, MTA1 was involved in the pathogenesis of gastric cancer and might be a candidate therapeutic target in gastric cancer. Keywords: cell cycle, cell adhesion, migration

  1. High K+-Induced Relaxation by Nitric Oxide in Human Gastric Fundus

    Kim, Dae Hoon; Choi, Woong; Sung, Rohyun; Kim, Hun Sik; Kim, Heon; Yoo, Ra Young; Park, Seon-Mee; Yun, Sei Jin; Song, Young-Jin; Xu, Wen-Xie; Lee, Sang Jin

    2012-01-01

    This study was designed to elucidate high K+-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high K+ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high K+-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 µM) and KT 5720 (1 µM) which block protein kinases (PKG and PKA) had no effect on high K+-induced relaxation. K+ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent K+ channel (KV) blocker, did not affect high K+-induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High K+-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high K+-induced relaxation that was activated by the nitric oxide/sGC pathway through a KV channel-dependent mechanism. PMID:23118553

  2. Adaptive Human Control Gains During Precision Grip

    Erik D. Engeberg

    2013-03-01

    Full Text Available Eight human test subjects attempted to track a desired position trajectory with an instrumented manipulandum (MN. The test subjects used the MN with three different levels of stiffness. A transfer function was developed to represent the human application of a precision grip from the data when the test subjects initially displaced the MN so as to learn the position mapping from the MN onto the display. Another transfer function was formed from the data of the remainder of the experiments, after significant displacement of the MN occurred. Both of these transfer functions accurately modelled the system dynamics for a portion of the experiments, but neither was accurate for the duration of the experiments because the human grip dynamics changed while learning the position mapping. Thus, an adaptive system model was developed to describe the learning process of the human test subjects as they displaced the MN in order to gain knowledge of the position mapping. The adaptive system model was subsequently validated following comparison with the human test subject data. An examination of the average absolute error between the position predicted by the adaptive model and the actual experimental data yielded an overall average error of 0.34mm for all three levels of stiffness.

  3. Gastric Cancer in the Setting of Persistently Elevated Human Chorionic Gonadotropin: A Case Report

    LaToya R. Walker

    2011-01-01

    Full Text Available A 35-year-old woman presented to the emergency room for the evaluation of failed surgical and medical management of a suspected ectopic pregnancy. When imaging studies were performed, she had lymphadenopathy and diffuse sclerosis of the osseous framework. Multiple biopsies were performed and revealed poorly differentiated metastatic carcinoma with signet ring features. Esophagogastroduodenoscopy confirmed the findings of a Stage IV gastric adenocarcinoma. Signs and symptoms of gastric carcinoma are vague. However, to our knowledge, an elevation in human chorionic gonadotropin (hCG is not an associated finding. Persistence of hCG has many causes from abnormal pregnancy to menopause and other forms of cancer.

  4. Gastric cancer in the setting of persistently elevated human chorionic gonadotropin: a case report.

    Walker, Latoya R; Erler, Brian

    2011-01-01

    A 35-year-old woman presented to the emergency room for the evaluation of failed surgical and medical management of a suspected ectopic pregnancy. When imaging studies were performed, she had lymphadenopathy and diffuse sclerosis of the osseous framework. Multiple biopsies were performed and revealed poorly differentiated metastatic carcinoma with signet ring features. Esophagogastroduodenoscopy confirmed the findings of a Stage IV gastric adenocarcinoma. Signs and symptoms of gastric carcinoma are vague. However, to our knowledge, an elevation in human chorionic gonadotropin (hCG) is not an associated finding. Persistence of hCG has many causes from abnormal pregnancy to menopause and other forms of cancer.

  5. Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823

    Wei Liu; Qing-Long Guo; Qi-Dong You; Li Zhao; Hong-Yan Gu; Sheng-Tao Yuan

    2005-01-01

    AIM: To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA.METHODS: Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR.RESULTS: After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells were exposedto GA for 24, 48 and 72 h, the IC50 value was 1.02±0.05, 1.41±0.20 and 1.14±0.19 μmol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by AnnexinV/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 μmol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR.CONCLUSION: The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis

  6. H pylori status and angiogenesis factors in human gastric carcinoma

    Anita Mangia; Alfredo Di Leo; Stefania Tommasi; Pasquale Berloco; Jian Ming Xu; Angelo Paradiso; Annalisa Chiriatti; Girolamo Ranieri; Ines Abbate; Maria Coviello; Giovanni Simone; Francesco Alfredo Zito; Severino Montemurro; Antonello Rucci

    2006-01-01

    AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels.METHODS: Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELI SA, respectively.RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041).Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026).CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic character istics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.

  7. Role of human GKN1 on APP processing in gastric cancer.

    Di Stadio, Chiara Stella; Altieri, Filomena; Minopoli, Giuseppina; Miselli, Giuseppina; Rippa, Emilia; Arcari, Paolo

    2017-04-01

    Gastrokine 1 (GKN1) is highly expressed in gastric tissue and is secreted into the stomach but is not expressed in gastric cancer. GKN1 belongs to the BRICHOS domain family and plays a major role in maintaining gastric mucosa integrity. We previously demonstrated that a recombinant human GKN1 protein was able to interact with the amyloid precursor protein (APP) and was endowed with an anti-amyloidogenic property because it inhibited polymerization of the Aβ(1-40) peptide released from APP upon its partial hydrolysis. Here, we report that GKN1 can act as a physiological suppressor of Aβ production in gastric cancer cells. GKN1 blocked the access of γ-secretase to APP, thereby facilitating the cleavage of APP by α- and β-secretases. GKN1 directly interacted with APP C-terminal fragments, C83 and C99. In addition, it did not affect γ-secretase activity in gastric cancer cells because it did not alter Notch1 processing. GKN1-mediated inhibition of APP processing might represent a new approach for the prevention and therapy of Alzheimer's disease (AD).

  8. Expression of differential nitric oxide synthase isoforms in human gastric mucosa infected with Helicobacter pylori

    屠振兴; 龚燕芳; 丁华; 许国铭; 李兆申; 满晓华

    2003-01-01

    Objective: To study the relationship between nitric oxide synthase (NOS) expression in human gastric mucosa and Helicobacter pylori (H.pylori) infection. Methods: Gastric mucosa samples were obtained from antrum of 33 patients received gastroendoscopy. H.pylori infection was confirmed by Giems staining and bacteria culture under microaerophilic conditions. Expression of iNOS, eNOS and nitrotyrosine were detected by immunohistochemistry. Results: (1) The positive rate of H. pylori infection was 66.7%(22/33). (2) iNOS positive staining in inflammatory cells was detected in 77.3%(17/22) of samples with H.pylori and 27.3%(3/11) without H.pylori infection (P0.05). (5) Moderate and severe infiltrations of inflammatory cells were found in 86.4%(19/22) of gastric biopsies with H. pylori and 9.1%(1/11) of samples without H. pylori infection (P<0.01). Conclusion: H.pylori infection might promote infiltration of mononuclear cells and macrophages in gastric mucosa and induce iNOS expression in these cells. The accumulated nitric oxide in local area may result in gastric mucosa damage.

  9. Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans

    Calbet, Jose A L; Holst, Jens Juul

    2004-01-01

    absorption and enterogastrone response, after the intragastric administration of complete cow milk proteins or their respective peptide hydrolysates in man. METHODS: Six healthy males were randomized to receive one of the following four solutions: whey whole protein (W), casein whole protein (C), whey......-like peptide-1 (GLP-1) and peptide YY (PYY) plasma responses were elicited by the four solutions. CONCLUSIONS: The rate of gastric emptying and the plasma GLP-1 and PYY responses to feeding with cow milk protein solutions in humans are independent of the degree of protein fractionation and are not altered...... by small differences in the amino acid composition or protein solubility. In contrast, the GIP response is accentuated when milk proteins are delivered as peptide hydrolysates....

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

    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.

  11. Reversion of multidrug resistance of human gastric cancer SGC7901/DDP cells by E2F-1 gene silencing

    廉超

    2014-01-01

    Objective To investigate the effects of E2F-1 gene silencing on multidrug resistance of human gastric cancer SGC7901/DDP cells and its possible mechanisms.Methods Gastric cancer SGC7901/DDP cells were seeded in 6 well plates and divided into three groups:the experimental group,blank control and the negative con-

  12. Redifferentiation of Human Gastric Cancer Cells Induced by Ascorbic Acid and Sodium Selenite

    2002-01-01

    Objective To explore the effects and mechanisms of ascorbic acid (AA) and sodium selenite (SS) on growth inhibition and redifferentiation in human gastric cancer cells. Methods In the present study, trypan blue dye exclusion method was used to determine the cell growth curve and mitotic index, cell electrophoresis and colonogenic potential were used as the indexes of redifferentiation. In order to find out the mechanisms of redifferentiation, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed, the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were evaluated. Results After treatment with AA 3 mol/L + SS 2μmol/L, the growth rate and mitotic index of human gastric cancer cells (MGc-803) decreased remarkably. The indexes related with cell malignancy were alleviated. For example, cell surface charge was obviously decreased, the electrophoresis rate was dropped from 2.21 to 1.15μm@s-1@V-1@cm-1. The indexes related with cell redifferentiation were promoted. For example, the colonogenic potential was decreased to 93.5%. These results indicated that redifferentiation of human gastric cancer cells was successfully induced by AA + SS. The activities of SOD and GPX were significantly higher, while the activity of CAT was slower in treated group than that in the control. The content of MDA was slightly decreased, GSH was sharply decreased, and H2O2 content was dramatically increased. Conclusion These results indicated that combination of ascorbic acid and sodium selenite may induce the redifferentiation of human gastric cancer cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and inducing the formation of H2O2, and altering the cell redox status. Combination of ascorbic acid and sodium selenite may be a potent anticancer agent for human gastric cancer.

  13. Growth inhibition and apoptosis induction of Sulindac on Human gastric cancer cells

    Yun-Lin Wu; Bo Sun; Xue-Jun Zhang; Sheng-Nian Wang; Heng-Yi He; Min-Min Qiao; Jie Zhong; Jia-Yu Xu

    2001-01-01

    AIM: To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC)cells. METHODS: The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG2and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX(2) and Bcl-2 were detected by Westem dot blotting. RESULTS: Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG2 and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG2 cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24hours incubation with sulindac at 2mmol. L-1 and 4mmol.L-1, the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG2 cells but not in MKN28 cells. CONCLUSION: Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater then that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.

  14. Epistatic adaptive evolution of human color vision.

    Shozo Yokoyama

    2014-12-01

    Full Text Available Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation. This initial step may be untangled by analyzing appropriate ancestral molecules, but it is a daunting task to recapitulate the evolution of non-additive (epistatic interactions of amino acids and function of a protein separately. To adapt to the ultraviolet (UV-free retinal environment, the short wavelength-sensitive (SWS1 visual pigment in human (human S1 switched from detecting UV to absorbing blue light during the last 90 million years. Mutagenesis experiments of the UV-sensitive pigment in the Boreoeutherian ancestor show that the blue-sensitivity was achieved by seven mutations. The experimental and quantum chemical analyses show that 4,008 of all 5,040 possible evolutionary trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Phylogenetic analysis further suggests that human ancestors achieved the blue-sensitivity gradually and almost exclusively by epistasis. When the final stage of spectral tuning of human S1 was underway 45-30 million years ago, the middle and long wavelength-sensitive (MWS/LWS pigments appeared and so-called trichromatic color vision was established by interprotein epistasis. The adaptive evolution of human S1 differs dramatically from orthologous pigments with a major mutational effect used in achieving blue-sensitivity in a fish and several mammalian species and in regaining UV vision in birds. These observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments.

  15. Epistatic Adaptive Evolution of Human Color Vision

    Yokoyama, Shozo; Xing, Jinyi; Liu, Yang; Faggionato, Davide; Altun, Ahmet; Starmer, William T.

    2014-01-01

    Establishing genotype-phenotype relationship is the key to understand the molecular mechanism of phenotypic adaptation. This initial step may be untangled by analyzing appropriate ancestral molecules, but it is a daunting task to recapitulate the evolution of non-additive (epistatic) interactions of amino acids and function of a protein separately. To adapt to the ultraviolet (UV)-free retinal environment, the short wavelength-sensitive (SWS1) visual pigment in human (human S1) switched from detecting UV to absorbing blue light during the last 90 million years. Mutagenesis experiments of the UV-sensitive pigment in the Boreoeutherian ancestor show that the blue-sensitivity was achieved by seven mutations. The experimental and quantum chemical analyses show that 4,008 of all 5,040 possible evolutionary trajectories are terminated prematurely by containing a dehydrated nonfunctional pigment. Phylogenetic analysis further suggests that human ancestors achieved the blue-sensitivity gradually and almost exclusively by epistasis. When the final stage of spectral tuning of human S1 was underway 45–30 million years ago, the middle and long wavelength-sensitive (MWS/LWS) pigments appeared and so-called trichromatic color vision was established by interprotein epistasis. The adaptive evolution of human S1 differs dramatically from orthologous pigments with a major mutational effect used in achieving blue-sensitivity in a fish and several mammalian species and in regaining UV vision in birds. These observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments. PMID:25522367

  16. Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.

    Murphy, D B

    2012-02-03

    BACKGROUND: Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. METHODS: In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg\\/kg morphine, or 0.09 mg\\/kg morphine plus 0.3 mg\\/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test. RESULTS: The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +\\/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +\\/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +\\/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +\\/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine. CONCLUSIONS: The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is

  17. Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells.

    Sabarwal, Akash; Agarwal, Rajesh; Singh, Rana P

    2017-02-01

    The anticancer effects of fisetin, a dietary agent, are largely unknown against human gastric cancer. Herein, we investigated the mechanisms of fisetin-induced inhibition of growth and survival of human gastric carcinoma AGS and SNU-1 cells. Fisetin (25-100 μM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells. We also observed that growth suppression and death of non-neoplastic human intestinal FHs74int cells were minimally affected by fisetin. Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells. DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP. Fisetin-induced apoptosis was observed to be independent of p53. DCFDA and MitoSOX analyses showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion. It also increased cellular nitrite and superoxide generation. Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin-induced DNA damage. The formation of comets were observed in only fisetin treated cells which was blocked by NAC pre-treatment. Further investigation of the source of ROS, using mitochondrial respiratory chain (MRC) complex inhibitors, suggested that fisetin caused ROS generation specifically through complex I. Collectively, these results for the first time demonstrated that fisetin possesses anticancer potential through ROS production most likely via MRC complex I leading to apoptosis in human gastric carcinoma cells. © 2016 Wiley Periodicals, Inc.

  18. Helicobacter pylori enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human gastric epithelial cells

    Yi-Ying Wu; Hwei-Fang Tsai; We-Cheng Lin; Ai-Hsiang Chou; Hui-Ting Chen; Jyh-Chin Yang; Ping-I Hsu; Ping-Ning Hsu

    2004-01-01

    AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori(H pylori) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL onthe surface of infiltrating T-cells in Hpylori-infected gastric mucosa.METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pylori in vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from H pylori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry.RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pylorialone. Interestingly,the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori (Control vsTRAIL and H pylori: 0.51±0.06 vs 2.29±0.27,P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pylori was dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori.CONCLUSION: H pylori can sensitize human gastric epithelial ceils and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection.

  19. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

    Fabien J Cousin

    Full Text Available BACKGROUND: Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. METHODOLOGY/PRINCIPAL FINDINGS: A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. CONCLUSIONS/SIGNIFICANCE: Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

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

    Rossella Terragni

    Full Text Available 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.

  1. Effects of nicotine, dimethylphenylpiperazinium and tetramethylammonium on smooth muscles from feline and human gastric corpus.

    Janković, S M; Beleslin, D B

    2000-05-01

    Both excitatory and inhibitory intrinsic neurons could be found within the gastric wall, both of them receiving innervation from vagal fibres and being sensitive to nicotine. The effects of three nicotine receptor agonists, nicotine, tetramethylammonium (TMA) and 1,1-dimethyl-4-phenylpiperazinium (DMPP), on contractile activity of preparations isolated from feline and human gastric corpus wall were investigated. While DMPP (3.5x10(-8) to 5.9x10(-4)m) did not affect either spontaneous contractions or basal tension of isolated preparations from both species, TMA produced concentration-dependent tonic contractions of both circular and longitudinal isolated preparations from human (3.66x10(-5) to 5.10x10(-3)m) and feline (6. 1x10(-7) to 2.1x10(-3)m) stomach. On the other hand, nicotine (4. 1x10(-8) to 7.0x10(-4)m) produced concentration-dependent relaxation of only circular isolated preparations from feline gastric corpus. The effect of nicotine was sensitive to mecamylamine, and not to pancuronium, while the effect of TMA was sensitive to both mecamylamine and pancuronium. Although in our experiments DMPP had no effect, its excitatory action on gastric intrinsic neurons through the hexamethonium-insensitive pathway had already been described. The results of our study suggest that two different types of ganglion nicotine receptor exist together within the wall of feline stomach: (1) type N(N1)which is involved in relaxation and is sensitive only to nicotine and mecamylamine, and not to DMPP, TMA and pancuronium; (2) and type N(N2)which is involved in contraction of gastric muscle and sensitive to DMPP, TMA, mecamylamine and pancuronium, and not to nicotine.

  2. Human gastric mucins differently regulate Helicobacter pylori proliferation, gene expression and interactions with host cells.

    Emma C Skoog

    Full Text Available Helicobacter pylori colonizes the mucus niche of the gastric mucosa and is a risk factor for gastritis, ulcers and cancer. The main components of the mucus layer are heavily glycosylated mucins, to which H. pylori can adhere. Mucin glycosylation differs between individuals and changes during disease. Here we have examined the H. pylori response to purified mucins from a range of tumor and normal human gastric tissue samples. Our results demonstrate that mucins from different individuals differ in how they modulate both proliferation and gene expression of H. pylori. The mucin effect on proliferation varied significantly between samples, and ranged from stimulatory to inhibitory, depending on the type of mucins and the ability of the mucins to bind to H. pylori. Tumor-derived mucins and mucins from the surface mucosa had potential to stimulate proliferation, while gland-derived mucins tended to inhibit proliferation and mucins from healthy uninfected individuals showed little effect. Artificial glycoconjugates containing H. pylori ligands also modulated H. pylori proliferation, albeit to a lesser degree than human mucins. Expression of genes important for the pathogenicity of H. pylori (babA, sabA, cagA, flaA and ureA appeared co-regulated in response to mucins. The addition of mucins to co-cultures of H. pylori and gastric epithelial cells protected the viability of the cells and modulated the cytokine production in a manner that differed between individuals, was partially dependent of adhesion of H. pylori to the gastric cells, but also revealed that other mucin factors in addition to adhesion are important for H. pylori-induced host signaling. The combined data reveal host-specific effects on proliferation, gene expression and virulence of H. pylori due to the gastric mucin environment, demonstrating a dynamic interplay between the bacterium and its host.

  3. Human β-defensin-3 induction in H pylori-infected gastric mucosal tissues

    K Kawauchi; A Yagihashi; N Tsuji; N Uehara; D Furuya; D Kobayashi; N Watanabe

    2006-01-01

    AIM: To examine human β-defensin-3 (hBD-3)expression in inflamed gastric mucosal tissues or MKN45 gastric cancer cells with or without H pylori infection for better understanding the innate immune response to H pylori.METHODS: We used reverse transcription-polymerase chain reactions and immunohistochemistry to examine hBD-3 expression in inflamed gastric mucosal tissues or MKN45 gastric cancer cells with or without H pylori.Effects of hBD-3 against H pylori were also evaluated.RESULTS: The mean mRNA expression of hBD-3 in H pylori-positive specimens was significantly higher than that in H pylori-negative specimens (P = 0.0002,Mann-Whitney). In addition, unlike uninfected samples,8 of 15 (53.33%) infected mucosal samples expressed hBD-3 protein. H pylori dose-dependently induced mRNA expression of hBD-3 in MKN45 cells, an effect inhibited by adding anti-toil-like receptor (TLR)-4 antibody. HBD-3 protein completely inhibited H pylori growth.CONCLUSION: Our results suggest that like hBD-2,hBD-3 may be involved in the pathophysiology of H pylori-induced gastritis.

  4. Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

    Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

    2011-01-01

    Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations.

  5. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

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

    2012-01-01

    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...

  6. Mechanism of Ascorbic Acid-induced Reversion Against Malignant Phenotype in Human Gastric Cancer Cells

    YA-XUAN SUN; QIU-SHENG ZHENG; GANG LI; DE-AN GUO; ZI-REN WANG

    2006-01-01

    Objective To find out the mechanisms of redifferentiation and reversion of malignant human gastric cancer cells induced by ascorbic acid. Methods Human gastric cancer cells grown in the laboratory were used. The Trypan blue dye exclusion method was used to determine the cell doubling time. The electrophoresis rate and colonogenic potential were the indices used to measure the rate of redifferentiation. The content of malondialdehyde (MDA) was measured using the thiobarbituric acid(TBA) method. The activities of superoxide dismutase (SOD), catalase (CAT) and the content of H2O2 were evaluated by spectrophotography. Results Six mmol/L ascorbic acid was used as a positive control. Human gastric cancer cells were treated with 75 μm hydrogen peroxide, which alleviated many of the malignant characteristics. For example, the cell surface charge obviously decreased and the electrophoresis rate dropped from 2.21 to 1.10 μm·s-1·V-1·cm-1. The colonogenic potential, a measure of cell differentiation, decreased 90.2%. After treatment with ascorbic acid, there was a concentration- and time-dependent increase in hydrogen peroxide (H2O2) and the activity of superoxide dismutase (SOD). However, the activity of catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and 3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically significant differences between the SOD and AT group and the H2O2 group. Conclusions Ascorbic acid induces growth inhibition and redifferentiation of human gastric cancer cells through the production of hydrogen peroxide.

  7. LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma

    Gang-Shi Wang; Meng-Wei Wang; Ben-Yan Wu; Xin-Yan Yang; Wei-Hua Wang; Wei-Di You

    2008-01-01

    AIM:To analyze the expression profiles of a human gastric-cancer-related gene,GCRG123,in human gastric signet-ring cell carcinoma tissues,and to perform bioinformatics analysis on GCRG123.METHODS:In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues,including 15 cases of signet-ring cell carcinoma,15 of intestinal-type adenocarcinoma,and 15 of normal gastric mucosa.Northnem blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues.Online software,including BLAST,Multalin and BLAT,were applied for bioinformatics analysis.National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses.RESULTS:The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm.Ten out of 15 cases of gastric signet ring cell carcinoma,normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression.Low GCRG123 expressionv was observed in gastric intestinal-type adenocarcinoma and normal gastric glands.Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue.BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1,L1).BLAT analysis indicated that GCRG123 mapped to all chromosomes.GCRG123 was found to integrate in the intron-17 and -23 of Rb,5' flanking region of IL-2 and clotting factor IX genes.CONCLUSION:GCRG123,an active member of the L1family,was up-regulated in human gastric signet-ring cell carcinoma.

  8. Etoposide Induces Mitochondria-Associated Apoptotic Cell Death in Human Gastric Carcinoma Cells

    LI Jing-hua; CHEN Yue; WANG Jia-si; KONG Wei; JIN Ying-hua

    2008-01-01

    Recent observations indicate that the resistance of apoptosis is an important process of tumor metastasis and metastases are the cause of 90% of human cancer death.Etoposide,a semisynthetic derivative of the podophyllotoxins,is a clinically used anti-cancer reagent,but the effects of it on metastatic gastric carcinoma cells are totally unknown.In this study,etoposide induced apoptotic cell death in human gastric adenocareinoma cell line SGC-7901,derived from metastatic lymph nodes,as evidenced by the analysis of DNA fragmentation,apoptotic body formation,caspase activation,and apoptosis specific changes in cell morphology is demonstrated.The depolarization of mitochondrial membrane and the release of cytochrome c were most early events in etoposide treated SGC-7901 cells,and were followed by caspase-3 activation and PARP cleavage.Caspase-8 activation was not detected under the same condition.Thus,it was proposed that etoposide induces caspase-associated apoptotic cell death in human metastatic gastric carcinoma,which is initiated by mitochondrial cytochrome c release.

  9. Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide

    Mao-tao HUANG; Zhi-xin CHEN; Bing WEI; Bo ZHANG; Chun-hui WANG; Ming-hui HUANG; Rui LIU; Cheng-wei TANG

    2007-01-01

    Aim:To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib (a cyclooxygenase [COX]-2 inhibitor) combined with octreotide. Methods:Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling (TUNEL) assay. Gastric cancer microvessel density (MVD) and the expression of COX-2 were evaluated by immunohistochemlcal staining. The expression of somatostatin receptor (SSTR)-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drugactivated gene (NAG)-I was measured by RT-PCR. Results:Compared with the control and celecoxib groups,more necrosis in the combination group was observed. The apoptotic rate in the combination group (7.06%±0.67%) was sig nificantly higher than that in the control group (6.23%±1.29%,P<0.05). The MVD decreased considerably in the combination group. The upregulation of NAG-1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib (48%) was significantly higher than that of control group (12%) after surgery (P<0.05). Conclusion:Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG-1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.

  10. Low intensity ultrasound-induced apoptosis in human gastric carcinoma cells

    Yi Feng; Zhong-Min Tian; Ming-Xi Wan; Zhao-Bin Zheng

    2008-01-01

    ALIM:To investigate the low intensity ultrasound(US)-induced apoptosis in human gastric carcinoma cells and its potential mechanism and to suggest a new therapeutic approach to gastric carcinoma.METHODS:Human SGC-7901 gastric carcinoma cells were cultured in vitro and irradiated by low intensity US for 10 min at different intensities with different incubation times after irradiation.Morphologic changes were examined under microscope with trypan blue staining and then the percentage of early apoptotic cells was detected by flow cytometry(FCM)with double staining of fluorescein isothiocyanate(FITC)-Annexin V/propidium iodide(PI).Two-dimensional electrophoresis(2DE)was used to get the protein profile and some proteins differently expressed after US irradiation were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Functional analysis was performed to investigate the mechanism of US-induced cell apoptosis.RESULTS:The percentage of apoptotic cells increased about 10% after US irradiation(12.0 W/cm2,12 h culture).The percentage of early apoptosis and secondary necrosis in the US-irradiated cells increased with the increased US intensity.Moreover,apoptotic cells increased with the increased culture time after US irradiation and reached its maximum at about 12 h.Several new proteins appeared after US irradiation and were up or down regulated more than 2 times.Some heat shock proteins(HSPs)were found to be associated with the signal process simulating the apoptosis of cells.CONCLUSION:Low intensity US could induce apoptosis in human gastric carcinoma cells.US-induced apoptosis is related to US intensity/culture time.US-induced apoptosis may be caspases-dependent and endoplasmic reticulum(ER)stress-triggered apoptosis may also contribute to it.Proteomic experimental system is useful in finding the protein alteration in carcinoma cells after US irradiation,helping to develop a new cancer therapy.

  11. SIGNIFICANCE OF Skp2 EXPRESSION IN HUMAN GASTRIC CARCINOMA AND THE RELATIONSHIP BETWEEN Skp2,p27 AND PTEN EXPRESSION

    MA Xiu-mei; ZUO Lian-fu

    2005-01-01

    Objective: S-phase kinase-associated protein 2 (Skp2) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis. In this study, we investigated significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression. Methods: Immunohistochemical analysis was performed on 138 surgical resected primary gastric carcinoma specimens, 102 paired metastasis carcinoma tissue specimens in lymph node from the same set of 138 surgical resected primary gastric carcinoma specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, and 20 normal gastric mucosa specimens for Skp2 and performed on the same set of 138 surgical resected primary gastric carcinoma specimens for p27 and PTEN. Results: Skp2 labeling frequency % was increased dramatically in intestinal metaplasia, dysplasia, and primary gastric carcinoma compared with normal gastric mucosa (P=0.000, all the same). Skp2 labeling frequency % in metastasis gastric carcinoma in lymph node was significantly higher than primary gastric carcinoma (P=0.037). Skp2 labeling frequency % was positively associated with differentiated degree (rho=0.315, P=0.000), vessel invasion (rho=0.303, P=0.000) and lymph node metastasis (rho=0.254, P=0.000) respectively.An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in gastric carcinoma (rho=-0.451, P=0.000) and with its putative negative regulator, the PTEN tumor suppressor protein (rho=-0.480, P=0.000).p27 expression had positive relationship with PTEN expression in gastric carcinoma (rho=0.642, P=0.000). Conclusion:Skp2 overexpression is correlated with carcinogenesis and progression of gastric carcinoma: elevated Skp2 expression is correlated with decreased p27 and PTEN in gastric carcinoma, and p27 expression is parallel with PTEN expression

  12. Visceral response to acute retrograde gastric electrical stimulation in healthy human

    Shu-Kun Yao; Mei-Yun Ke; Zhi-Feng Wang; Da-Bo Xu; Yan-Li Zhang

    2005-01-01

    AIM: To investigate the visceral response to acute retrograde gastric electrical stimulation (RGES) in healthy humans and to derive optimal parameters for treatment of patients with obesity.METHODS: RGES with a series of effective parameters were performed via a bipolar mucosal electrode implanted along the great curvature 5 cm above pylorus of stomach in 12 healthy human subjects. Symptoms associated with dyspepsia and other discomfort were observed and graded during RGES at different settings, including long pulse and pulse train. Gastric myoelectrical activity at baseline and during different settings of stimulation was recorded by a multi-channel electrogastrography.RESULTS: The gastric slow wave was entrained in all the subjects at the pacing parameter of 9 cpm in frequency, 500 ms in pulse width, and 5 mA in amplitude.The frequently appeared symptoms during stimulation were satiety, bloating, discomfort, pain, sting, and nausea. The total symptom score for each subject significantly increased as the amplitude or pulse width was adjusted to a higher scale in both long pulse and pulse train. There was a wide diversity of visceral responses to RGES among individuals.CONCLUSION: Acute RGES can result in a series of symptoms associated with dyspepsia, which is beneficial to the treatment of obesity. Optimal parameter should be determined according to the individual sensitivity to electrical stimulation.

  13. Characterization of gastrins and their receptor in solid human gastric adenocarcinomas

    Goetze, Jens Peter; Eiland, Signe; Svendsen, Lars Bo;

    2013-01-01

    OBJECTIVE: The gastrin and the gastrin/CCK-B receptor genes are co-expressed in several carcinomas. The primary translational product, progastrin, however, is processed to several peptides of which only those that are α-amidated at their C-terminus are receptor ligands. So far, characterization...... of the progastrin-derived peptides in gastric cancer has not been reported. The authors therefore examined the molecular nature of gastrin and its receptor in human gastric carcinomas. MATERIALS AND METHODS: Twenty patients with adenocarcinoma underwent partial or total gastrectomy. In samples from each carcinoma...... blotting. RESULTS: α-Amidated gastrins were detectable in 16 of 20 carcinomas (median concentration 2.1 pmol/g tissue; range 0-386 pmol/g tissue). The tissue concentrations correlated closely to the gastrin mRNA contents (r = 0.75, p amidated processing intermediates...

  14. From lifetime to evolution: timescales of human gut microbiota adaptation

    2014-01-01

    Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The gut microbiota continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily varia...

  15. Immunotherapy in gastric cancer.

    Matsueda, Satoko; Graham, David Y

    2014-02-21

    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.

  16. Transduction motif analysis of gastric cancer based on a human signaling network

    Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

    2014-04-04

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  17. The role of geography in human adaptation.

    Graham Coop

    2009-06-01

    Full Text Available Various observations argue for a role of adaptation in recent human evolution, including results from genome-wide studies and analyses of selection signals at candidate genes. Here, we use genome-wide SNP data from the HapMap and CEPH-Human Genome Diversity Panel samples to study the geographic distributions of putatively selected alleles at a range of geographic scales. We find that the average allele frequency divergence is highly predictive of the most extreme F(ST values across the whole genome. On a broad scale, the geographic distribution of putatively selected alleles almost invariably conforms to population clusters identified using randomly chosen genetic markers. Given this structure, there are surprisingly few fixed or nearly fixed differences between human populations. Among the nearly fixed differences that do exist, nearly all are due to fixation events that occurred outside of Africa, and most appear in East Asia. These patterns suggest that selection is often weak enough that neutral processes -- especially population history, migration, and drift -- exert powerful influences over the fate and geographic distribution of selected alleles.

  18. The role of geography in human adaptation.

    Coop, Graham; Pickrell, Joseph K; Novembre, John; Kudaravalli, Sridhar; Li, Jun; Absher, Devin; Myers, Richard M; Cavalli-Sforza, Luigi Luca; Feldman, Marcus W; Pritchard, Jonathan K

    2009-06-01

    Various observations argue for a role of adaptation in recent human evolution, including results from genome-wide studies and analyses of selection signals at candidate genes. Here, we use genome-wide SNP data from the HapMap and CEPH-Human Genome Diversity Panel samples to study the geographic distributions of putatively selected alleles at a range of geographic scales. We find that the average allele frequency divergence is highly predictive of the most extreme F(ST) values across the whole genome. On a broad scale, the geographic distribution of putatively selected alleles almost invariably conforms to population clusters identified using randomly chosen genetic markers. Given this structure, there are surprisingly few fixed or nearly fixed differences between human populations. Among the nearly fixed differences that do exist, nearly all are due to fixation events that occurred outside of Africa, and most appear in East Asia. These patterns suggest that selection is often weak enough that neutral processes -- especially population history, migration, and drift -- exert powerful influences over the fate and geographic distribution of selected alleles.

  19. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

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

    Bennett, M W

    2012-02-03

    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.

  1. Mechanisms behind changes in gastric acid and bicarbonate outputs during the human interdigestive motility cycle.

    Dalenbäck, J; Fändriks, L; Olbe, L; Sjövall, H

    1996-01-01

    Human gastric interdigestive acid and bicarbonate outputs vary cyclically in association with the migrating motor complex (MMC). These phenomena were studied in 26 healthy volunteers by constant-flow gastric perfusion, with continuous recording of pH and Pco2 in mixed gastric effluent and concomitant open-tip manometry of gastroduodenal motility. Stable acid and bicarbonate outputs were registered during less than 50% of the MMC cycle. Acid secretion started to increase 71 +/- 3% into the cycle, with maximum output during antral phase III. Bicarbonate output increased biphasically 1) 40 +/- 5% into the cycle, coinciding with reflux of bile, and 2) at the end of duodenal phase III when the aspirate was devoid of bile. The bicarbonate peak associated with phase III was abolished by atropine (0.01 mg/kg iv, n = 8) and by pyloric occlusion (n = 9) but remained unchanged after omeprazole (n = 10). The acid peak was abolished by both atropine and omeprazole. It is concluded that the MMC-related changes in acid and alkaline outputs represent two different and independent phenomena. Acid secretion cyclicity is due to periodical variations in cholinergic stimulation of the parietal cells. In contrast, the phase III-associated increase in bicarbonate output is due to duodenogastric reflux.

  2. Effect of bile salts and bile acids on human gastric mucosal epithelial cells

    Yinxue Song; Jun Gong

    2008-01-01

    Objective:To explore the effect of bile salt and bile acid on cultured eternalized human gastric mucosa epithelium GES-1 cells.Methods:Cultured eternalized human gastric mucosa epithelium GES-1 cells were treated with media containing 6 different kinds of bile salts and 3 different kinds of bile acids and their mixture with different concentrations: GCDC(glycochenodeoxycholate), GDC (glycodeoxycholate), GC(glycocholate), TCDC(taurochenodeoxycholate), TDC(taurodeoxycholate), TC (taurocholate), LCA (lithocholicacid), CA(cholic acid), DCA(deoxycholic acid)(50 μ mol/L,250 μ mol/L,500 μ mol/L, 1000 μ mol/L), DY(mixture of bile salts) and DS(mixture of bile acids)(250 μ mol/L,500 μ mol/L,1000 μ mol/L,1500 μ mol/L, 2000 μ mol/L), in comparison with thecontrol group(in normal media without bile salts and bile acids).Cell proliferation was assessed by MTT(3-[4,5-Dimethylthiaolyl]-2,5- diphenyl-tetrazolium bromide) assay for 72 hours with different concentrations and the apoptotic cells were assayed by flow cytometry (FCM) with Annex V-FITC conjugated with propidium iodide(PI) staining for 24 hours with different concentrations(1500,2000 μ mol/L).Results:There was no significant difference in morphology and cell proliferation in GC group after 24-72 h.Low concentration(50 μ mol/L) of GCDC, GDC, TCDC, TDC and TC accelerated gastric epithelial cell growth in a dosage-time dependent manner.At middle concentration (250-500 μ mol/L), it showed positive effect after 24-48 h, while negative effect after 72 h.At high concentration(1000 μ tool/L), it accelerated gastric epithelial cell growth after 24h and show consistent inhibition even leading to necrosis after 48-72 h.LCA and CA showed a positive effect on the concentration of 50 μ mol/L after 24-72 h, while 250-1000 It mol/L showed a trend towards apoptosis after 24-72 h.At 50-500 μ mol/L, DCA showed proliferation after 24 h and apoptosis after 48-72 h, but showed necrosis after 24-72 h at 1000 μ moiFL.DY and DS

  3. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres

    DeSano Jeffrey

    2008-09-01

    Full Text Available Abstract Background MicroRNAs (miRNAs, some of which function as oncogenes or tumor suppressor genes, are involved in carcinogenesis via regulating cell proliferation and/or cell death. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor. miR-34 targets Notch, HMGA2, and Bcl-2, genes involved in the self-renewal and survival of cancer stem cells. The role of miR-34 in gastric cancer has not been reported previously. In this study, we examined the effects of miR-34 restoration on p53-mutant human gastric cancer cells and potential target gene expression. Methods Human gastric cancer cells were transfected with miR-34 mimics or infected with the lentiviral miR-34-MIF expression system, and validated by miR-34 reporter assay using Bcl-2 3'UTR reporter. Potential target gene expression was assessed by Western blot for proteins, and by quantitative real-time RT-PCR for mRNAs. The effects of miR-34 restoration were assessed by cell growth assay, cell cycle analysis, caspase-3 activation, and cytotoxicity assay, as well as by tumorsphere formation and growth. Results Human gastric cancer Kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. Bcl-2 3'UTR reporter assay showed that the transfected miR-34s were functional and confirmed that Bcl-2 is a direct target of miR-34. Restoration of miR-34 chemosensitized Kato III cells with a high level of Bcl-2, but not MKN-45 cells with a low level of Bcl-2. miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth. Conclusion Our results demonstrate that in p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34 inhibits

  4. Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac

    Li Ma; Yong-Le Xie; Yi Yu; Qiu-Ning Zhang

    2005-01-01

    AIM: To investigate the effects of mitomycin (MMC)combined with sulindac on cell viability, apoptotic induction and expression of apoptosis-related gene Bcl-2 and cyclooxygenase-2 (COX-2)in gastric cancer SGC-7901cells.METHODS: Human gastric cancer SGC-7901 cells were divided into three treatment groups,namely sulindac treatment group, MMC treatment group and combined sulindac with MMC treatment group. After being treated with drugs, cell viability was examined by MTr assay.Flow cytometry was used to evaluate the cell cycle distribution and apoptotic rates. Morphology of the cells was observed under light microscope and interactive laser microscope. Expression of COX-2 and Bcl-2 was determined by immunocytochemical method.RESULTS: After exposure for 12 h to three kinds of drugs,gastric cancer SGC-7901 cells presented some morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Growth inhibition was more obvious in combined sulindac with MMC treatment group and sulindac treatment group than in MMC treatment group. The apoptotic rates in co-treated cells and MMC-treated cells 24 h after treatment were 12.0% and 7.2%, respectively.After exposure for 24 h to MMC, the expression of COX-2and Bcl-2 protein was up-regulated, COX-2 levels were down-regulated but Bcl-2 gene expression was not changed significantly in combined treatment group.CONCLUSION: MMC-induced apoptosis is reduced by up-regulating the expression of COX-2 and Bcl-2 genes.MMC combined with sulindac can suppress the growth of gastric cancer cells through induction of apoptosis mediated by down-regulation of apoptosis-related Bcl-2and COX-2 gene.

  5. TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells.

    Guleng, Bayasi; Han, Jia; Yang, Jin-Qiu; Huang, Qing-Wen; Huang, Jian-Kun; Yang, Xiao-Ning; Liu, Jing-Jing; Ren, Jian-Lin

    2012-04-01

    Increasing evidence indicates that in gastric epithelial cells, induction of TFF3 by hypoxia is mediated by HIF-1. Since VEGF is one of the most important angiogenic factors on cancer progression, we have started to investigate the possible link among HIF-1α, VEGF, and TFF3 in gastric cancer cells. We induced the hypoxic condition in SGC-7901cells using hypoxia-mimetic agent of CoCI2. SGC7901 cells were transfected with pcPUR + U6 plasmid carrying RNAi targeted to human TFF3 and selected puromycin-resistant pools to establish the stable knockdown of TFF3 cells. Our results showed the induction of HIF-1a via hypoxia and consequences of increased expressions of the TFF3 and VEGF in gastric cancer SGC-7901 cells. Overexpression of TFF3 upregulated the mRNA expressions of VEGF and HIF-1a induced by hypoxia, and stable knockdown of TFF3 impaired the mRNA upregulations of VEGF and HIF-1a induced by hypoxia. Furthermore, knockdown of TFF3 reduced the VEGF protein secretion: as VEGF secretion was increased time dependent manner in response to the hypoxia induction in TFF3-WT cells; however, VEGF production was significantly decreased in TFF3-KD cells (621 ± 89 vs. 264 ± 73 at 6 h and 969 ± 97 vs. 508 ± 69 at 12 h, P TFF3 mediated regulation of VEGF expression induced by hypoxia, and implicated that TFF3 might be applied as a potential anti-angiogenic target for treatment of gastric cancer.

  6. EFFECT OF ADENOVIRUS-MEDIATED p53 GENE TRANSFER ON APOPTOSIS AND RADIOSENSITIVITY OF HUMAN GASTRIC CARCINOMA CELL LINES

    张珊文; 肖绍文; 吕有勇

    2003-01-01

    Objective: To evaluate the effect of adenovirus- mediated p53 gene (Adp53) on apoptosis and radiosensitivity of human gastric carcinoma cell lines. Methods: Recombinant adenovirus expressing wild-type p53 gene was transferred into four human gastric carcinoma cell lines with different p53 genetic status. p53 protein expression was detected by immunohistochemistry assay and western blot assay. Cell survival was assessed using a clonogenic assay. TUNEL assay was used in determination of apoptosis. Four human gastric carcinoma cells infected with Adp53 were irradiated with 4Gy and cell cycle distribution and Sub-G1 peak were assayed by flow cytometry. Results: G2/M arrest, apoptosis and inhibition of tumor cell proliferation were induced by infection at Adp53 at 100 MOI which caused high transfer rate of wild-type p53 and strong expression of p53 protein in four human gastric carcinoma cells. The radio-enhancement ratio of Adp53 at 4Gy were 3.0 for W cell, 3.6 for M cell, 2.2 for neo cell and 2.5 for 823 cell in vitro. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and radiosensitivity of human gastric carcinoma cell lines in vitro independently on cellular intrinsic p53 status thus supporting the combination of p53 gene therapy with radiotherapy in clinical trials.

  7. Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest

    Long-Zhu Li; Hong-Xia Deng; Wen-Zhu Lou; Xue-Yan Sun; Meng-Wan Song; Jing Tao; Bing-Xiu Xiao; Jun-Ming Guo

    2012-01-01

    AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.

  8. Human urocortin II, a new CRF-related peptide, displays selective CRF(2)-mediated action on gastric transit in rats.

    Million, Mulugeta; Maillot, Céline; Saunders, Paul; Rivier, Jean; Vale, Wylie; Taché, Yvette

    2002-01-01

    Human urocortin (hUcn) II is a new member of the corticotropin-releasing factor (CRF) family that selectively binds to the CRF(2) receptor. We investigated the CRF receptors involved in mediating the effects of hUcn II and human/rat CRF (h/rCRF) on gut transit. Gastric emptying, 4 h after a solid meal, and distal colonic transit (bead expulsion time) were monitored simultaneously in conscious rats. CRF antagonists were given subcutaneously 30 min before intravenous injection of peptides or partial restraint (for 90 min). hUcn II (3 or 10 microg/kg i.v.) inhibited gastric emptying (by 45% and 55%, respectively) and did not influence distal colonic transit. The CRF(2) peptide antagonist astressin(2)-B blocked hUcn II action. h/rCRF, rat Ucn, and restraint delayed gastric emptying while accelerating distal colonic transit. The gastric response to intravenous h/rCRF and restraint was blocked by the CRF(2) antagonist but not by the CRF(1) antagonist CP-154,526, whereas the colonic response was blocked only by CP-154,526. None of the CRF antagonists influenced postprandial gut transit. These data show that intravenous h/rCRF and restraint stress-induced delayed gastric emptying involve CRF(2) whereas stimulation of distal colonic transit involves CRF(1). The distinct profile of hUcn II, only on gastric transit, is linked to its CRF(2) selectivity.

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

    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 lactose concentrations were associated with lower immediate postprandial % (all P intolerance.

  10. Morphological changes of apoptosis and cytotoxic effects induced by Caffeic acid phenethyl ester in AGS human gastric cancer cell line

    Amini-Sarteshnizi Nematollah

    2014-04-01

    Full Text Available Introduction: Gastric cancer is the fourth prevalent cancer and the second reason for cancer-associated mortalities worldwide. Caffeic acid phenethyl ester (CAPE is one of the main medicinal components of propolis. The aim of this study was to investigate the morphological apoptotic changes and cytotoxic effects of CAPE in human gastric adenocarcinoma cell line (AGS cell. Methods: AGS human gastric cancer cell line was cultured in Dulbecco’s Modified Eagle’s Medium (DMEM medium in vitro. Cytotoxic effects and morphological changes induced by 72 h treatment with CAPE at different concentrations on AGS cells were investigated by MTT assay test and inverted microscope, respectively. Results: CAPE in a concentration dependent fashion reduced viability of AGS cells. IC50 was obtained approximately 10 μM at 72 h treatment. Also, CAPE induced concentration-dependent morphological apoptotic changes and promoted complete apoptosis program in AGS human gastric cancer cell line. Conclusion: Our results strongly suggest that CAPE stimulates apoptotic process and leads to cell death. Therefore, CAPE could be useful in developing chemotherapeutic agents for treating human gastric cancer.

  11. Human Adaptive Mechatronics and Human-System Modelling

    Satoshi Suzuki

    2013-03-01

    Full Text Available Several topics in projects for mechatronics studies, which are ʹHuman Adaptive Mechatronics (HAMʹ and ʹHuman‐System Modelling (HSMʹ, are presented in this paper. The main research theme of the HAM project is a design strategy for a new intelligent mechatronics system, which enhances operatorsʹ skills during machine operation. Skill analyses and control system design have been addressed. In the HSM project, human modelling based on hierarchical classification of skills was studied, including the following five types of skills: social, planning, cognitive, motion and sensory‐motor skills. This paper includes digests of these research topics and the outcomes concerning each type of skill. Relationships with other research activities, knowledge and information that will be helpful for readers who are trying to study assistive human‐mechatronics systems are also mentioned.

  12. Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice

    Dao-Ming Liang; Jia-Yong Chen; Yi Zhang; Ping Gan; Jie Lin; An-Bao Chen

    2006-01-01

    AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo.METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model wasestablished successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method.RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%,58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P <0.05), whereas there were no significant differences (P >0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group.CONCLUSION: rhGH does not accelerate the proliferation of human gastric cancer cell in vivo.

  13. Astragalus saponins induce apoptosis in human gastric adenocarcinoma cells via a caspase 3-dependent pathway

    JOSHUA K S Ko; Kathy K W Auyeung

    2008-01-01

    Objective Many Asian countriea including China, Japan and Korea have very high incidence of gastric cancer, in which about 42 % cases occur in mainland China. The precise targets and underlying mechanisms are not well understood. Our previous study revealed that Astragalus saponins (AST) showed promising effects on the suppression of the growth of HT-29 human colon cancer cells and tumor xenograft by inhibiting cell proliferation and promoting apoptosis. In the present study, we investigated the anti-carcinogenic effects of AST in AGS human gastric adenocarcinoma cells and attempted to elucidate the underlying mechanisms. Methods Growth inhibition of AGS cells was determined by using the MTT viability test. Involvement of different members of the apoptotic cascade and other growth-related factors was explored by assessment of their protein expression using Western blot analysis. Distribution of cells in different phases of the cell cycle was assessed by flow eytometry. Results Our data indicate that AST induced growth-inhibition and apoptosis in AGS cells by activating caspase 3 with subsequent poly (ADP-ribose) polymerase (PARP) cleavage. Cell cycle arrest at the G2/M phase had been observed in AST-treated AGS cells. The anti-proliferative effect of AST was associated with modulation of eydin B1 and p21. We then demonstrate that AST could downregulate the expression of VEGF, of which interaction with its receptors is important for angiogenesis during tumor formation. Conclusions Our findings suggest that AST is an effective agent in gastric cancer treatment by inducing cell cycle arrest and apoptosis, of which anti-angiogenesis could be an alternative mode of action.

  14. Anomalous human behavior detection: an adaptive approach

    van Leeuwen, Coen; Halma, Arvid; Schutte, Klamer

    2013-05-01

    Detection of anomalies (outliers or abnormal instances) is an important element in a range of applications such as fault, fraud, suspicious behavior detection and knowledge discovery. In this article we propose a new method for anomaly detection and performed tested its ability to detect anomalous behavior in videos from DARPA's Mind's Eye program, containing a variety of human activities. In this semi-unsupervised task a set of normal instances is provided for training, after which unknown abnormal behavior has to be detected in a test set. The features extracted from the video data have high dimensionality, are sparse and inhomogeneously distributed in the feature space making it a challenging task. Given these characteristics a distance-based method is preferred, but choosing a threshold to classify instances as (ab)normal is non-trivial. Our novel aproach, the Adaptive Outlier Distance (AOD) is able to detect outliers in these conditions based on local distance ratios. The underlying assumption is that the local maximum distance between labeled examples is a good indicator of the variation in that neighborhood, and therefore a local threshold will result in more robust outlier detection. We compare our method to existing state-of-art methods such as the Local Outlier Factor (LOF) and the Local Distance-based Outlier Factor (LDOF). The results of the experiments show that our novel approach improves the quality of the anomaly detection.

  15. Human induced pluripotent stem cells labeled with lfuorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

    Chao Li; Wei-Lin Jin; Da-Xiang Cui; Jing Ruan; Meng Yang; Fei Pan; Guo Gao; Su Qu; You-Lan Shen; Yong-Jun Dang; Kan Wang

    2015-01-01

    Objective: Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with lfuorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cellsin vivo. Methods: Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. hTe mouse model was observed using a small-animal imaging system. hTe nude mice were irradiated under an external alternating magnetic ifeld and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cellsin vivo, as well as inhibited cancer growthin vivo through the external magnetic ifeld. Conclusion: FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.

  16. Tumorigenicity, Motility and Liver Metastasis of Human Gastric Carcinoma Lines with High Metastatic Potential in the Liver of Nude Mice

    1995-01-01

    To analyze the human gastric carcinoma metastasis to the liver, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded in vitro and subsequently injected into the spleens of nude mice. By repeating these proce-dures five times, we were able to obtain a cell line, designated AZ-H5c, with high metastatic potential in nude mice. It was observed that animals had liver metastasis in 10 of 12 (83%) c...

  17. Overexpression of SULT2B1b Promotes Angiogenesis in Human Gastric Cancer

    Wen Chen

    2016-03-01

    Full Text Available Background/Aims: Overexpression of cytosolic sulfotransferase 2B1b (SULT2B1b has been commonly found in colorectal and hepatocellular carcinoma, suggesting that SULT2B1b might act as a potential oncogenic protein. However, its clinical significance and biological role in gastric cancer progression remain largely unknown. Methods: Expressions of SULT2B1b in clinical gastric cancer (GC samples were examined using qRT-PCR and Western blot. Results: SULT2B1b was markedly overexpressed in human GC samples, and positively correlated with vessel density and associated with poor clinical features. We also demonstrated that overexpression of SULT2B1b resulted in increased tumor angiogenesis and tumor growth in mouse GC models. In addition, ablation of SULT2B1b in human GC cells lines BGC823 and MKN45 decreased the capability of the cells to recruit endothelial cells. Moreover, depletion of SULT2B1b in GC cells reduced VEGF-A expression by downregulating SP1 and AP2. Conclusion: Our results suggested that the SULT2B1b-mediated angiogenic pathway could serve as biomarkers for GC diagnosis and prognosis, and suppressing SULT2B1b-mediated angiogenic signaling might be a promising strategy for developing novel GC treatment.

  18. A Preliminary Observation of Weight Loss Following Left Gastric Artery Embolization in Humans

    Andrew J. Gunn

    2014-01-01

    Full Text Available Background/Objectives. Embolization of the left gastric artery (LGA, which preferentially supplies the gastric fundus, has been shown to produce weight loss in animal models. However, weight loss after LGA embolization in humans has not been previously established. The aim of this study was to evaluate postprocedural weight loss in patients following LGA embolization. Subjects/Methods. A retrospective analysis of the medical records of patients who underwent LGA embolization for upper gastrointestinal (GI bleeding was performed. Postprocedural weight loss in this group was compared to a control group of patients who had undergone embolization of other arteries for upper GI bleeding. Results. The experimental group (N=19 lost an average of 7.3% of their initial body weight within three months of LGA embolization, which was significantly greater than the 2% weight loss observed in the control group (N=28 (P=0.006. No significant differences were seen between the groups in preprocedural body mass index (BMI, age, postprocedural care in the intensive care unit, history of malignancy, serum creatinine, or left ventricular ejection fraction. Conclusions. The current data suggest that body weight in humans may be modulated via LGA embolization. Continued research is warranted with prospective studies to further investigate this phenomenon.

  19. Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil

    Jian Liu; Wei Tang; Xian-Jun Qu; Wen-Fang Xu; Shu-Xiang Cui; Yong Zhou; Yun-Xia Yuan; Ming-Hui Chen; Ruo-Han Wang; Ruo-Yan Gai; Masatoshi Makuuchi

    2006-01-01

    AIM:To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil (TFU)on human gastric carcinoma cell lines SGC-7901 and MKN-45.METHODS:Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo,RESULTS:TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight.CONCLUSION:TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.

  20. Effect of Evodiamine on Inducing Apoptosis of Human Gastric Cancer Cell Line SGC-7901 in Vitro

    LIU Shao-ping

    2014-09-01

    Full Text Available Objective: To explore the proliferation inhibition and apoptosis-inducing effect of evodiamine in human gastric cancer SGC-7901 cells. Methods: After 48 or 24 h exposure to different concentrations of evodiamine, cell proliferation was analyzed using tetrazolium blue (MTT assay while apoptosis and cell-cycle phase distribution using flow cytometry. Results: In 0.01~30.00 μg/mL range of concentrations, evodiamine inhibited the proliferation of SGC-7901 cells in dose-dependent manner, and the overall mean IC50 was (3.79±0.16 μg/mL; the apoptosis rate was increased from 3.4% to 7.0%, 13.8% and 36.3% at concentrations of 0, 0.5, 1.5 and 30 μg/mL of evodiamine, respectively; the percentage of cells accumulated in G2/M phase was increased from 17.26% to 98.92% in the cells treated with evodiamine for 24 h in 0.01~30.00 μg/mL range of concentrations. Conclusion: Evodiamine can inhibit the proliferation, induce apoptosis in human gastric cancer cell line SGC-7901 in vitro and arrest the cell cycle at the G2/M phase.

  1. Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype

    Jing Ye; Yun-Lin Wu; Shu Zhang; Zi Chen; Li-Xia Guo; Ruo-Yu Zhou; Hong Xie

    2005-01-01

    AIM: To investigate the inhibitory effect of specialized human telomerase antisense oligodeoxyribonucleotides on the growth of well (MKN-28), moderately (SGC-7901)and poorly (MKN-45) differentiated gastric cancer cell lines under specific conditions and its inhibition mechanism,and to observe the correlation between the growth inhibition ratio and the tumor pathologic subtype of gastric cancer cells.METHODS: Telomerase activity in three gastric cancer cell lines of variant tumor pathologic subtype was determined by modified TRAP assay before and after the specialized human telomerase antisense oligodeoxyribonucleotides were dealt with under specific conditions. Effect of antisense oligomer under specific conditions of the growth and viability of gastric cancer cell lines was explored by using trypan blue dye exclusion assay, and cell apoptosis was detected by cell morphology observation, flow cytometry and TUNEL assay.RESULTS: Telomerase activity was detected in well,moderately and poorly differentiated gastric cancer cell lines (the quantification expression of telomerase activity was 43.7TPG, 56.5TPG, 76.7TPG, respectively).Telomerase activity was controlled to 30.2TPG, 36.3TPG and 35.2TPG for MKN-28, SGC-7901 and MKN-45 cell lines respectively after treatment with human telomerase antisense oligomers at the concentration of 5 μmol/L, and was entirely inhibited at 10 μmol/L, against the template region of telomerase RNA component, whereas no inhibition effect was detected in missense oligomers (P<0.05). After treatment with antisense oligomers at different concentrations under specific conditions for 96 h, significant growth inhibition effects were found in MKN-45 and SGC-7901gastric cancer cell lines (the inhibition ratio was 40.89%and 71.28%), but not in MKN-28 cell lines (15.86%). The ratio of inactive SGC-7901 cells increased according to the prolongation of treatment from 48 to 96 h. Missense oligomers could not lead to the same effect (P<0

  2. Human Maternal Brain Plasticity: Adaptation to Parenting

    Kim, Pilyoung

    2016-01-01

    New mothers undergo dynamic neural changes that support positive adaptation to parenting and the development of mother-infant relationships. In this article, I review important psychological adaptations that mothers experience during pregnancy and the early postpartum period. I then review evidence of structural and functional plasticity in human…

  3. Effects of aqueous extract from Silybum marianum on adenosine deaminase activity in cancerous and noncancerous human gastric and colon tissues

    Bahadır Öztürk

    2015-01-01

    Full Text Available Objective: Investigation of possible effects of Silybum marianum extract (SME on adenosine deaminase (ADA activity in cancerous and noncancerous human gastric and colon tissues to obtain information about possible mechanism of anticancer action of S. marianum. Materials and Methods: Cancerous and noncancerous human gastric and colon tissues removed from patients by surgical operations were used in the studies. The extract was prepared in distilled water. Before and after treatment with the extract, ADA activities in the samples were measured. Results: ADA activity was found to be lowered significantly in cancerous gastric tissues but not in noncancerous gastric tissues after treatment with the SME. In the colon tissues, ADA activities were however found to increase after the treatment of SME. Conclusion: Our results suggest that the aqueous extract from S. marianum inhibits ADA activity in cancerous gastric tissues significantly. It is suggested that in addition to other proposed mechanisms, accumulated adenosine due to the inhibition of ADA might also play a part in the anticancer properties of the S. marianum.

  4. Adaptive Brake By Wire: From Human Factors to Adaptive Implementation

    Spadoni, Andrea

    2013-01-01

    The introduction of the Brake By Wire is replacing the traditional mechanical control systems with ECUs and it is raising the need to reproduce feelings of eliminated static mechanical components (i.e. hydraulic fluids, pumps and cylinders). Thanks to electromechanical actuators and human-machine interfaces (i.e. active pedal) it is possible to reproduce such feelings and, therefore, arbitrarily change their features. In this way it will be possible to customize the pedal feelings and the veh...

  5. Ghrelin stimulates gastric emptying and hunger in normal-weight humans

    Levin, F; Edholm, T; Schmidt, P T;

    2006-01-01

    CONTEXT: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. MAIN OBJECTIVE: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion...

  6. Effects of allitridi on cell cycle arrest of human gastric cancer cells

    Min-Wen Ha; Rui Ma; Li-Ping Shun; Yue-Hua Gong; Yuan Yuan

    2005-01-01

    AIM: To determine the effect of allitridi on cell cycle of human gastric cancer (HGC) cell lines MGC803 and SGC7901 and its possible mechanism.METHODS: Trypan blue dye exclusion was used to evaluate the proliferation, inhibition of cells and damages of these cells were detected with electron microscope.Flow cytometry and cell mitotic index were used to analyze the change of cell cycle, immunohistochemistry, and RT-PCR was used to examine expression of the p21WAF1 gene.RESULTS: MGC803 cell growth was inhibited by allitridi with 24 h IC50 being 6.4 μg/mL. SGC7901 cell growth was also inhibited by allitridi with 24 h IC50 being 7.3 μg/mL.After being treated with allitridi at the concentration of 12 μg/mL for 24 h, cells were found to have direct cytotoxic effects, including broken cellular membrane, swollen and vesiculated mitochondria and rough endoplasmic reticula,and mass lipid droplet. When cells were treated with allitridi at the concentration of 3, 6, and 9 μg/mL for 24 h, the percentage of G0/G1 phase cells was decreased and that of G2/M phase cells was significantly increased (P = 0.002)compared with those in the group. When cells were treated with allitridi at the concentration of 6 μg/mL, cell mitotic index was much higher (P = 0.003) than that of control group, indicating that allitridi could cause gastric cancer cell arrest in M phase. Besides, the expression levels of p21WAF1 gene of MGC803 cells and p21WAF1 gene of SGC7901 cells were remarkably upregulated after treatment.CONCLUSION: Allitridi can cause gastric cancer cell arrest in M phase, and this may be one of the mechanisms for inhibiting cell proliferation. Effect of allitridi on cells in M phas e may be associated with the upregulation of p21WAF1 genes. This study provides experimental data for clinical use of allitridi in the treatment of gastric carcinoma.

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

    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.

  8. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

    Yang Yang

    Full Text Available Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA, which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS, down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

  9. INHIBITION OF HUMAN EXPERIMENTAL GASTRIC CARCINOMA METASTASIS IN VIVO BY P-SELECTIN MONOCLONAL ANTIBODY

    陈金联; 陈维雄; 朱金水; 陈尼维; 姚明; 周同

    2001-01-01

    Objeetive To study the role of cell adhesion molecule P-selectin monoclonal antibody ( MAb ) in tumor metastasis of an orthotopic metastatic model. Methods SCID mice were implanted orthotopically SGC-7901 human gastric cancer tissue. 3d later, animals received i. v. injections of PBS or P-selectin MAb ( 100μg /injection ) twice weekly for 3 weeks. 42d after operation, all animals were sacrificed. Tissues from all organs were obtained for histopathological evaluation. Results 10 of the animals ( n = 11 ) treated with PBS were found to develop metastatic tumors in the regional lymph nodes, liver, and lung. In contrast, 2 of the animals ( n = 9 ) treated with P-selectin MAb developed metastatic tumors in the organs examined. The expression of P-selectin mRNA in gastric cancer tissue of SCID mice with tumor metastasis was higher than that without such metastasis. Conclusion P-selectin expression is associated with tumor metastasis, and the metastasis may be inhibited by the MAb.

  10. CLONING AND IDENTIFICATION OF A GENE RELATED TO THE DIFFERENTIATION OF HUMAN GASTRIC ADENOCARCINOMA CELLS

    王建华; 陈诗书

    2002-01-01

    Objective: To compare the differential expression of mRNA between MKN-28 (highly differentiated) and MKN-45 (poorly differentiated) gastric adenocarcinoma cells and identify genes involved in human gastric adenocarcinoma differentiation. Methods: Differential expression of mRNA between MKN-28 and MKN-45 adenocarcinoma cells was investigated by fluorescent differential display (FDD). Differentially expressed cDNA was analyzed by bio-informatics and confirmed by RT-PCR and Northern-blot. Results: 45 differential fragments were finally attained. One of them (No. 10) was an approximate 750 bp cDNA and highly up-regulated in MKN-45 cells as compared with MKN-28 cells. By using Blastn and UniGene database analysis, we found the fragment was mapped to chromosome 14q11.2(q12 and showed a significant homology to Bcl-2 binding protein gene (BNip3), which was recently identified encoding pro-apoptosis protein located in mitochondrial. Conclusion: The BNip3 induced apoptosis could be suppressed by interacting with bcl-2. The BNip3 gene in tumor cells might be up-regulated by the hypoxia response element through the HIF1a transcription factor, causing death of the hypoxic cells at the center of the tumor where vascularization is usually poor in the process of tumor development.

  11. Capsaicin-induced cell death in a human gastric adenocarcinoma cell line

    Yi-Ching Lo; Yuan-Chen Yang; I-Chieh Wu; Fu-Chen Kuo; Chi-Ming Liu; Hao-Wei Wang; Chao-Hung Kuo; Jeng-Yi Wu; Deng-Chyang Wu

    2005-01-01

    AIM: Capsaicin, a pungent ingredient found in red pepper,has long been used in spices, food additives, and drugs.Cell death induced by the binding of capsaicin was examined in a human gastric adenocarcinoma cell line (AGS cells).METHODS: By using XTT-based cytotoxicityassay, flow cytometry using the TUNEL method, and quantitation of DNA fragmentation, both cell death and DNA fragmentation were detected in AGS cells treated with capsaicin. By using Western blotting methods, capsaicin reduced the expression of Bcl-2, the antiapoptotic protein, in AGS cells in a concentration-dependent manner.RESULTS: After incubation of AGS cells with capsaicin for 24 h, cell viability decreased significantly in a dose-dependent manner. After incubation of AGS cells with capsaicin for 24 h, apoptotic bodies also significantly increased, and were again correlated with the dose of capsaicin. When the concentration of capsaicin was 1 mmol/L, the amount of DNA fragments also increased. Similar results werealso in the lower traces.CONCLUSION: These results suggest that capsaicininduced cell death might be via a Bcl-2 sensitive apoptotic pathway. Therefore, capsaicin might induce protection from gastric cancer.

  12. Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection

    Wang Yan

    2007-10-01

    Full Text Available Abstract Background The incidence of gastric cardiac adenocarcinoma (GCA has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised. Methods In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM from paired surgical specimens of human GCA. Results Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses. Conclusion These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.

  13. Genomic dysregulation in gastric tumors.

    Janjigian, Yelena Y; Kelsen, David P

    2013-03-01

    Gastric cancer is among the most common human malignancies and the second leading cause of cancer-related death. The different epidemiologic and histopathology of subtypes of gastric cancer are associated with different genomic patterns. Data suggests that gene expression patterns of proximal, distal gastric cancers-intestinal type, and diffuse/signet cell are well separated. This review summarizes the genetic and epigenetic changes thought to drive gastric cancer and the emerging paradigm of gastric cancer as three unique disease subtypes.

  14. PIV and CFD studies on analyzing intragastric flow phenomena induced by peristalsis using a human gastric flow simulator.

    Kozu, Hiroyuki; Kobayashi, Isao; Neves, Marcos A; Nakajima, Mitsutoshi; Uemura, Kunihiko; Sato, Seigo; Ichikawa, Sosaku

    2014-08-01

    This study quantitatively analyzed the flow phenomena in model gastric contents induced by peristalsis using a human gastric flow simulator (GFS). Major functions of the GFS include gastric peristalsis simulation by controlled deformation of rubber walls and direct observation of inner flow through parallel transparent windows. For liquid gastric contents (water and starch syrup solutions), retropulsive flow against the direction of peristalsis was observed using both particle image velocimetry (PIV) and computational fluid dynamics (CFD). The maximum flow velocity was obtained in the region occluded by peristalsis. The maximum value was 9 mm s(-1) when the standard value of peristalsis speed in healthy adults (UACW = 2.5 mm s(-1)) was applied. The intragastric flow-field was laminar with the maximum Reynolds number (Re = 125). The viscosity of liquid gastric contents hardly affected the maximum flow velocity in the applied range of this study (1 to 100 mPa s). These PIV results agreed well with the CFD results. The maximum shear rate in the liquid gastric contents was below 20 s(-1) at UACW = 2.5 mm s(-1). We also measured the flow-field in solid-liquid gastric contents containing model solid food particles (plastic beads). The direction of velocity vectors was influenced by the presence of the model solid food particle surface. The maximum flow velocity near the model solid food particles ranged from 8 to 10 mm s(-1) at UACW = 2.5 mm s(-1). The maximum shear rate around the model solid food particles was low, with a value of up to 20 s(-1).

  15. Effects of 5-FU combined compound Ginseng and Astragalus on biological behavior of human gastric cancer MGC-803 cells

    韦尉元

    2013-01-01

    Objective To observe the in vitro effects of 5-fluorouracil(5-FU) combined Compound Ginseng and Astragalus(CGA) on the biological behaviors such as the proliferation,the cloning,apoptosis and migration of human gastric cancer MGC-803 cells. Methods The cell proliferation inhibition rate was detected by MTT assay,

  16. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR

    Xiao-qing TANG; Hu BI; Jian-qiang FENG; Jian-guo CAO

    2005-01-01

    Aim: To investigate the reversal effects of curcumin on multidrug resistance (MDR)in a resistant human gastric carcinoma cell line. Methods: The cytotoxic effect of vincristine (VCR) was evaluated by MTT assay. The cell apoptosis induced by VCR was determined by propidium iodide (PI)-stained flow cytometry (FCM) and a morphological assay using acridine orange (AO)/ethidium bromide (EB) dual staining. P-glycoprotein (P-gp) function was demonstrated by the accumulation and efflux of rhodamine123 (Rh123) using FCM. The expression of P-gp and the activation of caspase-3 were measured by FCM using fluorescein isothiocyanate (FITC)-conjugated anti-P-gp and anti-cleaved caspase-3 antibodies, respectively.Results: Curcumin, at concentrations of 5 μmol/L, 10 μmol/L, or 20 μmol/L, had no cytotoxic effect on a parent human gastric carcinoma cell line (SGC7901) or its VCR-resistant variant cell line (SGC7901/VCR). The VCR-IC50 value of the SGC7901/VCR cells was 45 times more than that of the SGC7901cells and the SGC7901/VCR cells showed apoptotic resistance to VCR. SGC7901/VCR cells treated with 5μmol/L, 10 μmol/L, or 20 μmol/L curcumin decreased the IC50 value of VCR and promoted VCR-mediated apoptosis in a dose-dependent manner. Curcumin (10μmol/L) increased Rh 123 accumulation and inhibited the efflux of Rh 123 in S GC7901/VCR cells, but did not change the accumulation and efflux of Rh123 in SGC7901cells. P-gp was overexpressed in SGC7901/VCR cells, whereas it was downregulated after a 24-h treatment with curcumin (10 μmol/L). Resistant cells treated with 1μmol/L VCR alone showed 77% lower levels of caspase-3 activation relative to SGC7901 cells, but the activation of caspase-3 in the resistant cell line increased by 44% when cells were treated with VCR in combination with curcumin.Conclusion: Curcumin can reverse the MDR of the human gastric carcinoma SGC7901/VCR cell line. This might be associated with decreased P-gp function and expression, and the promotion of

  17. Effects of mifepristone on proliferation of human gastric adenocarcinoma cell line SGC-7901 in vitro

    Da-Qiang Li; Zhi-Biao Wang; Jin Bai; Jie Zhao; Yuan Wang; Kai Hu; Yong-Hong Du

    2004-01-01

    AIM: To explore the effects of mifepristone, a progesterone receptor (PR) antagonist, on the proliferation of human gastric adenocarcinoma cell line SGC-7 901 in vitro and the possible mechanisms involved.METHODS: In situ hybridization was used to detect theexpression of PR mRNA in SGC-7 901 cells. After treatment with various concentrations of mifepristone (2.5, 5, 10,20 μmol/L) at various time intervals, the ultrastructural changes, cell proliferation, cell-cycle phase distribution, and the expression of caspase-3 and Bcl-XL were analyzed using transmission electron microscopy (TEM), tetrazolium blue(MTT) assay, 3H-TdR incorporation, flow cytometry, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Mifepristone markedly induced apoptosis and inhibited cell proliferation of PR- positive SGC-7 901 cells revealed by TEM, MTT assay and 3H-TdR incorporation, in a dose- and time-dependent manner. The inhibitory rate was increased from 8.98% to 51.29%. Flow cytometric analysis showed mifepristone dose-dependently decreased cells in S and G2/M phases, increased cells in Go/G1 phase,reduced the proliferative index from 57.75% to 22.83%. In addition, mifepristone up-regulated the expression of caspase-3, and down- regulated the Bcl-XL expression, dose-dependently.CONCLUSION: Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7 901 in vitro through multiple mechanisms, and may be a beneficial agent against human adenocarcinoma.

  18. Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells

    Ming-Quan Song; Jin-Shui Zhu; Jin-Lian Chen; Long Wang; Wei Da; Li Zhu; Wei-Ping Zhang

    2007-01-01

    AIM:To investigate the synergistic effect of oxymatrine (OM) and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cell lines SGC-7901,MKN-45,MKN-74.METHODS:Human gastric cancer lines SGC-7901,MKN-45,MKN-74 were treated with OM in the absence and presence of NM-3. The inhibitory rates were detected by MTT assay. Synergistic effect of OM and NM-3 on the growth of survivin,bcl-2,bax and p53 in SGC-7901 cells were examined by semiquantitative RT-PCR and Western blotting,and their growth inhibitory effects were also observed on SGC-7901 tumor xenograft in nude mice.RESULTS:OM combined with NM-3 exhibited a synergistic inhibitory effect on the growth of SGC-7901,MKN-45 and MKN-74 cells in a time-dependent manner. Twenty-four hours after treatment with OM,NM-3 alone and their combination,mRNA expression of survivin and bcl-2 in SGC-7901 cells decreased,p53 mRNA expression increased. OM (4 g/L) combined with NM-3 significantly increased the expression of p53 mRNA and decreased the expression of survivin and bcl-2 compared with either agent alone (193% ± 34% vs 129% ± 12%; 44% ± 18% vs 92% ± 18%; 36 ± 17% vs 93% ± 23%, P<0.05). Western blotting showed that the synergistic effect of OM and NM-3 on protein translation of survivin, bcl-2 and p53 was in accordance with their mRNAs. Furthermore, OM/NM-3 combination obviously exhibited antitumor growth effect in xenografted human gastric cancer cells SGC-7901 compared with either agent alone.CONCLUSION:OM combined with NM-3 has synergistic inhibitory effects on human gastric cancer cells in vitroand can suppress the growth of xenografted human gastric cancer cells SGC-7901 in vivo.

  19. Human Adaptation and the Ingenuity Gap

    Thomas Homer-Dixon

    2003-07-01

    Full Text Available I have been working for many years on the problem of adaptation: how societies or organisms, species, or systems of various kinds adapt to complex and rapid change. In this paper, I will outline my theories and my thinking about adaptation as summarized in the book, The Ingenuity Gap. I will also highlight five aspects of education for the future: education for complexity and what that means; education for reconnection to the micro and macro scales around us; education that increases our respect for experiential knowledge; education that will encourage a recognition of our connectivity through time, from the present into the future; and finally, education to broaden our conception of values. I’ll touch on each one of these points in my presentation today.

  20. Dual adaptation and adaptive generalization of the human vestibulo-ocular reflex

    Welch, R. B.; Bridgeman, B.; Williams, J. A.; Semmler, R.

    1998-01-01

    In two experiments, we examined the possibility that the human vestibulo-ocular reflex (VOR) is subject to dual adaptation (the ability to adapt to a sensory rearrangement more rapidly and/or more completely after repeated experience with it) and adaptive generalization (the ability to adapt more readily to a novel sensory rearrangement as a result of prior dual adaptation training). In Experiment 1, the subjects actively turned the head during alternating exposure to a visual-vestibular rearrangement (target/head gain = 0.5) and the normal situation (target/head gain = 0.0). These conditions produced both adaptation and dual adaptation of the VOR but no evidence of adaptive generalization when tested with a target/head gain of 1.0. Experiment 2, in which exposure to the 0.5 gain entailed externally controlled (i.e., passive) whole body rotation, resulted in VOR adaptation but no dual adaptation. As in Experiment 1, no evidence of adaptive generalization was found.

  1. Effects of garlic oil on tumoragenecity and intercellular communication in human gastric cancer cell line

    2000-01-01

    Previous studies have demonstrated that garlic oil (GO) and its anti-tumor compound could inhibit DNA and RNA synthesis in human cancer cells.In order to explore the effects of garlic oil on carcinoma cells,a gastric carcinoma cell line,BGC-823 was studied at cellular and molecular levels after garlic oil treatment.Data showed that the cell differentiation and suppression of tumorigenicity were significantly induced in tumor cells after garlic oil treatment.There was a correlation between the cell-cell communication recovery and the increase of p53 and waf1/p21 gene expression in garlic oil-treated cells.This result suggested that tumor suppressor gene waf1/p21 and wt p53 might play an important role in this effect.

  2. Effects of garlic oil on tumoragenecity and intercellular communication in human gastric cancer cell line

    李晓光; 谢锦玉; 李文梅; 季加孚; 崔建涛; 赵敏; 孙梅; 吕有勇

    2000-01-01

    Previous studies have demonstrated that garlic oil (GO) and its anti-tumor compound could inhibit DNA and RNA synthesis in human cancer cells. In order to explore the effects of garlic oil on carcinoma cells, a gastric carcinoma cell line, BGC-823 was studied at cellular and molecular levels after garlic oil treatment. Data showed that the cell differentiation and suppression of tumorigenicity were significantly induced in tumor cells after garlic oil treatment. There was a correlation between the cell-cell communication recovery and the increase of p53 and waf1/p21 gene expression in garlic oil-treated cells. This result suggested that tumor suppressor gene waf1/p21 and wt p53 might play an important role in this effect.

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

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    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.

  4. Adaptations to local environments in modern human populations.

    Jeong, Choongwon; Di Rienzo, Anna

    2014-12-01

    After leaving sub-Saharan Africa around 50000-100000 years ago, anatomically modern humans have quickly occupied extremely diverse environments. Human populations were exposed to further environmental changes resulting from cultural innovations, such as the spread of farming, which gave rise to new selective pressures related to pathogen exposures and dietary shifts. In addition to changing the frequency of individual adaptive alleles, natural selection may also shape the overall genetic architecture of adaptive traits. Here, we review recent advances in understanding the genetic architecture of adaptive human phenotypes based on insights from the studies of lactase persistence, skin pigmentation and high-altitude adaptation. These adaptations evolved in parallel in multiple human populations, providing a chance to investigate independent realizations of the evolutionary process. We suggest that the outcome of adaptive evolution is often highly variable even under similar selective pressures. Finally, we highlight a growing need for detecting adaptations that did not follow the classical sweep model and for incorporating new sources of genetic evidence such as information from ancient DNA.

  5. Alphastatin downregulates vascular endothelial cells sphingosine kinase activity and suppresses tumor growth in nude mice bearing human gastric cancer xenografts

    Lin Chen; Tao Li; Rong Li; Bo Wei; Zheng Peng

    2006-01-01

    AIM: To investigate whether alphastatin could inhibit human gastric cancer growth and furthermore whether sphingosine kinase (SPK) activity is involved in this process.METHODS: Using migration assay, MTT assay and Matrigel assay, the effect of alphastatin on vascular endothelial cells (ECs) was evaluated in vitro. SPK and endothelial differentiation gene (EDG)-1, -3, -5 mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR). SPK activity assay was used to evaluate the effect of alphastatin on ECs. Matrigel plug assay in nude mice was used to investigate the effect of alphastatin on angiogenesis in vivo. Female nude mice were subcutaneously implanted with human gastric cancer cells (BGC823) for the tumor xenografts studies.Micro vessel density was analyzed in Factor Ⅷ-stained tumor sections by the immunohistochemical SP method.RESULTS: In vitro, alphastatin inhibited the migration and tube formation of ECs, but had no effect on proliferation of ECs. RT-PCR analysis demonstrated that ECs expressed SPK and EDG-1, -3, -5 mRNAs. In vivo,alphastatin sufficiently suppressed neovascularization of the tumor in the nude mice. Daily administration of alphastatin produced significant tumor growth suppression. Immunohistochemical studies of tumor tissues revealed decreased micro vessel density in alphastatin-treated animals as compared with controls.CONCLUSION: Downregulating ECs SPK activity may be one of the mechanisms that alphastatin inhibits gastric cancer angiogenesis. Alphastatin might be a useful and relatively nontoxic adjuvant therapy in the treatment of gastric cancer.

  6. High concentrations of human β-defensin 2 in gastric juice of patients with Helicobacter pylori infection

    Hajime Isomoto; Shigeru Kohno; Hiroshi Mukae; Hiroshi Ishimoto; Yoshito Nishi; Chun-Yang Wen; Akihiro Wada; Ken Ohnita; Toshiya Hirayama; Masamitsu Nakazato

    2005-01-01

    AIM: Human β-defensin (HBD)-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori (H pylori). We sought to determine HBD-1 and HBD-2 concentrations in gastric juice duringH pylori infection.METHODS: HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 H pylori-infected and 33 uninfected subjects and before and after anti-H pyloritreatment in 13 patients with H pylori-associated gastritis. Interleukin (IL)-1β and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography (RP-HPLC)was used to identify HBD-2.RESULTS: HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in H pylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in H pylori-infected mucosa by RPHPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1β levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1concentrations were similar in H pylori-infected and uninfected subjects.CONCLUSION: Our results place the β-defensins, especially HBD-2, in the front line of innate immune defence.Moreover, HBD-2 may be involved in the pathogenesis of H pylori-associated gastritis, possibly through its function as immune and inflammatory mediator.

  7. The direct effect of estrogen on cell viability and apoptosis in human gastric cancer cells.

    Qin, Jian; Liu, Min; Ding, Qianshan; Ji, Xiang; Hao, Yarong; Wu, Xiaomin; Xiong, Jie

    2014-10-01

    Epidemiology researches indicated that gastric cancer is a male-predominant disease; both expression level of estrogen and expression pattern of estrogen receptors (ERs) influence its carcinogenesis. But the direct effect of estrogen on gastric cancer cells is still unclear. This study aimed to explore the direct effect of β-estradiol (E2) on gastric cancer cells. SGC7901 and BGC823 were treated with a serial of concentrations of E2. The survival rates of both the cell lines were significantly reduced, and the reduction of viability was due to apoptosis triggered by E2 treatment. Caspase 3 was activated in response to the increasing E2 concentration in both SGC7901 and BGC823. Cleaved Caspase 3 fragments were detected, and the expression levels of Bcl-2 and Bcl-xL were reduced. Apoptosis was further confirmed by flow cytometry. The expression level of PEG10, an androgen receptor target gene, was reduced during E2 treatment. Both ERα and ERβ were expressed in these cell lines, and the result of bioinformatics analysis of gastric cancer from GEO datasets indicated that the expression levels of both ERα and ERβ were significantly higher in noncancerous gastric tissues than in gastric cancer tissues. Our research indicated that estrogen can reduce cell viability and promote apoptosis in gastric cancer cells directly; ERs expression level is associated with gastric cancer. Our research will help to understand the mechanism of gender disparity in gastric cancer.

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

    Ming-Ming Tsai

    2016-06-01

    Full Text Available 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.

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

    Xue, Gang [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Zou, Xi [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Zhou, Jin-Yong [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Sun, Wei [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Wu, Jian [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Xu, Jia-Li [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Wang, Rui-Ping, E-mail: ruipingwang61@hotmail.com [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    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.

  10. From lifetime to evolution: timescales of human gut microbiota adaptation.

    Quercia, Sara; Candela, Marco; Giuliani, Cristina; Turroni, Silvia; Luiselli, Donata; Rampelli, Simone; Brigidi, Patrizia; Franceschi, Claudio; Bacalini, Maria Giulia; Garagnani, Paolo; Pirazzini, Chiara

    2014-01-01

    Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota (GM) is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The GM continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies.

  11. From lifetime to evolution: timescales of human gut microbiota adaptation

    Sara eQuercia

    2014-11-01

    Full Text Available Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The gut microbiota continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies.

  12. Down-regulation of AP-4 inhibits proliferation, induces cell cycle arrest and promotes apoptosis in human gastric cancer cells.

    Xinghua Liu

    Full Text Available BACKGROUND: AP-4 belongs to the basic helix-loop-helix leucine-zipper subgroup; it controls target gene expression, regulates growth, development and cell apoptosis and has been implicated in tumorigenesis. Our previous studies indicated that AP-4 was frequently overexpressed in gastric cancers and may be associated with the poor prognosis. The purpose of this study is to examine whether silencing of AP-4 can alter biological characteristics of gastric cancer cells. METHODS: Two specific siRNAs targeting AP-4 were designed, synthesized, and transfected into gastric cancer cell lines and human normal mucosa cells. AP-4 expression was measured with real-time quantitative PCR and Western blot. Cell proliferation and chemo-sensitivity were detected by CCK-8 assay. Cell cycle assay and apoptosis assay were performed by flow cytometer, and relative expression of cell cycle regulators were detected by real-time quantitative PCR and Western blot, expression of the factors involved in the apoptosis pathway were examined in mRNA and protein level. RESULTS: The expression of AP-4 was silenced by the siRNAs transfection and the effects of AP-4 knockdown lasted 24 to 96 hrs. The siRNA-mediated silencing of AP-4 suppressed the cellular proliferation, induced apoptosis and sensitized cancer cells to anticancer drugs. In addition, the expression level of p21, p53 and Caspase-9 were increased when AP-4 was knockdown, but the expression of cyclin D1, Bcl-2 and Bcl-x(L was inhibited. It didn't induce cell cycle arrest when AP-4 was knockdown in p53 defect gastric cancer cell line Kato-III. CONCLUSIONS: These results illustrated that gene silencing of AP-4 can efficiently inhibited cell proliferation, triggered apoptosis and sensitized cancer cells to anticancer drugs in vitro, suggesting that AP-4 siRNAs mediated silencing has a potential value in the treatment of human gastric cancer.

  13. Expression of Dnmt1, demethylase, MeCP2 and methylation of tumor-related genes in human gastric cancer

    Jing-Yuan Fang; Zhong-Hua Cheng; Ying-Xuan Chen; Rong Lu; Li Yang; Hong-Yin Zhu; Lun-Gen Lu

    2004-01-01

    AIM: To explore the effect of DNA methyltransferase,demethylase and methyl-CpG binding protein MeCP2 on the expressions and methylation of hMSH2 and protooncogene in human gastric cancer.METHODS: Paired samples of primary gastric cancer and corresponding para-cancerous, non-cancerous gastric mucosae were obtained from surgically resected specimens of 28 patients. Transcription levels of Dnmt1, mbd2, MeCP2, p16INK4A,hMSH2 and c-myc were detected by using real-time PCR or RT-PCR. Promoter methylation of p16INK4A, c-myc and hMSH2 genes was assayed by methylation-specific PCR (MSP) and sequencing (mapping). Their relationships were analyzed by Fisher's exact test using the software SPSS. RESULTS: The average mRNA level of Dnmt1 gene from cancerous tissue was higher and that of mbd2 gene from cancerous tissue was lower than that from non-cancerous tissue, respectively. mbd2 was lower in cancerous tissue than in non-cancerous tissue in 14 (50.0%) of patients but higher in 3 cases (10.7%) of non-cancerous gastric tissue (P<0.001). c-myc expression was up-regulated in cancer tissues (P<0.05). The up-regulation of mbd2 was found in all patients with hypomethylated c-myc. The transcriptional levels of p16INK4A and MeCP2 genes did not display any differencebetween gastric cancerous and matched non-cancerous tissues. There were down-regulation and hypermethylation of hMSH2 in cancer tissues, and the hypermethylation of hMSH2 coexisted with down-regulated transcription.However, the transcription level of the above genes was not associated with biological behaviours of gastric cancers.CONCLUSION: The up-regulation of proto-oncogene may be the consequence of epigenetic control of gene expression by demethylase, and mbd2 is involved in the regulation of hMSH2 expression in human gastric cancer.

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

    Bahadır Öztürk

    2016-01-01

    Full Text Available 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.

  15. Limited Value of KAI1/CD82 Protein Expression as a Prognostic Marker in Human Gastric Cancer

    Maximilian Knoener

    2012-01-01

    Full Text Available The cell surface glycoprotein KAI1/CD82 suppresses tumor growth and metastasis in animal models. This study aimed to evaluate the prognostic relevance of KAI1/CD82 protein expression in human gastric cancer. Primary gastric carcinomas (n = 271 with amean clinical follow-up time of 48months were immunostained using the monoclonal anti-KAI1/CD82 antibody G2. Staining was evaluated as negative versus positive for statistical analysis. KAI1/CD82 immunoreactivity was absent in 103/271 (38% cases. There was a trend towards KAI1/CD82 negativity in poorly differentiated cases (p = 0.0679. Moreover, KAI1/CD82-negative carcinomas were associated with a higher pT status (p = 0.0222, metastatic lymph node involvement (p = 0.0018 and a higher clinical tumor stage (p = 0.0050. The median overall survival times of KAI1/CD82-negative and KAI1/CD82-positive gastric carcinomas were 20 and 37 months, respectively (p = 0.2305. These results are in line with the proposed function of KAI1/CD82 as a suppressor of tumor growth and metastasis. However, these data suggest that KAI1/CD82, as detected by immunohistochemistry, is of limited value as a prognostic marker for gastric cancer in routine histological workup.

  16. Rapid interaction of Helicobacter pylori with microvilli of the polar human gastric epithelial cell line NCI-N87.

    Diesing, Anne-Kathrin; Nossol, Constanze; Faber-Zuschratter, Heidi; Zuschratter, Werner; Renner, Lydia; Sokolova, Olga; Naumann, Michael; Rothkötter, Hermann-Josef

    2013-12-01

    Infection with Helicobacter pylori results often in chronic gastritis, gastric ulcers or even gastric tumor development. Little is known about the initial interaction between gastric epithelial cells and H. pylori. The aim of the present study was to analyze the initial host contact to the bacteria. Monolayers of the human gastric epithelial cell line NCI-N87 grown on porous membranes were used and the apical side of the epithelium was exposed to the H. pylori wild-type strain P1 for 1 hr. Many epithelial cells were colonized by bacteria within the period of 60 min. Using scanning electron microscopy we detected that the bacteria were in close contact with the epithelia via microvilli. Further, transmission electron microscopy of the contact sites revealed no difference in the morphology of the microvilli in comparison to those not attached to the bacteria. The present study demonstrates the importance of microvilli on apical epithelial cells during the initial contact of the host by colonizing H. pylori.

  17. Interleukin-8 associates with adhesion, migration, invasion and chemosensitivity of human gastric cancer cells

    Wen-Xia Kuai; Qiong wang; Xiao-Zhong Yang; Yao Zhao; Ren Yu; Xiao-Jun Tang

    2012-01-01

    AIM:To investigate the relationship between Interleukin-8 (IL-8) and proliferation,adhesion,migration,invasion and chemosensitivity of gastric cancer (GC) cells.METHODS:The IL-8 cDNA was stably transfected into human GC cell line MKN-45 and selected IL-8-secreting transfectants.The expression of IL-8 in human GC cell line KATO-Ⅲ was inhibited by RNA interference.The expressions of mRNA and protein of IL-8 in GC cells were detected by real-time reverse transcriptionpolymerase chain reaction or enzyme-linked immunosorbent assay (ELISA).RESULTS:The overexpression of IL-8 resulted in an increased cell adhesion,migration and invasion,and a significant resistance to oxaliplatin in MKN-45 cells.Inhibition of IL-8 expression with small interfering RNA decreased the adhesion,migration and invasion functions and oxaliplatin resistance in KATO-Ⅲ cells.IL-8 increased NF-кB and Akt activities and adhesion molecules ICAM-1,VCAM-1,and CD44 expression in GC cells.CONCLUSION:Overexpression of IL-8 promotes the adhesion,migration,invasion,and chemoresistance of GC cells,indicating that IL-8 is an important therapeutic target in GC.

  18. Genotoxicity of low dose N-nitroso propoxur to human gastric cells.

    Kuo, H H; Shyu, S S; Wang, T C

    2008-05-01

    Propoxur is among the most popular insect control agents in subtropical countries such as Taiwan. As a member of the N-methylcarbamate insecticide group, propoxur is notorious for its potential for conversion into highly genotoxic N-nitroso derivatives. Due to the fact that the stomach has been identified as the major target for N-nitroso N-methylcarbamates, this investigation used a human gastric cell line, SC-M1, in order to obtain results pertinent to the authentic adverse effects of this compound on human health. This report reveals that at dose levels inhibiting propoxur induced significant amounts of DNA damage. Most of the damaged DNA was repaired within 24 h after treatment removal, such that an outcome with a significant induction of chromosomal aberrations was not observed. Gene mutations and anchorage independence, on the other hand, were significantly induced by this same treatment. In conclusion, exposure to low doses of N-nitroso propoxur is not cytotoxic nor clastogenic, nevertheless, has the potential to increase genetic instability and, possibly as a result, to enhance the malignant potential of treated cells. We suggest that although the damaged DNA was repaired during the transient G2/M arrest period, it was probably not done in an appropriate way which would preserve the original genetic stability.

  19. Adaptive Human aware Navigation based on Motion Pattern Analysis

    Tranberg, Søren; Svenstrup, Mikael; Andersen, Hans Jørgen

    2009-01-01

    Respecting people’s social spaces is an important prerequisite for acceptable and natural robot navigation in human environments. In this paper, we describe an adaptive system for mobile robot navigation based on estimates of whether a person seeks to interact with the robot or not. The estimates...... in a real world setting. The results demonstrate that the system is able to learn to navigate based on past interaction experiences, and to adapt to different behaviors over time....

  20. Expression of E-selectin, integrin β1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance

    Jin-Jing Ke; Qin-Shu Shao; Zhi-Qiang Ling

    2006-01-01

    AIM: To study the expression levels of E- selectin, integrin β1 and immunoglobulin supperfamily memberintercellular adhesion molecule-1 (ICAM-1) in human gastric carcinoma cells, and to explore the relationship between these three kinds of cell adhesion molecules and gastric carcinoma.METHODS: The serum contents of E-selectin, integrin β1 and ICAM-1 were detected by enzyme-linked immunosorbent assay (ELISA), in 47 healthy individuals (control group) and in 57 patients with gastric carcinoma (gastric carcinoma group) respectively prior to operation and 7 d after operation.RESULTS: The serum E-selectin, ECAM-1 and integrin β1were found to be expressed in both control and gastric carcinoma groups. However, they were highly expressed in patients with gastric carcinoma patients before operation or with unresectable tumours. The expression levels of ICAM-1 and integrin β1 were significantly higher in gastric carcinoma patients than in controls (P <0.01). A comparison of the E-selectin levels between the two groups showed statistically insignificant differnce (P = 0.64) In addition, the expression levels were all decreased substantially in the postoperative patients subjected to radical resection of the tumours, indicating that the high level expressions of these compounds might be the important factor for predicting the prognosis of these patients.CONCLUSION: Serum E-selectin, ICAM-1 and integrin β1 expression levels are probably related to the metastasis and relapse of gastric cancer.

  1. Roles of Fas signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells

    Kun Wu; Yao Li; Yan Zhao; Yu-Juan Shan; Wei Xia; Wei-Ping Yu; Lan Zhao

    2002-01-01

    AIM: To investigate the roles of Fas signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS: Human gastric cancer SGC-7901 cells were treated with VES at 5, 10, 20 mg@L-1, succinic acid and vitamin E as vehicle control and condition media only as untreated (UT) control. Apoptotic morphology was observed by DAPI staining. Western blot analysis was applied to measure the expression of Fas, FADD and caspase-8 proteins. After the cells were transiently transfected with Fas and FADD antisense oligonucleotides, respectively, caspase-8 activity was determined by flurometric method.RESULTS: The morphologically apoptotic changes were observed after VES treatment by DAPI staining. 23.7 % and 89.6 % apoptosis occurred after 24 h and 48 h of 20 mg@L-1 VES treatment, respectively. The protein levels of Fas, FADD and caspase-8 were evidently increased in a dose-dependent manner after 24 h of VES treatment. The blockage of Fas by transfection with Fas antisense oligonucleotides obviously inhibited the expression of FADD protein. After SGC-7901 cells were transfected with Fas and FADD antisense oligonucleotides, caspase-8 activity was obviously decreased (P<0.01), whereas Fas blocked more than FADD.CONCLUSION: VES-induced apoptosis in human gastric cancer SGC-7901 cells involves Fas signaling pathway including the interaction of Fas, FADD and caspase-8.

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

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com; Cao, Zhifei, E-mail: hunancao@163.com

    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.

  3. Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

    Mariko Oki; Hiroyuki Yamamoto; Hiroaki Taniguchi; Yasushi Adachi; Kohzoh Imai; Yasuhisa Shinomura

    2008-01-01

    AIM: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (RGFR1) and ephrin ligands.METHODS: Eleven gastric carcinoma cell lines,24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue,74 conventional formalin-fixed,paraffin-embedded tumor specimens,and 55 specimens spotted on tissue microarray (TMA)were analyzed.Reverse transcription-PCR (RT-PCR),real-time RT-PCR,immunohistochemistry,and cell growth assays were performed.RESULTS: Overexpression of EphA4 mRNA expression was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues.Overexpression of EphA4,analyzed by immunohistochemistry,was observed in 62 (48%) of 129 gastric cancer tissues.EphA4 overexpression,at the protein level,was significantly associated with depth of invasion and recurrence.EphA4 overexpression was also correlated with FGFR1 overexpression.Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P= 0.0008).The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues.Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth.CONCLUSION: Our results suggest that overexpression of EphA4 plays a role in gastric cancer.

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

    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 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.

  5. Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis

    Zhang, Xuan; Zhao, Jing; Gao, Xiangyang; Pei, Dongsheng; Gao, Chao

    2017-01-01

    As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis.

  6. Effects of Spinach Powder Fat-Soluble Extract on Proliferation of Human Gastric Adenocarcinoma Cells

    HE TAo; HUANG CHENG-YU; CHEN HAl; HOU YUN-HUA

    1999-01-01

    Four kinds of assays were used to study the effect of a fat-soluble extract of spinach powder(SPFE) on the proliferation of human gastric adenocarcinoma cell line (SGC-7901) in vitro.These studies included: ( i ) cell growth assay, ( ii ) colony forming assay, ( iii ) MTT colorimetric assay, and ( iv ) 3H-TdR incorporation assay. The concentrations of SPFE expressed as the level of β-carotene in the medium were 2 × 10-s, 2 × 10-7 and 2 × 10-6 mol/L β-carotene in assays ( i ) ~ ( iii ), but 4 × 10-8, 4 × 10-7 and 4 × 10-6 mol/L β-carotene in assay ( iV ) respectively. The results indicated that SPFE inhibited the proliferation and colony forming ability of SGC-7901 cells. And in MTT assay, SPFE inhibited the viability of SGC-7901 cells, but no inhibitory effect of SPFE was observed on the viability of lymphocytes in peripheral blood of healthy people. Finally, in the 3H-TdR incorporation test, both SPFE and β-carotene showed significant inhibitory effects on DNA synthesis in SGC-7901 cells, but SPFE was more effective than 3-carotene.

  7. Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against the human gastric cancer.

    Igarashi, Akira; Konno, Hiroyuki; Tanaka, Tatsuo; Nakamura, Satoshi; Sadzuka, Yasuyuki; Hirano, Toru; Fujise, Yutaka

    2003-11-30

    Photodynamic therapy (PDT) has been established as a potent and less invasive treatment for gastrointestinal tumors. The aim of the present study was to investigate whether or not liposomalization of the photosensitizer enhanced the therapeutic efficacy of PDT. Photofrin (PF) was entrapped in multilammelar liposomes. Mice implanted with a human gastric cancer xenograft, were divided into a PF group and a liposomal photofrin (LPF) group and intravenously administered 10 mg/kg of PF or LPF (as a dose of PF), respectively. At 8 h after injection PF level in tumor tissue in the LPF group was significantly higher level by 2.4-fold of that in the PF group, whereas the PF levels in the skin were almost equal. Irradiation was performed with the excimer dye laser at 150 mW/cm(2), total dose 40 J, at 8 h after PF or LPF administration. The results revealed that the volume of necrotic tumor tissue was significantly higher in the LPF group than in the PF group. The apoptotic index of the tumor was also significantly higher in the LPF group. In conclusion, the liposomalization of the photosensitizer increased its tumor accumulation, with a resulting enhancement of the therapeutic effect of PDT.

  8. Relational adaptivity - enacting human-centric systems design

    Petersen, Kjell Yngve

    2016-01-01

    Human centered design approaches places the experiencing human at the center of concern, situated in relation to the dynamics of the environmental condition and the variables of the system of control and sensing. Taking the approach of enacted design methods to enforce the experience...... of the inhabitant as core in human-centered design solutions, the intelligence of the connected sensors is suggested to be developed as an actual learning and self-adjusting adaptive environment, where the adaptive system is part of a negotiation with users on the qualities of the environment. We will present...... and activity, driven by detailed encounters with human centered investigations and experiential accounts. The sensor system is a test environment, using a very elaborate system design to enable extensive variations in the sensor and network parameters. But, the suggestion is, that by using this kind of high...

  9. Effect of antisense human telomerase RNA on malignant behaviors of gastric carcinoma cell line SGC-7901

    YANG Jin-liang; FANG Dian-chun; YANG Shi-ming; LUO Yuan-hui; LUO Kun-lun; LU Rong; LIU Wei-wen

    2001-01-01

    Objective: To study the effects of antisense human telomerase RNA (ahTR) transfection on the malignant behaviors of gastric carcinoma cell line SGC-7901 and its potential role in gene therapy for tumor. Methods: An antisense hTR eukaryotic expression vector containing the sequence of template region of telomere repeats was transfected into gastric carcinoma cell line SGC-7901 with liposome DOTAP. The expressions of hTR RNA and antisense hTR RNA were observed with RT-PCR, telomerase activity with PCR-ELISA. Telomere length was measured with Southern blot. Cell morphology and cellular proliferation capacity were studied with MTT assay. Cell cycle distribution and apoptotic state were observed with flow cytometry. Efficiency of clone formation in soft agar and tumorigencity in nude mice were examined and evaluated in ahTR-transfected 7901 cells, and plasmid pCL-neo transfected 7901 cells and parental 7901 cells served as control. Results: An antisense hTR eukaryotic expression vector was transfected into 7901 cells successfully. The telomerase activity in ahTR-transfected 7901 cells was decreased from 100% to about 25%, and telomere length in the cells shortened from 4.08 kb to 3.35 kb at 60 population doublings (PDs). Compared with parental 7901 and pCL-neo transfected 7901 cells, ahTR-transfected 7901 cells displayed some morphological changes, including decreased cell atypia and nucleus/cytoplasm ratio under light microscope. Furthermore, ahTR-transfected 7901 cells displayed growth inhibition, decreased invasive capacity in Borden's chamber invasive model, increased G0/G1 phase rate and apoptotic rate, and restored contact inhibition and density inhibition. Surprisingly, ahTR-transfected 7901 cells lost their capacity of clone formation in soft agar and carcinogensis in nude mice. Conclusion: Antisense hTR transfection can induce 7901 cell differentiation and reverse its malignant phenotype. This study provides an exciting approach for cancer therapy through the

  10. Detection of cancer clones in human gastric adenoma by increased DNA-instability and other biomarkers

    A Sun

    2009-06-01

    Full Text Available An immunohistochemical differential staining of cancerous cells with anti-cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N HCl at 30°C for 20 min (DNA-instability test has been used as a marker of malignancy. The test was applied to bioptic tissues of human gastric polyp assessed histopathologically as foveolar hyperplastic polyp (13 cases, mild (58 cases, moderate (86 cases, and severe (20 cases dysplasia, and adenocarcinomas (14 cases. The serial sections of the same tissues were also subjected to immunohistochemical staining for Ki67, p53, DNA-fragmentation factor (DFF45, and basic fibroblast growth factor (bFGF. The DNA-instability test was positive in 14 (100% adenocarinoma cases, 20 (100% severe dysplasia cases, 52 (60.5% moderate dysplasia cases, and 12 (20.7% mild dysplasia cases, indicating malignancy. All foveolar hyperplastic polyps were negative to the DNA-instability testing. Furthermore, the percentage of glands positive in the DNA-instability test steadily increased in going from mild (10%, to moderate (40%, to severe (100% dysplasia, and adenocarcinoma (100%. All other biological markers tested in the present study showed significantly higher values in the adenoma glands, being positive to DNA-instability testing, irrespective of the dysplasia grade, as compared to those in the adenoma glands that were negative to DNA-instability testing. Furthermore, the former values were comparable to those in adenocarcinoma. These results indicate that cancer cell clones are already present at the adenoma stages showing a positive DNA-instability test, enhanced proliferative activity, p53 mutation, induction of DFF45 and bFGF. These factors allow cancer cell proliferation, producing heterogeneous subclones due to DNA-instability, enhancing their survival by escaping apoptosis, and providing abundant nutrients during the early-stage progression of gastric cancer. Based on these findings, we herein propose the

  11. Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR Activation Increases Hypoxia Inducible Factor-1α to Promote Loss of Cyclin D1 and G0/G1 Cell Cycle Arrest in Human Gastric Cells

    Canales, Jimena; Valenzuela, Manuel; Bravo, Jimena; Cerda-Opazo, Paulina; Jorquera, Carla; Toledo, Héctor; Bravo, Denisse; Quest, Andrew F. G.

    2017-01-01

    Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection.

  12. Sequencing of 50 human exomes reveals adaptation to high altitude

    Yi, Xin; Liang, Yu; Huerta-Sanchez, Emilia;

    2010-01-01

    Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which...... represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency...... difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus...

  13. Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts.

    Kudo, Masahisa; Yamamoto, Yoshiyuki; Koga, Yoshikatsu; Hamaguchi, Tetsuya; Akimoto, Tetsuo; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-12-01

    Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC-6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S-1 and NC-6004 were compared with those of S-1 and CDDP in a human gastric cancer model. In vitro cytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC-6004 and 5-fluorouracil (5-FU) were compared with the effects of CDDP and 5-FU using the combination index method. The in vivo antitumor effects of S-1/NC-6004 and S-1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, the in vivo antitumor effects did not differ between the S-1/NC-6004 and S-1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S-1/CDDP-treated mice. Our data warrant a clinical evaluation of S-1/NC-6004 combination therapy.

  14. Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer

    Pei-Hong Jiang; Yoshiharu Motoo; Stéphane Garcia; Juan Lucio Iovanna; Marie-Josèphe Pébusque; Norio Sawabu

    2006-01-01

    AIM: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1and p53 expression in gastric cancer.METHODS: TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed.RESULTS: TP53INP1 was expressed in 98% (139/142cases) of non-cancerous gastric tissues and was downexpressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%).Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3%vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients).P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues.A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed,loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P= 0.0006).CONCLUSION: TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may

  15. The human vestibulo-ocular reflex : effects of adaptation

    L.J.J.M. Boumans (Leon)

    1982-01-01

    textabstractThis thesis systematically investigates the influence of adaptation on the human VOR-response. Various types of angular acceleration around the vertical axis are used to determine the time constants of the VOR-system. Care is taken as far as possible to avoid fatigue, habituation and the

  16. Emigrating Beyond Earth Human Adaptation and Space Colonization

    Smith, Cameron M

    2012-01-01

    For four million years humankind has been actively expanding geographically and in doing so has adapted to a wide variety of hostile environments. Now we are looking towards the ultimate adaptation - the colonization of space. Emigrating Beyond Earth illustrates that this is not a technocratic endeavor, but a natural continuation of human evolution; a journey not just for the engineer and rocket scientist, but for everyman. Based on the most current understanding of our universe, human adaptation and evolution, the authors explain why space colonization must be planned as an adaptation to, rather than the conquest of, space. Emigrating Beyond Earth argues that space colonization is an insurance policy for our species, and that it isn't about rockets and robots, it's about humans doing what we've been doing for four million years: finding new places and new ways to live. Applying a unique anthropological approach, the authors outline a framework for continued human space exploration and offer a glimpse of a po...

  17. Inhibition of PKB/Akt activity involved in apigenin-induced apoptosis in human gastric carcinoma cells

    YUAN LinHong; XIA Wei; ZHAO XiuJuan; ZHANG XiaoHua; ZHANG Ling; WU Kun

    2007-01-01

    Apigenin is a flavonoid widely distributed in fruits and vegetables.It possesses growth inhibitory properties against numerous cancer cell lines.However, the molecular mechanism(s) by which apigenin elicits its effects have not been fully elucidated.Here we studied whether apigenin inhibits growth and induces apoptosis in human gastric carcinoma cells.We showed that the flavonoid inhibited growth of the cells and caused apoptosis, as evidenced by DNA Ladder, cleavage of pro-caspase-3 in a time-dependent manner.Induction of apoptosis was dependent on inhibition of the PKB/Akt activity.We found that while apigenin had no effect on the expression of Akt and Bad, it inhibited specific phosphorylation of the two proteins that are associated with pro-survival mechanisms.We propose that this important flavonoid induces apoptosis in gastric cancer cells by inhibiting Akt activity.Since Akt is often activated in cancers, our findings may have clinical implications.

  18. 15d-PGJ2 inhibits cell growth and induces apoptosis of MCG-803 human gastric cancer cell line

    Yun-Xian Chen; Xue-Yun Zhong; Yan-Fang Qin; Wang Bing; Li-Zhen He

    2003-01-01

    AIM: To investigate the influence of peroxisome proliferator activated receptor γ (PPARγ) ligand, 15-deoxy-△12, 14-prostaglandin J2 (15dPGJ2) on the proliferation and apoptosis of MCG-803 human gastric cancer cell lines.METHODS: Cell proliferation was measured by 3H-TdR assay. Apoptosis was determined by ELISA and TUNEL staining. Protein and mRNA level of bcl-2 family and COXs were measured by Western blotting and Northern blotting respectively. PGE2 production was examined by RIA.RESULTS: 15dPGJ2 inhibited cell growth and induced apoptosis of MlCG-803 cells. The COX-2 and bcl-2/bax ratios were decreased following 15dPGJ2 treatment. The PGE2production in supernatants was also decreased. These changes were in a dose-dependent manner.CONCLUSION: 15dPGJ2 may be a useful therapeutic agent for the treatment of gastric cancer.

  19. Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer.

    Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong

    2015-08-01

    Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.

  20. Down-regulated miR-9 and miR-433 in human gastric carcinoma

    Nie Na

    2009-06-01

    Full Text Available Abstract Background MircoRNAs(miRNAs are short, endogenously non-coding RNAs. The abnormal expression of miRNAs may be valuable for the diagnosis and treatment of tumors. Methods To screening the special miRNAs in gastric carcinoma, expression level of miRNAs in gastric carcinoma and normal gaster samples were detected by miRNA gene chip. Then, the expressions of miR-9 and miR-433 in gastric carcinoma tissue and SGC7901 cell line were validated by qRT-PCR. GRB2 and RAB34, targets of miR-433 and miR-9 respectively, were detected by Western blot. Results We found 19 miRNAs and 7 miRNAs were down-regulated and up-regulated respectively. Compared with normal gaster samples, our data showed that miR-9 and miR-433 were down-regulated in gastric carcinoma. Meanwhile, we also found that miR-433 and miR-9 regulated the expression levels of GRB2 and RAB34 respectively. Conclusion Our data show miR-9 and miR-433 was down-regulated in gastric carcinoma. The targets of miR-433 and miR-9 were tumor-associated proteins GRB2 and RAB34 respectively. This result provided the related information of miRNAs in gastric carcinoma.

  1. Human cytomegalovirus detection in gastric cancer and its possible association with lymphatic metastasis.

    Zhang, Liang; Guo, Gangqiang; Xu, Jianfeng; Sun, Xiangwei; Chen, Wenjing; Jin, Jinji; Hu, Changyuan; Zhang, Peichen; Shen, Xian; Xue, Xiangyang

    2017-02-08

    Increasing evidence suggests that human cytomegalovirus (HCMV) is associated with many human malignancies. However, its prevalence in gastric cancer (GC) and clinical association remain unknown. HCMV IgG and IgM antibodies in the sera of 80 GC patients and 80 healthy controls were detected using a microparticle enzyme immunoassay. The prevalence of HCMV UL47, UL55, UL56, and UL77 genes among 102 GC tumor tissues and adjacent normal specimens was measured by polymerase chain reaction (PCR) or nested PCR. Quantitative real-time PCR (Q-PCR) was used to determine viral load. Virus localization in neoplastic tissues was determined by immunohistochemistry. No significant difference of HCMV IgG and IgM seropositivity was found between GC patients and the healthy group. However, the overall HCMV DNA positivity rate was significantly higher in GC cancerous tissue compared with in paired normal tissue (P<0.01). HCMV infection was mainly localized in the tumorous epithelium. Q-PCR in HCMV-positive specimens indicated that the viral copy number was notably higher in GC tissues than in adjacent normal specimens (P<0.001). Clinical statistical analysis indicated that HCMV load in GC tumor tissue was positively associated with lymphatic metastasis (P=0.043), the area under the receiver operating characteristic (ROC) curve was 0.6638. Our data clearly provide the prevalence of HCMV in GC patients. We conclude that HCMV infection in malignant tissues might be associated with carcinogenesis or progression of GC and possibly relates to lymphatic metastasis.

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

    Saralamma, Venu Venkatarame Gowda; 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

    2015-09-18

    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.

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

    Venu Venkatarame Gowda Saralamma

    2015-09-01

    Full Text Available 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.

  4. Alterations in gastric mucin synthesis by Helicobacter p ylori

    James C. Byrd; Robert S. Bresalier

    2000-01-01

    Helicobacter pylori is recognized as a cause of chronic active gastritis, gastric and duodenal ulcers, and gastric cancer, though the mechanisms of pathogenesis for H. pylori-associated diseases are not yet well understood[1 -4] The ecological niche to which H. pylori is well-adapted is the mucous layer of the human gastric antrum, which has mucin glycoproteins as major constituents. Mucins, highmolecular weight carbohydrate-rich glycoproteins that coat the surface of the stomach and are secreted into the lumen, function to protect the stomach and could be important in H. pylori colonization. For further understanding the pathogenesis of H. pylori-related diseases, it is important to consider whether H. pylori colonization of the surface epithelium is associated, as cause or effect, with changes in the gastric mucin synthesized by surface mucous cells.

  5. Evolutionary Developmental Biology and Human Language Evolution: Constraints on Adaptation.

    Fitch, W Tecumseh

    2012-12-01

    A tension has long existed between those biologists who emphasize the importance of adaptation by natural selection and those who highlight the role of phylogenetic and developmental constraints on organismal form and function. This contrast has been particularly noticeable in recent debates concerning the evolution of human language. Darwin himself acknowledged the existence and importance of both of these, and a long line of biologists have followed him in seeing, in the concept of "descent with modification", a framework naturally able to incorporate both adaptation and constraint. Today, the integrated perspective of modern evolutionary developmental biology ("evo-devo") allows a more subtle and pluralistic approach to these traditional questions, and has provided several examples where the traditional notion of "constraint" can be cashed out in specific, mechanistic terms. This integrated viewpoint is particularly relevant to the evolution of the multiple mechanisms underlying human language, because of the short time available for novel aspects of these mechanisms to evolve and be optimized. Comparative data indicate that many cognitive aspects of human language predate humans, suggesting that pre-adaptation and exaptation have played important roles in language evolution. Thus, substantial components of what many linguists call "Universal Grammar" predate language itself. However, at least some of these older mechanisms have been combined in ways that generate true novelty. I suggest that we can insightfully exploit major steps forward in our understanding of evolution and development, to gain a richer understanding of the principles that underlie human language evolution.

  6. A ROBUST ADAPTIVE VIDEO ENCODER BASED ON HUMAN VISUAL MODEL

    Yin Hao; Zhang Jiangshan; Zhu Yaoting; Zhu Guangxi

    2003-01-01

    A Robust Adaptive Video Encoder (RAVE) based on human visual model is proposed. The encoder combines the best features of Fine Granularity Scalable (FGS) coding, framedropping coding, video redundancy coding, and human visual model. According to packet loss and available bandwidth of the network, the encoder adjust the output bit rate by jointly adapting quantization step-size instructed by human visual model, rate shaping, and periodically inserting key frame. The proposed encoder is implemented based on MPEG-4 encoder and is compared with the case of a conventional FGS algorithm. It is shown that RAVE is a very efficient robust video encoder that provides improved visual quality for the receiver and consumes equal or less network resource. Results are confirmed by subjective tests and simulation tests.

  7. A ROBUST ADAPTIVE VIDEO ENCODER BASED ON HUMAN VISUAL MODEL

    YinHao; ZhangJiangshan

    2003-01-01

    A Robust Adaptive Video Encoder (RAVE) based on human visual model is proposed.The encoder combines the best features of Fine Granularity Scalabla (FGS) coding,frame-dropping coding,video redundancy coding,and human visual model.According to packet loss and available bandwidth of the network,the encoder adjust the output bit rate by jointly adapting quantization step-size instructed by human visual model,rate shaping,and periodically inserting key frame.The proposed encoder is implemented based on MPEG-4 encoder and is compared with the case of a conventional FGS algorithm.It is shown that RAVE is a very efficient robust videl encoder that provides improved visual quality for the receiver and consumes equal or less network resource.Results are confirmed by subjective tests and simulation tests.

  8. Adaptations to climate-mediated selective pressures in humans.

    Angela M Hancock

    2011-04-01

    Full Text Available Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans.

  9. Localizing recent adaptive evolution in the human genome

    Williamson, Scott H; Hubisz, Melissa J; Clark, Andrew G;

    2007-01-01

    Identifying genomic locations that have experienced selective sweeps is an important first step toward understanding the molecular basis of adaptive evolution. Using statistical methods that account for the confounding effects of population demography, recombination rate variation, and single......-nucleotide polymorphism ascertainment, while also providing fine-scale estimates of the position of the selected site, we analyzed a genomic dataset of 1.2 million human single-nucleotide polymorphisms genotyped in African-American, European-American, and Chinese samples. We identify 101 regions of the human genome......, clusters of olfactory receptors, genes involved in nervous system development and function, immune system genes, and heat shock genes. We also observe consistent evidence of selective sweeps in centromeric regions. In general, we find that recent adaptation is strikingly pervasive in the human genome...

  10. The apoptotic effect of apigenin on human gastric carcinoma cells through mitochondrial signal pathway.

    Chen, Jiayu; Chen, Jiaqi; Li, Zhaoyun; Liu, Chibo; Yin, Lihui

    2014-08-01

    This study aims to explore the apoptotic function of apigenin on the gastric cancer cells and the related mechanism. The gastric cancer cell lines HGC-27 and SGC-7901, and normal gastric epithelial cell line GES1 were treated with different concentrations of apigenin. Cell proliferation was tested. Morphological changes of the apoptotic cells were observed after Hoechst33342 staining. The apoptosis rate of the gastric cancer cells were measured with flow cytometry. Changes of the cell cycle were explored. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Bcl-2 family proteins and caspases-3 expression with apigenin treatment was analyzed by real-time PCR. Cell proliferation of HGC-27 and SGC-7901 was inhibited by apigenin, and the inhibition was dose-time-dependent. Gastric carcinoma cells treated by apigenin had no obvious cell cycle arrest, but were observed with the higher apoptosis rate and the typical apoptotic morphological changes of the cell nucleus. JC-1 staining showed that apigenin could reduce mitochondrial membrane potential of gastric carcinoma cells. Real-time PCR results showed that apigenin significantly increased caspase-3 and Bax expression level, and down-regulated Bcl-2 expression in a dose-dependent manner in gastric carcinoma cells. However, the GES1 was almost not affected by apigenin treatment. Apigenin can inhibit cell lines HGC-27 and SGC-7901 proliferation in a time and dose-dependent manner, reduce anti-apoptotic protein Bcl-2 levels, enhance apoptosis-promoting protein Bax level, result in mitochondrial membrane potential decreasing and caspase-3 enzyme activating, then lead to cell apoptosis.

  11. rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy

    Guang-Xia Chen; Li-Hong Zheng; Shi-Yu Liu; Xiao-Hua He

    2011-01-01

    AIM:To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.METHODS:Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone,oxaliplatin (OXA) alone,or a combination of both.Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-yl)-3,5-diphenytetrazoli-umromide assay and the expression levels of p53,Bax and Bcl-2 were determined by immunohistochemistry.The presence of apoptosis and the expression of cas-pase-3 were determined using flow cytometry.RESULTS:Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose-dependent manner;moreover,significant synergistic effects were observed when these treatments were combined.Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone,OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells.Furthermore,flow cytometry showed that rAd-p53 alone,OXA alone or combination treatment induced apoptosis of gastric cancer cells,which was accompanied by increased expression of caspase-3.CONCLUSION:rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis.Thus,our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.

  12. Relation of overexpression of S phase kinase-associated protein 2 with reduced expression of p27 and PTEN in human gastric carcinoma

    Xiu-Mei Ma; Ying Liu; Jian-Wen Guo; Jiang-Hui Liu; Lian-Fu Zuo

    2005-01-01

    AIM: To investigate the significance of S phase kinaseassociated protein 2 (Skp2) expression in human gastric carcinoma and the relation between expressions of Skp2,p27 and PTEN.METHODS: Immunohistochemical analysis was performed on 138 gastric carcinoma specimens, their paired adjacent mucosa specimens, 102 paired lymphatic metastatic carcinoma tissue specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, 10chronic superficial gastritis specimens and 5 normal gastric mucosa specimens for Skp2 expression and on 138 gastric carcinoma specimens for p27 and PTEN expression.RESULTS: Skp2 labeling frequency was significantly higher in intestinal metaplasia (12.68±0.86) and adjacent mucosa (19.32±1.22) than in normal gastric mucosa (0.53±0.13) and chronic superficial gastritis (0.47±0.19) (P = 0.000); in dysplasia (16.74±0.82) than in intestinal metaplasia (P = 0.000); in gastric primary carcinoma (31.34±2.17) than in dysplasia and adjacent mucosa (P = 0.000); in metastasis gastric carcinoma in lymph nodes (39.76±2.00) than in primary gastric carcinoma (P = 0.037), respectively. Skp2 labeling frequency was positively associated with differentiation degree (rho = 0.315, P = 0.000), vessel invasion (rho = 0.303, P = 0.000) and lymph node metastasis (rho = 0.254, P = 0.000) of gastric cancer. Expression of Skp2 was negatively associated with p27(rho = -0.451, P = 0.000) and PTEN (rho = -0.480,P = 0.000) expression in gastric carcinoma. p27 expression was positively associated with PTEN expression in gastric carcinoma (rho = 0.642, P = 0.000).CONCLUSION: Skp2 overexpression may be involved in carcinogenesis and progression of human gastric carcinoma in vivo, possibly via p27 proteolysis. PTEN may regulate the expression of p27 by negatively regulating Skp2 expression.

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

    Charlotta Hedner

    Full Text Available 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.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.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.

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

    Chiara Di Lorenzo

    2016-07-01

    Full Text Available 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 (TNFα-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.

  15. Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line

    Jing-Pin Lin; Jai-Sing Yang; Jau-Hong Lee; Wen-Tsong Hsieh; Jing-Gung Chung

    2006-01-01

    AIM: To investigate the relationship between the inhibited growth (cytotoxic activity) of berberine and apoptotic pathway with its molecular mechanism of action.METHODS: The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub-G1 group (apoptosis) were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting.RESULTS: For SNU-5 cell line, the IC (50) was found to be 48 μmol/L of berberine. In SNU-5 cells treated with 25-200 μmol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25-200 μmol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-G0 cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca2+, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis.CONCLUSION: Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.

  16. Quantitative expression of the homeobox and integrin genes in human gastric carcinoma.

    Rossi Degl'Innocenti, Duccio; Castiglione, Francesca; Buccoliero, Anna Maria; Bechi, Paolo; Taddei, Gian Luigi; Freschi, Giancarlo; Taddei, Antonio

    2007-10-01

    The homeobox (HOX) genes are a large family of regulator genes involved in the control of developmental processes and cell differentiation. The HOX genes encode transcription factors, and an increasing number of studies have shown that these genes may be implicated in the growth and the progression of many types of tumours. The present study investigated the expression of the HOX and integrin genes and their relationships in gastric carcinoma. We analyzed the RNA expression of 13 HOX genes from HOXA, C and D clusters and alphaV, alpha5 and alpha8 integrin genes in 24 gastric cancer samples by quantitative real-time PCR. The results showed that the HOXA2 gene and the alpha8 integrin gene had a lower expression in tumour samples than in normal gastric mucosas. The comparison between the HOX and integrin genes showed that HOXA2 and alphaV integrin expression presented the same trend in 83% of the samples. Moreover, in cancer samples that expressed the HOXD11 gene, the expression of alphaV integrin was lower with respect to normal mucosas. The different roles of HOX and integrin genes in gastric carcinoma remain to be fully elucidated. These findings suggest that the HOX genes may play a critical role in the genesis, maintenance and diffusion of gastric carcinoma.

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

    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.

  18. Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

    Hai-hong ZHANG; Ai-zhen CAI; Xue-ming WEI; Li DING; Feng-zhi LI; Ai-ming ZHENG; Da-jiang DAI

    2013-01-01

    Objective:Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer.Many kinds of cell lines and tissues have demonstrated the presence of SP cells,including several gastric cancer cell lines.This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45.Methods:We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells.Results:This study found that the SP cells had higher clone formation efficiency than major population (MP) cells.Five stemness-related gene expression profiles,including OCT-4,SOX-2,NANOG,CD44,and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2,were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).Western blot was used to show the difference of protein expression between SP and MP cells.Both results show that there was significantly higher protein expression in SP cells than in MP cells.When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice,SP cells show higher tumorigenesis tendency than MP cells.Conclusions:These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

  19. Heparanase expression,degradation of basement membrane and low degree of infiltration by immunocytes correlate with invasion and progression of human gastric cancer

    Zun-Jiang Xie; Ying Liu; Li-Min Jia; Ye-Chun He

    2008-01-01

    AIM: To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients.METHODS: The heparanase expression,continuity of basement,degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry,in situ hybridization and transmission electron microscopy.RESULTS: Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients.In the early stage gastric cancer tissues,basement membrane (BlVl) appeared intact,whereas in the late stage,discontinuous BM was often present.The density of $100 protein positive tumor infiltrating dendritic cells (TIDC) in the early stage gastric cancer tissues was higher than that in the late stage.The infiltrating degree of tumor infiltrating lymphocytes (TIL) in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC.There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers,but many cancer cells were found outside of the defective BM of cancer nests in the late stage.CONCLUSION: Our results suggest that strong heparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis.However,high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.

  20. Modelling Adaptive Learning Behaviours for Consensus Formation in Human Societies

    Yu, Chao; Tan, Guozhen; Lv, Hongtao; Wang, Zhen; Meng, Jun; Hao, Jianye; Ren, Fenghui

    2016-06-01

    Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people’s adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics.

  1. Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice

    Hai-Bo Zhou; Juan-Juan Chen; Wen-Xia Wang; Jian-Ting Cai; Qin Du

    2005-01-01

    AIM: To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2and bax.METHODS: A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. Resveratrol (500 mg/kg, 1000 mg/kg and 1500 mg/kg) was directly injected beside tumor body 6 times at an interval of 2 d. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alterations by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis-regulated genes bcl-2and bax by immunohistochemical staining and PT-PCR.RESULTS: Resveratrol could significantly inhibit carcinoma growth when it was injected near the carcinoma. An inhibitory effect was observed in all therapeutic groups and the inhibition rate of resveratrol at the dose of 500 mg/kg,1 000 mg/kg and 1 500 mg/kg was 10.58%, 29.68% and 39.14%, respectively. Resveratrol induced implanted tumor cells to undergo apoptosis with apoptotic characteristics,including morphological changes of chromatin condensation,chromatin crescent formation, nucleus fragmentation. The inhibition rate of 0.2 mL of normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol, and 1 500 mg/kg resveratrol was L3.68±0.37%, 13.8±0.43%,48.7±1.07%, 56.44±1.39% and 67±0.96%, respectively. The positive rate of bcl-2 protein of each group was 29.48±0.51%,27.56±1.40%, 11.86±0.97%, 5.7±0.84% and 3.92±0.85%,respectively by immunohistochemical staining. The positive rate of bax protein of each group was 19.34±0.35%,20.88±0.91%, 40.02±1.20%, 45.72±0.88% and 52.3±1.54%,respectively by immunohistochemical staining. The density of bcl-2 mRNA in 0.2 mL normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1 000 mg/kg resveratrol,and 1 500 mg

  2. MYC and gastric adenocarcinoma carcinogenesis

    Danielle Queiroz Calcagno; Mariana Ferreira Leal; Paulo Pimentel Assumpcao; Marilia de Arruda Cardoso Smith; Rommel Rodriguez Burbano

    2008-01-01

    MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications.

  3. A novel dynamic scintigraphic technique for assessing duodenal contractions during gastric emptying in humans: a feasibility study.

    Kubo, Tadeu T A; Moraes, Eder R; Secaf, Marie; Troncon, Luiz E A

    2015-01-01

    Duodenal contractions are thought to play a role in the control of gastric emptying. Although noninvasive techniques, such as ultrasonography and MRI, have been proposed for studying duodenal contractile activity in humans, there are no reports on the use of scintigraphy for this purpose. This work aimed to describe a novel scintigraphic technique for assessing duodenal contractility during gastric emptying in humans, and to present preliminary data on the frequency and amplitude of contractions detected in three different duodenal segments. Fasted young healthy volunteers (N=12) were given either a liquid or a solid test meal of similar calorie content (400 kcal) labeled with 99mTc-phytate. Static images were collected to determine gastric emptying. Dynamic images of the anterior aspect of the abdomen (1 frame/s) were also acquired periodically in a standard position for 256 s at 15-30 min intervals. 'Activity versus time' curves were generated for regions of interest corresponding to the proximal, middle, and distal duodenal segments. Curves were digitally filtered and processed to estimate both dominant frequency (fast Fourier transform) and amplitude (mean ejection fraction) of postprandial duodenal contractions. There were no significant differences regarding dominant frequency among proximal, middle, and distal duodenal regions of interest. In addition, there were no significant differences between the liquid and the solid meal in terms of either frequency or amplitude of duodenal contractions. Characterization of duodenal contractions in humans using scintigraphy is feasible and yields consistent data for both the frequency and the amplitude of postprandial contractions, which seems to be rather independent of meal consistency.

  4. Effect of NHE1 antisense gene transfection on the biological behavior of SGC-7901 human gastric carcinoma cells

    Hai-Feng Liu; Xiao-Chun Teng; Jing-Chen Zheng; Gang Chen; Xing-Wei Wang

    2008-01-01

    AIM: To study the effect of type 1 Na+/H+ exchanger (NHE1) antisense human gene transfection on the biological behavior of gastric carcinoma cell line SGC-7901.METHODS: Antisense NHE1 eukaryotic expression on vector pcDNA3.1 was constructed by recombinant DNA technique and transfected into gastric carcinoma cell line SGC-7901 with DOTAP liposome transfection method.Morphological changes of cells were observed with optic and electron microscopes. Changes in cell proliferative capacity, apoptosis, intracellular pH (pH1), cell cycle,clone formation in two-layer soft agar, and tumorigenicity in nude mice were examined.RESULTS: Antisense eukaryotic expressing vectors were successfully constructed and transfected into 5GC-7901.The transfectant obtained named 7901-antisense (7901-,45) stablely produced antisense NHE1. There was a significant difference between the pH1 of 7901-AS cells (6.77 ± 0.05) and that of 7901-zeo cells and SGC-7901 cells (7.24 ± 0.03 and 7.26 ± 0.03, P < 0.01). Compared with SGC-7901 and 7901-zeo cells, 7901-AS cells mostly showed cell proliferation inhibition, G1/Go phase arrest, increased cell apoptotic rate, recovery of contact inhibition, and density contact. The tumorigenicity in nude mice and cloning efficiency in the two-layer soft agar were dearly inhibited.CONCLUSION: NHE1 antisense gene significantly restrains the malignant behavior of human gastric carcinoma cells, suppresses cell growth and induces cell apoptosis, and partially reverses the malignant phenotypes of SGC-7901. These results suggest a potential role for human tumor gene therapy.

  5. Effects of vitamin E succinate on the expression of Fas and PCNA proteins in human gastric carcinoma cells and its clinical significance

    Kun Wu; Lan Zhao; Yao Li; Yu-Juan Shan; Li-Jie Wu

    2004-01-01

    AIM: To investigate the effects of vitamin E succinate (VES) on the expression of Fas and PCNA proteins as well as its clinical significance in human gastric carcinoma, and to explore the mechanism of VES-induced inhibition of gastric carcinoma cell growth.METHODS: Immunohistochemical methods were used to detect Fas and PCNA expression both in human gastric cancer SGC-7901 cells treated with VES at different doses and in human gastric carcinoma tissues.RESULTS: After the SGC-7901 cells were treated with VES at 5, 10, 20 mg/L for 48 h, the positive rates of Fas expression were 16%, 27% and 48%, respectively, significantly increased compared to that of control group (P<0.05); while the positive rates of PCNA expression in groups treated with different doses of VES were 20%, 18% and 7%, respectively, which were significantly decreased compared to that of the control group (P<0.05). In human gastric carcinoma tissues, the Fas positive expression rate was 42.4%(25/59), which declined with the decrease in the degree of tumor differentiation (P<0.05) and with the existence of lymph node metastasis (P<0.001). While the PCNA positive expression rate was 91.5%(54/59), no relationship was observed between PCNA expression and clinicopathologic parameters.CONCLUSION: VES inhibited the growth of gastric cancer cells by inducing Fas expression and inhibiting PCNA expression.It is, therefore, considered that the expression of Fas and PCNA genes, through tumor cell apoptosis and proliferation,respectively, may be useful as a clinical predictive index in the application of VES to gastric carcinoma therapy, where as Fas may be of more value than PCNA.

  6. Heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901

    Zhi-Gang Zhao; Wen-Lu Shen

    2005-01-01

    AIM: Heat shock protein (HSP)70 is over-expressed in human gastric cancer and plays an important role in the progression of this cancer. We investigated the effects of antisense HSP70 oligomer on human gastric cancer cell line SGC-7901, and its potential role in gene therapy for this cancer.METHODS: Human gastric cancer cell line SGC-7901 was treated in vitro with various concentrations of antisense HSP70 oligonucleotides at different intervals. Growth inhibition was determined as percentage by trypan blue dye exclusion test. Extracted DNA was electrophoresed on agarose gel, and distribution of cell cycle and kinetics of apoptosis induction were analyzed by propidium iodide DNA incorporation using flow cytometry, which was also used to detect the effects of antisense oligomer pretreatment on the subsequent apoptosis induced by heat shock in SGC-7901 cells. Proteins were extracted for simultaneous measurement of HSP70 expression level by SDS-PAGE Western blotting.RESULTS: The number of viable cells decreased in a doseand time-dependent manner, and ladder-like patterns of DNA fragments were observed in SGC-7901 cells treated with antisense HSP70 oligomers at a concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h, which were consistent with inter-nucleosomal DNA fragmentation. Flow cytometric analysis showed a dose- and time-dependent increase in apoptotic rate by HSP70 antisense oligomers. This response was accompanied with a decrease in the percentage of cells in the G1 and S phases of the cell cycle, suggesting inhibition of cell proliferation. In addition, flow cytometry also showed that pretreatment of SGC-7901 cells with HSP70 antisense oligomers enhanced the subsequent apoptosis induced by heat shock treatment. Western blotting demonstrated that HSP70 antisense oligomers inhibited HSP70 expression, which preceded apoptosis, and HSP70 was undetectable at the concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h.CONCLUSION: Antisense HSP70 oligomers

  7. The protective effect of genistein postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells

    Yu LI; Jian-fu ZHANG; Yong-mei ZHANG; Xiao-bo MA

    2009-01-01

    Aim: The aim of this study was to investigate the protective effect of genistein postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells and to begin a tentative discussion on the mechanism behind this protection.Methods: A model of hypoxia/reoxygenation-induced injury was established in the human gastric epithelial cell line (GES-1). All cells in our present study were randomly divided into five groups: a normal control group (N), a hypoxia/reoxygenation group (H/R), a genistein postconditioning group (GP), a capsazepine+genistein postconditioning group (C+GP) and a DMSO vehicle postconditioning group (DM). The methods used included MTT assays to test cell viability,flow cytometric analyses to quantify the percentage of cell apoptosis, Western blot analyses to measure the protein expression of calcitonin gene-related peptide (CGRP), Bcl-2, and Bax, and immtunocytochemistry assays to detect the expression of CGRP in each group.Results: The MTT assays indicated that the cell viabilities of the groups were 100.0%±0%, 51.4%±4.1%, 66.7%±2.0%,56.1%±2.8%, and 50.7%±2.4%, respectively. Compared with the H/R group, the viability of the GP group was significantly increased (P<0.01). Flow cytometric analysis showed that the cell apoptosis percentage of each group was 2.28%±0.44%,12.17%±2.15%, 5.40%±1.22%, 10.43%±1.37%, and 11.02%±2.19%, respectively. Western blot analysis demonstrated that CGRP, Bcl-2, and Bax were expressed in normal human gastric epithelial cells. Compared with the H/R group, the GP group exhibited increased expression of CGRP and Bcl-2 and decreased expression of Bax. Immunocytochemistry assays indicated that the number of CGRP-positive cells in the GP group was significantly increased.Conclusion: Genistein postconditioning has a protective effect on hypoxia/reoxygenation-induced injury in human gastric epithelial cells. The mechanism by which genistein exerts this protection may be via activation of cellular

  8. In vitro effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 cells

    Li-Feng Qi; Zi-Rong Xu; Yan Li; Xia Jiang; Xin-Yan Han

    2005-01-01

    AIM: To investigate the effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 in vitro and the possible mechanisms involved.METHODS: Chitosan nanoparticles were characterized by particle size, zeta potential, and morphology. After treatment with various concentrations of chitosan nanoparticles (25, 50, 75, 100 μg/mL) at various time intervals, cell proliferation, ultrastructural changes, DNA fragmentation, mitochondrial membrane potential (MMP),cell cycle phase distribution and apoptotic peaks of MGC803 cells were analyzed by MTT assay, electron microscopy,DNA agarose gel electrophoresis, and flow cytometry.RESULTS: Chitosan nanoparticles exhibited a small particle size as 65 nm and a high surface charge as 52 mV.Chitosan nanoparticles markedly inhibited cell proliferation of MGC803 cells with an IC50 value of 5.3 μg/mL 48 h after treatment. After treatment with chitosan nanoparticles,the typical necrotic cell morphology was observed by electron microscopy, a typical DNA degradation associated with necrosis was determined by DNA agarose electrophoresis.Flow cytometry showed the loss of MMP and occurrence of apoptosis in chitosan nanoparticles-treated cells.CONCLUSION: Chitosan nanoparticles effectively inhibit the proliferation of human gastric carcinoma cell line MGC803 in vitro through multiple mechanisms, and may be a beneficial agent against human carcinoma.

  9. Clinical significance of human kallikrein 12 gene expression in gastric cancer

    En-Hao Zhao; Zhi-Yong Shen; Hua Liu; Xin Jin; Hui Cao

    2012-01-01

    AIM:To investigate whether the expression of kallikrein 12 (KLK12) is related to the development of gastric cancer (GC) and to determine the role of KLK12 in gastric cancer cells growth,invasion and migration.METHODS:Between September 2007 and March 2008,133 patients with histologically confirmed GC were recruited for the study.Expression of KLK12 was detected in samples from GC patients by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry.The relationship between KLK12 protein expression and clinicopathological features of GC was analyzed.The difference in 5-year survival rates between the high KLK12 protein expression group and the low KLK12 expression group was compared.Additionally,the expression of KLK12 was examined in various human GC cell lines,including MKN-28,SGC-7901 and MKN-45.Small interfering RNA (siRNA) was used to inhibit KLK12 expression in MKN-45 cells.Cell clones stably transfected with KLK12 siRNA were tested for KLK12 expression by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting.Furthermore,a series of functional assays were performed in this study to assess the biological features of transfected cells.Cell proliferation was assessed using the methylthiazolyltetrazoliumassay.Finally,cell migration and invasion were assessed using transwell chamber assays.RESULTS:Of the 133 GC patients induded in the study,126 (94.7%) showed a higher expression level of KLK12 mRNA when compared to noncancerous tissue specimens.Expression of KLK12 mRNA was significantly higher in GC tissues than in normal tissue (P < 0.001).KLK12 protein expression was detected in 96 of 133 (72.2%) GC samples with moderate or strong staining primarily in the cytoplasm.In contrast,negative immunostaining for KLK12 protein was observed in the corresponding normal gastric mucosal tissue.Overexpression of KLK12 protein was significantly associated with lymph node metastasis (P =0

  10. Mutations in the hedgehog pathway genes SMO and PTCH1 in human gastric tumors.

    Xi-De Wang

    Full Text Available The causal role of the hedgehog pathway in cancer has been best documented in basal cell carcinoma of the skin. To assess potential DNA alterations of the hedgehog pathway in gastric cancer, we sequenced SMO and PTCH1 genes in a set of 39 gastric tumors. Tumors were classified by histology based on the Lauren classification and Sanger sequencing was performed to obtain full length coding sequences. Genomic instability was evident in these tumors as a number of silent or missense mutations were found. In addition to those that are potential germline polymorphisms, we found three SMO missense mutations, and one PTCH1 frameshift mutation that are novel and have not been documented in basal cell carcinoma. Mutations were found in both intestinal and diffuse type gastric tumors as well as in tumors that exhibit both intestinal and diffuse features. mRNA expression of hedgehog pathway genes was also examined and their levels do not indicate unequivocal higher pathway activity in tumors with mutations than those without. In summary, SMO and/or PTCH1 mutations are present at low frequency in different histologic subtypes of gastric tumors and these do not appear to be driver mutations.

  11. Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety

    Schmidt, P T; Näslund, E; Grybäck, P

    2003-01-01

    Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel to the circulation after a meal. Intravenous (IV) GLP-1 has an inhibitory effect on gastric emptying, hunger and food intake in man. In rodents, central administration of GLP-2 increases satiety similar...

  12. Expression and significance of intratumoral interleukin-12 and interleukin-18 in human gastric carcinoma

    Zheng-Bao Ye; Tao Ma; Hao Li; Xiao-Long Jin; Hai-Min Xu

    2007-01-01

    AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma.METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system.RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors.CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.

  13. Immunohistochemical analysis of ras oncogene p21 product in human gastric carcinomas and their adjacent mucosas.

    Carneiro, F; David, L; Sunkel, C; Lopes, C; Sobrinho-Simões, M

    1992-04-01

    In an attempt to clarify the relationship between ras oncogene expression and the clinico-pathological features of malignant and pre-malignant lesions of the stomach we undertook the immunohistochemical study of the expression of ras gene p21 product in a series of eighty gastric carcinomas and their respective adjacent mucosas. In two cases the mRNA of Ha-ras was also studied by in situ hybridization. The majority of gastric carcinomas as well as their adjacent non-neoplastic mucosas expressed ras gene product. There was a significant relationship between the expression of ras gene p21 product and the morphologic pattern of the tumours. An enhanced ras expression was found in several conditions regarded as precursor lesions of intestinal and/or diffuse types of gastric carcinoma (dysplasia, foveolar hyperplasia and even the neck zone of normal-appearing gastric glands, namely in the mucosa adjacent to diffuse carcinomas). Ras expression was actually more prominent in most of these conditions than in their respective adjacent carcinomas. No significant relationship was found between ras expression and invasiveness of the wall, nodal metastases and venous invasion.

  14. Correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistance in human gastric cancer

    Hong-mei ZHANG

    2015-11-01

    Full Text Available Objective To investigate the correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistant gastric cancer in humans. Methods Fifty-two patients who were confirmed to have advanced gastric cancer with the aid of electronic endoscopy and pathology in the Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, were enrolled in the study. According to the effect of FOL-FOX4 chemotherapy that these patients had experienced, they were divided into three groups: CR+PR (complete remission+partial remission group, SD (stable disease group and PD (progressive disease group. The expression levels of HIF-2α, ABCG2, and OCT-4 mRNA and protein were assessed in different groups by using RT-PCR and immunocytochemistry. Results Two patients achieved CR , 19 achieved PR , 25 showed SD, and 6 showed PD. In other words, CR+PR were seen in 21 patients (40.4%, SD in 25(48.1%, PD in 6(11.5%. In CR+PR group, the expression levels of HIF-2α, ABCG2 and OCT4 mRNA and protein were low, but the above mentioned expressions were significantly increased in SD group and PD group. The expression levels of HIF-2α, ABCG2 and Oct-4 mRNA and protein were highest in the PD group, lower in the SD group, and lowest in the CR + PR groups (all P<0.05. Conclusions The expression of the markers HIF-2α, ABCG2 and OCT4 in human tumor tissues is related to the effect of chemotherapy for gastric cancer. A high expression of tumor markers is perhaps the main reason for low efficacy of chemotherapy due to drug resistance. DOI: 10.11855/j.issn.0577-7402.2015.10.09

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

    Schlosser, Paul M., E-mail: schlosser.paul@epa.gov; 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.

  16. INHIBITORY EFFECTS OF MIFEPRISTONE ON THE GROWTH OF HUMAN GASTRIC CANCER CELL LINE MKN-45 IN VITRO AND IN VIVO

    Da-qiang Li; Li-hua Pan; Zhi-min Shao

    2004-01-01

    Objective To explore the effects of mifepristone on the growth of human gastric cancer cell line MKN-45 and its possible mechanisms.Methods In situ hybridization was used to detect the expression of progesterone receptor (PR) mRNA in MKN-45cells. Proliferation, cell cycle distribution, and the expression of Bcl-xL and vascular endothelial growth factor (VEGF) of MKN-45 cells incubated with various concentrations of mifepristone (1, 5, 10, and 20 μmol/L) were analyzed using MTT reduction assay, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoabsorbent assay (ELISA), respectively. After transplantation of MKN-45 cells underneath the skin of athymic mice, mifepristone proliferating cell nuclear antigen (PCNA) in xenografted tumors were detected using transmission electron microscopy and immunohistochemical staining, respectively.Results PR mRNA was highly expressed in cultured MKN-45 cell. Mifepristone dose-dependently inhibited the proliferation of MKN-45 cells, and the inhibitory rate was dramatically increased from 7.21% to 47.23%. The inhibitory effect was accompanied by a dose-dependent increase in the percentage of cells in G0/G1 phase, and with a concurrent decrease in the proportion of S- and G2/M-phase cells and the proliferative index from 57.65% to 24.54%. Meanwhile,mifepristone dom-regulated the expression of Bcl-xL and VEGF in a dose-dependent manner. In vivo, mifepristone effectively inhibited the growth of xenografted tumors in nude mice (55.14% for inhibitory rate), induced apoptosis, and down-regulated PCNA expression in gastric cancer.Conclusion Mifepristone exerts significant growth inhibitory effects on PR-positive human MKN-45 gastric cancer cells via multiple mechanisms, and may be a beneficial agent against the tumor.

  17. Expression pattern of leptin and leptin receptor (OB-R) in human gastric cancer

    Makoto Ishikawa; Joji Kitayama; Hirokazu Nagawa

    2006-01-01

    AIM: To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia.METHODS: By immunohistochemical staining using specific antibodies, we evaluated the expression of leptin and OB-R in 207 gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their relationship with clinicopathological features.RESULTS: Both normal gastric epithelium and carcinoma cells expressed a significant level of leptin. In cases with OB-R staining, carcinoma cells showed OB-Rpositive expression, but the intensity was weaker than that in normal mucosa. The expression of OB-R showed a significant correlation with the level of leptin expression. The expression levels of both leptin and OB-R tend ed to increase as the depth of tumor invasion or TMN stage increased (P < 0.01). Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases. Both venous and lymphatic invasion also tended to be observed frequently in positive tumors as compared with negative tumors. Interestingly,in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) patients. In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis.CONCLUSION: Overexpression of leptin and expression of OB-R may play a positive role in the process of progression in gastric cancer. Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer.

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

    Gunassekaran, G.R., E-mail: gunassekaran@yahoo.co.in [Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu (India); Kalpana Deepa Priya, D.; Gayathri, R.; Sakthisekaran, D. [Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu (India)

    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

  19. Convergence of the innate and adaptive immunity during human aging

    Branca Isabel Pereira

    2016-11-01

    Full Text Available Aging is associated with profound changes in the human immune system, a phenomenon referred to as immunosenescence. This complex immune remodeling affects the adaptive immune system and the CD8+ T cell compartment in particular, leading to the accumulation of terminally differentiated T cells, which can rapidly exert their effector functions at the expenses of a limited proliferative potential. In this review we will discuss evidence suggesting that senescent αβCD8+ T cells acquire the hallmarks of innate-like T cells and use recently acquired NK cell receptors as an alternative mechanism to mediate rapid effector functions. These cells concomitantly lose expression of co-stimulatory receptors and exhibit decreased TCR signaling suggesting a functional shift away from antigen specific activation. The convergence of innate and adaptive features in senescent T cells challenges the classic division between innate and adaptive immune systems. Innate-like T cells are particularly important for stress and tumor surveillance and we propose a new role for these cells in aging, where the acquisition of innate-like functions may represent a beneficial adaptation to an increased burden of malignancy with age, although it may also pose a higher risk of autoimmune disorders.

  20. Release of prostaglandin E2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans

    Rask-Madsen, J; Bukhave, K; Hovendal, C P

    1981-01-01

    To investigate the causal relationship, if any, between gastric PG formation and gastric acid output, the release of PGE2 into gastric juice has been studied in eight beagle dogs with a gastric fistula, using sustained half-maximal stimulation by bethanechol and pentagastrin, and in eight duodenal.......2-18 ng/Meq H+). The findings are consistent with the hypothesis that activation of muscarinic receptors represents the physiologic mechanism by which gastric release of PGs is regulated. Cyclic variations in gastric PG formation appear to occur in response to vagal stimulation since the peaks in PGE2...

  1. Activation of prostaglandin E2-receptor EP2 and EP4 pathways induces growth inhibition in human gastric carcinoma cell lines.

    Okuyama, T; Ishihara, S; Sato, H; Rumi, M A K; Kawashima, K; Miyaoka, Y; Suetsugu, H; Kazumori, H; Cava, C F Ortega; Kadowaki, Y; Fukuda, R; Kinoshita, Y

    2002-08-01

    The effect of prostaglandin E2 (PGE2) on the proliferation of gastric cancer cells is still unclear. PGE2 receptors are divided into four subtypes - EP1, EP2, EP3, and EP4 - which are coupled to three different intracellular signal-transduction systems. Stimulation of EP2 and EP4 is linked with cyclic adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA). In some human gastric cancer cells, PGE2 has been suggested to have an antiproliferative effect by way of increased cAMP production. Expression of EP2 and EP4 in human gastric carcinoma cells, however, has not been examined. We examined the expression of EP2 and EP4 and the antiproliferative effects of specific EP2 and EP4 agonists on four different human gastric cancer cell lines. Our data clarified that all the cell lines investigated in this study expressed EP2 and EP4 and that the specific agonists of these receptors induced growth inhibition with an accompanying increase in cAMP production. In summary, gastric cancer cells have EP2 and EP4 receptors, and their selective activation is linked with the decreased cell proliferation.

  2. Genetic adaptation of the antibacterial human innate immunity network

    Lazarus Ross

    2011-07-01

    Full Text Available Abstract Background Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

  3. Unilateral adaptation of the human angular vestibulo-ocular reflex.

    Migliaccio, Americo A; Schubert, Michael C

    2013-02-01

    A recent study showed that the angular vestibulo-ocular reflex (VOR) can be better adaptively increased using an incremental retinal image velocity error signal compared with a conventional constant large velocity-gain demand (×2). This finding has important implications for vestibular rehabilitation that seeks to improve the VOR response after injury. However, a large portion of vestibular patients have unilateral vestibular hypofunction, and training that raises their VOR response during rotations to both the ipsilesional and contralesional side is not usually ideal. We sought to determine if the vestibular response to one side could selectively be increased without affecting the contralateral response. We tested nine subjects with normal vestibular function. Using the scleral search coil and head impulse techniques, we measured the active and passive VOR gain (eye velocity / head velocity) before and after unilateral incremental VOR adaptation training, consisting of self-generated (active) head impulses, which lasted ≈ 15 min. The head impulses consisted of rapid, horizontal head rotations with peak-amplitude 15°, peak-velocity 150°/s and peak-acceleration 3,000°/s(2). The VOR gain towards the adapting side increased after training from 0.92 ± 0.18 to 1.11 ± 0.22 (+22.7 ± 20.2 %) during active head impulses and from 0.91 ± 0.15 to 1.01 ± 0.17 (+11.3 ± 7.5 %) during passive head impulses. During active impulses, the VOR gain towards the non-adapting side also increased by ≈ 8 %, though this increase was ≈ 70 % less than to the adapting side. A similar increase did not occur during passive impulses. This study shows that unilateral vestibular adaptation is possible in humans with a normal VOR; unilateral incremental VOR adaptation may have a role in vestibular rehabilitation. The increase in passive VOR gain after active head impulse adaptation suggests that the training effect is robust.

  4. A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies

    Oriol Calvete

    2016-09-01

    Full Text Available By whole exome sequencing, we recently identified a missense mutation (p.R703C in the human ATP4a gene, which encodes the proton pump responsible for gastric acidification. This mutation causes an aggressive familial type I gastric neuroendocrine tumor in homozygous individuals. Affected individuals show an early onset of the disease, characterized by gastric hypoacidity, hypergastrinemia, iron-deficiency anemia, gastric intestinal metaplasia and, in one case, an associated gastric adenocarcinoma. Total gastrectomy was performed as the definitive treatment in all affected individuals. We now describe the generation and characterization of a knockin mouse model for the ATP4aR703C mutation to better understand the tumorigenesis process. Homozygous mice recapitulated most of the phenotypical alterations that were observed in human individuals, strongly suggesting that this mutation is the primary alteration responsible for disease development. Homozygous mice developed premalignant condition with severe hyperplasia, dysplasia and glandular metaplasia in the stomach. Interestingly, gastric acidification in homozygous mice, induced by treatment with 3% HCl acid in the drinking water, prevented (if treated from birth or partially reverted (if treated during adulthood the development of glandular metaplasia and dysplasia in the stomach and partially rescued the abnormal biochemical parameters. We therefore suggest that, in this model, achlorhydria contributes to tumorigenesis to a greater extent than hypergastrinemia. Furthermore, our mouse model represents a unique and novel tool for studying the pathologies associated with disturbances in gastric acid secretion.

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

    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.

  6. Hyperthermia combined with 5-fluorouracil promoted apoptosis and enhanced thermotolerance in human gastric cancer cell line SGC-7901

    Liu T

    2015-05-01

    Full Text Available Tao Liu,* Yan-Wei Ye,* A-li Zhu, Zhen Yang, Yang Fu, Chong-Qing Wei, Qi Liu, Chun-Lin Zhao, Guo-Jun Wang, Xie-Fu Zhang Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Abstract: This study was designed to investigate the proliferation inhibition and apo­ptosis-promoting effect under hyperthermia and chemotherapy treatment, at cellular level. Human gastric cancer cell line SGC-7901 was cultivated with 5-fluorouracil at different temperatures. Cell proliferation and apoptosis were determined, and expression of Bcl-2 and HSP70 was measured at different treatments. Cell survival rates and inhibition rates in chemotherapy group, thermotherapy group, and thermo-chemotherapy group were drastically lower than the control group (P<0.05. For tumor cells in the thermo-chemotherapy group, survival rates and inhibition rates at three different temperatures were all significantly lower than those in chemotherapy group and thermotherapy group (P<0.05. 5-Fluorouracil induced apoptosis of SGC-7901 cells with a strong temperature dependence, which increased gradually with increase in temperature. At 37°C and 43°C there were significant differences between the thermotherapy group and chemotherapy group and between the thermo-chemotherapy group and thermotherapy group (P<0.01. The expression of Bcl-2 was downregulated and HSP70 was upregulated, with increase in temperature in all groups. Cell apoptosis was not significant at 46°C (P>0.05, which was probably due to thermotolerance caused by HSP70 accumulation. These results suggested that hyperthermia combined with 5-fluorouracil had a synergistic effect in promoting apoptosis and enhancing thermotolerance in gastric cancer cell line SGC-7901. Keywords: gastric cancer, thermotherapy, 5-fluorouracil, Bcl-2, HSP70, thermotolerance

  7. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    . METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  8. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2015-02-01

    Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

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

    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

  10. Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

    TieLi Peng; Jie Chen; Wei Mao; Xin Liu; Yu Tao; Lian-Zhou Chen; Min-Hu Chen

    2009-01-01

    AIM: To determine the functional significance of aryl hydrocarbon receptor (AhR) in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer (GC) treatment. METHODS: RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells. RESULTS: AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase. CONCLUSION: AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.

  11. Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors.

    Vegesna, Anil K; Braverman, Alan S; Miller, Larry S; Tallarida, Ronald J; Tiwana, Mansoor I; Khayyam, Umar; Ruggieri, Michael R

    2010-04-01

    To compare the gastroesophageal junction of the human with the pig, M(2) and M(3) receptor densities and the potencies of M(2) and M(3) muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M(2) receptors are higher in pig than human clasp and sling fibers. M(3) receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M(3) receptors than sling fibers in both humans and pigs. Similar to human clasp fibers, pig clasp fibers contract significantly less than pig sling fibers. Analysis of the methoctramine Schild plot suggests that M(2) receptors are involved in mediating contraction in pig clasp and sling fibers. Darifenacin potency suggests that M(3) receptors mediate contraction in pig sling fibers and that M(2) and M(3) receptors mediate contraction in pig clasp fibers. Taken together, the data suggest that both M(2) and M(3) muscarinic receptors mediate the contraction in both pig clasp and sling fibers similar to human clasp and sling fibers.

  12. Gastric Lipase Secretion in Children with Gastritis

    Krystyna Sztefko; Krzysztof Fyderek; Andrzej Zając; Andrzej Wędrychowicz; Iwona Rogatko; Tomasik, Przemyslaw J

    2013-01-01

    Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), ...

  13. Pancreatic lipase-related protein 2 digests fats in human milk and formula in concert with gastric lipase and carboxyl ester lipase

    Johnson, Karin; Ross, Leah; Miller, Rita; Xiao, Xunjun; Lowe, Mark E.

    2013-01-01

    INTRODUCTION Dietary fats must be digested into fatty acids and monoacylglycerols prior to absorption. In adults, colipase-dependent pancreatic triglyceride lipase (PTL) contributes significantly to fat digestion. In newborn rodents and humans, the pancreas expresses low levels of PTL. In rodents, a homologue of PTL, pancreatic lipase related protein 2 (PLRP2) and carboxyl ester lipase (CEL) compensate for the lack of PTL. In human newborns, the role for PLRP2 in dietary fat digestion is unclear. To clarify the potential of human PLRP2 to influence dietary fat digestion in newborns, we determined PLRP2 activity against human milk and infant formula. METHODS The activity of purified recombinant PLRP2, gastric lipase and CEL against fats in human milk and formula was measured with each lipase alone and in combination with a standard pH-stat assay. RESULTS Colipase added to human milk stimulated fat digestion. PLRP2 and CEL had activity against human milk and formula. Pre-digestion with gastric lipase increased PLRP2 activity against both substrates. Together, CEL and PLRP2 activity was additive with formula and synergistic with human milk. CONCLUSIONS PLRP2 can digest fats in human milk and formula. PLRP2 acts in concert with CEL and gastric lipase to digest fats in human milk in vitro. PMID:23732775

  14. Adaptation or exaptation? The case of the human hand

    Marta Linde-Medina

    2011-09-01

    A controversy of relevance to the study of biological form involves the concept of adaptation. This controversy is illustrated by the structure and function of the human hand. A review of the principal definitions of adaptation points to two main problems: (1) they are qualitative and make reference to the whole structure (or substructural feature) and (2) they are based on the idea of natural selection as a moulding factor. The first problem would be solved by a definition that encompasses quantitative measures of the effects of selection, drawing on new advances in the comparative method. The second problem is deeper and presents greater conceptual difficulties. I will argue that the idea of natural selection as a moulding factor depends on the notion of a genetic program for development. But regarding the hand, experimental evidence on limb development challenges the idea of a genetic program for skeletal pattern formation, undermining a simple application of standard adaptationist concepts. These considerations lead to a revised definition of adaptation and interpretation of the evolutionary determinants of the hand’s form.

  15. Human papillomavirus as a potential risk factor for gastric cancer: a meta-analysis of 1,917 cases

    Zeng ZM

    2016-11-01

    Full Text Available Zhi-ming Zeng,1 Fei-fei Luo,2 Lin-xia Zou,3 Rong-quan He,1 Deng-hua Pan,2 Xin Chen,2 Ting-ting Xie,2 Yuan-qing Li,2 Zhi-gang Peng,1 Gang Chen2 1Department of Medical Oncology, 2Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, 3Department of Children Rehabilitation Medicine, Guangxi Maternal and Child Health Hospital, Nanning, China Background: Human papillomaviruses (HPVs are causally associated with the tumorigenesis of several classes of cancers. However, the prevalence of HPV in gastric cancer (GC has not yet been systematically reviewed. Hence, a meta-analysis was conducted to estimate the HPV prevalence in patients with GC, and its potential etiologic significance was assessed. Methods: The pooled HPV prevalence and 95% confidence intervals (CIs were estimated among all GC patients. Heterogeneity was described by using the I2 statistic. Sources of heterogeneity were explored by meta-regression and stratified analyses. The meta-influence was applied to evaluate the influence of a single study on the pooled estimates. Odds ratios (ORs and 95% CIs were computed for case–control studies. For research providing clinicopathological parameters of age, sex, pathological, differentiated, and clinical stages, and HPV subtypes, the corresponding pooled ORs and 95% CIs were also calculated. Results: Thirty studies were included in the current meta-analysis, involving 1,917 patients with GC and 576 controls. The pooled HPV prevalence was 28.0% (95% CI: 23.2%, 32.7% among all the patients with GC, and the I2 was 96.9% (P<0.001. A pooled OR of 7.388 (95% CI: 3.876, 14.082 was achieved based on 15 case–control studies (I2=56.7%, P=0.004. Moreover, the HPV prevalence was significantly higher in patients from China than in those from non-Chinese regions (31% vs 9%, I2=95.0%, P<0.001. The pooled prevalence of HPV16 was 21% in GC tissues, and the pooled prevalence of HPV18 was 7% with an OR of 3.314 (95% CI =1.617, 6

  16. Antisense bcl-2 retrovirus vector increases the sensitivity of a human gastric adenocarcinoma cell line to photodynamic therapy.

    Zhang, W G; Ma, L P; Wang, S W; Zhang, Z Y; Cao, G D

    1999-05-01

    The bcl-2 oncoprotein directly prolongs cellular survival by blocking apoptosis and its overexpression is associated with cellular resistance to killing by chemotherapeutic drugs and gamma-irradiation. Meanwhile, it has been shown that bcl-2 antisense oligonucleotide can induce apoptosis or increase toxicity of the treatment in tumors in vivo and in vitro. However, it is difficult to obtain stable transfection by this approach and there are no reports about the effect of an antisense bcl-2 on the sensitivity to oxidative stress induced by photodynamic therapy (PDT). Here we investigated the effect of an antisense bcl-2 RNA retrovirus vector transfer on the sensitivity of 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA) photosensitization in a human gastric adenocarcinoma MGC803 cell line. The results indicate that antisense bcl-2-infected MGC803 cells expressed exogenous antisense bcl-2 mRNA measured by reverse transcription polymerase chain reaction and significantly reduced bcl-2 protein determined by western blotting analysis. The decreased expression of bcl-2 protein was accompanied by increased phototoxicity and susceptibility to apoptosis induced by 2-BA-2-DMHA PDT. Our finding suggests that reduction of bcl-2 protein in gastric cancers, and possibly also in a variety of other tumors, may be a novel and rational approach to improve photosensitivity and the treatment outcome.

  17. HIV-1 Vif adaptation to human APOBEC3H haplotypes.

    Ooms, Marcel; Brayton, Bonnie; Letko, Michael; Maio, Susan M; Pilcher, Christopher D; Hecht, Frederick M; Barbour, Jason D; Simon, Viviana

    2013-10-16

    Several human APOBEC3 deaminases can inhibit HIV-1 replication in vitro. HIV-1 Vif counteracts this restriction by targeting APOBEC3 for proteasomal degradation. Human APOBEC3H (A3H) is highly polymorphic, with natural variants differing considerably in anti-HIV-1 activity in vitro. To examine HIV-1 adaptation to variation in A3H activity in a natural infection context, we determined the A3H haplotypes and Vif sequences from 76 recently infected HIV-1 patients. We detected A3H-specific Vif changes suggesting viral adaptation. The patient-derived Vif sequences were used to engineer viruses that specifically differed in their ability to counteract A3H. Replication of these Vif-variant viruses in primary T cells naturally expressing active or inactive A3H haplotypes showed that endogenously expressed A3H restricts HIV-1 replication. Proviral DNA from A3H-restricted viruses showed high levels of G-to-A mutations in an A3H-specific GA dinucleotide context. Taken together, our data validate A3H expressed at endogenous levels as a bona fide HIV-1 restriction factor.

  18. Effect of Actinidia chinensis planch polysaccharide on the growth and apoptosis,and p-p38 expression in human gastric cancer SGC-7901 cells

    宋文瑛

    2014-01-01

    Objective To investigate the effect of Actinidia chinensis Planch polysaccharide(ACPS)on the growth and apoptosis of human gastric cancer SGC-7901 cells,and to explore the effect of SGC-7901 cells on p-p38 expression.Methods The inhibition rates at different concentrations of ACPS on SGC-7901 cells at 24,48,and

  19. Molecular mechanisms of paclitaxel and NM-3 on human gastric cancer in a severe combined immune deficiency mice orthotopic implantation model

    Jin-Shui Zhu; Ming-Quan Song; Guo-Qiang Chen; Qin Li; Qun Sun; Qiang Zhang

    2007-01-01

    AIM: To explore the molecular mechanisms of action of paclitaxel and NM-3 on human gastric cancer in severe combined immune deficiency (SCID) mice.METHODS: Human gastric cancer cells SGC-7901 were implanted into SCID mice and mice were treated with paclitaxel and NM-3. The effects of paclitaxel and NM-3 on apoptosis of human gastric cancer cells were analyzed using flow cytometry, TUNEL assays, and DNA fragment analyses.RESULTS: Apoptosis of SGC-7901 cells was successfully induced by paclitaxel, NM-3, and the combination of paclitaxel and NM-3 24 h after injection as shown by the presence of apoptotic hypodiploid peaks on the flow cytometer before G1-S and a characteristic apoptotic band pattern in the DNA electrophoresis. The apoptotic rate detected by TUNEL assay was found to be significantly higher in the paclitaxel/NM-3 compared to the control group (38.5% ± 5.14% vs 13.2% ± 1.75%,P < 0.01).CONCLUSION: Paclitaxel in combination with NM-3 is able to induce apoptosis of the human gastric cancer cells in SCID mice effectively and synergistically.

  20. The glucagon-like peptide-1 metabolite GLP-1-(9-36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans

    Meier, Juris J; Gethmann, Arnica; Nauck, Michael A;

    2006-01-01

    Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7-36) amide is degraded to the metabolite GLP-1-(9-36) amide. The effects of GLP-1-(9-36) amide in humans are less well characterized. Fourteen he...

  1. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    Kun Wu; Yan Zhao; Bai-He Liu; Yao Li; Fang Liu; Jian Guo; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of growth inhibition ofhuman gastric cancer SGC-7901 cell with RRR-α-tocopherylsuccinate (VES), a derivative of natural Vitamin E, viainducing apoptosis and DNA synthesis arrest.METHODS: Human gastric cancer SGC-7901 cells wereregularly incubated in the presence of VES at 5, 10 and20mg@ L 1(VES was dissolved in absolute ethanol anddiluted in RPMI 1640 complete condition mediacorrespondingly to a final concentration of VES and 1mL@L-1 ethanol), succinic acid and ethanol equivalents asvehicle (VEH) control andcondition media only asuntreated (UT) control. Trypan blue dye exclusionanalysis and MTT assay were applied to detect the cellproliferation. 37kBq of tritiated thymidine was added tocells and [3H] TdR uptake was measured to observe DNAsynthesis. Apoptotic morphology was observed byelectron microscopy and DAPI staining. Flow cytometryand terminal deoxynucleotidyl transferase-mediated dUTPnick end labeling (TUNEL) assay were performed to detectVES-triggered apoptosis.RESULTS: VES inhibited SGC-7901 cell growth in a dose-dependent manner. The growth curve showed suppressionby 24.7%, 49.2% and 68.7% following 24h of VEStreatment at 5, 10 and 20 mg@L 1, respectively, similar tothe findings from MTT assay. DNA synthesis wasevidently reduced by 35%, 45% and 98% after 24h VEStreatment at 20 mg@ L-1 and 48h at 10 and 20 mg@ L 1,respectively. VES induced SGC-7901 cells to undergoapoptosis with typically apoptotic characteristics,including morphological changes of chromatincondensation, chromatin crescent formation/margination,nucleus fragmentation and apoptotic body formation,typical apoptotic sub-G1 peak by flow cytometry andincrease of apoptotic cells by TUNEL assay in which 90%of cells underwent apoptosis after 48h of VES treatment at20 mcg@L-1.CONCLUSION: VES can inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesisarrest. Inhibition of SGC-7901 cell growth by VES is dose-and time

  2. Clusters of adaptive evolution in the human genome

    Laura B. Scheinfeldt

    2011-09-01

    Full Text Available Considerable work has been devoted to identifying regions of the human genome that have been subjected to recent positive selection. Although detailed follow-up studies of putatively selected regions are critical for a deeper understanding of human evolutionary history, such studies have received comparably less attention. Recently, we have shown that ALMS1 has been the target of recent positive selection acting on standing variation in Eurasian populations. Here, we describe a careful follow-up analysis of genetic variation across the ALMS1 region, which unexpectedly revealed a cluster of substrates of positive selection. Specifically, through the analysis of SNP data from the HapMap and HGDP-CEPH samples as well sequence data from the region, we find compelling evidence for three independent and distinct signals of recent positive selection across this 3 Mb region surrounding ALMS1. Moreover, we analyzed the HapMap data to identify other putative clusters of independent selective events and conservatively discovered 19 additional clusters of adaptive evolution. This work has important implications for the interpretation of genome-scans for positive selection in humans and more broadly contributes to a better understanding of how recent positive selection has shaped genetic variation across the human genome.

  3. Effects of Wei Chang An on expression of multiple genes in human gastric cancer grafted onto nude mice

    Ai-Guang Zhao; Ting Li; Sheng-Fu You; Hai-Lei Zhao; Ying Gu; Lai-Di Tang; Jin-Kun Yang

    2008-01-01

    AIM:To investigate the expression of multiple genes in Chinese jianpi herbal recipe Wei Chang An (WCA) in human gastric cancer cell line SGC-7901.METHODS:A human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mice was used as the animal model.The mice were randomly divided into 3 groups,one control and the two representing experimental conditions.Animals in the two experimental groups received either WCA over a 34-d period or 5-fluorouracil (5-FU) over 6-d period starting at 8th d after grafting.Control animals received saline on an identical schedule.Animals were killed 41 d after being grafted.The expression profiles in paired WCA treated gastric cancer samples and the N.S.control samples were studied by using a cDNA array representing 14181 cDNA clusters.The alterations in gene expression levels were confirmed by Real-time Quantitative polymerase chain reaction (qPCR).RESULTS:When compared with controls,the average tumor inhibitory rate in WCA group was 44.32%±5.67% and 5-FU 47.04% 4±11.33% (P<0.01,respectively).The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group.Apoptotic index (AI) was significantly increased to 9.72%±4.51% using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method in WCA group compared with the controls 2.45%±1.37%.5-FU group was also found to have a significantly increased AI compared with the controls.The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively.There were 45 different expressed sequence tags (ESTs) among the control sample pool and WCA sample pool.There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated.By using qPCR,the expression level of Stat3,rap2 interacting protein x (RIPX),regulator of differentiation 1 (ROD1) and Bcl-2 was lower in WCA group than that in control

  4. c-Jun N-terminal kinase is required for thermotherapy-induced apoptosis in human gastric cancer cells

    Feng Xiao; Bin Liu; Qing-Xian Zhu

    2012-01-01

    AIM:To investigate the role of c-Jun N-terminal kinase (JNK) in thermotherapy-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS:Human gastric cancer SGC-7901 cells were cultured in vitro.Following thermotherapy at 43 ℃ for 0,0.5,1,2 or 3 h,the cells were cultured for a further 24 h with or without the JNK specific inhibitor,SP600125 for 2 h.Apoptosis was evaluated by immunohistochemistry [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] and flow cytometry (Annexin vs propidium iodide).Cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.The production of p-JNK,Bcl-2,Bax and caspase-3 proteins was evaluated by Western blotting.The expression of JNK at mRNA level was determined by reverse transcription polymerase chain reaction.RESULTS:The Proliferation of gastric carcinoma SGC-7901 cells was significantly inhibited following thermotherapy,and was 32.7%,30.6%,43.8% and 52.9% at 0.5,1,2 and 3 h post-thermotherapy,respectively.Flow cytometry analysis revealed an increased population of SGC-7901 cells in G0/G1 phase,but a reduced population in S phase following therrnotherapy for 1 or 2 h,compared to untreated cells (P < 0.05).The increased number of SGC-7901 cells in G0/G1 phase was consistent with induced apoptosis (flow cytometry) following thermotherapy for 0.5,1,2 or 3 h,compared to the untreated group (46.5% ± 0.23%,39.9% ± 0.53%,56.6% ±0.35% and 50.4% ± 0.29% vs 7.3% ± 0.10%,P < 0.01),respectively.This was supported by the TUNEL assay (48.2% ± 0.4%,40.1% ± 0.2%,61.2% ± 0.29% and 52.0% ± 0.42% vs 12.2% ± 0.22%,P < 0.01) respectively.More importantly,the expression of p-JNK protein and JNK mRNA levels were significantly higher at 0.5 h than at 0 h post-treatment (P < 0.01),and peaked at 2 h.A similar pattem was detected for Bax and caspase-3 proteins.Bcl-2 increased at 0.5 h,peaked at 1 h,and then decreased

  5. Gene expression profiling in human gastric mucosa infected with Helicobacter pylori.

    Hofman, Véronique J; Moreilhon, Chimène; Brest, Patrick D; Lassalle, Sandra; Le Brigand, Kevin; Sicard, Dominique; Raymond, Josette; Lamarque, Dominique; Hébuterne, Xavier A; Mari, Bernard; Barbry, Pascal Jp; Hofman, Paul M

    2007-09-01

    Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway.

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

    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.

  7. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis

    Clara; Luz; Sampieri; Sol; de; la; Pea; Mariana; Ochoa-Lara; Roberto; Zenteno-Cuevas; Kenneth; León-Córdoba

    2010-01-01

    AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction.Normalization was carried out using three different factors.Proteins were analyzed by quantitative gelatin zymography(qGZ).RESULTS:18S ribosomal RNA(18SRNA)was very highly expressed,while hypoxanthine ribosyltransferase-1(HPRT-1)was mode...

  8. Ziyuglycoside II-induced apoptosis in human gastric carcinoma BGC-823 cells by regulating Bax/Bcl-2 expression and activating caspase-3 pathway

    Zhu, A.K. [Department of General Surgery, Nanjing Medical University, Affiliated Hangzhou Hospital, Hangzhou (China); Zhou, H.; Xia, J.Z. [Department of General Surgery, Nanjing Medical University, Affiliated Wuxi Second Hospital, Wuxi (China); Jin, H.C. [Department of General Surgery, Nanjing Medical University, Affiliated Hangzhou Hospital, Hangzhou (China); Wang, K. [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Yan, J.; Zuo, J.B. [Department of General Surgery, Nanjing Medical University, Affiliated Wuxi Second Hospital, Wuxi (China); Zhu, X. [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Shan, T. [Department of General Surgery, Nanjing Medical University, Affiliated Wuxi Second Hospital, Wuxi (China)

    2013-08-13

    Ziyuglycoside II is an active compound of Sanguisorba officinalis L. that has anti-inflammation, antioxidation, antibiosis, and homeostasis properties. We report here on the anticancer effect of ziyuglycoside II on human gastric carcinoma BGC-823 cells. We investigated the effects of ziyuglycoside II on cell growth, cell cycle, and cell apoptosis of this cell line. Our results revealed that ziyuglycoside II could inhibit the proliferation of BGC-823 cells by inducing apoptosis but not cell cycle arrest, which was associated with regulation of Bax/Bcl-2 expression, and activation of the caspase-3 pathway. Our study is the first to report the antitumor potential of ziyuglycoside II in BGC-823 gastric cancer cells. Ziyuglycoside II may become a potential therapeutic agent against gastric cancer in the future.

  9. The specificity of stimulus-specific adaptation in human auditory cortex increases with repeated exposure to the adapting stimulus.

    Briley, Paul M; Krumbholz, Katrin

    2013-12-01

    The neural response to a sensory stimulus tends to be more strongly reduced when the stimulus is preceded by the same, rather than a different, stimulus. This stimulus-specific adaptation (SSA) is ubiquitous across the senses. In hearing, SSA has been suggested to play a role in change detection as indexed by the mismatch negativity. This study sought to test whether SSA, measured in human auditory cortex, is caused by neural fatigue (reduction in neural responsiveness) or by sharpening of neural tuning to the adapting stimulus. For that, we measured event-related cortical potentials to pairs of pure tones with varying frequency separation and stimulus onset asynchrony (SOA). This enabled us to examine the relationship between the degree of specificity of adaptation as a function of frequency separation and the rate of decay of adaptation with increasing SOA. Using simulations of tonotopic neuron populations, we demonstrate that the fatigue model predicts independence of adaptation specificity and decay rate, whereas the sharpening model predicts interdependence. The data showed independence and thus supported the fatigue model. In a second experiment, we measured adaptation specificity after multiple presentations of the adapting stimulus. The multiple adapters produced more adaptation overall, but the effect was more specific to the adapting frequency. Within the context of the fatigue model, the observed increase in adaptation specificity could be explained by assuming a 2.5-fold increase in neural frequency selectivity. We discuss possible bottom-up and top-down mechanisms of this effect.

  10. Co-expression of heat shock protein 70 and glucose-regulated protein 94 in human gastric carcinoma cell line BGC-823

    Xiao-Ping Wang; Jing Liao; Guo-Zhen Liu; Xing-Cui Wang; Hong-Wei Shang

    2005-01-01

    AIM: To investigate the co-expression and significance of heat shock protein 70 (HSP70) and glucose-regulatedprotein 94 (grp94) in human gastric carcinoma cell line BGC-823.METHODS: The expression and localization of HSP70 and grp94 in human gastric carcinoma cell line BGC-823 were determined by immunocytochemistry and indirect immunofiuorescence cytochemical staining. Flow cytometry was used to analyze the correlation between expression of HSP70, grpg4 and cell cycle in BGC-823 cell line.RESULTS: Gastric cancer cell line BGC-823 expressed high level of HSP70 and grp94. The positive rate of HSP70 and grp94 was 84.9±4.94% and 79.6±5.16%, respectively. Bothof them were stained in cell plasma. There was a significant difference compared with control group (1.9±0.94%,P<0.01). During the cell cycle, HSP70 and grp94 were continuously expressed in BGC-823.CONCLUSION: HSP70 and grp94 are highly expressed in human gastric carcinoma BGC-823 cells through the whole cell cycle. There is no relationship between expression of HSP70, grp94 and cell cycle.

  11. Oxidized DNA induces an adaptive response in human fibroblasts

    Kostyuk, Svetlana V., E-mail: svet.kostyuk@gmail.com [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Tabakov, Viacheslav J.; Chestkov, Valerij V.; Konkova, Marina S.; Glebova, Kristina V.; Baydakova, Galina V.; Ershova, Elizaveta S.; Izhevskaya, Vera L. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Baranova, Ancha, E-mail: abaranov@gmu.edu [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Center for the Study of Chronic Metabolic Diseases, School of System Biology, George Mason University, Fairfax, VA 22030 (United States); Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

    2013-07-15

    Highlights: • We describe the effects of gDNAOX on human fibroblasts cultivated in serum withdrawal conditions. • gDNAOX evokes an adaptive response in human fibroblasts. • gDNAOX increases the survival rates in serum starving cell populations. • gDNAOX enhances the survival rates in cell populations irradiated at 1.2 Gy dose. • gDNAOX up-regulates NRF2 and inhibits NF-kappaB-signaling. - Abstract: Cell-free DNA (cfDNA) released from dying cells contains a substantial proportion of oxidized nucleotides, thus, forming cfDNA{sup OX}. The levels of cfDNA{sup OX} are increased in the serum of patients with chronic diseases. Oxidation of DNA turns it into a stress signal. The samples of genomic DNA (gDNA) oxidized by H{sub 2}O{sub 2}in vitro (gDNA{sup OX}) induce effects similar to that of DNA released from damaged cells. Here we describe the effects of gDNA{sup OX} on human fibroblasts cultivated in the stressful conditions of serum withdrawal. In these cells, gDNA{sup OX} evokes an adaptive response that leads to an increase in the rates of survival in serum starving cell populations as well as in populations irradiated at the dose of 1.2 Gy. These effects are not seen in control populations of fibroblasts treated with non-modified gDNA. In particular, the exposure to gDNA{sup OX} leads to a decrease in the expression of the proliferation marker Ki-67 and an increase in levels of PSNA, a decrease in the proportion of subG1- and G2/M cells, a decrease in proportion of cells with double strand breaks (DSBs). Both gDNA{sup OX} and gDNA suppress the expression of DNA sensors TLR9 and AIM2 and up-regulate nuclear factor-erythroid 2 p45-related factor 2 (NRF2), while only gDNA{sup OX} inhibits NF-κB signaling. gDNA{sup OX} is a model for oxidized cfDNA{sup OX} that is released from the dying tumor cells and being carried to the distant organs. The systemic effects of oxidized DNA have to be taken into account when treating tumors. In particular, the damaged DNA

  12. Matrine alters microRNA expression profiles in SGC-7901 human gastric cancer cells.

    Li, Hailong; Xie, Shoupin; Liu, Xiaojun; Wu, Hongyan; Lin, Xingyao; Gu, Jing; Wang, Huping; Duan, Yongqiang

    2014-11-01

    Matrine, a major alkaloid extracted from Sophora flavescens, has been reported to possess antitumor properties in several types of cancers, including gastric cancer. However, its mechanisms of action on gastric cancer remain poorly understood. Dysregulation of microRNAs, a class of small, non-coding, regulatory RNA molecules involved in gene expression, is strongly correlated with cancer. The aim of the present study was to demonstrate that matrine treatment altered miRNA expression in SGC7901 cells. Using miRCURY™ microarray analysis, we identified 128 miRNAs substantially exhibiting >2-fold expression changes in matrine-treated cells relative to their expression levels in untreated cells. RT-qPCR was used to show that the levels of 8 miRNAs whose target genes were clustered in the cell cycle pathway increased, while levels of 14 miRNAs whose target genes were clustered in the MAPK signaling pathway decreased. These results were consistent with those from the miRNA microarray experiment. Bioinformatical analysis revealed that the majority of 57 identified enrichment pathways were highly involved in tumorigenesis. In conclusion, the results demonstrated that matrine induces considerable changes in the miRNA expression profiles of SGC7901 cells, suggesting miRNA microarray combined with RT-qPCR validation and bioinformatical analysis provide a novel and promising approach to identify anticancer targets and the mechanisms of matrine involved.

  13. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis

    Sampieri, Clara Luz; de la Peña, Sol; Ochoa-Lara, Mariana; Zenteno-Cuevas, Roberto; León-Córdoba, Kenneth

    2010-01-01

    AIM: To assess expression of matrix metalloproteinases 2 (MMP2) and MMP9 in gastric cancer, superficial gastritis and normal mucosa, and to measure metalloproteinase activity. METHODS: MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction. Normalization was carried out using three different factors. Proteins were analyzed by quantitative gelatin zymography (qGZ). RESULTS: 18S ribosomal RNA (18SRNA) was very highly expressed, while hypoxanthine ribosyltransferase-1 (HPRT-1) was moderately expressed. MMP2 was highly expressed, while MMP9 was not detected or lowly expressed in normal tissues, moderately or highly expressed in gastritis and highly expressed in cancer. Relative expression of 18SRNA and HPRT-1 showed no significant differences. Significant differences in MMP2 and MMP9 were found between cancer and normal tissue, but not between gastritis and normal tissue. Absolute quantification of MMP9 echoed this pattern, but differential expression of MMP2 proved conflictive. Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2, total MMP-9, 250 and 110 kDa bands. CONCLUSION: MMP9 expression is enhanced in gastric cancer compared to normal mucosa; interpretation of differential expression of MMP2 is difficult to establish. PMID:20333791

  14. Reversal of multidrug resistance in vincristine-resistant human gastric cancer cell line SGC7901/VCR by LY980503

    Da-Long Wu; Ying Xu; Li-Xin Yin; Huan-Zhang Lu

    2007-01-01

    AIM: To investigate the reversal effect of LY980503,a benflumetol derivative, on multidrug resistance in vincristine (VCR) -resistant human gastric carcinoma cell line SGC7901/VCR.METHODS: Cells of a human gastric cancer cell line,SGC7901, and its VCR-resistant variant, SGC7901/VCR,were cultivated with LY980503 and/or doxorubicin (DOX).The cytotoxicity of drugs in vitro was assayed by MTT method. Based on the flow cytometric technology, the uptake of DOX was detected in these cells by measuring DOX -associated mean fluorescence intensity (MFI).RESULTS: SGC7901/VCR cells were 23.5 times more resistant to DOX in comparison with SGC7901 cells.LY980503 at the concentrations of 2.0 μmol/L -10 μmol/L had no obvious cytotoxicity to SGC7901 and SGC7901/VCR cells. After simultaneous treatment with LY980503 at the concentrations of 2.0, 4.0 and 10 μmol/L, the ICs0 of DOX to SGC7901/VCR cells decreased from 1.6± 0.12 μmol/L to 0.55 ± 0.024, 0.25 ± 0.032 and 0.11± 0.015 μmol/L, respectively, thus, increasing the DOX sensitivity by 2.9-fold (P < 0. 05), 6.4-fold (P < 0. 01)and 14.5-fold (P < 0. 01), respectively. In the uptake study of DOX, simultaneous incubation of SGC7901/VCR cells with LY980503 significantly increased the DOX -associated MFI in SGC7901/VCR cells. No such results were found in parental SGC7901 cells.CONCLUSION: LY980503 at non-cytotoxic concentrations can effectively circumvent resistance of SGC7901/VCR cells to DOX by increasing intracellular DOX accumulation.

  15. Effect of NPC15199 on [Ca²⁺]i and viability in SCM1 human gastric cancer cells.

    Cheng, He-Hsiung; Chou, Chiang-Ting; Liang, Wei-Zhe; Cheng, Jin-Shiung; Chang, Hong-Tai; Kuo, Chun-Chi; Chen, I-S; Lu, Ti; Yu, C-C; Chen, Fu-An; Kuo, Daih-Huang; Shieh, Pochuen; Jan, Chung-Ren

    2016-10-31

    NPC15199 is a synthesized compound that inhibits inflammation in some models. However, whether NPC15199 affects Ca²⁺ homeostasis in human gastric cancer is unclear. This study examined the effect of NPC15199 on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) and viability in SCM1 human gastric cancer cells. The Ca²⁺-sensitive fluorescent dye fura-2 was used to measure [Ca²⁺]i. NPC15199 evoked [Ca²⁺]i rises concentration-dependently. The response was reduced by removing extracellular Ca²⁺. NPC15199-evoked Ca²⁺ entry was not inhibited by store-operated channel inhibitors (nifedipine, econazole and SKF96365) and protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA), or PKC inhibitor (GF109203X). In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished NPC15199-evoked [Ca²⁺]i rises. Conversely, treatment with NPC15199 also nearly abolished thapsigargin or BHQ-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 did not affect NPC15199-evoked [Ca²⁺]i rises. NPC15199 at concentrations of 100-900 μM induced concentration-dependent, Ca²⁺-independent decrease in viability. Together, in SCM1 cells, NPC15199 induced [Ca²⁺]i rises that involved Ca²⁺ entry through PKC-insensitive non-store-operated Ca²⁺ channels and PLC-independent Ca²⁺ release from the endoplasmic reticulum. NPC15199 also induced Ca²⁺-independent cell death.

  16. Correlation of particle properties with cytotoxicity and cellular uptake of hydroxyapatite nanoparticles in human gastric cancer cells

    Cui, Xinhui [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Liang, Tong [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Liu, Changsheng [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Yuan, Yuan, E-mail: yyuan@ecust.edu.cn [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Qian, Jiangchao, E-mail: jiangchaoqian@ecust.edu.cn [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2016-10-01

    Three types of hydroxyapatite nanoparticles (HAPNs) were synthesized employing a sonochemistry-assisted microwave method by changing microwave power (from 200 to 300 W) or using calcination treatment: L200 (200 W, lyophilization), L300 (300 W, lyophilization) and C200 (200 W, 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. - Highlights: • Three types of HAPNs (L200, L300 and C200) were synthesized employing a sonochemistry-assisted microwave method. • L200 exhibited the greatest cytotoxicity to human gastric cancer (MGC80-3) cells. • L200 showed a smaller size and higher specific surface area. • The L200 nanoparticles were more efficiently uptaken by MGC80-3 cells through energy-dependent pathways. • L200 caused the most significant increase in the intracellular calcium level.

  17. The origins of music as an adaptive trait in humans

    Amodeo, Martín Raúl

    2014-04-01

    Full Text Available Throughout human history, people have developed the faculty to appreciate and create music. Musical thinking implies the development of cognitive and emotional faculties by complex neural processes. How could such a complex behavior as music be originated by evolution? This article reviews the main evolutionary approaches that have been proposed to explain this process. The main hypotheses state that music has emerged from adaptive processes such as communication and emotional coordination between mother and infant, the conformation of large cohesive groups, mate selection or the development of cognitive and emotional flexibility through play. Natural selection could have enabled the establishment of this faculty, whereas cultural evolution and gene-culture interaction could have led to the establishment of music as we know it.

  18. Mammalian target of rapamycin pathway inhibition enhances the effects of 5-aza-dC on suppressing cell proliferation in human gastric cancer cell lines

    2008-01-01

    The present study aimed to evaluate the relationship between mTOR signaling pathway and DNA methylation in cell survival,cell cycle,gene expression and protein level on human gastric cancer cells. Human gastric cancer cell lines,MKN45 and SGC7901 were treated with 5-aza-dC,rapamycin and/or LY294002.Cell viability was analyzed by MTT.Cell cycle distribution was evaluated by flow cytometry (FCM).The transcription level of PTEN and p27 Kip1 genes was detected by using real-time PCR.Protein expressions were detected by Western blotting.We found that cell viability was moderately reduced when treated with 5-aza-dC alone,but remarkably reduced when mTOR pathway was inhibited together (P<0.01).mTOR inhibition enhances the effects of 5-aza-dC on arresting cell cycle at G2 phase in human gastric cancer cell lines.The expression of PTEN and p27 Kip1 mRNA was remarkably increased in the gastric cancer cells treated with combind drugs(P<0.01).Phosphorylation of Akt,p70S6K and 4E-BP1 were significantly reduced in the cells treated with LY294002 or RAPA(P<0.01),but we failed to find that 5-aza-dC enhance these effects.We suggested that mTOR inhibition could enhance the effects of 5-aza-dC on suppressing cell proliferation and arresting cell cycle in human gastric cancer cell lines, which might be a potential target for tumor therapy.

  19. Relationship between the expression of human telomerase reverse transcriptase gene and cell cycle regulators in gastric cancer and its significance

    Jin-Chen Shao; Ji-Feng Wu; Dao-Bin Wang; Rong Qin; Hong Zhang

    2003-01-01

    AIM: To investigate the expression of human telomerase reverse transcriptase gene (hTRT) in gastric cancer (GC)and its relevance with cell cycle regulators including P16INK4,cyclin and P53.METHODS: In situ hybridization (ISH) for hTRT mRNA was performed in 53 cases of gastric cancer and adjacent cancerous tissues. Immunohistochemical staining (S-Pmethod) for hTRT protein, P16INK4, cyclinD1 and P53 was performed in 53 cases of GC and adjacent cancerous tissues.RESULTS: Of 53 cases of GC, the expression of hTRT mRNA and hTRT protein was significantly higher than the expression of hTRT mRNA and hTRT protein in adjacent canerous tissues (P<0.01), the positive rates of hTRTmRNA and hTRT protein were 79.2 % and 88.6 %. There was a stastical difference of the expression of hTRT protein among well differentiated adenocarcinoma, poorly differentiated adenocarcinoma and mucoid carcinoma. And there was a highly significant positive correlation between the expression of hTRT mRNA and hTRT protein (r=0.625, P<0.01). However, the expression of hTRT mRNA and its protein in GC were not related with other clinicopathological parameters including gender, age, location and size of neoplasm, invasion depth, lymph node metastasis and clinical stage. There was a significant positive correlation between the expression of hTRT mRNA and cyclinD1 protein (r=0.350, P<0.01). There was a significant positive correlation between the expression of cyclinD1 protein and hTRT protein (r=0.549, P<0.01), so was between P53 and hTRT protein (r=0.319, P<0.05).CONCLUSION: The expression of hTRT gene is correlated significantly to the specific defects of cell cycle on G1/S check point; telomerase activity may depend on cell cycle in gastric cancer and it is available to clarify the molecular mechanism of telomerase activity regulation. The expression of hTRT mRNA and hTRT protein in GC is significantly different from the expression of hTRT mRNA and hTRT protein in adjacent cancerous tissue

  20. INDUCTION OF APOPTOSIS IN HUMAN GASTRIC CARCINOMA CELL LINE MGC-803 BY MONOCLONAL ANTIBODY PD4

    Xiao Hai; Dong Zhiwei; Shou Chengchao

    1998-01-01

    Objective: To study the effect of McAb PD4 on the cell cycle and on cell injury in the gastric carcinoma cell line,MGC-803. Methods: The effects of McAb PD4 on cell proliferation cycle and cell injury of MGC-803 cells were examined by flow cytometry analysis, DNA electrophoresis and terminal deoxynucle otidyl transferase assay. Fas antigen was investigated by ELISA.Results: McAb PD4 inhibited tumor-growth of MGC-803cells in nude mice by inducing apoptosis. Conclusion:P40 is a tumor-associated antigen distinct from the Fas antigen. Molecular cloning of P40 will define the pathway and mechanism of apoptosis induced by McAb PD4.Induction of apoptosis by McAb PD4 may be a useful therapeutic approach in treating cancer.

  1. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    Albers, Peter H; Bojsen-Møller, Kirstine N; Dirksen, Carsten

    2015-01-01

    12 months post-surgery. Adipose tissue from glucose tolerant subjects was the most responsive to RYGB compared to 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......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 week, 3 and 12 months after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 months post...

  2. Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells.

    Reis, Filipa S; Lima, Raquel T; Morales, Patricia; Ferreira, Isabel C F R; Vasconcelos, M Helena

    2015-09-29

    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.

  3. Effects of Chinese Jianpi herbs on cell apoptosis and related gene expression in human gastric cancer grafted onto nude mice

    Ai-Guang Zhao; Hai-Lei Zhao; Xiao-Jie Jin; Jin-Kun Yang; Lai-Di Tang

    2002-01-01

    AIM: To explore the mechanism of the Sijunzi decoction and another Chinese herbal recipe (SRRS) based mainly on the Sijunzi decoction in treatment of gastric cancer.METHODS: A human gastric adenocarcinoma cell line SGC7901 grafted onto nude mouse was used as the animal model. The mice were divided into 3 groups, one control and the two representative experimental conditions. Ahimals in the two experimental groups received either Sijunzi decoction or SRRS over a 40-day period starting at 1st day after grafting. Control animals received saline on an identical schedule. Animals were killed 41 days after being grafted.The effect of therapy was assessed by two ways: (1)tumor size was periodically measured during the life of the animals; (2) tumor weight was determined by a electron balance immediately after the animals killed. For detection of apoptotic cells, apoptotic indices(AI) were examined by the terminal deoxynucleotidyl transferase-mediated deoxyuddine tdphosphate fluorescence nick end labeling (TUNEL) method.Morphological alterations were observed with electron microscopy. S-P immunohistochemical method was used to detect the expression of Ki-67 in xenografts. Expression of bcl-2 and p53 was semiquantitatively detected using a reverse transcriptase-polymerase chain reaction (RT-PCR)technique.RESULTS: When compared with controls, tumor growth (size and weight) was significantly inhibited by treatment with the Sijunzi decoction (P<0.05) or SRRS (P<0.01). The tumor inhibitory rate in the Sijunzi decoction group was 34.33 % and SRRS group 46.53 %. AI of human gastric cancer xenografts in nude mice was significantly increased to 16.24±3.21% using TUNEL method and 11.38±6.46 % by FACScan in the Sijunzi decoction group compared with the controls (TUNEL: 2.63±1.03 %, P<0.01; FACScan: 7.15± 1.32 %, P<0.05). SRRS group was also found a significantly increased AI by using TUNEL method and flow cytometry analysis compared with the controls (TUNEL: 13.18±3

  4. Social interactions model and adaptability of human behavior

    Kun eZhao

    2011-12-01

    Full Text Available Human social networks evolve on the fast timescale of face-to face interactions and of interactions mediated by technology such as a telephone calls or video conferences. The resulting networks have a strong dynamical component that changes significantly the properties of dynamical processes. In this paper we study a general model of pairwise human social interaction intended to model both face-to face interactions and mobile phone communication. We study the distribution of durations of social interactions in whitin the model. This distribution in one limit is a power law, for other values of the parameters of the model this distribution is given by a Weibull function. Therefore the model can be used to model both face-to-face interactions data, where the distribution of duration has been shown to be fat-tailed, and mobile phone communication data where the distribution of duration is given by a Weibull distribution.The highly adaptable social interaction model propose in this paper has a very simple algorithmic implementation and can be used to simulate dynamical processes occurring in dynamical social interaction networks.

  5. Synthesis and characterization of C@CdS dots in aqueous solution and their application in labeling human gastric carcinoma cells

    Dong, Wei, E-mail: dongwei5873@126.com [Shenyang Medical College, Department of Chemistry (China); Zhou, Siqi [Fengtian Hospital Affiliated to Shenyang Medical College, ICU (China); Dong, Yan [Shenyang Pharmaceutical University, Experiment Center of Traditional Chinese Medicine Department (China); Wang, Jingwen; Liu, Shuang; Zhu, Pengxia [Shenyang Medical College, Department of Chemistry (China)

    2015-03-15

    Colloidal carbon spheres coated with cadmium sulfide nanoparticle quantum dots (C@CdS dots) with the particle size smaller than 50 nm were synthesized by an aqueous approach. The effects of different reaction times, temperatures, and pH values were carefully investigated to optimize the synthesis conditions. The as-prepared C@CdS dots were linked with mouse anti-human carcinoembryonic antigen antibody and goat anti-mouse immunoglobulin (IgG) to directly and indirectly label fixed human gastric carcinoma cells, respectively. The cytotoxicity of the C@CdS dots was also tested using the human gastric carcinoma cells. No apparent cytotoxicity was observed, which suggested the potential application of the as-prepared C@CdS dots in bioimaging.

  6. Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer.

    Santini, Daniele; Vincenzi, Bruno; Fratto, Maria Elisabetta; Perrone, Giuseppe; Lai, Raymond; Catalano, Vincenzo; Cass, Carol; Ruffini, Pier Adelchi; Spoto, Chiara; Muretto, Pietro; Rizzo, Sergio; Muda, Andrea Onetti; Mackey, John R; Russo, Antonio; Tonini, Giuseppe; Graziano, Francesco

    2010-05-01

    Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1-32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph-node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph-node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions.

  7. Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway

    Kang Y

    2016-12-01

    Full Text Available Yanting Kang,1,2,* Wanle Hu,3,* Encheng Bai,1,2 Hailun Zheng,1 Zhiguo Liu,1 Jianzhang Wu,1 Rong Jin,2 Chengguang Zhao,1 Guang Liang1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, 2Department of Epidemiology, First Affiliated Hospital, 3Department of Coloproctology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China *These authors contributed equally to this work Abstract: Fluorouracil (5-FU is the most commonly used chemotherapeutic agent for gastric cancer (GC. However, the occurrence of resistance to 5-FU treatment poses a major problem for its clinical efficacy. In this study, we found that the NFκB-signaling pathway can mediate 5-FU resistance in GC cells. We developed a 5-FU-resistant GC cell line named SGCR/5-FU and found that the 5-FU-induced resistance increased cytosolic IκBα degradation and promoted NFκB nuclear translocation in GC cells. These findings were further confirmed by the activation of the NFκB survival-signaling pathway in clinical specimens. Curcumin, a natural compound, can reverse 5-FU resistance and inhibits proliferation in GC cells by downregulating the NFκB-signaling pathway. Moreover, it can also decrease the expression level of TNFα messenger RNA. Flow cytometry and Western blot analysis results showed that the combination of curcumin and 5-FU caused synergistic inhibition of growth and induction of potent apoptosis in the resistant cancer cell lines in vitro. In conclusion, our results demonstrate that the combination of 5-FU and curcumin could be further developed as a potential therapy for human GC. Keywords: 5-FU, curcumin, NFκB, drug resistance, gastric cancer

  8. iTRAQ-Based Proteomic Analysis of Ginsenoside F2 on Human Gastric Carcinoma Cells SGC7901

    Qian Mao

    2016-01-01

    Full Text Available Ginsenoside F2 (F2, a protopanaxdiol type of saponin, was reported to inhibit human gastric cancer cells SGC7901. To better understand the molecular mechanisms of F2, an iTRAQ-based proteomics approach was applied to define protein expression profiles in SGC7901 cells in response to lower dose (20 μM and shorter duration (12 hour of F2 treatment, compared with previous study. 205 proteins were screened in terms of the change in their expression level which met our predefined criteria. Further bioinformatics and experiments demonstrated that F2 treatment downregulated PRR5 and RPS15 and upregulated RPL26, which are implicated in ribosomal protein-p53 signaling pathway. F2 also inhibited CISD2, Bcl-xl, and NLRX1, which are associated with autophagic pathway. Furthermore, it was demonstrated that F2 treatment increased Atg5, Atg7, Atg10, and PUMA, the critical downstream effectors of ribosomal protein-p53 signaling pathway, and Beclin-1, UVRAG, and AMBRA-1, the important molecules in Bcl-xl/Beclin-1 pathway. The 6 differentially abundant proteins, PRR5, CISD2, Bcl-xl, NLRX1, RPS15, and RPL26, were confirmed by western blot. Taken together, ribosomal protein-p53 signaling pathway and Bcl-xl/Beclin-1 pathway might be the most significantly regulated biological process by F2 treatment in SGC7901 cells, which provided valuable insights into the deep understanding of the molecular mechanisms of F2 for gastric cancer treatment.

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

    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.

  10. Effects of a novel porphyrin-based photosensitizer on sensitive and multidrug-resistant human gastric cancer cell lines.

    Chen, Jingjing; Mao, Lina; Liu, Shuping; Liang, Yanling; Wang, Sicheng; Wang, Yeyu; Zhao, Qiang; Zhang, Xiaojing; Che, Yanjun; Gao, Lijing; Liu, Tianjun

    2015-10-01

    Photodynamic therapy (PDT) has been considered to be a possible candidate approach in combating multidrug resistance (MDR) phenomenon during the treatment of cancer. To investigate the photocytotoxicity of a novel porphyrin-based photosensitizer, meso-5-[ρ-DTPA-aminophenyl]-10, 15, 20-triphenyl-porhyrin (DTP) (Fig. 1A), on MDR cells, the intracellular DTP uptake, phototoxicity and subcellular DTP localization were studied by using a human gastric cancer MGC803 cell line and its paclitaxel selected subline MGC803/PA expressing MDR phenotype. No significant difference was observed in intracellular DTP accumulation between sensitive and resistant cell lines after exposure to 1.56 μM concentration for 6h. DTP-PDT induced significant photocytotoxicity on both MGC803 and MGC803/PA cell lines and the photokilling was greater in MGC803 cell line in comparison to MGC803/PA. The fluence that caused 50% cell death was 4.42 and 6.29 J/cm(2) in MGC803 and MGC803/PA cell lines, respectively. The presence of Pgp inhibitors verapamil and cyclosporin A could not modify the intracellular DTP level in MGC803/PA cell line and the phototoxic effects. DTP was localized at lysosomes of MGC803 cell line but at lysosomes and mitochondria of MGC803/PA. Our results indicated that DTP-mediated PDT could eradicate gastric cancer cells whether or not they express MDR although the efficacy is slightly reduced in the MDR cells. The photokilling in MDR cells could not be altered by MDR inhibitor verapamil. The slightly different photocytotoxicity between sensitive and resistant cell lines could not explained by classical Pgp MDR and might be attributed to the differential intracellular DTP localization sites.

  11. Adaptive Human-Aware Robot Navigation in Close Proximity to Humans

    Svenstrup, Mikael; Hansen, Søren Tranberg; Andersen, Hans Jørgen

    2011-01-01

    system that uses a potential field to derive motion that respects the personʹs social zones and perceived interest in interaction. The operation of the system is evaluated in a controlled scenario in an open hall environment. It is demonstrated that the robot is able to learn to estimate if a person...... wishes to interact, and that the system is capable of adapting to changing behaviours of the humans in the environment....

  12. Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

    Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

    2016-01-01

    Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change.

  13. Helicobacter pylori induces Snail expression through ROS-mediated activation of Erk and inactivation of GSK-3β in human gastric cancer cells.

    Ngo, Hoang-Kieu-Chi; Lee, Hee Geum; Piao, Juan-Yu; Zhong, Xiancai; Lee, Ha-Na; Han, Hyeong-Jun; Kim, Wonki; Kim, Do-Hee; Cha, Young-Nam; Na, Hye-Kyung; Surh, Young-Joon

    2016-12-01

    Helicobacter pylori (H. pylori) infection has been known to be implicated in human gastric carcinogenesis. Snail, the zinc-finger transcription factor known as a key inducer of changes in the cell shape and morphogenetic movement, is aberrantly overexpressed and correlates with lymph node metastasis in gastric cancer. In the present study, we investigated whether H. pylori could induce Snail activation to provoke these changes. Using a cell scatter assay, we noticed that human gastric cancer AGS cells infected with H. pylori underwent morphological changes as well as disruption of cell-cell interaction, which was then reversed by silencing of Snail by use of small interfering RNA (siRNA). In addition, infection with H. pylori resulted in an increased intracellular level of Snail in gastric cancer cells, which was abrogated in the presence of U0126 and LY294002, inhibitors of MEK/Erk and PI3K/Akt pathways, respectively. Cycloheximide pulse-chase experiments coupled with immunocytochemical analysis revealed that the induction of Snail by H. pylori was regulated at multiple levels, including increased transcription of Snail mRNA, inhibition of protein degradation, and enhancement of nuclear translocation of Snail. Pre-treatment of AGS cells with N-acetylcysteine, a well-known reactive oxygen species (ROS) scavenger, attenuated the H. pylori-induced activation of Erk, its binding to Snail promoter, inactivation of GSK-3β, and accumulation of Snail. Collectively, these findings suggest that the upregulation of Snail expression induced by H. pylori and transformation to a spindle-like shape as a consequence in gastric cancer cells are attributable to ROS-mediated activation of Erk and the inhibition of GSK-3β signaling. © 2016 Wiley Periodicals, Inc.

  14. Amperometric microsensor for direct probing of ascorbic acid in human gastric juice.

    Hutton, Emily A; Pauliukaitė, Rasa; Hocevar, Samo B; Ogorevc, Božidar; Smyth, Malcolm R

    2010-09-30

    This article reports on a novel microsensor for amperometric measurement of ascorbic acid (AA) under acidic conditions (pH 2) based on a carbon fiber microelectrode (CFME) modified with nickel oxide and ruthenium hexacyanoferrate (NiO-RuHCF). This sensing layer was deposited electrochemically in a two-step procedure involving an initial galvanostatic NiO deposition followed by a potentiodynamic RuHCF deposition from solutions containing the precursor salts. Several important parameters were examined to characterize and optimize the NiO-RuHCF sensing layer with respect to its current response to AA by using cyclic voltammetry, and scanning electron microscopy-energy dispersive X-ray spectroscopy methods. With the NiO-RuHCF coated CFME, the AA oxidation potential under acidic conditions was shifted to a less positive value for about 0.2 V (E(p) of ca. 0.23 V vs. Ag/AgCl) as compared to a bare CFME, which greatly improves the electrochemical selectivity. Using the hydrodynamic amperometry mode, the current vs. AA concentration in 0.01 M HCl, at a selected operating potential of 0.30 V, was found to be linear over a wide range of 10-1610 μM (n=22, r=0.999) with a calculated limit of detection of 1.0 μM. The measurement repeatability was satisfactory with a relative standard deviation (r.s.d.) ranging from 4% to 5% (n=6), depending on the AA concentration, and with a sensor-to-sensor reproducibility (r.s.d.) of 6.9% at 100 μM AA. The long-term reproducibility, using the same microsensor for 112 consecutive measurements of 20 μM AA over 11 h of periodic probing sets over 4 days, was 16.1% r.s.d., thus showing very good stability at low AA levels and suitability for use over a prolonged period of time. Moreover, using the proposed microsensor, additionally coated with a protective cellulose acetate membrane, the calibration plot obtained in the extremely complex matrix of real undiluted gastric juice was linear from 10 to 520 μM (n=14, r=0.998). These results

  15. Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells.

    Jeong, Jin Boo; Hong, Se Chul; Jeong, Hyung Jin; Koo, Jin Suk

    2011-10-01

    Gastric cancer is a leading cause of cancer-related deaths, worldwide being second only to lung cancer as a cause of death. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms of arctigenin for anti-tumor effect on gastric cancer have not been examined. This study examined the biological effects of arctigenin on the human gastric cancer cell line SNU-1 and AGS. Cell proliferation was determined by MTT assay. In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by arctigenin in a time and dose dependent manner, as compared with SNU-1 and AGS cells cultured in the absence of arctigenin. Inhibition of cell proliferation by arctigenin was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bcl-2 to Bax by arctigenin. Also, arctigenin blocked cell cycle arrest from G(1) to S phase by regulating the expression of cell cycle regulatory proteins such as Rb, cyclin D1, cyclin E, CDK4, CDK2, p21Waf1/Cip1 and p15 INK4b. The antiproliferative effect of arctigenin on SNU-1 and AGS gastric cancer cells revealed in this study suggests that arctigenin has intriguing potential as a chemopreventive or chemotherapeutic agent.

  16. Immunohistochemical localization of the antioxidant enzymes biliverdin reductase and heme oxygenase-2 in human and pig gastric fundus.

    Colpaert, Erwin E; Timmermans, Jean Pierre; Lefebvre, Romain A

    2002-04-01

    The intrinsic antioxidant capacities of the bile pigments biliverdin and bilirubin are increasingly recognized since both heme degradation products can exert beneficial cytoprotective effects due to their scavenging of oxygen free radicals and interaction with antioxidant vitamins. Several studies have been published on the localization of the carbon monoxide producing enzyme heme oxygenase-2 (HO-2), which concomitantly generates biliverdin; histochemical data on the distribution of biliverdin reductase (BVR), converting biliverdin to bilirubin, are still very scarce in large mammals including humans. The present study revealed by means of immunohistochemistry the presence of BVR and HO-2 in mucosal epithelial cells and in the endothelium of intramural vessels of both human and porcine gastric fundus. In addition, co-labeling with the specific neural marker protein-gene product 9.5 (PGP 9.5) demonstrated that both BVR and HO-2 were present in all intrinsic nerve cell bodies of both submucous and myenteric plexuses, while double labeling with c-Kit antibody confirmed their presence in intramuscular interstitial cells of Cajal (ICC). Our results substantiate the hypothesis that BVR, through the production of the potent antioxidant bilirubin, might be an essential component of normal physiologic gastrointestinal defense in man and pig.

  17. Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric Tumor Cells

    Filipa S. Reis

    2015-09-01

    Full Text Available 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.

  18. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer

    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

  19. Prolactin, psychological stress and environment in humans: adaptation and maladaptation.

    Sobrinho, Luis Gonçalves

    2003-01-01

    Non-puerperal lactation and/or hyperprolactinemia in humans have been related to psychological variables in a variety of ways: (1) Non-puerperal nursing; (2) Pseudopregnancy; (3) Rapid weight gain; (4) Psychogenic galactorrhea; (5) Acute prolactin responses to psychological stress; (6) High prolactin levels in persons who cope passively in real life stress situations; (7) Paternal deprivation in women with pathological hyperprolactinemia; (8) Clinical onset of prolactinomas following life-events. Publications on the above subjects are scattered in the literature as curiosities, anecdotal case-reports or unexplained associations, as there is no theoretical frame of reference to accommodate them. We propose that prolactin is a component of a biological, "maternal", subroutine, adaptive to the care of the young, which promotes accumulation of fat for the extraordinary expenses of pregnancy and lactation, the production of milk and maternal behavior. In an attempt to characterize the stimuli responsible for the activation of the maternal subroutine in the absence of pregnancy we studied the hormonal profiles of female volunteers during three types of sessions under hypnosis: (1) Relaxation-only, control sessions; (2) Sessions in which a fantasy of "nursing" was induced; (3) Sessions of evocations of memories. Prolactin surges were related to the evocation, with rage, of humiliating experiences, but not with the fantasy of nursing. Cortisol surges were related to surprise and shock and were negatively associated with prolactin. In conclusion--Prolactin and cortisol are measurable markers of two different, and alternative, coping strategies to "psychological stress".

  20. Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming

    Elizabeth G. Hanna

    2015-07-01

    Full Text Available Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses.

  1. Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming.

    Hanna, Elizabeth G; Tait, Peter W

    2015-07-15

    Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses.

  2. In vivo cellular visualization of the human retina using optical coherence tomography and adaptive optics

    Olivier, S S; Jones, S M; Chen, D C; Zawadzki, R J; Choi, S S; Laut, S P; Werner, J S

    2006-01-05

    Optical coherence tomography (OCT) sees the human retina sharply with adaptive optics. In vivo cellular visualization of the human retina at micrometer-scale resolution is possible by enhancing Fourier-domain optical-coherence tomography with adaptive optics, which compensate for the eye's optical aberrations.

  3. Direct Detection of Helicobacter pylori Mutations Associated with Macrolide Resistance in Gastric Biopsy Material Taken from Human Immunodeficiency Virus-Infected Subjects

    Scarpellini, Paolo; Carrera, Paola; Cavallero, Annalisa; Cernuschi, Massimo; Mezzi, Gianni; Testoni, Pier Alberto; Zingale, Anna; Lazzarin, Adriano

    2002-01-01

    One hundred forty gastric biopsies were tested by microbiological methods and by amplifying a sequence of 23S rRNA and identifying mutations associated to clarithromycin resistance. Seventy-six specimens were positive for Helicobacter pylori. Mutational analysis revealed alterations in 18 (39.1%) of 46 and 2 (8.7%) of 23 samples from human immunodeficiency virus-seropositive and -seronegative persons, respectively. The results of the mutational analysis fully correlated with those of the susceptibility tests. PMID:12037095

  4. Gastric carcinogenesis

    Ismail Gomceli; Baris Demiriz; Mesut Tez

    2012-01-01

    Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths.Despite complete resection of gastric cancer and lymph node dissection,as well as improvements in chemotherapy and radiotherapy,there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis.None of the treatment modalities we have been applying today can influence the overall survival rates:at present,the overall 5-year relative survival rate for gastric cancer is about 28%.Cellular metaplasia due to chronic inflammation,injury and repair are the most documented processes for neoplasia.It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating,sustaining and advancing tumor growth.It is also evident that not all inflammation is tumorigenic.Additional mutations can be acquired,and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype.Intestinalization of gastric units,which is called "intestinal metaplasia";phenotypic antralization of fundic units,which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cell zone are three pathways that have been described for gastric carcinogenesis.Also,an important factor for the development of gastrointestinal cancers is peritumoral stroma.However,the initiating cellular event in gastric metaplasia is still controversial.Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation,and our paper attempts to high-light recent progress in this field of cancer research.

  5. Distinct genomic signatures of adaptation in pre- and postnatal environments during human evolution.

    Uddin, Monica; Goodman, Morris; Erez, Offer; Romero, Roberto; Liu, Guozhen; Islam, Munirul; Opazo, Juan C; Sherwood, Chet C; Grossman, Lawrence I; Wildman, Derek E

    2008-03-04

    The human genome evolution project seeks to reveal the genetic underpinnings of key phenotypic features that are distinctive of humans, such as a greatly enlarged cerebral cortex, slow development, and long life spans. This project has focused predominantly on genotypic changes during the 6-million-year descent from the last common ancestor (LCA) of humans and chimpanzees. Here, we argue that adaptive genotypic changes during earlier periods of evolutionary history also helped shape the distinctive human phenotype. Using comparative genome sequence data from 10 vertebrate species, we find a signature of human ancestry-specific adaptive evolution in 1,240 genes during their descent from the LCA with rodents. We also find that the signature of adaptive evolution is significantly different for highly expressed genes in human fetal and adult-stage tissues. Functional annotation clustering shows that on the ape stem lineage, an especially evident adaptively evolved biological pathway contains genes that function in mitochondria, are crucially involved in aerobic energy production, and are highly expressed in two energy-demanding tissues, heart and brain. Also, on this ape stem lineage, there was adaptive evolution among genes associated with human autoimmune and aging-related diseases. During more recent human descent, the adaptively evolving, highly expressed genes in fetal brain are involved in mediating neuronal connectivity. Comparing adaptively evolving genes from pre- and postnatal-stage tissues suggests that different selective pressures act on the development vs. the maintenance of the human phenotype.

  6. EP4 agonist alleviates indomethacin-induced gastric lesions and promotes chronic gastric ulcer healing

    Guang-Liang Jiang; Wha Bin Im; Yariv Donde; Larry A Wheeler

    2009-01-01

    AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indomethacin (20 mg/kg), an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethacin (3 mg/kg). In cultured human gastric mucous cells, EP4 agonist effect on indomethacininduced apoptosis was assessed by flow cytometry. RESULTS: The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro , the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis. CONCLUSION: EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and indomethacin-aggravated gastric ulcers, via promoting proliferation and survival of mucous epithelial cells.

  7. Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender

    Grybaeck, P. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden); Naeslund, E. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden); Hellstroem, P.M. [Department of Internal Medicine, Karolinska Hospital, Stockholm (Sweden); Jacobsson, H. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden)]|[Department of Nuclear Medicine, Karolinska Hospital, Stockholm (Sweden); Backman, L. [Department of Surgery, Karolinska Institute at Danderyd Hospital, Stockholm (Sweden)

    1996-12-01

    It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies. (orig.). With 6 figs., 4 tabs.

  8. Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway

    VGM Naidu; Bandari Uma Mahesh; Ashwini Kumar Giddam; Kuppan Rajendran Dinesh Babu; Jian Ding; K Suresh babu; B Ramesh; Rajeswara Rao Pragada; Gopalakrishnakone P

    2013-01-01

    Objective: To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule (EtAc-LME) in MKN-74, NUGC gastric cancer cells and non cancerous gastric mucous cells (GES-1), and to explore the mechanism of EtAc-LME induced apoptosis. Methods: The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases, PARP cleavage, expression of cytochrome-c (Cyt-c) was determined by western blotting, mRNA expression of Bcl-2, Bax by RT-PCR, loss of mitochondrial potential using DiOC6 dye, annexin binding assay and its influence on cell cycle arrest by flow cytometry. Results: The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells (NUGC and MKN-74) compared to normal gastric cells (GES-1), suggesting more specific cytotoxicity to the malignant cells. Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway. Conclusions: The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.

  9. Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma.

    Heideman, D A; Snijders, P J; Bloemena, E; Meijer, C J; Offerhaus, G J; Meuwissen, S G; Gerritsen, W R; Craanen, M E

    2001-08-01

    The c-met proto-oncogene, encoding the hepatocyte growth factor receptor, can be activated by various mechanisms. These include, among others, gene amplification with concomitant overexpression and the tpr-met oncogenic rearrangement. In the case of gastric cancer, contradictory results on the presence of the tpr-met oncogenic rearrangement have been published. The current study aimed therefore to assess the prevalence of tpr-met expression in Caucasian gastric adenocarcinomas, to evaluate the importance of this oncogene in their carcinogenesis. In addition, the level of c-met expression was determined, to evaluate the role of this alternative mode of activation of the proto-oncogene. A series of Caucasian gastric adenocarcinomas (n=43) and normal gastric mucosal samples (n=14) was analysed for tpr-met and c-met expression. Expression of tpr-met mRNA in the samples was performed by two reverse transcriptase polymerase chain reaction (RT-PCR) assays, with excellent correlation. The specificity of both methods was confirmed by direct sequencing of the PCR products of the MNNG-HOS cell line, which is known to contain the rearrangement. The level of c-met expression was assessed using semi-quantitative RT-PCR assays and immunohistochemistry (IHC). None of the normal gastric mucosal or gastric adenocarcinoma samples expressed tpr-met mRNA, as determined by both RT-PCR assays. Seventy per cent of the adenocarcinomas showed overexpression of c-met, according to elevated c-met mRNA levels, compared with the expression level of normal gastric mucosa. A significant correlation was found between the level of c-met mRNA and protein expression. In conclusion, these results strongly suggest that tpr-met activation does not play a role in Caucasian gastric carcinogenesis, while overexpression of the c-met gene occurs in the majority of Caucasian gastric adenocarcinomas.

  10. Hereditary Diffuse Gastric Cancer

    ... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 11/2015 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is an inherited ...

  11. Developmental evidence for obstetric adaptation of the human female pelvis.

    Huseynov, Alik; Zollikofer, Christoph P E; Coudyzer, Walter; Gascho, Dominic; Kellenberger, Christian; Hinzpeter, Ricarda; Ponce de León, Marcia S

    2016-05-10

    The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the "obstetrical dilemma" hypothesis: Giving birth to large-brained/large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic morphology. Here we address this issue from a developmental perspective. We use methods of biomedical imaging and geometric morphometrics to analyze changes in pelvic morphology from late fetal stages to adulthood in a known-age/known-sex forensic/clinical sample. Results show that, until puberty, female and male pelves exhibit only moderate sexual dimorphism and follow largely similar developmental trajectories. With the onset of puberty, however, the female trajectory diverges substantially from the common course, resulting in rapid expansion of obstetrically relevant pelvic dimensions up to the age of 25-30 y. From 40 y onward females resume a mode of pelvic development similar to males, resulting in significant reduction of obstetric dimensions. This complex developmental trajectory is likely linked to the pubertal rise and premenopausal fall of estradiol levels and results in the obstetrically most adequate pelvic morphology during the time of maximum female fertility. The evidence that hormones mediate female pelvic development and morphology supports the view that solutions of the obstetrical dilemma depend not only on selection and adaptation but also on developmental plasticity as a response to ecological/nutritional factors during a female's lifetime.

  12. Australia's dengue risk driven by human adaptation to climate change.

    Nigel W Beebe

    Full Text Available BACKGROUND: The reduced rainfall in southeast Australia has placed this region's urban and rural communities on escalating water restrictions, with anthropogenic climate change forecasts suggesting that this drying trend will continue. To mitigate the stress this may place on domestic water supply, governments have encouraged the installation of large domestic water tanks in towns and cities throughout this region. These prospective stable mosquito larval sites create the possibility of the reintroduction of Ae. aegypti from Queensland, where it remains endemic, back into New South Wales and other populated centres in Australia, along with the associated emerging and re-emerging dengue risk if the virus was to be introduced. METHODOLOGY/PRINCIPAL FINDINGS: Having collated the known distribution of Ae. aegypti in Australia, we built distributional models using a genetic algorithm to project Ae. aegypti's distribution under today's climate and under climate change scenarios for 2030 and 2050 and compared the outputs to published theoretical temperature limits. Incongruence identified between the models and theoretical temperature limits highlighted the difficulty of using point occurrence data to study a species whose distribution is mediated more by human activity than by climate. Synthesis of this data with dengue transmission climate limits in Australia derived from historical dengue epidemics suggested that a proliferation of domestic water storage tanks in Australia could result in another range expansion of Ae. aegypti which would present a risk of dengue transmission in most major cities during their warm summer months. CONCLUSIONS/SIGNIFICANCE: In the debate of the role climate change will play in the future range of dengue in Australia, we conclude that the increased risk of an Ae. aegypti range expansion in Australia would be due not directly to climate change but rather to human adaptation to the current and forecasted regional drying

  13. Cytosolic chloride ion is a key factor in lysosomal acidification and function of autophagy in human gastric cancer cell.

    Hosogi, Shigekuni; Kusuzaki, Katsuyuki; Inui, Toshio; Wang, Xiangdong; Marunaka, Yoshinori

    2014-06-01

    The purpose of the present study was to clarify roles of cytosolic chloride ion (Cl(-) ) in regulation of lysosomal acidification [intra-lysosomal pH (pHlys )] and autophagy function in human gastric cancer cell line (MKN28). The MKN28 cells cultured under a low Cl(-) condition elevated pHlys and reduced the intra-lysosomal Cl(-) concentration ([Cl(-) ]lys ) via reduction of cytosolic Cl(-) concentration ([Cl(-) ]c ), showing abnormal accumulation of LC3II and p62 participating in autophagy function (dysfunction of autophagy) accompanied by inhibition of cell proliferation via G0 /G1 arrest without induction of apoptosis. We also studied effects of direct modification of H(+) transport on lysosomal acidification and autophagy. Application of bafilomycin A1 (an inhibitor of V-type H(+) -ATPase) or ethyl isopropyl amiloride [EIPA; an inhibitor of Na(+) /H(+) exchanger (NHE)] elevated pHlys and decreased [Cl(-) ]lys associated with inhibition of cell proliferation via induction of G0 /G1 arrest similar to the culture under a low Cl(-) condition. However, unlike low Cl(-) condition, application of the compound, bafilomycin A1 or EIPA, induced apoptosis associated with increases in caspase 3 and 9 without large reduction in [Cl(-) ]c compared with low Cl(-) condition. These observations suggest that the lowered [Cl(-) ]c primarily causes dysfunction of autophagy without apoptosis via dysfunction of lysosome induced by disturbance of intra-lysosomal acidification. This is the first study showing that cytosolic Cl(-) is a key factor of lysosome acidification and autophagy.

  14. Decreased expression of microRNA let-7i and its association with chemotherapeutic response in human gastric cancer

    Liu Kun

    2012-10-01

    Full Text Available Abstract Background MicroRNA let-7i has been proven to be down-regulated in many human malignancies and correlated with tumor progression and anticancer drug resistance. Our study aims to characterize the contribution of miRNA let-7i to the initiation and malignant progression of locally advanced gastric cancer (LAGC, and evaluate its possible value in neoadjuvant chemotherapeutic efficacy prediction. Methods Eighty-six previously untreated LAGC patients who underwent preoperative chemotherapy and radical resection were included in our study. Let-7i expression was examined for pairs of cancer tissues and corresponding normal adjacent tissues (NATs, using quantitative RT-PCR. The relationship of let-7i level to clinicopathological characteristics, pathologic tumor regression grades after chemotherapy, and overall survival (OS was also investigated. Results Let-7i was significantly down-regulated in most tumor tissues (78/86: 91% compared with paired NATs (P P =0.024 independently of other clinicopathological factors, including tumor node metastasis (TNM stage (HR = 3.226, P = 0.013, depth of infiltration (HR = 4.167, P P = 0.037. Conclusions These findings indicate that let-7i may be a good candidate for use a therapeutic target and a potential tissue marker for the prediction of chemotherapeutic sensitivity and prognosis in LAGC patients.

  15. Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell

    Eun-Hwa Park

    2014-01-01

    Results and Conclusion: HAG significantly reduced the cancer cell proliferation, and the contents of ginsenosides Rb1 and Re were markedly decreased, whereas the peaks of less-polar ginsenosides [20(S,R-Rg3, Rk1, and Rg5] were newly detected. Based on the activity-guided fractionation of HAG, ginsenoside 20(S-Rg3 played a key role in inducing apoptosis in human gastric cancer AGS cells, and it was generated mainly from ginsenoside Rb1. Ginsenoside 20(S-Rg3 induced apoptosis through activation of caspase-3, caspase-8, and caspase-9, as well as regulation of Bcl-2 and Bax expression. Taken together, these findings suggest that heat-processing serves as an increase in the antitumor activity of American ginseng in AGS cells, and ginsenoside 20(S-Rg3, the active component produced by heat-processing, induces the activation of caspase-3, caspase-8, and caspase-9, which contributes to the apoptotic cell death.

  16. Recombinant Human Leptin Does Not Alter Gut Hormone Levels after Gastric Bypass but May Attenuate Sweet Cravings

    Rushika Conroy

    2014-01-01

    Full Text Available Bariatric surgery improves glucose homeostasis and alters gut hormones partly independent of weight loss. Leptin plays a role in these processes; levels are decreased following bariatric surgery, creating a relative leptin insufficiency. We previously showed that leptin administration in a weight-reduced state after Roux-en-Y gastric bypass (RYGB caused no further weight loss. Here, we discuss the impact of leptin administration on gut hormones, glucostasis, and appetite. Weight stable women after RYGB were randomized to receive placebo or recombinant human metreleptin (0.05 mg/kg twice daily. At weeks 0 and 16, a liquid meal challenge was performed. Glucose, insulin, C-peptide, GLP-1, PYY, glucagon, and ghrelin (total, acyl, and desacyl were measured fasting and postprandially. Appetite was assessed using a visual analog scale. Mean post-op period was 53±2.3 months; mean BMI was 34.6±0.2 kg/m2. At 16 weeks, there was no significant change in weight within or between groups. Fasting PYY was significantly different between groups and the leptin group had lower sweets craving at week 16 than the placebo group (P<0.05. No other differences were observed. Leptin replacement does not alter gut hormones or glucostasis but may diminish sweet cravings compared to placebo in this population of post-RYGB women.

  17. Cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells.

    Lim, Young-Cheol; Yoo, Je-Ok; Kang, Seong-Sik; Kim, Young-Myeong; Ha, Kwon-Soo

    2011-03-01

    We investigated cellular responses to chlorin-based photosensitizer DH-II-24 under darkness in human gastric adenocarcinoma AGS cells. Cells were loaded with 0.5-10 μg/mL DH-II-24 for 12 h, and intracellular reactive oxygen species (ROS) and intracellular Ca(2+) levels, in situ tissue transglutaminase (tTGase) activity, cell viability, cell morphology and cell cycle were examined. DH-II-24 treatment had no effect on intracellular ROS production or cell morphology, and did not induce cell detachment at any concentrations tested. In addition, cell viability and cell cycle progression were not altered by the photosensitizer. However, DH-II-24 treatment elevated the basal level of intracellular Ca(2+) in a dose-dependent manner and inhibited tTGase activity without affecting tTGase expression levels. Furthermore, DH-II-24 inhibited lysophosphatidic acid-induced activation of tTGase in a dose-dependent manner. In contrast, photodynamic therapy (PDT) with 1 μg/mL DH-II-24 significantly elevated intracellular ROS and in situ tTGase activity in parallel with a rapid and large increase in intracellular Ca(2+) levels. DH-II-24-mediated PDT decreased cell viability and induced cell detachment. These results demonstrate that DH-II-24 treatment alone under darkness induced different cellular responses to DH-II-24-mediated PDT.

  18. Mouse Models of Gastric Cancer

    Timothy C. Wang

    2013-01-01

    Full Text Available Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field.

  19. Non-detection of Epstein-Barr virus and human papillomavirus in a region of high gastric cancer risk indicates a lack of a role for these viruses in gastric carcinomas

    Xiao-yan Yuan

    2013-01-01

    Full Text Available Gastric mucosa tissue was collected from patients with gastroduodenal diseases in a region of norrteastern China showing a high risk of gastric cancer incidence. The presence of EBV and HPV were assayed to investigate the relationship between gastric carcinomas and virus infection. Neither EBV nor HPV DNA was detected in tissue from the patients. The role of EBV and HPV in gastric cancer is not well understood and still needs to be clarified.

  20. Amorphous Silica Particles Relevant in Food Industry Influence Cellular Growth and Associated Signaling Pathways in Human Gastric Carcinoma Cells

    Anja Wittig

    2017-01-01

    Full Text Available Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the toxicological effects of commercially available nano-scaled silica with a nominal primary diameter of 12 nm were investigated on the human gastric carcinoma cell line GXF251L. Besides the analysis of cytotoxic and proliferative effects and the comparison with effects of particles with a nominal primary diameter of 200 nm, emphasis was also given to their influence on the cellular epidermal growth factor receptor (EGFR and mitogen-activated protein kinases (MAPK signaling pathways—both of them deeply involved in the regulation of cellular processes like cell cycle progression, differentiation or proliferation. The investigated silica nanoparticles (NPs were found to stimulate cell proliferation as measured by microscopy and the sulforhodamine B assay. In accordance, the nuclear level of the proliferation marker Ki-67 was enhanced in a concentration-dependent manner. At high particle concentrations also necrosis was induced. Finally, silica NPs affected the EGFR and MAPK pathways at various levels dependent on concentration and time. However, classical activation of the EGFR, to be reflected by enhanced levels of phosphorylation, could be excluded as major trigger of the proliferative stimulus. After 45 min of incubation the level of phosphorylated EGFR did not increase, whereas enhanced levels of total EGFR protein were observed. These results indicate interference with the complex homeostasis of the EGFR protein, whereby up to 24 h no impact on the transcription level was detected. In addition, downstream on the level of the MAP kinases ERK1/2 short term incubation appeared to affect total protein levels without clear increase in phosphorylation. Depending on the

  1. Amorphous Silica Particles Relevant in Food Industry Influence Cellular Growth and Associated Signaling Pathways in Human Gastric Carcinoma Cells.

    Wittig, Anja; Gehrke, Helge; Del Favero, Giorgia; Fritz, Eva-Maria; Al-Rawi, Marco; Diabaté, Silvia; Weiss, Carsten; Sami, Haider; Ogris, Manfred; Marko, Doris

    2017-01-13

    Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the toxicological effects of commercially available nano-scaled silica with a nominal primary diameter of 12 nm were investigated on the human gastric carcinoma cell line GXF251L. Besides the analysis of cytotoxic and proliferative effects and the comparison with effects of particles with a nominal primary diameter of 200 nm, emphasis was also given to their influence on the cellular epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) signaling pathways-both of them deeply involved in the regulation of cellular processes like cell cycle progression, differentiation or proliferation. The investigated silica nanoparticles (NPs) were found to stimulate cell proliferation as measured by microscopy and the sulforhodamine B assay. In accordance, the nuclear level of the proliferation marker Ki-67 was enhanced in a concentration-dependent manner. At high particle concentrations also necrosis was induced. Finally, silica NPs affected the EGFR and MAPK pathways at various levels dependent on concentration and time. However, classical activation of the EGFR, to be reflected by enhanced levels of phosphorylation, could be excluded as major trigger of the proliferative stimulus. After 45 min of incubation the level of phosphorylated EGFR did not increase, whereas enhanced levels of total EGFR protein were observed. These results indicate interference with the complex homeostasis of the EGFR protein, whereby up to 24 h no impact on the transcription level was detected. In addition, downstream on the level of the MAP kinases ERK1/2 short term incubation appeared to affect total protein levels without clear increase in phosphorylation. Depending on the concentration

  2. Effect of Allitridi on Inducing Mitotic Arrest in Human Gastric Cell Line SGC-7901 and Its Possible Mechanism

    CHEN Tie-jun; HA Min-wen; GONG Yue-hua; XU Qian; YUAN Yuan

    2008-01-01

    Objective:To learn the effect of allitridi on inducing mitotic arrest in human gastric cell line SGC-7901 and its possible mechanisms.Methods:We treated SGC-7901 cells with ailitridi,and observed the proliferation inhibitory rate with MTT colometric assay,changes of cell cycle using flow cytometry and Switzerland-Giemsa's staining,and morphologic changes of the microtubule structure and location changes of cyclin B1 expression using immunofluorescence and confocal laser scanning microscope.Furthermore,the expression of cyclin B1 was analyzed quantitatively using Leica confocal software.Results:SGC-7901 cells were inhibited after exposure tO allitridi and the IC50 was 7.2μg/ml for 24 h,20μg/ml for 72 h.When the cells were treated with allitridi at concentrations of 3,6,and 9μg/ml for 24 h respectively,there was a declining tendency in the percentage of G0/G1 cell but an increasing tendency in G2/M cell in the allitridi treated group compared with that of control (P<0.01).When cells were treated allitridi at concentration of 6 μg/ml for 24 h,its mitotic index was much higher(P<0.01) than that of control,suggesting that allitridi caused arrest of gastric cancer cells in M phase.The cells were treated with allitridi became more shrunken and nepheioid,in which the microtubule networks disappeared,while the control cell exhibited an intact microtubule network.Contrasting with normal existence mainly in the cytoplasm,the cyclin B1 was expressed more significantly and concentrated in the nucleus after exposure tO allitridi.Fluorescence intensity of cyclin B1 protein in cells treated with allitridi was much more higher than that of control(P<0.001).Conclusion:Allitridi can induce arrest of SGC-7901 cells in M phase,probably through enhancing microtubule depolymerization by elevating the expression of cyclin B1.

  3. From Environment to Man: Genome Evolution and Adaptation of Human Opportunistic Bacterial Pathogens

    Estelle Jumas-Bilak; Hélène Marchandin; Brigitte Lamy; Anne Lotthé; Fabien Aujoulat; Frédéric Roger; Alice Bourdier

    2012-01-01

    Environment is recognized as a huge reservoir for bacterial species and a source of human pathogens. Some environmental bacteria have an extraordinary range of activities that include promotion of plant growth or disease, breakdown of pollutants, production of original biomolecules, but also multidrug resistance and human pathogenicity. The versatility of bacterial life-style involves adaptation to various niches. Adaptation to both open environment and human specific niches is a major challe...

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

    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.

  5. Stimulation of growth of the human gastric pathogen Helicobacter pylori by atmospheric level of oxygen under high carbon dioxide tension

    Lee Na

    2011-05-01

    Full Text Available Abstract Background Helicobacter pylori (Hp, a human pathogen that is associated with gastritis, peptic ulcer, and gastric cancer, has been considered a microaerophile, but there is no general consensus about its specific O2 requirements. A clear understanding of Hp physiology is needed to elucidate the pathogenic mechanism(s of Hp infection. Results We cultured Hp under a range of O2 levels with or without 10% CO2 and evaluated growth profiles, morphology, intracellular pH, and energy metabolism. We found that, in the presence of 10% CO2, the normal atmospheric level of O2 inhibited Hp growth at low density but stimulated growth at a higher density. Field emission scanning electron microscopy and fluorescence microscopy of Hp cells cultured under 20% O2 tension revealed live spiral-shaped bacteria with outer membrane vesicles on a rugged cell surface, which became smooth during the stationary phase. Fermentation products including acetate, lactate, and succinate were detected in cell culture media grown under microaerobic conditions, but not under the aerobic condition. CO2 deprivation for less than 24 h did not markedly change cytoplasmic or periplasmic pH, suggesting that cellular pH homeostasis alone cannot account for the capnophilic nature of Hp. Further, CO2 deprivation significantly increased intracellular levels of ppGpp and ATP but significantly decreased cellular mRNA levels, suggesting induction of the stringent response. Conclusions We conclude, unlike previous reports, that H. pylori may be a capnophilic aerobe whose growth is promoted by atmospheric oxygen levels in the presence of 10% CO2. Our data also suggest that buffering of intracellular pH alone cannot account for the CO2 requirement of H. pylori and that CO2 deprivation initiates the stringent response in H. pylori. Our findings may provide new insight into the physiology of this fastidious human pathogen.

  6. Event driven adaptation, land use and human coping strategies

    Reenberg, Anette; Birch-Thomsen, Torben; Fog, Bjarne

    The paper focuses on assessing the wider perspectives of adaptive resource management strategies in former subsistence agriculture societies in the SW Pacific. Firstly, we will briefly introduce the theoretical context related to the livelihood framework, adaptation to socio-environmental change...... on the entire household livelihood portfolio and reveal that the natural resources remains a widespread activity, yet increasingly supplemented by other income generating activities( ex. shop keeping, private business, government employment). Group interviews have been employed to reveal how local farmers...

  7. Complete-proteome mapping of human influenza A adaptive mutations: implications for human transmissibility of zoonotic strains.

    Olivo Miotto

    Full Text Available BACKGROUND: There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. CONCLUSIONS: Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an

  8. Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone

    Da-Qiang Li; Zhi-Biao Wang; Jin Bai; Jie Zhao; Yuan Wang; Kai Hu; Yong-Hong Du

    2004-01-01

    AIM: To explore the reversal effect of mifepristone on multidrug resistance (MDR) in drug-resistant human gastric cancer cell line SGC7901/VCR and its mechanisms.METHODS: Expression of multidrug resistance-associated protein(MRP) was detected using reverse transcriptionpolymerase chain reaction(RT-PCR). Flow cytometry was used to assay the expression of P-glycoprotein(P-gp), Bcl-2,Bax, and the mean fluorescent intensity of intracellular rhodamine 123 in the cells. Meanwhile, the protein levels of Bcl-2 and Bax were also detected by Western blotting analysis. The sensitivity of cells to the anticancer agent,vincrimycin(VCR), and the intracellular [3H]VCR accumulation were determined by tetrazolium blue (MTT) assay and a liquid scintillation counter, respectively.RESULTS: Expression of MRP and P-gp in SGC7901/VCR cells was 6.04-and 8.37-fold higher as compared with its parental SGC7901 cells, respectively. After treatment with 1, 5, 10, and 20 μmol/L mifepristone, SGC7901/VCR cells showed a 1.34-, 2.29-, 3.11-, and 3.71-fold increase in the accumulation of intracellular VCR, a known substrate of MRP,and a 1.03-, 2.04-, 3.08-, and 3.68-fold increase in the retention of rhodamine 123, an indicator of P-gp function, respectively.MTT assay revealed that the resistance of SGC7901/VCR cells to VCR was 11.96-fold higher than that of its parental cells. The chemosensitivity of SGC7901/VCR cells to VCR was enhanced by 1.02-, 7.19-, 12.84-, and 21.17-fold after treatment with mifepristone at above-mentioned dose. After 96 h of incubation with mifepristone 10 μmol/L, a concentration close to plasma concentrations achievable in human, the expression of Bcl-2 protein was decreased to (9.21±0.65)%from (25.32±1.44)%, whereas the expression of Bax protein was increased to (19.69±1.13)% from (1.24±0.78)%(P<0.01). Additionally, the effects of mifepristone on the expression of Bcl-2 and Bax proteins in SGC7901/VCR cells were further demonstrated by Western blotting analysis

  9. Epidemiologic Study of Human Epidermal Growth Factor Receptor 2 Expression in Advanced/Metastatic Gastric Cancer: an Assessment of Human Epidermal Growth Factor Receptor 2 Status in Tumor Tissue Samples of Gastric and Gastro-Esophageal Junction Cancer

    Seo, Kyung Won; Jeon, Taeyong; Kim, Sewon; Kim, Sung Soo; Kim, Kwanghee; Suh, Byoung-Jo; Hwang, Sunhwi; Choi, SeongHee; Ryu, Seungwan; Min, Jae Seok; Lee, Young-Joon; Jee, Ye Seob; Chae, Hyeondong

    2017-01-01

    Purpose The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients. Materials and Methods Tumor samples collected from 1,695 patients with histologically proven GC or GE junction enrolled at 14 different hospitals in Korea were examined. After gathering clinicopathological data of all patients, HER2 status was assessed by immunohistochemistry (IHC) at each hospital, and IHC 2+ cases were subjected to silver-enhanced in situ hybridization at 3 central laboratories. Results A total of 182 specimens tested positive for HER2, whereas 1,505 tested negative. Therefore, the overall HER2-positive rate in this study was 10.8% (95% confidence interval=9.3%–12.3%). The HER2-positive rate was higher among intestinal-type cases (17.6%) than among other types, and was higher among patients older than 70 years and 50 years of age, compared to other age groups. Conclusions Our evaluation of the HER2 positivity rate (10.8%) among Korean patients with GC and GE junction indicated the necessity of epidemiological data when conducting studies related to HER2 expression in GC and GE junction.

  10. PCR-SSCP-DNA sequencing method in detecting PTEN gene mutation and its significance in human gastric cancer

    Chuan-Yong Guo; Xuan-Fu Xu; Jian-Ye Wu; Shu-Fang Liu

    2008-01-01

    AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer.METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric cancer and paracancerous tissues using PCR-SSCP-DNA sequencing method based on microdissection and to observe the protein expression by immunohistochemistry technique.RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation sites were found in 5 of 53 gastric cancer specimens.One kind of mutation was found in exons.AA-TCC mutation was located at 40bp upstream of 3' lateral exert 7 (115946 AA-TCC).Such mutations led to terminator formation in the 297th codon of the PTEN gene.The other 3 kinds of mutation were found in introns,including a G-C point mutation at 91 bp upstream of 5' lateral exon 5(90896 G-C),a T-G point mutation at 24 bp upstream of 5' lateral exon 5 (90963 T-G),and a single base A mutation at 7 bp upstream of 5' lateral exon 5 (90980 A del).The PTEN protein expression in gastric cancer and paracancerous tissues detected using immunohistochemistry technique indicated that the total positive rate of PTEN protein expression was 66% in gastric cancer tissue,which was significantly lower than that (100%) in paracancerous tissues (P<0.005).CONCLUSION: PTEN gene mutation and expression may play an important role in the occurrence and development of gastric cancer.(C)2008 The WJG Press.All rights reserved.

  11. Human hyolaryngeal movements show adaptive motor learning during swallowing.

    Humbert, Ianessa A; Christopherson, Heather; Lokhande, Akshay; German, Rebecca; Gonzalez-Fernandez, Marlis; Celnik, Pablo

    2013-06-01

    The hyoid bone and larynx elevate to protect the airway during swallowing. However, it is unknown whether hyolaryngeal movements during swallowing can adjust and adapt to predict the presence of a persistent perturbation in a feed-forward manner (adaptive motor learning). We investigated adaptive motor learning in nine healthy adults. Electrical stimulation was administered to the anterior neck to reduce hyolaryngeal elevation, requiring more strength to swallow during the perturbation period of this study. We assessed peak hyoid bone and laryngeal movements using videofluoroscopy across thirty-five 5-ml water swallows. Evidence of adaptive motor learning of hyolaryngeal movements was found when (1) participants showed systematic gradual increases in elevation against the force of electrical stimulation and (2) hyolaryngeal elevation overshot the baseline (preperturbation) range of motion, showing behavioral aftereffects, when the perturbation was unexpectedly removed. Hyolaryngeal kinematics demonstrates adaptive, error-reducing movements in the presence of changing and unexpected demands. This is significant because individuals with dysphagia often aspirate due to disordered hyolaryngeal movements. Thus, if rapid motor learning is accessible during swallowing in healthy adults, patients may be taught to predict the presence of perturbations and reduce errors in swallowing before they occur.

  12. Apoptotic depletion of infiltrating mucosal lymphocytes associated with Fas ligand expression by Helicobacter pylori-infected gastric mucosal epithelium: human glandular stomach as a site of immune privilege.

    Koyama, S

    2000-04-01

    H. pylori infection almost invariably results in chronic gastritis, but only a proportion of patients develops severe destruction of epithelial glandular structure or peptic ulcer. To confirm the recent data obtained in testis and eye, showing that Fas ligand is involved in the phenomenon of "immune privilege," expression of Fas receptor and its ligand of the stomach was investigated in a panel of gastric biopsies obtained from patients H. pylori-positive (N = 42) and with H. pylori-negative (N = 18) by two-color flow cytometry. The results show that membrane-bound Fas ligand protein is constitutively expressed on freshly isolated human gastric mucosal epithelium coupled with infiltrating lymphocytes. There was significant overexpression of Fas receptor and its ligand, and a higher frequency of apoptotic cell death detected by TUNEL in epithelium and infiltrating lymphocytes in H. pylori-infected patients. These findings suggest that involvement of Fas receptor and its ligand system contributes to some extent to mucosal damage in H. pylori-associated gastritis. However, the more specific findings are apoptotic depletion of invading mucosal lymphocytes associated with Fas ligand expression by gastric epithelium. These provide the first direct quantitative evidence to support Fas receptor counterattack and/or paracrine fratricide as a mechanism of immune privilege in vivo in the H. pylori-infected glandular stomach.

  13. IL-26 promotes the proliferation and survival of human gastric cancer cells by regulating the balance of STAT1 and STAT3 activation.

    Wei You

    Full Text Available Interleukin-26 (IL-26 is one of the cytokines secreted by Th17 cells whose role in human tumors remains unknown. Here, we investigated the expression and potential role of IL-26 in human gastric cancer (GC. The expression of IL-26 and related molecules such as IL-20R1, STAT1 and STAT3 was examined by real-time PCR and immunohistochemisty. The effects of IL-26 on cell proliferation and cisplatin-induced apoptosis were analyzed by BrdU cooperation assay and PI-Annexin V co-staining, respectively. Lentiviral mediated siRNA was used to explore its mechanism of action, and IL-26 related signaling was analyzed by western blotting. Human GC tissues showed increased levels of IL-26 and its related molecules and activation of STAT3 signaling, whereas STAT1 activation did not differ significantly between GC and normal gastric tissues. Moreover, IL-26 was primarily produced by Th17 and NK cells. IL-26 promoted the proliferation and survival of MKN45 and SGC-7901 gastric cancer cells in a dose-dependent manner. Furthermore, IL-20R2 and IL-10R1, which are two essential receptors for IL-26 signaling, were expressed in both cell lines. IL-26 activated STAT1 and STAT3 signaling; however, the upregulation of the expression of Bcl-2, Bcl-xl and c-myc indicated that the effect of IL-26 is mediated by STAT3 activation. Knockdown of STAT1 and STAT3 expression suggested that the proliferative and anti-apoptotic effects of IL-26 are mediated by the modulation of STAT1/STAT3 activation. In summary, elevated levels of IL-26 in human GC promote proliferation and survival by modulating STAT1/STAT3 signaling.

  14. Effect of MUC2 Antisense Oligodeoxynucleotide on Cell Proliferation, Adhesion, and Proteolytic Enzyme in Human Gastric Carcinoma in vitro

    YANG Ya-ying; YI yong-fen; ZHANG Xiao-yan; XIAO Chun-wei; LIN Xiao; ZHOU Wen-wen

    2007-01-01

    Objective: To investigate the effect of MUC2 antisense oligodeoxynucleotide (ASODN) on cell proliferation, adhesion and proteolytic enzyme in human gastric carcinoma cell line (SGC7901). Methods: Phosphorothioate MUC2 ASODN was synthesized and packaged by lipofectin, and then transfected to SGC7901 cells. The expression of MUC2 mRNA and protein after transfection was detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical method respectively,and the effect of MUC2 ASODN on cell proliferation,adhesion and proteolytic enzyme was determined by flow cytometry(FCM), MTT method, Rose Bengal and immunohistochemical method. Results: Compared with the blank control group, ASODN efficiently downregulated the expression of MUC2 mRNA and protein in SGC7901 cells 48h after transfection(P<0.01). Various concentrations of ASODN could significantly inhibit the growth of SGC7901, and the inhibition peaked at the 48th hour after transfection(P<0.05). The apoptosis rate of the experimental group was about 4.38%, and the percentage of S-phase cells rose while G0/G1-phase cells fell because most of them were blocked at S-phase. In addition, cells treated with MUC2 ASODN showed lower adhesion ability with matrix and endothelial cells than control cells in vitro(P<0.01). By immunohistochemical method, the upregulation of E-cadherin proteins and the downregulation of MMP2 and cathepsinD proteins were also observed(P<0.05). Conclusion: MUC2 ASODN could efficiently inhibit SGC7901 cell proliferation, reduce cell adhesion ability and downregulate the expression levels of proteolytic enzyme in vitro.

  15. Synergistic inhibitory effect of berberine and d-limonene on human gastric carcinoma cell line MGC803.

    Zhang, Xiu-Zhen; Wang, Ling; Liu, Dong-Wu; Tang, Guang-Yan; Zhang, Hong-Yu

    2014-09-01

    This study aims at evaluating the anticancer effects of berberine hydrochloride (berberine) and d-limonene, alone and in combination, on human gastric carcinoma cell line MGC803 to determine whether berberine and d-limonene work synergistically and elucidate their mechanisms. MGC803 cells were treated with berberine and d-limonene, alone and in combination, for 24-48 h. The inhibitory effects of these drugs on growth were determined by MTT assay. The combination index and drug reduction index were calculated with the Chou-Talalay method based on the median-effect principle. Flow cytometry and laser scanning confocal microscopy were employed to evaluate the effects of both drugs on cell-cycle perturbation and apoptosis, generation of reactive oxygen species (ROS), mitochondrial membrane potential, and expression of Bcl-2 and caspase-3 in MGC803 cells. Berberine or d-limonene alone can inhibit the growth of MGC803 cells in a dose- and time-dependent manner. Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect on anti-MGC803 cells. The two drugs distinctly induced intracellular ROS generation, reduced the mitochondrial transmembrane potential (ΔΨm), enhanced the expression of caspase-3, and decreased the expression of Bcl-2. The combination of berberine and d-limonene showed more remarkable effects compared with drugs used singly in MGC803 cells. The combination of berberine and d-limonene exerted synergistic anticancer effects on MGC803 cells by cell-cycle arrest, ROS production, and apoptosis induction through the mitochondria-mediated intrinsic pathway.

  16. Differential cytotoxic responses to low- and high-dose photodynamic therapy in human gastric and bladder cancer cells.

    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.

  17. Conventional cytogenetic characterization of a new cell line, ACP01, established from a primary human gastric tumor

    E.M. Lima

    2004-12-01

    Full Text Available Gastric cancer is the second most frequent type of neoplasia and also the second most important cause of death in the world. Virtually all the established cell lines of gastric neoplasia were developed in Asian countries, and western countries have contributed very little to this area. In the present study we describe the establishment of the cell line ACP01 and characterize it cytogenetically by means of in vitro immortalization. Cells were transformed from an intestinal-type gastric adenocarcinoma (T4N2M0 originating from a 48-year-old male patient. This is the first gastric adenocarcinoma cell line established in Brazil. The most powerful application of the cell line ACP01 is in the assessment of cytotoxicity. Solid tumor cell lines from different origins have been treated with several conventional and investigational anticancer drugs. The ACP01 cell line is triploid, grows as a single, non-organized layer, similar to fibroblasts, with focus formation, heterogeneous division, and a cell cycle of approximately 40 h. Chromosome 8 trisomy, present in 60% of the cells, was the most frequent cytogenetic alteration. These data lead us to propose a multifactorial triggering of gastric cancer which evolves over multiple stages involving progressive genetic changes and clonal expansion.

  18. Human Adaptation to Space: Space Physiology and Countermeasures

    Fogarty, Jennifer

    2009-01-01

    This viewgraph presentation reviews human physiological responses to spaceflight, and the countermeasures taken to prevent adverse effects of manned space flight. The topics include: 1) Human Spaceflight Experience; 2) Human Response to Spaceflight; 3) ISS Expeditions 1-16; 4) Countermeasure; and 5) Biomedical Data;

  19. 13-Acetoxysarcocrassolide Induces Apoptosis on Human Gastric Carcinoma Cells Through Mitochondria-Related Apoptotic Pathways: p38/JNK Activation and PI3K/AKT Suppression

    Ching-Chyuan Su

    2014-10-01

    Full Text Available 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.

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

    Susana eDelgado

    2015-01-01

    Full Text Available 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 towards 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.

  1. Visuomotor control of human adaptive locomotion: Understanding the anticipatory nature

    Takahiro eHiguchi

    2013-05-01

    Full Text Available To maintain balance during locomotion, the central nervous system (CNS accommodates changes in the constraints of spatial environment (e.g., existence of an obstacle or changes in the surface properties. Locomotion while modifying the basic movement patterns in response to such constraints is referred to as adaptive locomotion. The most powerful means of ensuring balance during adaptive locomotion is to visually perceive the environmental properties at a distance and modify the movement patterns in an anticipatory manner to avoid perturbation altogether. For this reason, visuomotor control of adaptive locomotion is characterized, at least in part, by its anticipatory nature. The purpose of the present article is to review the relevant studies which revealed the anticipatory nature of the visuomotor control of adaptive locomotion. The anticipatory locomotor adjustments for stationary and changeable environment, as well as the spatio-temporal patterns of gaze behavior to support the anticipatory locomotor adjustments are described. Such description will clearly show that anticipatory locomotor adjustments are initiated when an object of interest (e.g., a goal or obstacle still exists in far space. This review also show that, as a prerequisite of anticipatory locomotor adjustments, environmental properties are accurately perceived from a distance in relation to individual’s action capabilities.

  2. Context-specific adaptation of pursuit initiation in humans

    Takagi, M.; Abe, H.; Hasegawa, S.; Usui, T.; Hasebe, H.; Miki, A.; Zee, D. S.; Shelhauser, M. (Principal Investigator)

    2000-01-01

    PURPOSE: To determine if multiple states for the initiation of pursuit, as assessed by acceleration in the "open-loop" period, can be learned and gated by context. METHODS: Four normal subjects were studied. A modified step-ramp paradigm for horizontal pursuit was used to induce adaptation. In an increasing paradigm, target velocity doubled 230 msec after onset; in a decreasing paradigm, it was halved. In the first experiment, vertical eye position (+/-5 degrees ) was used as the context cue, and the training paradigm (increasing or decreasing) changed with vertical eye position. In the second experiment, with vertical position constant, when the target was red, training was decreasing, and when green, increasing. The average eye acceleration in the first 100 msec of tracking was the index of open-loop pursuit performance. RESULTS: With vertical position as the cue, pursuit adaptation differed between up and down gaze. In some cases, the direction of adaptation was in exact accord with the training stimuli. In others, acceleration increased or decreased for both up and down gaze but always in correct relative proportion to the training stimuli. In contrast, multiple adaptive states were not induced with color as the cue. CONCLUSIONS: Multiple values for the relationship between the average eye acceleration during the initiation of pursuit and target velocity could be learned and gated by context. Vertical position was an effective contextual cue but not target color, implying that useful contextual cues must be similar to those occurring naturally, for example, orbital position with eye muscle weakness.

  3. INNATE, ADAPTIVE AND INTRINSIC IMMUNITY IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION

    Suneth S. Perera

    2012-01-01

    Full Text Available The first line of defence of the innate immune system functions by recognizing highly conserved sets of molecular structures specific to the microbes, termed pathogen-associated molecular patterns, or PAMPs via the germ line-encoded receptors Pattern-Recognition Receptors (PRRs. In addition to the innate immune system, the vertebrates have also evolved a second line of defence termed adaptive immune system, which uses a diverse set of somatically rearranged receptors T-Cell Receptors (TCRs and B Cell Receptors (BCRs, which have the inherent ability to effectively recognise diverse antigens. The innate and adaptive immune systems are functionally tied in with the intrinsic immunity, which comprises of endogenous antiviral factors. Thus, this effective response to diverse microbial infections, including HIV, requires a coordinated interaction at several functional levels between innate, adaptive and intrinsic immune systems. This review provides a snapshot of roles played by the innate, adaptive and the intrinsic immune systems during HIV-infection, along with discussing recent developments highlighting the genomic basis of these responses and their regulation by micro-RNA (miRNAs.

  4. The role of nitrogen oxides in human adaptation to hypoxia

    Levett, D.Z.; Fernandez, B.O.; Riley, H.L.; Martin, D.S.; Mitchell, K.; Leckstrom, C.A.; Ince, C.; Whipp, B.J.; Mythen, M.G.; Montgomery, H.E.; Grocott, M.P.; Feelisch, M.

    2011-01-01

    Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma

  5. Identification of miRNomes in human stomach and gastric carcinoma reveals miR-133b/a-3p as therapeutic target for gastric cancer.

    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.

  6. From Environment to Man: Genome Evolution and Adaptation of Human Opportunistic Bacterial Pathogens

    Aujoulat, Fabien; Roger, Frédéric; Bourdier, Alice; Lotthé, Anne; Lamy, Brigitte; Marchandin, Hélène; Jumas-Bilak, Estelle

    2012-01-01

    Environment is recognized as a huge reservoir for bacterial species and a source of human pathogens. Some environmental bacteria have an extraordinary range of activities that include promotion of plant growth or disease, breakdown of pollutants, production of original biomolecules, but also multidrug resistance and human pathogenicity. The versatility of bacterial life-style involves adaptation to various niches. Adaptation to both open environment and human specific niches is a major challenge that involves intermediate organisms allowing pre-adaptation to humans. The aim of this review is to analyze genomic features of environmental bacteria in order to explain their adaptation to human beings. The genera Pseudomonas, Aeromonas and Ochrobactrum provide valuable examples of opportunistic behavior associated to particular genomic structure and evolution. Particularly, we performed original genomic comparisons among aeromonads and between the strictly intracellular pathogens Brucella spp. and the mild opportunistic pathogens Ochrobactrum spp. We conclude that the adaptation to human could coincide with a speciation in action revealed by modifications in both genomic and population structures. This adaptation-driven speciation could be a major mechanism for the emergence of true pathogens besides the acquisition of specialized virulence factors. PMID:24704914

  7. Human case of gastric infection by a fourth larval stage of Pseudoterranova decipiens (Nematoda, Anisakidae

    Rubén Mercado

    1997-04-01

    Full Text Available Only three cases of human infection by anisakid nematodes have been reported in Chile since 1976. In the present case, an anisakid worm, identified as a fourth-stage Pseudoterranova decipiens larva, was removed with a gastroendoscopic biopsy clipper from the stomach of a 45 year-old man from southern Chile. The patient, who presented acute epigastric pain and a continuous sensation of having an empty stomach, reported having eaten smoked fish. The worm was fixed in 70% ethanol and cleaned in lactophenol for morphological study. The morphometric characteristics of the worm are described and drawn. Anisakid larvae in fish flesh can be killed by freezing or cooking.

  8. [Gastric cancer].

    Belén Fraile, M; Serra Bartual, M; Segarra Sánchez, J; Richart Rufino, M J

    1991-11-01

    Gastric cancer represents a disorder which incidence has come down last years. Its etiology is unknown, but diet is the principal determinant risk of suffering it. Clinic history is not much useful, because in the early stage symptoms can fail and in the late stage are inespecific. Election diagnosis is endoscopy. Surgery is the only curative treatment. By these features, it would be useful to left under vigilance to: a) patients 40 years older with dispepsia; b) patients following gastric operations; c) patients with disorders presenting aclorhidria. The authors report a clinic case that can be of frequent presentation in primary assistance.

  9. Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

    Strickertsson, Jesper A. B; Desler, Claus; Martin-Bertelsen, Tomas

    2013-01-01

    Background Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we...... therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods To separate the changes induced by bacteria from those of the inflammatory cells...... we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression...

  10. Human Topological Task Adapted for Rats: Spatial Information Processes of the Parietal Cortex

    Goodrich-Hunsaker, Naomi J.; Howard, Brian P.; Hunsaker, Michael R.; Kesner, Raymond P.

    2008-01-01

    Human research has shown that lesions of the parietal cortex disrupt spatial information processing, specifically topological information. Similar findings have been found in nonhumans. It has been difficult to determine homologies between human and non-human mnemonic mechanisms for spatial information processing because methodologies and neuropathology differ. The first objective of the present study was to adapt a previously established human task for rats. The second objective was to bette...

  11. Dynamic Range Adaptation to Spectral Stimulus Statistics in Human Auditory Cortex

    Schlichting, Nadine; Obleser, Jonas

    2014-01-01

    Classically, neural adaptation refers to a reduction in response magnitude by sustained stimulation. In human electroencephalography (EEG), neural adaptation has been measured, for example, as frequency-specific response decrease by previous stimulation. Only recently and mainly based on animal studies, it has been suggested that statistical properties in the stimulation lead to adjustments of neural sensitivity and affect neural response adaptation. However, it is thus far unresolved which statistical parameters in the acoustic stimulation spectrum affect frequency-specific neural adaptation, and on which time scales the effects take place. The present human EEG study investigated the potential influence of the overall spectral range as well as the spectral spacing of the acoustic stimulation spectrum on frequency-specific neural adaptation. Tones randomly varying in frequency were presented passively and computational modeling of frequency-specific neural adaptation was used. Frequency-specific adaptation was observed for all presentation conditions. Critically, however, the spread of adaptation (i.e., degree of coadaptation) in tonotopically organized regions of auditory cortex changed with the spectral range of the acoustic stimulation. In contrast, spectral spacing did not affect the spread of frequency-specific adaptation. Therefore, changes in neural sensitivity in auditory cortex are directly coupled to the overall spectral range of the acoustic stimulation, which suggests that neural adjustments to spectral stimulus statistics occur over a time scale of multiple seconds. PMID:24381293

  12. A Conceptual Framework for Planning Systemic Human Adaptation to Global Warming.

    Tait, Peter W; Hanna, Elizabeth G

    2015-08-31

    Human activity is having multiple, inter-related effects on ecosystems. Greenhouse gas emissions persisting along current trajectories threaten to significantly alter human society. At 0.85 °C of anthropogenic warming, deleterious human impacts are acutely evident. Additional warming of 0.5 °C-1.0 °C from already emitted CO₂ will further intensify extreme heat and damaging storm events. Failing to sufficiently address this trend will have a heavy human toll directly and indirectly on health. Along with mitigation efforts, societal adaptation to a warmer world is imperative. Adaptation efforts need to be significantly upscaled to prepare society to lessen the public health effects of rising temperatures. Modifying societal behaviour is inherently complex and presents a major policy challenge. We propose a social systems framework for conceptualizing adaptation that maps out three domains within the adaptation policy landscape: acclimatisation, behavioural adaptation and technological adaptation, which operate at societal and personal levels. We propose that overlaying this framework on a systems approach to societal change planning methods will enhance governments' capacity and efficacy in strategic planning for adaptation. This conceptual framework provides a policy oriented planning assessment tool that will help planners match interventions to the behaviours being targeted for change. We provide illustrative examples to demonstrate the framework's application as a planning tool.

  13. A Conceptual Framework for Planning Systemic Human Adaptation to Global Warming

    Tait, Peter W.; Hanna, Elizabeth G.

    2015-01-01

    Human activity is having multiple, inter-related effects on ecosystems. Greenhouse gas emissions persisting along current trajectories threaten to significantly alter human society. At 0.85 °C of anthropogenic warming, deleterious human impacts are acutely evident. Additional warming of 0.5 °C–1.0 °C from already emitted CO2 will further intensify extreme heat and damaging storm events. Failing to sufficiently address this trend will have a heavy human toll directly and indirectly on health. Along with mitigation efforts, societal adaptation to a warmer world is imperative. Adaptation efforts need to be significantly upscaled to prepare society to lessen the public health effects of rising temperatures. Modifying societal behaviour is inherently complex and presents a major policy challenge. We propose a social systems framework for conceptualizing adaptation that maps out three domains within the adaptation policy landscape: acclimatisation, behavioural adaptation and technological adaptation, which operate at societal and personal levels. We propose that overlaying this framework on a systems approach to societal change planning methods will enhance governments’ capacity and efficacy in strategic planning for adaptation. This conceptual framework provides a policy oriented planning assessment tool that will help planners match interventions to the behaviours being targeted for change. We provide illustrative examples to demonstrate the framework’s application as a planning tool. PMID:26334285

  14. A Conceptual Framework for Planning Systemic Human Adaptation to Global Warming

    Peter W. Tait

    2015-08-01

    Full Text Available Human activity is having multiple, inter-related effects on ecosystems. Greenhouse gas emissions persisting along current trajectories threaten to significantly alter human society. At 0.85 °C of anthropogenic warming, deleterious human impacts are acutely evident. Additional warming of 0.5 °C–1.0 °C from already emitted CO2 will further intensify extreme heat and damaging storm events. Failing to sufficiently address this trend will have a heavy human toll directly and indirectly on health. Along with mitigation efforts, societal adaptation to a warmer world is imperative. Adaptation efforts need to be significantly upscaled to prepare society to lessen the public health effects of rising temperatures. Modifying societal behaviour is inherently complex and presents a major policy challenge. We propose a social systems framework for conceptualizing adaptation that maps out three domains within the adaptation policy landscape: acclimatisation, behavioural adaptation and technological adaptation, which operate at societal and personal levels. We propose that overlaying this framework on a systems approach to societal change planning methods will enhance governments’ capacity and efficacy in strategic planning for adaptation. This conceptual framework provides a policy oriented planning assessment tool that will help planners match interventions to the behaviours being targeted for change. We provide illustrative examples to demonstrate the framework’s application as a planning tool.

  15. c-Jun N-terminal kinase is required for vitamin E succinate-induced apoptosis in human gastric cancer cells

    Kun Wu; Yan Zhao; Gui-Chang Li; Wei-Ping Yu

    2004-01-01

    AIM: To investigate the roles of c-Jun N-terminal kinase (JNK)signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS: Human gastric cancer cell lines (SGC-7901)were treated with vitamin E succinate (VES) at 5, 10, 20 mg/L.Succinic acid and vitamin E were used as vehicle controls and condition medium only as an untreated (UT) control.Apoptosis was observed by 4′, 6-diamidine-2′-phenylindole dihydrochloride (DAPI) staining for morphological changes and by DNA fragmentation for biochemical alterations.Western blot analysis was applied to measure the expression ofJNK and phosphorylated JNK. After the cells were transiently transfected with dominant negative mutant of JNK (DNJNK) followed by treatment of VES, the expression of JNK and c-Jun protein was determined.RESULTS: The apoptotic changes were observed after VES treatment by DNA fragmentation. DNA ladder in the 20 mg/L VES group was more clearly seen than that in 10 mg/L VES group and was not detected following treatment of UT control, succinate and vitamin E. VES at 5, 10 and 20 mg/L increased the expression of p-JNK by 2.5-, 2.8- and 4.2-fold, respectively. VES induced the phosphorylation of JNK beginning at 1.5 h and produced a sustained increase for 24 h with the peak level at 12 h. Transient transfection of DN-JNK blocked VES-triggered apoptosis by 52%. DN-JNK significantly increased the level of JNK, while decreasing the expression of VES-induced c-Jun protein.CONCLUSION: VES-induced apoptosis in human gastric cancer SGC-7901 cells involves JNK signaling pathway via c-Jun and its downstream transcription factor.

  16. LABELING McAb 3H11 AND ITS Fab FRAGMENT WITH 211At AND THEIR IMMUNOREACTIVITIES AND INJURY EFFECTS ON HUMAN GASTRIC CANCER CELLS

    刘宁; 罗德元; 等

    1995-01-01

    An antigastric cancer monoclonal antibody,3H11,and its Fab fragment,were labeled using p-(211At)-astatobenzoic acid(pAtBA) intermediate,in the yields of more than 30%.The results of in vitro experiments show that 211 At-3H11 and 211At-3H11 Fab are stable,and have specific immunoreactivities and cytotoxic effects to human gastric cancer cell M85,The cytotoxic effects are dependent on the concentration of 211At-3H11 or 211 At-3H11 Fab and obviously stronger than that of Na211At.

  17. Gastric lipoma

    Zameer M

    2010-01-01

    Full Text Available We report a 12-year-old-boy with gastric lipoma. Upper gastrointestinal (GI endoscopy with biopsy and abdominal computed tomogram (CT scan revealed the diagnosis. Open surgical excision of the mass with stomach preservation was done. The clinical presentation and management are discussed and the literature reviewed here. This is the sixth pediatric case reported in the English literature.

  18. Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning.

    Maxwell, Sean L; Venter, Oscar; Jones, Kendall R; Watson, James E M

    2015-10-01

    The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation.

  19. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    Madsen, Jan Lysgård; Rasmussen, S L; Linnet, J;

    2004-01-01

    measured using scintigraphic and manometric techniques. Isosorbide dinitrate did not change the area under the curve of gastric retention versus time, and did not influence the frequency of antral contractions as assessed at 15-min intervals or the integrated duodenal motility index, as recorded over...

  20. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    Madsen, J L; Rasmussen, S L; Linnet, J;

    2004-01-01

    Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying and...

  1. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

    Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J;

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were...

  2. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  3. Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries.

    Goodman, Morris; Sterner, Kirstin N; Islam, Munirul; Uddin, Monica; Sherwood, Chet C; Hof, Patrick R; Hou, Zhuo-Cheng; Lipovich, Leonard; Jia, Hui; Grossman, Lawrence I; Wildman, Derek E

    2009-12-01

    Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed approximately 6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and dN/dS ratios were determined. Then, from gene ontology information on genes with the higher dN/dS ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage.

  4. Gastric Sleeve Surgery

    ... A Week of Healthy Breakfasts Shyness Gastric Sleeve Surgery KidsHealth > For Teens > Gastric Sleeve Surgery Print A ... buying healthy food ) continue Preparing for Gastric Sleeve Surgery Preparing for this major operation takes months of ...

  5. What gastric cancer proteomic studies show about gastric carcinogenesis?

    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.

  6. Possible human impacts on adaptive radiation: beak size bimodality in Darwin's finches.

    Hendry, Andrew P; Grant, Peter R; Rosemary Grant, B; Ford, Hugh A; Brewer, Mark J; Podos, Jeffrey

    2006-08-01

    Adaptive radiation is facilitated by a rugged adaptive landscape, where fitness peaks correspond to trait values that enhance the use of distinct resources. Different species are thought to occupy the different peaks, with hybrids falling into low-fitness valleys between them. We hypothesize that human activities can smooth adaptive landscapes, increase hybrid fitness and hamper evolutionary diversification. We investigated this possibility by analysing beak size data for 1755 Geospiza fortis measured between 1964 and 2005 on the island of Santa Cruz, Galápagos. Some populations of this species can display a resource-based bimodality in beak size, which mirrors the greater beak size differences among species. We first show that an historically bimodal population at one site, Academy Bay, has lost this property in concert with a marked increase in local human population density. We next show that a nearby site with lower human impacts, El Garrapatero, currently manifests strong bimodality. This comparison suggests that bimodality can persist when human densities are low (Academy Bay in the past, El Garrapatero in the present), but not when they are high (Academy Bay in the present). Human activities may negatively impact diversification in 'young' adaptive radiations, perhaps by altering adaptive landscapes.

  7. MicroRNA-191 targets N-deacetylase/N-sulfotransferase 1 and promotes cell growth in human gastric carcinoma cell line MGC803

    Xuejun Shi; Shicang Su; Jian Long; Bing Mei; Yajun Chen

    2011-01-01

    As a family of post-transcriptional regulator of gene expression,the microRNAs (miRNAs) control a wide array of biological processes including cell differentiation,proliferation and apoptosis,and the dysregulation of miRNAs is a hallmark of cancer.Here,we found that the microRNA-191 (miR-191) was at a high-expression level in human gastric adenocarcinoma cell line MGC803 and human gastric cancer tissues.The results of 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays showed that miR-191 could promote cell growth and suppress apoptosis of MGC803 cells.The N-deacetylase/N-sulfotransferase 1 (NDST1) was confirmed to be a direct target gene of miR-191 by enhanced green fluorescent protein reporter experiment.The mRNA and protein levels of NDST1 were inversely correlated with miR-191 in MGC803 cells,suggesting the negative regulation of NDST1 by miR-191.Furthermore,NDST1 played an inhibitory role and could suppress MGC803 cell proliferation.Our findings suggested that miR-191 could act as an oncogene in MGC803 cells,and the cellular function was partially due to its negative regulation of NDST1.

  8. Induction of Apoptosis by L-NMMA, via FKHRL1/ROCK Pathway in Human Gastric Cancer Cells

    YONG-ZHONG WANG; ZHEN-QING FENG

    2006-01-01

    To investigate the apoptosis-inducing effect of endogenous nitric oxide (NO) suppression in gastric cancer cells and its mechanisms. Methods Apoptosis of gastric cancer cells was detected by flow cytometry. Expression of phosphorylated FKHRL1 (thr-32, ser-253) and FKHRL1 in gastric cancer cells was analyzed using Western blotting.Immunofluorescence assay was performed to localize the intracellular phosphorylated FKHRL1 (thr-32, ser-253) and FKHRL1.Transfection of FKHRL1-HA wild type and mutant FKHRL1-HA T32A constructs was performed by lipofectamine plus reagent. NO generation was determined by Griess reaction. Results Gastric cancer cells were significantly apoptotic after treatment with NG-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor), compared with the control (P<0.01).The apoptosis of gastric cancer cells induced by L-NMMA was dose-dependent and time-independent. However, the Z-DEVD-fmk, a caspase-3, 6, 7, 8, 10 inhibitor, did not prevent the apoptosis. The immunofluorescence assays showed that FKHRL1 protein was strongly expressed in the nucleu and p-FKHRL1 thr-32 protein was strongly expressed in the cytoplasm of SGC-7901 cells when endogenous nitric oxide generation was blocked by L-NMMA, but no change in FKHRL1 ser-253phosphorylation. Nevertheless, ROCK protein was strongly expressed in p-FKHRL1 thr-32-positive SGC-7901 cells. The wortmannin, an inhibitor of phosphoinositol-3-OH kinase (PI3K), did not block the phosphorylated FKHRL1 thr-32 protein induced by L-NMMA. However, Y-27632, a specific inhibitor of the protein kinase ROCK, significantly blocked apoptosis induced by phosphorylated FKHRL1 thr-32 (P<0.01), which was mediated by L-NMMA. A significant decrease in NO generation (P<0.01) and a significant increase in apoptosis (P<0.01) were observed when FKHRL1-HA wild-type cells were transfected, which caused increased FKHRL1 thr-32 phosphorylation. Conclusions L-NMMA triggers gastric carcinoma cell apoptosis, possibly by

  9. Reasoning about Human Participation in Self-Adaptive Systems

    2015-01-16

    Cheng et al. [19] X X X X Oreizy et al. [25] X X Dorn & Taylor [14] X X X Business Process BPMN [27] X X Modelling WSBPEL4People [13] X X Cyber-Human...ter Hofstede, and N. Russell. On the suitability of BPMN for business process modelling. In S. Dustdar, J. L. Fiadeiro, and A. P. Sheth, editors

  10. Effect of non-anticoagulant N-desulfated heparin on expression of vascular endothelial growth factor, angiogenesis and metastasis of orthotopic implantation of human gastric carcinoma

    Jin-Lian Chen; Jing Hong; Jin-Lai Lu; Ming-Xiang Chen; Wei-Xiong Chen; Jin-Shui Zhu; Ni-Wei Chen; Guo-Qiang Chen; Jian-Guo Geng

    2007-01-01

    AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of orthotopic implantation of human gastric carcinoma in male severe combined immune deficiency (SCID) mice.METHODS: Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SCID mice.The mice were randomly divided into normal saline group and N-desulfated heparin group. One week after operation, the mice in N-desulfated heparin group received i.v. injections of N-desulfated heparin (Shanghai Institute of Cell Biology, Chinese Academy of Sciences,10 mg/kg.d) twice weekly for 3 wk. The mice in normal saline group received i.v. injections of normal saline (100pL) twice weekly for 3 wk. The mice were sacrificed six weeks after implantation. Tumor metastasis was evaluated histologically for metastasis under microscope. Intratumoral microvessel density (MVD) and VEGF expression were evaluated immuohistochemically. VEGF mRNA expression in gastric tissue of SCID mice was detected by real time PCR.RESULTS: The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated heparin group(P < 0.05). MVD was 8.0±3.1 in normal saline group and 4.3±1.8 in N-desulfated heparin group (P < 0.05).VEGF positive immunostaining was found in cytoplasm of cancer cells. The rate of VEGF positive expression was higher in normal saline group than in N-desulfated heparin treated group (90% VS 20%, P < 0.05). VEGF mRNA expression was significantly inhibited by N-desulfated heparin and was higher in normal saline group than in N-desulfated heparin group (Ct value 19.51±1.01 vs22.55±1.36, P < 0.05). N-desulfated heparin significantly inhibited the expression of VEGF mRNA in cancer cells. No bleeding occurred in N-desulfated heparin group.CONCLUSION: N-desulfated heparin can inhibit metastasis of gastric cancer by suppressing tumor VEGF expression and tumor angiogenesis, but has no obvious

  11. THE ESTABLISHMENT OF A NEW ANIMAL MODEL FOR GASTRIC CANCER STUDY BY ORTHOTO PIC IMPLANTATION OF GASTRIC CANCER CELLS INTO ATHYMIC NUDE MICE

    曾知真; 施尧; 萧树东; 江绍基; 张素胤; 殳裕华

    1992-01-01

    An animal model mimicking human gastric cancer by gastric wall implantation technique in athymic nude mice was reported. Two human gastric cancer cell lines. MKN-45 and MKN-28, were used in this study. All animals with gastric wall implantation of cancer cells of these two cell lines developed grossly visible gastric tumors after 3-4 weeks of implantation. Histopathological examination showed that tumors prirnarily grew at serosal side of stomach, and progressively invaded the gastric mucosa, but none showed metastasis in this study. All tumor-bearing animals died within 5-8 weeks after implantation. These results indicated that gastric wall of nude mice provided a good soil for growth and propagation of human gastric cancer cells. The model was useful for in vivo study on biological behavior of various types of human gastric cancers.

  12. Culture adaptation alters transcriptional hierarchies among single human embryonic stem cells reflecting altered patterns of differentiation.

    Gokhale, Paul J; Au-Young, Janice K; Dadi, SriVidya; Keys, David N; Harrison, Neil J; Jones, Mark; Soneji, Shamit; Enver, Tariq; Sherlock, Jon K; Andrews, Peter W

    2015-01-01

    We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal ('Culture Adapted') human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation.

  13. Adapting human pluripotent stem cells to high-throughput and high-content screening.

    Desbordes, Sabrina C; Studer, Lorenz

    2013-01-01

    The increasing use of human pluripotent stem cells (hPSCs) as a source of cells for drug discovery, cytotoxicity assessment and disease modeling requires their adaptation to large-scale culture conditions and screening formats. Here, we describe a simple and robust protocol for the adaptation of human embryonic stem cells (hESCs) to high-throughput screening (HTS). This protocol can also be adapted to human induced pluripotent stem cells (hiPSCs) and high-content screening (HCS). We also describe a 7-d assay to identify compounds with an effect on hESC self-renewal and differentiation. This assay can be adapted to a variety of applications. The procedure involves the culture expansion of hESCs, their adaptation to 384-well plates, the addition of small molecules or other factors, and finally data acquisition and processing. In this protocol, the optimal number of hESCs plated in 384-well plates has been adapted to HTS/HCS assays of 7 d.

  14. A microarray-based gastric carcinoma prewarning system

    Da-Xiang Cui; Jin-Rong Zhao; Fen-Chan Han; Ju Zhang; Jia-Le Hu; Dai-Ming Fan; Hua-Jian Gao; Li Zhang; Xiao-Jun Yan; Ling-Xia Zhang; Jun-Rong Xu; Yan-Hai Guo; Gui-Qiu Jin; Giovani Gomez; Ding Li

    2005-01-01

    AIM: To develop a microarray-based prewarning system consisting of gastric cancer chip, prewarning data and analysissoftware for early detection of gastric cancer and pre-cancerous lesions.METHODS: Two high-density chips with 8 464 human cDNA sites were used to primarily identify potential genes specific for normal gastric mucosa, pre-cancerous lesion and gastric cancer. The low-density chips, composed of selected genes associated with normal gastric mucosa,precancerous lesion and gastric cancer, were fabricated and used to screen 150 specimens including 60 specimens of gastric cancer, 60 of pre-cancerous tissues and 30 of normal gastric mucosa. CAD software was used to screen out the relevant genes and their critical threshold values of expression levels distinguishing normal mucosa from pre-cancerous lesion and cancer. All data were stored in a computer database to establish a prewarning data library for gastric cancer. Two potential markers brcaa1 and ndr1were identified by Western blot and immunohistochemistry.RESULTS: A total of 412 genes associated with three stages of gastric cancer development were identified.There were 216 genes displaying higher expression in gastric cancer, 85 genes displaying higher expression in pre-cancerous lesion and 88 genes displaying higher expression in normal gastric mucosa. Also 15 genes associated with metastasis of gastric cancer and 8 genes associated with risk factors were screened out for target genes of diagnosis chip of early gastric cancer. The threshold values of 412 selected genes to distinguish gastric cancer, pre-cancerous lesion from normal gastric mucosa were defined as 6.01±2.40, 4.86±1.94 and 5.42±2.17, respectively. These selected 412 genes and critical threshold values were compiled into an analysis software, which can automatically provide reports by analyzing the results of 412 genes obtained by examining gastric tissues. All data were compiled into a prewarning database for gastric cancer by CGO

  15. Binding of Helocobacter pyori to Human Gastric Mucose: Identification and Characterization of a Lewis b Bingind Protein.

    1995-06-01

    putative virulence factors of H. pylori have been identified to date. These factors include a urease , flagella, a mucinase, a cytotoxin, and two adhesins...The urease is believed to aid in bacterial survival of the harsh gastric environment by generating ammonia from urea to neutralize the low pH (Segal...cells. This vacuolization inevitably leads to host-cell death (Cover and Blaser, 1992). The proton pump inhibitor , Bafilomycin Al, blocks the cytotoxin

  16. Enterococcus faecalis infection causes inflammation, intracellular oxphos-independent ROS production, and DNA damage in human gastric cancer cells.

    Jesper A B Strickertsson

    Full Text Available BACKGROUND: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. METHODS: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA. Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR. Mitochondrial mutations were determined by sequencing. RESULTS: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos. Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. CONCLUSIONS: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-κB inflammatory response as well as impaired DNA damage response and cell cycle control gene

  17. Association between endogenous gene expression and growth regulation induced by TGF-β1 in human gastric cancer cells

    Xue Li; Yun-Yan Zhang; Qi Wang; Song-Bin Fu

    2005-01-01

    AIM: To investigate the association between endogenous gene expression and growth regulation including proliferation and apoptosis induced by transforming growth factor-β1(TGF-β1) in human gastric cancer (GC) cells.METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the main components of the TGF-β1/Smads signal pathway in human poorly differentiated GC cell line BGC-823. Localization of Smad proteins was also determined using immunofluorescence.Then, the BGC-823 cells were cultured in the presence or absence of TGF-β1 (10 ng/mL) for 24 and 48 h, and the effects of TGF-β1 on proliferation and apoptosis were measured by cell growth curve and flow cytometry (FCM)analysis. The ultrastructural features of BGC-823 cells with or without TGF-β1 treatment were observed under transmission electron microscope. The apoptotic cells were visualized by means of the terminal deoxynucleotidyl transferase (TdT)-mediated dTUPin situ nick end-labeling (TUNEL) method. Meanwhile, the expression levels of endogenous p15, p21 and Smad7 mRNA and the corresponding proteins in the cells were detected at 1, 2and 3 h after culture in the presence or absence of TGF-β1(10 ng/mL) by semi-quantitative RT-PCR and Western blot,respectively.RESULTS: The TGF-β1/Smad signaling was found to be intact and functional in BGC-823 cells. The growth curve revealed the most evident inhibition of cell proliferation by TGF-β1 at 48 h, and FCM assay showed G1 arrest accompanied with apoptosis induced by TGF-β1. The typical morphological changes of apoptosis were observed in cells exposed to TGF-β1. The apoptosis index (AI) in TGF-β1-treated cells was significantly higher than that in the untreated controls (10.7±1.3% vs 0.32±0.06%, P<0.01).The levels of p15, p21 and Smad7mRNA and corresponding proteins in cells were significantly up-regulated at 1 h, but gradually returned to basal levels at 3 h following TGF-β1(10 ng/mL) treatment.CONCLUSION: TGF-β1

  18. Effects of Gossypol in Inducing Apoptosis of Human Gastric Cancer Cell Line SGC-7901%棉酚对人胃癌细胞SGC-7901的抑制作用

    俞耀军; 卢明东; 孙维建; 李丕宏; 周香; 王飞海; 郑志强; 游涛

    2012-01-01

    Objective: To study the mode of action of gossypol on human gastric cancer cell line SGC-7901. Methods: Gastric cancer cell line SGC-7901 treated with various concentrations of gossypol were assessed. MTT assay was used to observe evidence of apoptosis and proliferation. Results: Cell proliferation of Gastric cancer cell line SGC-7901 was decreased and the apoptosis was observed. Apoptotic death is to be dose and time dependent. Conclusions: Cossypol induces apoptosis and decreases cell proliferation in human gastric cancer cell line SGC-7901. It is Suggested that gossypol might be apotential alternative of chemotherapy agent for gastric cancer.%目的 研究棉酚(gossypol)对胃癌细胞的增殖抑制作用.方法 将不同浓度棉酚与胃癌细胞株SGC-7901作用,采用MTT法检测凋亡情况.结果 经棉酚处理后增殖能力降低,细胞显示明显凋亡征象,并随药物浓度增加和作用时间延长而增加.结论 棉酚在体外能诱导胃癌细胞SGC-7901发生凋亡,抑制细胞增殖,是一种具有潜在抗肿瘤作用的药物,值得进一步临床试验.

  19. Fourier transform infrared microspectroscopy as a diagnostic tool for distinguishing between normal and malignant human gastric tissue

    Abasalt Hosseinzadeh Colagar; Mohammad Javad Chaichi; Tahereh Khadjvand

    2011-09-01

    Fourier transform infrared (FTIR) microspectroscopy can be considered to be a fast and non-invasive tool for distinguishing between normal and cancerous cells and tissues without the need for laborious and invasive sampling procedures. Gastric samples from four patients (age, 65±2 years) were analysed. Samples were obtained from the organs removed during gastrectomy and then classified as normal or cancerous. Classification was based on histopathological examinations at our institution. Formalin-fixed sections of gastric tissue were analysed by FTIR-microspectroscopy. To characterize differences between sections of normal and cancerous tissue, specific regions of the spectra were analysed to study variations in the levels of metabolites. To distinguish between two conditions (normal and cancerous), changes in the relative intensity of bands in the range 600–4000 cm−1 were analysed. A FTIR spectral map of the bands in the region 2800–3100 cm–1 and 900–1800 cm–1 were created to analyse pathological changes in tissues. The limited data available showed that normal gastric tissue had stronger absorption than cancerous tissue over a wide region in the four patients. There was a significant decrease in total biomolecular components for cancerous tissue compared with normal tissue.

  20. CD21-independent Infection of Epstein-Barr Virus in Human Signet Ring Gastric Carcinoma Cell Line

    罗兵; MasanaoMurakami; MakotoFukuta; KazuyoshiYanagihara; TakeshiSairenji

    2003-01-01

    To study the mechanism of infection of Epstein-Barr virus (EBV) in gastric carcinoma cells, the Akata and P3HR-1 strains of EBV were used as the test strains of viruses, and the signet ring cell line HSC-39 of gastric carcinoma cells was used as the target cells of infection. The virus-infected cell clones were isolated by limited dilution method. It was found that the EBV-encoded small RNA (EBER) could be detected in the infected cells. The Akata and P3HR-1 EBV infected parental cells and most of clones expressed EBNA1, but not EBNA2. Latent membrane protein (LMP-1) and LMP-2,and the Q promoter (p), but not the Cp/Wp for EBNA gene transcription was active in the infected parental cells as well as all the clones. Uninfected HSC-39 cells did not express CD21, however, Akata but not P3HR-1 EBV-infected clones ex-pressed low level of CD21 mRNA. These results demonstrate that HSC-39 cells are susceptible to both EBV strains and EBVinfects HSC-39 cells through the CD21-independent pathway. This study defines a signet ring type of gastric carcinoma cellsline as a unique target cells for the study of EBV infection mechanism.

  1. Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

    Őri, Zsolt P

    2016-08-03

    A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

  2. Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer

    Yasutaka Sukawa; Hiroyuki Yamamoto; Katsuhiko Nosho; Hiroaki Kunimoto; Hiromu Suzuki; Yasushi Adachi; Mayumi Nakazawa

    2012-01-01

    AIM:To investigate human epidermal growth factor receptor 2 (HER2)-phosphatidylinositol 3-kinase (PI3K)-v-Akt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry (IHC) using the HercepTestTM kit.Standard criteria for HER2 positivity (0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt (pAkt)was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide (PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus (EBV)infection was analyzed by in situ hybridization targeting EBV-encoded small RNA (EBER) with an EBER-RNA probe.Microsatellite instability (MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167 (72%),32 (14%),12 (5%) and 20 (8.7%) samples,respectively.HER2 overexpression (IHC 3+) significantly correlated with intestinal histological type (15/20 vs 98/205,P =0.05).PIK3CA mutations were present in 20 cases (8.7%) and significantly correlated with MSI (10/20 vs 9/211,P < 0.01).The mutation frequency was high (21%) in T4 cancers and very low (6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5 (2%),9 (4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R (6/20,30%) in exon20.Eighteen cancers (8%) were EBV-positive and this

  3. Adaptation of group A Streptococcus to human amniotic fluid.

    Izabela Sitkiewicz

    Full Text Available BACKGROUND: For more than 100 years, group A Streptococcus has been identified as a cause of severe and, in many cases, fatal infections of the female urogenital tract. Due to advances in hospital hygiene and the advent of antibiotics, this type of infection has been virtually eradicated. However, within the last three decades there has been an increase in severe intra- and post-partum infections attributed to GAS. METHODOLOGY: We hypothesized that GAS alters its transcriptome to survive in human amniotic fluid (AF and cause disease. To identify genes that were up or down regulated in response to growth in AF, GAS was grown in human AF or standard laboratory media (THY and samples for expression microarray analysis were collected during mid-logarithmic, late-logarithmic, and stationary growth phases. Microarray analysis was performed using a custom Affymetrix chip and normalized hybridization values derived from three biological replicates were collected at each growth point. Ratios of AF/THY above a 2-fold change and P-value <0.05 were considered significant. PRINCIPAL FINDINGS: The majority of changes in the GAS transcriptome involved down regulation of multiple adhesins and virulence factors and activation of the stress response. We observed significant changes in genes involved in the arginine deiminase pathway and in the nucleotide de novo synthesis pathway. CONCLUSIONS/SIGNIFICANCE: Our work provides new insight into how pathogenic bacteria respond to their environment to establish infection and cause disease.

  4. Model reference adaptive impedance control for physical human-robot interaction

    Bakur ALQAUDI; Hamidreza MODARES; Isura RANATUNGA; Shaikh M TOUSIF; Frank L LEWIS; Dan O POPA

    2016-01-01

    This paper presents a novel enhanced human-robot interaction system based on model reference adaptive control. The presented method delivers guaranteed stability and task performance and has two control loops. A robot-specific inner loop, which is a neuroadaptive controller, learns the robot dynamics online and makes the robot respond like a prescribed impedance model. This loop uses no task information, including no prescribed trajectory. A task-specific outer loop takes into account the human operator dynamics and adapts the prescribed robot impedance model so that the combined human-robot system has desirable characteristics for task performance. This design is based on model reference adaptive control, but of a nonstandard form. The net result is a controller with both adaptive impedance characteristics and assistive inputs that augment the human operator to provide improved task performance of the human-robot team. Simulations verify the performance of the proposed controller in a repetitive point-to-point motion task. Actual experimental implementations on a PR2 robot further corroborate the effectiveness of the approach.

  5. Gastric infarction following gastric bypass surgery

    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

  6. Molecular networks of human muscle adaptation to exercise and age.

    Bethan E Phillips

    2013-03-01

    Full Text Available Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44 who then undertook 20 weeks of supervised resistance-exercise training (RET. Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%, and when applying Ingenuity Pathway Analysis (IPA up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR signaling associating with growth (P = 1.4 × 10(-30. Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6 × 10(-13 and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = -2.3; P = 3 × 10(-7 with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET, they appear to represent "generic" physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52, with a continuum of subject ages (18-78 y, the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1 × 10(-6 and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to

  7. Role of Helicobacter pylori in gastric cancer: Updates

    2016-01-01

    Helicobacter pylori (H. pylori ) infection is highly prevalentin human, affecting nearly half of the world'spopulation; however, infection remains asymptomaticin majority of population. During its co-existence withhumans, H. pylori has evolved various strategies tomaintain a mild gastritis and limit the immune responseof host. On the other side, presence of H. pylori is alsoassociated with increased risk for the development ofvarious gastric pathologies including gastric cancer (GC).A complex combination of host genetics, environmentalagents, and bacterial virulence factors are consideredto determine the susceptibility as well as the severityof outcome in a subset of individuals. GC is one of themost common cancers and considered as the third mostcommon cause of cancer related death worldwide. Manystudies had proved H. pylori as an important risk factorin the development of non-cardia GC. Although both H.pylori infection and GC are showing decreasing trendsin the developed world, they still remain a major threatto human population in the developing countries. Thecurrent review attempts to highlight recent progress inthe field of research on H. pylori induced GC and aimsto provide brief insight into H. pylori pathogenesis,the role of major virulence factors of H. pylori thatmodulates the host environment and transform thenormal gastric epithelium to neoplastic one. This reviewalso emphasizes on the mechanistic understanding ofhow colonization and various virulence attributes of H.pylori as well as the host innate and adaptive immuneresponses modulate the diverse signaling pathways thatleads to different disease outcomes including GC.

  8. Reversion of malignancy in human gastric cancer MKN—45 cells through the transfection of transforming growth factor—β type Ⅱ receptor gene

    SUNHONG; WEIKANGSHI; 等

    1996-01-01

    Human gastric cancer MKN-45 cells which are resistant to TGF-β growth inhibition and possess TGF-β type I and type Ⅲ receptors,but not type Ⅱ receptors,have been used as a model system to reconstitute these cancer cells with TGF-β RII cDNA.The results of these experiments indicated that the reexpression of TGF-β RII gene in MKN-45 cells can restore their sensitivity to TGF-β growth inhibition,decrease their growth rate,reduce their cloning efficiency in soft agar and tumorigenicity in nude mice in stable transfectants,in comparison with their control MKN-45 cells.Among different RII transfectants,their difference in the changes of these parameters,as a result of the regain of autocrine negative growth control by TGF-β,is roughly proportional to their level of expression of transfected RII mRNA.From these data,it is concluded that the inactivation of TGF-β RII gene is related to the escape of growth control by TGF-β in MKN-45 cells.The importance of the study of the interplay of TGF-β and its receptor system in the negative growth control of gastric cancer,and possibly also of other cancers,is discussed.

  9. Induction of apoptosis by genipin inhibits cell proliferation in AGS human gastric cancer cells via Egr1/p21 signaling pathway.

    Ko, Hyeonseok; Kim, Jee Min; Kim, Sun-Joong; Shim, So Hee; Ha, Chang Hoon; Chang, Hyo Ihl

    2015-10-01

    Natural compounds are becoming important candidates in cancer therapy due to their cytotoxic effects on cancer cells by inducing various types of programmed cell deaths. In this study, we investigated whether genipin induces programmed cell deaths and mediates in Egr1/p21 signaling pathways in gastric cancer cells. Effects of genipin in AGS cancer cell lines were observed via evaluation of cell viability, ROS generation, cell cycle arrest, and protein and RNA levels of p21, Egr1, as well as apoptotic marker genes. The cell viability of AGS cells reduced by genipin treatment via induction of the caspase 3-dependent apoptosis. Cell cycle arrest was observed at the G2/M phase along with induction of p21 and p21-dependent cyclins. As an upstream mediator of p21, the transcription factor early growth response-1 (Egr1) upregulated p21 through nuclear translocation and binding to the p21 promoter site. Silencing Egr1 expression inhibited the expression of p21 and downstream molecules involved in apoptosis. We demonstrated that genipin treatment in AGS human gastric cancer cell line induces apoptosis via p53-independent Egr1/p21 signaling pathway in a dose-dependent manner.

  10. BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS

    Skoog, Emma C.; Padra, Médea; Åberg, Anna; Gideonsson, Pär; Obi, Ikenna; Quintana-Hayashi, Macarena P.; Arnqvist, Anna; Lindén, Sara K.

    2017-01-01

    Mucins in the gastric mucus layer carry a range of glycan structures, which vary between individuals, can have antimicrobial effect or act as ligands for Helicobacter pylori. Mucins from various individuals and disease states modulate H. pylori proliferation and adhesin gene expression differently. Here we investigate the relationship between adhesin mediated binding, aggregation, proliferation and adhesin gene expression using human gastric mucins and synthetic adhesin ligand conjugates. By combining measurements of optical density, bacterial metabolic activity and live/dead stains, we could distinguish bacterial aggregation from viability changes, enabling elucidation of mechanisms behind the anti-prolific effects that mucins can have. Binding of H. pylori to Leb-glycoconjugates inhibited the proliferation of the bacteria in a BabA dependent manner, similarly to the effect of mucins carrying Leb. Furthermore, deletion of arsS lead to a decrease in binding to Leb-glycoconjugates and Leb-decorated mucins, accompanied by decreased aggregation and absence of anti-prolific effect of mucins and Leb-glycoconjugates. Inhibition of proliferation caused by adhesin dependent binding to mucins, and the subsequent aggregation suggests a new role of mucins in the host defense against H. pylori. This aggregating trait of mucins may be useful to incorporate into the design of adhesin inhibitors and other disease intervention molecules. PMID:28106125

  11. Pan-Genome Analysis of Human Gastric Pathogen H. pylori: Comparative Genomics and Pathogenomics Approaches to Identify Regions Associated with Pathogenicity and Prediction of Potential Core Therapeutic Targets

    Amjad Ali

    2015-01-01

    Full Text Available Helicobacter pylori is a human gastric pathogen implicated as the major cause of peptic ulcer and second leading cause of gastric cancer (~70% around the world. Conversely, an increased resistance to antibiotics and hindrances in the development of vaccines against H. pylori are observed. Pan-genome analyses of the global representative H. pylori isolates consisting of 39 complete genomes are presented in this paper. Phylogenetic analyses have revealed close relationships among geographically diverse strains of H. pylori. The conservation among these genomes was further analyzed by pan-genome approach; the predicted conserved gene families (1,193 constitute ~77% of the average H. pylori genome and 45% of the global gene repertoire of the species. Reverse vaccinology strategies have been adopted to identify and narrow down the potential core-immunogenic candidates. Total of 28 nonhost homolog proteins were characterized as universal therapeutic targets against H. pylori based on their functional annotation and protein-protein interaction. Finally, pathogenomics and genome plasticity analysis revealed 3 highly conserved and 2 highly variable putative pathogenicity islands in all of the H. pylori genomes been analyzed.

  12. BabA dependent binding of Helicobacter pylori to human gastric mucins cause aggregation that inhibits proliferation and is regulated via ArsS.

    Skoog, Emma C; Padra, Médea; Åberg, Anna; Gideonsson, Pär; Obi, Ikenna; Quintana-Hayashi, Macarena P; Arnqvist, Anna; Lindén, Sara K

    2017-01-20

    Mucins in the gastric mucus layer carry a range of glycan structures, which vary between individuals, can have antimicrobial effect or act as ligands for Helicobacter pylori. Mucins from various individuals and disease states modulate H. pylori proliferation and adhesin gene expression differently. Here we investigate the relationship between adhesin mediated binding, aggregation, proliferation and adhesin gene expression using human gastric mucins and synthetic adhesin ligand conjugates. By combining measurements of optical density, bacterial metabolic activity and live/dead stains, we could distinguish bacterial aggregation from viability changes, enabling elucidation of mechanisms behind the anti-prolific effects that mucins can have. Binding of H. pylori to Le(b)-glycoconjugates inhibited the proliferation of the bacteria in a BabA dependent manner, similarly to the effect of mucins carrying Le(b). Furthermore, deletion of arsS lead to a decrease in binding to Le(b)-glycoconjugates and Le(b)-decorated mucins, accompanied by decreased aggregation and absence of anti-prolific effect of mucins and Le(b)-glycoconjugates. Inhibition of proliferation caused by adhesin dependent binding to mucins, and the subsequent aggregation suggests a new role of mucins in the host defense against H. pylori. This aggregating trait of mucins may be useful to incorporate into the design of adhesin inhibitors and other disease intervention molecules.

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

    Xian Li

    2013-04-01

    Full Text Available 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.

  14. Practice explains abolished behavioural adaptation after human dorsal anterior cingulate cortex lesions.

    van Steenbergen, H; Haasnoot, E; Bocanegra, B R; Berretty, E W; Hommel, B

    2015-04-08

    The role of mid-cingulate cortex (MCC), also referred to as dorsal anterior cingulate cortex, in regulating cognitive control is a topic of primary importance in cognitive neuroscience. Although many studies have shown that MCC responds to cognitive demands, lesion studies in humans are inconclusive concerning the causal role of the MCC in the adaptation to these demands. By elegantly combining single-cell recordings with behavioural methods, Sheth et al. [Sheth, S. et al. Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation. Nature 488, 218-22 (2012).] recently were able to show that neurons in MCC encode cognitive demand. Importantly, this study also claimed that focal lesions of the MCC abolished behavioural adaptation to cognitive demands. Here we show that the absence of post-cingulotomy behavioural adaptation reported in this study may have been due to practice effects. We run a control condition where we tested subjects before and after a dummy treatment, which substituted cingulotomy with a filler task (presentation of a documentary). The results revealed abolished behavioural adaptation following the dummy treatment. Our findings suggest that future work using proper experimental designs is needed to advance the understanding of the causal role of the MCC in behavioural adaptation.

  15. The effect of retinal image error update rate on human vestibulo-ocular reflex gain adaptation.

    Fadaee, Shannon B; Migliaccio, Americo A

    2016-04-01

    The primary function of the angular vestibulo-ocular reflex (VOR) is to stabilise images on the retina during head movements. Retinal image movement is the likely feedback signal that drives VOR modification/adaptation for different viewing contexts. However, it is not clear whether a retinal image position or velocity error is used primarily as the feedback signal. Recent studies examining this signal are limited because they used near viewing to modify the VOR. However, it is not known whether near viewing drives VOR adaptation or is a pre-programmed contextual cue that modifies the VOR. Our study is based on analysis of the VOR evoked by horizontal head impulses during an established adaptation task. Fourteen human subjects underwent incremental unilateral VOR adaptation training and were tested using the scleral search coil technique over three separate sessions. The update rate of the laser target position (source of the retinal image error signal) used to drive VOR adaptation was different for each session [50 (once every 20 ms), 20 and 15/35 Hz]. Our results show unilateral VOR adaptation occurred at 50 and 20 Hz for both the active (23.0 ± 9.6 and 11.9 ± 9.1% increase on adapting side, respectively) and passive VOR (13.5 ± 14.9, 10.4 ± 12.2%). At 15 Hz, unilateral adaptation no longer occurred in the subject group for both the active and passive VOR, whereas individually, 4/9 subjects tested at 15 Hz had significant adaptation. Our findings suggest that 1-2 retinal image position error signals every 100 ms (i.e. target position update rate 15-20 Hz) are sufficient to drive VOR adaptation.

  16. Delayed gastric emptying rate as a potential mechanism for lowered glycemia after eating sourdough bread: studies in humans and rats using test products with added organic acids or an organic salt.

    Liljeberg, H G; Björck, I M

    1996-12-01

    The possible effects of organic acids or an organic salt on the rate of gastric emptying was studied to identify the cause for reduced postmeal responses of blood glucose and insulin to foods containing such components, eg, sourdough bread. Paracetamol was included in bread products with added lactic acid or sodium propionate and used as a marker for the rate of gastric emptying in healthy subjects. In parallel, postprandial glycemia, insulinemia, and satiety were evaluated. The influence of lactic acid, propionic acid, and sodium propionate was also studied in rats after they were tube-fed with glucose solutions. The bread products with lactic acid or sodium propionate both lowered blood glucose and insulin responses. The bread with sodium propionate also prolonged satiety. The reason for the lowered metabolic responses with sodium propionate was probably a lowered gastric emptying rate, as judged from reduced blood paracetamol concentrations; there was no such effect observed with bread with added lactic acid. A similar amount of lactic acid in solution tube-fed to rats did not affect the disappearance of glucose from the stomach. In contrast with the finding in humans, sodium propionate had no effect on the rate of gastric emptying in rats whereas an equimolar solution of propionic acid reduced gastric emptying rate in rats. Possibly, less of this acid was produced in the gastric contents after a bolus load of a sodium propionate solution (in rats) than in an eating situation. Also, the pH and/or the osmolarity may be important, and when provided in excessive amounts, lactic acid reduced the gastric emptying rate in rats. A hydrochloric acid solution of similar pH was much less effective in this respect.

  17. The long non-coding RNA H19-derived miR-675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1

    Zhuang, Ming [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu (China); Gao, Wen; Xu, Jing; Wang, Ping [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Shu, Yongqian, E-mail: shuyongqian39000@163.com [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China)

    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.

  18. Practice explains abolished behavioural adaptation after human dorsal anterior cingulate cortex lesions

    van Steenbergen, H.; E. Haasnoot; Bocanegra, B.R.; Berretty, E.W.; Hommel, B.

    2015-01-01

    The role of mid-cingulate cortex (MCC), also referred to as dorsal anterior cingulate cortex, in regulating cognitive control is a topic of primary importance in cognitive neuroscience. Although many studies have shown that MCC responds to cognitive demands, lesion studies in humans are inconclusive concerning the causal role of the MCC in the adaptation to these demands. By elegantly combining single-cell recordings with behavioural methods, Sheth et al. [Sheth, S. et al. Human dorsal anteri...

  19. Dietary Change and Adaptive Evolution of enamelin in Humans and Among Primates

    Kelley, Joanna L; Swanson, Willie J.

    2008-01-01

    Scans of the human genome have identified many loci as potential targets of recent selection, but exploration of these candidates is required to verify the accuracy of genomewide scans and clarify the importance of adaptive evolution in recent human history. We present analyses of one such candidate, enamelin, whose protein product operates in tooth enamel formation in 100 individuals from 10 populations. Evidence of a recent selective sweep at this locus confirms the signal of selection foun...

  20. Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

    Thøgersen, Juliane Charlotte

    modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... to phenotype at a systemic level. Particular metabolic subsystems were identified as important for metabolic adaptation in P. aeruginosa. One altered metabolic phenotype was connected to a genetic change; a finding that was possible through the systems characterization and which was not identi-­‐ fied...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....

  1. High-speed adaptive optics line scan confocal retinal imaging for human eye

    Wang, Xiaolin; Zhang, Yuhua

    2017-01-01

    Purpose Continuous and rapid eye movement causes significant intraframe distortion in adaptive optics high resolution retinal imaging. To minimize this artifact, we developed a high speed adaptive optics line scan confocal retinal imaging system. Methods A high speed line camera was employed to acquire retinal image and custom adaptive optics was developed to compensate the wave aberration of the human eye’s optics. The spatial resolution and signal to noise ratio were assessed in model eye and in living human eye. The improvement of imaging fidelity was estimated by reduction of intra-frame distortion of retinal images acquired in the living human eyes with frame rates at 30 frames/second (FPS), 100 FPS, and 200 FPS. Results The device produced retinal image with cellular level resolution at 200 FPS with a digitization of 512×512 pixels/frame in the living human eye. Cone photoreceptors in the central fovea and rod photoreceptors near the fovea were resolved in three human subjects in normal chorioretinal health. Compared with retinal images acquired at 30 FPS, the intra-frame distortion in images taken at 200 FPS was reduced by 50.9% to 79.7%. Conclusions We demonstrated the feasibility of acquiring high resolution retinal images in the living human eye at a speed that minimizes retinal motion artifact. This device may facilitate research involving subjects with nystagmus or unsteady fixation due to central vision loss. PMID:28257458

  2. Evidence for Human Adaptation and Foodborne Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus

    Larsen, Jesper; Stegger, Marc; Andersen, Paal S.;

    2016-01-01

    We investigated the evolution and epidemiology of a novel live-stock-associated methicillin-resistant Staphylococcus aureus strain, which colonizes and infects urban-dwelling Danes even without a Danish animal reservoir. Genetic evidence suggests both poultry and human adaptation, with poultry meat...

  3. Effects of human-machine interface design for intelligent speed adaptation on driving behavior and acceptance

    Rook, A.M.; Hogema, J.H.

    2005-01-01

    The effects of human-machine interface (HMI) design for intelligent speed adaptation (ISA) on driving behavior and acceptance were measured in a moving-base research driving simulator. Sixty-four experienced drivers participated in two simulator experiments (32 in each). During the simulated runs wi

  4. Adaptive function of soil consumption: An in vitro study modeling the human stomach and small intestine

    Dominy, N.J.; Davoust, E.; Minekus, M.

    2004-01-01

    Despite occurring in a wide variety of taxa, deliberate soil consumption (geophagy) is a poorly understood behavior. In humans, geophagy is sometimes considered aberrant or a sign of metabolic dysfunction. However, geophagy is normally assigned an adaptive function in nonhuman primates and various o

  5. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism

    Patti, Mary-Elizabeth; Houten, Sander M; Bianco, Antonio C;

    2009-01-01

    .02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P lipid metabolism in patients......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...

  6. RNAi‑mediated knockdown of PRL‑3 inhibits cell invasion and downregulates ERK 1/2 expression in the human gastric cancer cell line, SGC‑7901.

    Cao, Yi; Tu, Yi; Mei, Jinhong; Li, Zhengrong; Jie, Zhigang; Xu, Shan; Xu, Linlin; Wang, Shanshan; Xiong, Yifeng

    2013-06-01

    The deregulated expression of members of the phophatase of regenerating liver (PRL) family is important in the metastatic progression of multiple human cancers; however, the underlying mechanisms are not well understood. Previous studies have demonstrated that PRLs are able to enhance the activation of extracellular signal‑regulated kinase 1/2 (ERK 1/2) in cancer cells, which may contribute to tumor metastasis. However, the effect of PRL‑3 activation in gastric cancer (GC) remains unclear. The present study aimed to investigate whether the downregulation of PRL‑3 by small interfering RNA (siRNA) was able to inhibit cell motility and affect ERK 1/2 expression in human GC. The results demonstrated that the downregulation of PRL‑3 expression by siRNA in human GC cells significantly inhibited cell invasion and migration in vitro; accordingly, inhibition of PRL‑3 also prevented ERK1/2 protein and mRNA expression, and reduced the mRNA level of matrix metalloproteinase‑7 (MMP‑7), the downstream target of ERK 1/2 signaling. Our data demonstrated that RNAi‑mediated downregulation of PRL‑3 expression leads to potent antitumor activity in human GC. Furthermore, ERK 1/2 and MMP‑7 may contribute to the carcinogenesis and development of human GC in combination with PRL‑3.

  7. Gastric emptying measured by ultrasonography

    1999-01-01

    @@ A number of different methods have been used to estimate gastric emptying in humans, and all have their advantages and disadvantages. The method of choice will depend on whether solid or liquid meals are studied, the level of precision required, the degree of invasiveness that the subject or patient will tolerate, ethical considerations, and not at least the facilities available.

  8. [Ultrastructural changes and regeneration of the endocrine apparatus of the human gastric mucosal glandular epithelium in patients with chronic erosive gastritis].

    Ivanova, V F; Puzyrev, A A; Draĭ, R V

    2010-01-01

    The aim of this investigation was to study the structure and regeneration of the endocrine apparatus of the human gastric mucosal glandular epithelium. Using electron microscopy, the mucosal biopsy specimens obtained from 14 patients with chronic erosive Helicobacter pylori-associated gastritis, were studied. The most pronounced changes were seen both in the numbers and ultrastructure of G- and P-endocrinocytes. The changes were detected in the nucleus structure, endocrine granule and polysome content, and he mitochondrial structure. The regeneration of the endocrine cells took place through the differentiation of the committed precursors via the "agranular" cell stage, transformation of the exocrine cells into the endocrine ones, and as a result of the formation of the epithelial cords on the erosion surfaces that consisted of the cells in diverse differentiation stages (from the undifferentiated to specialized cells of all the endocrine and exocrine types).

  9. The human environment and the vitamin D compromise: Scotland as a case study in human biocultural adaptation and disease susceptibility.

    Chaplin, George; Jablonski, Nina G

    2013-08-01

    Year-round human habitation of environments with highly seasonal regimes of ultraviolet B radiation (UVB) depended on adaptive complexes of biological and cultural traits to ensure adequacy of vitamin D. Perturbations of such adaptive complexes resulting from changes in the physical environment, human behavior and culture, or both have had unexpected and untoward consequences for health. Scotland is an excellent case study of the changing nature of human biocultural adaptation to low-UVB environments. Occupation of Scotland after the last Pleistocene glaciation event about 14,000 YBP was made possible by maximally depigmented skin, which facilitated cutaneous biosynthesis of vitamin D3, and by a diet that emphasized foods rich in vitamin D. Changes in human subsistence and diet began with the introduction of agriculture and grazing about 5,000 YBP and accelerated greatly in the last 200 years through industrialization and urbanization. The resulting changes in domiciles, patterns of daily activity and behavior, and diet have led to reduced exposure to UVB and reduced consumption of vitamin D-rich foods. This has perturbed the "vitamin D compromise," an adaptive complex established in Scotland during the Mesolithic and Neolithic. We describe the UVB environment of Scotland from remotely sensed data and combine these data with information from the archaeological record to describe the vitamin D compromise in Scotland. Changes in human exposure to UVB and vitamin D consumption, which occurred as the result of urbanization and the dietary shift away from the consumption of oily fish, are traced. Vitamin D deficiency contributes to increased disease prevalence in Scotland, including that of the autoimmune disease multiple sclerosis, a debilitating neurodegenerative disease caused by demyelination of the central nervous system. These conditions have created an "imperfect storm" of poor health that should command the attention of public health experts and policy makers.

  10. Ghrelin and gastric acid secretion

    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 t...

  11. The human milk oligosaccharide 2'-fucosyllactose augments the adaptive response to extensive intestinal.

    Mezoff, Ethan A; Hawkins, Jennifer A; Ollberding, Nicholas J; Karns, Rebekah; Morrow, Ardythe L; Helmrath, Michael A

    2016-03-15

    Intestinal resection resulting in short bowel syndrome (SBS) carries a heavy burden of long-term morbidity, mortality, and cost of care, which can be attenuated with strategies that improve intestinal adaptation. SBS infants fed human milk, compared with formula, have more rapid intestinal adaptation. We tested the hypothesis that the major noncaloric human milk oligosaccharide 2'-fucosyllactose (2'-FL) contributes to the adaptive response after intestinal resection. Using a previously described murine model of intestinal adaptation, we demonstrated increased weight gain from 21 to 56 days (P < 0.001) and crypt depth at 56 days (P < 0.0095) with 2'-FL supplementation after ileocecal resection. Furthermore, 2'-FL increased small bowel luminal content microbial alpha diversity following resection (P < 0.005) and stimulated a bloom in organisms of the genus Parabacteroides (log2-fold = 4.1, P = 0.035). Finally, transcriptional analysis of the intestine revealed enriched ontologies and pathways related to antimicrobial peptides, metabolism, and energy processing. We conclude that 2'-FL supplementation following ileocecal resection increases weight gain, energy availability through microbial community modulation, and histological changes consistent with improved adaptation.

  12. Measurement of the intracellular ph in human stomach cells: a novel approach to evaluate the gastric acid secretory potential of coffee beverages.

    Weiss, Carola; Rubach, Malte; Lang, Roman; Seebach, Elisabeth; Blumberg, Simone; Frank, Oliver; Hofmann, Thomas; Somoza, Veronika

    2010-02-10

    As the consumption of coffee beverages sometimes is reported to cause gastric irritation, for which an increased stomach acid secretion is one of the promoting factors, different processing technologies such as steam-treatment have been developed to reduce putative stomach irritating compounds. There is evidence-based data neither on the effect of detailed processing variations nor on individual coffee components affecting the proton secretory activity (PSA). This work aimed at developing a screening model suitable for investigating the effects of commercial coffee beverages and components thereof on human parietal cells. Human gastric cancer cells (HGT-1) were treated with reconstituted freeze-dried coffee beverages prepared from customary coffee products such as regular coffee (RC, n = 4), mild bean coffee (MBC, n = 5), stomach friendly coffee (SFC, n = 4), and SFC decaffeinated (SFCD, n = 3). PSA was analyzed by flow cytometry using the pH-sensitive dye SNARF-AM. Treatment of the cells with MBC did not result in a PSA different from RC treatment (p

  13. FAT10 level in human gastric cancer and its relation with mutant p53 level, lymph node metastasis and TNM staging

    Feng Ji; Xi Jin; Chun-Hua Jiao; Qin-Wei Xu; Zi-Wei Wang; Yue-Liang Chen

    2009-01-01

    AIM: To investigate the role of FAT10 and mutant p53 in the pathogenesis, severity and prognosis of gastric cancer. METHODS: FAT10, mutant p53 mRNA and protein levels were measured by reverse transcription (RT)-PCR and immunohistochemistry in gastric cancer tissue ( n = 62), tumor-adjacent tissue ( n = 62) and normal gastric tissue ( n = 62). Relation of FAT10 and mutant p53 expression with clinicopathological features and clinical outcomes of gastric cancer patients were analyzed. RESULTS: The FAT10, mutant p53 mRNA and protein levels were significantly higher in gastric cancer than in its adjacent and normal tissue. The FAT10 and mutant p53 levels in gastric cancer tissue were significantly correlated with lymph node metastasis and tumor, nodes, metastasis (TNM) staging. Moreover, the high FAT10 level was associated with the overall survival rate of patients. Multivariate Cox-proportional hazards model analysis showed that mRNA and protein levels of FAT10 and mutant p53, lymph node metastasis, distant metastasis and TNM stage were the independent prognostic factors for gastric cancer. CONCLUSION: FAT10 may be involved in gastric carcinogenesis, and is a potential marker for the prognosis of gastric cancer patients. FAT10 and mutant p53 may play a common role in the carcinogenesis of gastric cancer.

  14. Pose Estimation and Adaptive Robot Behaviour for Human-Robot Interaction

    Svenstrup, Mikael; Hansen, Søren Tranberg; Andersen, Hans Jørgen

    2009-01-01

    Abstract—This paper introduces a new method to determine a person’s pose based on laser range measurements. Such estimates are typically a prerequisite for any human-aware robot navigation, which is the basis for effective and timeextended interaction between a mobile robot and a human. The robot......’s pose. The resulting pose estimates are used to identify humans who wish to be approached and interacted with. The interaction motion of the robot is based on adaptive potential functions centered around the person that respect the persons social spaces. The method is tested in experiments...

  15. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    Wroblewski, Lydia E; Peek, Richard M

    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.

  16. Experimental adaptation of wild-type canine distemper virus (CDV) to the human entry receptor CD150.

    Bieringer, Maria; Han, Jung Woo; Kendl, Sabine; Khosravi, Mojtaba; Plattet, Philippe; Schneider-Schaulies, Jürgen

    2013-01-01

    Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red) adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2) pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5) pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

  17. Experimental adaptation of wild-type canine distemper virus (CDV to the human entry receptor CD150.

    Maria Bieringer

    Full Text Available Canine distemper virus (CDV, a close relative of measles virus (MV, is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2 pfu/ml in Vero cells expressing human CD150 (Vero-hSLAM. After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5 pfu/ml. Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L and Gly to Glu (G71E, and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

  18. Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

    Leach, Michelle D; Tyc, Katarzyna M; Brown, Alistair J P; Klipp, Edda

    2012-01-01

    Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

  19. Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

    Michelle D Leach

    Full Text Available Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

  20. Feedback effect of human physical and psychological adaption on time period of thermal adaption in naturally ventilated building

    liu, weiwei; Huangfu, Hao; Xiong, Jing

    2014-01-01

    This study proposed a method to determine time period of thermal adaption for occupants in naturally ventilated building, and analyzed the synergistic and separate feedback effect of the physical and psychological adaption modes on the time period of thermal adaption. Using the method, the values......, under the synergistic feedback effect of the physical and psychological adaption modes. The time period of thermal adaption increased to 13 days, if only the feedback effect of the physical adaption mode was accounted for. The difference between the two values of the time period of thermal adaption...... of the time period of thermal adaption were obtained on the basis of the data from a long-term field survey conducted in two typical naturally ventilated offices located in Changsha, China. The results showed that the occupants need to take 4.25 days to fully adapt to a step-change in outdoor air temperature...

  1. Science Letters: Human-centered modeling for style-based adaptive games

    Chee-onn WONG; Jon-gin KIM; Eun-jung HAN; Kee-chui JUNG

    2009-01-01

    This letter proposes a categorization matrix to analyze the playing style of a computer game player for a shooting game genre. Our aim is to use human-centered modeling as a strategy for adaptive games based on entertainment measure to evaluate the playing experience. We utilized a self-organizing map (SOM) to cluster the player's style with the data obtained while playing the game. We further argued that style-based adaptation contributes to higher enjoyment, and this is reflected in our experiment using a supervised multilayered perceptron (MLP) network.

  2. Expression of Telomerase Activity in Gastric Cancer Cells

    2002-01-01

    Objective To study the relationship between telomerase activity and biological behavior in human gastric cells and appraise the clinical significance of detecting telomerase activity. Methods The telomerase activity in 47 gastric cancer tissue samples,their matched nomal tissues,7 gastric ulcer and 2 gastric cancer cell lines was detected using a PCR-based non-radioisotopic telomeric repeat amplification protocol(TRAP) assay. Results None of the 47 samples from normal gastric tissues expressed telomerase activity.The 41 of 47 cases of gastric cancer presented telomerase activity with an 87.2% positive rate (P<0.001). 2/2 gastric cancer cell lines and 0/7 gastric ulcer line were also positive for telmerase activity.The activity of telomerase was associated with the pathological differentiation of gastric cancer. Conclusion Telomerase activity may be related to the biological behavior of gastric cancer and can help in assessing the malignant poten-tial of gastric cancer.Telomerase activity will be a good diagnostic marker for the detection of gastric cancer.

  3. Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans.

    Judith M Fonville

    Full Text Available Adaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus have been found in all sequenced human strains, while these substitutions have not been detected in any non-human A/H7N9 sequences. Given the currently available information, this observation suggests that the human-adaptive PB2 substitution might confer a fitness advantage to the virus in these human hosts that allows it to rise to proportions detectable by consensus sequencing over the course of a single human infection. We use a mathematical model of within-host virus evolution to estimate the fitness advantage required for a substitution to reach predominance in a single infection as a function of the duration of infection and the fraction of mutant present in the virus population that initially infects a human. The modeling results provide an estimate of the lower bound for the fitness advantage of this adaptive substitution in the currently sequenced A/H7N9 viruses. This framework can be more generally used to quantitatively estimate fitness advantages of adaptive substitutions based on the within-host prevalence of mutations. Such estimates are critical for models of cross-species transmission and host-adaptation of influenza virus infections.

  4. Exploring the physiologic role of human gastroesophageal reflux by analyzing time-series data from 24-h gastric and esophageal pH recordings.

    Lu, Luo; Mu, John C; Sloan, Sheldon; Miner, Philip B; Gardner, Jerry D

    2014-07-16

    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.

  5. Controlling a virtual forehand prosthesis using an adaptive and affective Human-Machine Interface.

    Rezazadeh, I Mohammad; Firoozabadi, S M P; Golpayegani, S M R Hashemi; Hu, H

    2011-01-01

    This paper presents the design of an adaptable Human-Machine Interface (HMI) for controlling virtual forearm prosthesis. Direct physical performance measures (obtained score and completion time) for the requested tasks were calculated. Furthermore, bioelectric signals from the forehead were recorded using one pair of electrodes placed on the frontal region of the subject head to extract the mental (affective) measures while performing the tasks. By employing the proposed algorithm and above measures, the proposed HMI can adapt itself to the subject's mental states, thus improving the usability of the interface. The quantitative results from 15 subjects show that the proposed HMI achieved better physical performance measures in comparison to a conventional non-adaptive myoelectric controller (p < 0.001).

  6. Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation.

    Liying Hou

    Full Text Available Vitamin E succinate (VES, a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ and 3-methyladenine (3-MA. Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR axis. Then we used 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3 punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis

  7. Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.

    Zhe-Ming Lu

    Full Text Available BACKGROUND: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation "seeding" sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC samples (36/40 was significantly higher than that observed in gastritis (19/45 or normal samples (7/13 (P<0.01. Extensive clone sequencing of these sMSP products showed that the density of methylated-CpGs in p16 CpG islands increased gradually along with the severity of pathological changes in gastric tissues. In gastritis lesions the methylation was frequently observed in the region corresponding to the exon-1 coding-nucleosome and the 5'UTR-nucleosome; the methylation was further extended to the region corresponding to the promoter-nucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal tissues. The significantly inversed relationship between the p16 exon-1 methylation and its transcription was observed in GC samples. An exact p16 promoter-specific 83 bp-MSP assay confirms the result of sMSP (33/55 vs. 1/6, P<0.01. In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens. CONCLUSIONS/SIGNIFICANCE: It was determined that de novo methylation was initiated in the coding region of p16 exon-1 in gastritis, then progressed to its 5'UTR, and ultimately to the proximal promoter in GCs. Nucleosomes may function as the basic extension/progression unit of de novo methylation of p16 CpG islands in vivo.

  8. The effect of aloe emodin-encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells.

    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

  9. Notch2 regulates matrix metallopeptidase 9 via PI3K/AKT signaling in human gastric carcinoma cell MKN-45

    Ling-Yun Guo; Yu-Min Li; Liang Qiao; Tao Liu; Yuan-Yuan Du; Jun-Qiang Zhang; Wen-Ting He

    2012-01-01

    AIM:To clarify the role of activated Notch2 in the invasiveness of gastric cancer.METHODS:To investigate the invasiveness of silencing Notch2 gene expression,we established a Notch2 small interfering RNA (siRNA) transfected cell line using the MKN-45 gastric cancer cell line.After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting,migration and invasion assays were employed to evaluate the aggressiveness of the gastric cancer.RT-PCR and Western blottings were employed to confirm the down-regulation of Notch2 and to evaluate the expression of epithelial mesenchymal transition-related gene matrix metallopeptidase 9 (MMPg),Akt,p-Akt.To confirm the relationship between PI3K-Akt and MMP9,the PI3K inhibitor LY294002 was used to treat MKN-45 cells.RESULTS:Notch2 expression was dramatically decreased after Notch2 siRNA transfection (100.00% ±9.74% vs 11.61% ± 3.85%,P < 0.01 by qRT-PCR).There was also a marked reduction of Notch target gene Hes1 (100.00% ± 4.74% vs 61.61% ± 3.58%,P < 0.05)at the mRNA,indicating an inhibition of Notch signaling.Inhibition of Notch signaling was also confirmed by the marked reduction of Notch2 intracellular domain at the protein levels (100.00% ± 9.74% vs 65.61% ± 7.58%,P < 0.05).Down-regulation of Notch2 by siRNA enhanced tumor cell invasion (100.00% ± 21.64% vs 162.22% ± 16.84%,P < 0.05) and expression of MMP9 (1.56 fold,P < 0.05),and activated the pro-MMP9 protein to its active form (1.48 fold,P < 0.05).There was no significant difference in the protein levels of Akt between the two groups (100.00% ± 10.87% vs 96.61% ± 7.33%,P > 0.05),while down-regulation of Notch2 elevated p-Akt expression (100.00% ± 9.87% vs 154.61% ± 13.10%,P < 0.05).Furthermore,p-Akt and MMP9 was down-regulated in response to the inhibitor LY294002 (p-Akt 100.00% ± 8.87% vs 58.27% ± 5.01%,P < 0.05; MMP9

  10. Optimal primary culture conditions of human gastric mucosal fibroblasts%人胃黏膜成纤维细胞原代培养条件的优化

    张浩; 申晓军; 唐古生; 毕建威

    2009-01-01

    目的 通过优化人胃黏膜成纤维细胞的原代培养条件,提高培养成功率,为进一步研究胃癌相关成纤维细胞奠定基础.方法 原代培养采用植块法,利用免疫组织化学、细胞形态学和电镜等方法进行细胞鉴定;分析不同培养表面、培养基和培养液pH值对原代细胞培养游出情况的影响,筛选适合的培养条件.结果 Logistic逐步回归分析提示RPMI 1640培养基的Waldχ2值=32.4533,P0.05),而且各培养条件之间无交互作用.结论 通过优化培养表面、培养基种类和pH值等培养条件,可以提高人胃黏膜成纤维细胞原代培养的成功率.%Objective To optimize primary culture conditions of human gastric mucosal fibre- blasts for further investigations of gastric cancer associated fibroblasts. Methods The fibroblasts were cul-tured primarily by explant method, and identified by immunohistochemistry, morphology and electron mi-croscopy. The effects of different culture conditions on emigration ratios of ceils were investigated to opti-mize the culture surface, medium and pH in primary culture of gastric mucosal fibroblasts. Results When the other conditions were the same,no significandy different emigration rate was found on the mouse tail-coated surface,fetal bovine serum-coated surface ,and nothing coated surface (P > 0.05 ). As to the role of different culture media including RPMI 1640 medium, DMEM and high-gluco DMEM,there was signifi-cantly higher emigration rate in the RPMI 1640 medium compared with other two media (P < 0.01, stand- ardized estimate = 0. 4688 ). Different pH values(pH = 7.0,7.4 and 7.8)of culture solution led to differ-ent emigration rate,and the best emigration rate was found in pH = 7.4 solution(P < 0.01, standardized estimate =0.5857 ). Furthermore, there was no interaetional effect on the cell emigration rate among cul- ture conditions. Conclusion The primary culture of human gastric mucosal fibroblasts can be greatly im-proved by

  11. Assessing employability capacities and career adaptability in a sample of human resource professionals

    Melinde Coetzee

    2015-03-01

    Full Text Available Orientation: Employers have come to recognise graduates’ employability capacities and their ability to adapt to new work demands as important human capital resources for sustaining a competitive business advantage.Research purpose: The study sought (1 to ascertain whether a significant relationship exists between a set of graduate employability capacities and a set of career adaptability capacities and (2 to identify the variables that contributed the most to this relationship.Motivation for the study: Global competitive markets and technological advances are increasingly driving the demand for graduate knowledge and skills in a wide variety of jobs. Contemporary career theory further emphasises career adaptability across the lifespan as a critical skill for career management agency. Despite the apparent importance attached to employees’ employability and career adaptability, there seems to be a general lack of research investigating the association between these constructs.Research approach, design and method: A cross-sectional, quantitative research design approach was followed. Descriptive statistics, Pearson product-moment correlations and canonical correlation analysis were performed to achieve the objective of the study. The participants (N = 196 were employed in professional positions in the human resource field and were predominantly early career black people and women.Main findings: The results indicated positive multivariate relationships between the variables and showed that lifelong learning capacities and problem solving, decision-making and interactive skills contributed the most to explaining the participants’ career confidence, career curiosity and career control.Practical/managerial implications: The study suggests that developing professional graduates’ employability capacities may strengthen their career adaptability. These capacities were shown to explain graduates’ active engagement in career management strategies

  12. Essential role of Her3 in two signaling transduction patterns: Her2/Her3 and MET/Her3 in proliferation of human gastric cancer.

    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.

  13. Altered temporal dynamics of neural adaptation in the aging human auditory cortex.

    Herrmann, Björn; Henry, Molly J; Johnsrude, Ingrid S; Obleser, Jonas

    2016-09-01

    Neural response adaptation plays an important role in perception and cognition. Here, we used electroencephalography to investigate how aging affects the temporal dynamics of neural adaptation in human auditory cortex. Younger (18-31 years) and older (51-70 years) normal hearing adults listened to tone sequences with varying onset-to-onset intervals. Our results show long-lasting neural adaptation such that the response to a particular tone is a nonlinear function of the extended temporal history of sound events. Most important, aging is associated with multiple changes in auditory cortex; older adults exhibit larger and less variable response magnitudes, a larger dynamic response range, and a reduced sensitivity to temporal context. Computational modeling suggests that reduced adaptation recovery times underlie these changes in the aging auditory cortex and that the extended temporal stimulation has less influence on the neural response to the current sound in older compared with younger individuals. Our human electroencephalography results critically narrow the gap to animal electrophysiology work suggesting a compensatory release from cortical inhibition accompanying hearing loss and aging.

  14. Human action classification using adaptive key frame interval for feature extraction

    Lertniphonphan, Kanokphan; Aramvith, Supavadee; Chalidabhongse, Thanarat H.

    2016-01-01

    Human action classification based on the adaptive key frame interval (AKFI) feature extraction is presented. Since human movement periods are different, the action intervals that contain the intensive and compact motion information are considered in this work. We specify AKFI by analyzing an amount of motion through time. The key frame is defined to be the local minimum interframe motion, which is computed by using frame differencing between consecutive frames. Once key frames are detected, the features within a segmented period are encoded by adaptive motion history image and key pose history image. The action representation consists of the local orientation histogram of the features during AKFI. The experimental results on Weizmann dataset, KTH dataset, and UT Interaction dataset demonstrate that the features can effectively classify action and can classify irregular cases of walking compared to other well-known algorithms.

  15. Human Impacts Flatten Rainforest-Savanna Gradient and Reduce Adaptive Diversity in a Rainforest Bird

    Freedman, Adam H.; Wolfgang Buermann; Mitchard, Edward T A; DeFries, Ruth S.; Smith, Thomas B

    2010-01-01

    Ecological gradients have long been recognized as important regions for diversification and speciation. However, little attention has been paid to the evolutionary consequences or conservation implications of human activities that fundamentally change the environmental features of such gradients. Here we show that recent deforestation in West Africa has homogenized the rainforest-savanna gradient, causing a loss of adaptive phenotypic diversity in a common rainforest bird, the little greenbul...

  16. Adaptive changes of human islets to an obesogenic environment in the mouse

    Gargani, Sofia

    2013-01-01

    Introduction: Under normal healthy conditions, organisms maintain a dynamic endocrinecell mass throughout life. Pancreatic beta cell mass are able to maintain plasma glucose levels increasing insulin secretion in conditions as obesity. Beta cell inability to compensate in insulin demand provokes hyperglycemia and Type 2 Diabetes. Clinically, most obese individuals do not develop diabetes because islets compensate for insulin resistance. Direct evidence that human islet mass adapts longitudina...

  17. Human response and adaptation to drought in the arid zone: lessons from southern Africa

    W. R.J. Dean; S. J. Milton; P.J. O'Farrell; P. M.L. Anderson

    2009-01-01

    Human adaptation and response to drought is primarily through evasion or endurance. A review of historical agricultural practices in southern Africa demonstrates evidence of drought evasion response strategies in well-established transhumance routes, where herders move livestock on a seasonal basis in order to exploit resources subject to different climatic regimes. European settlers to the arid regions of South Africa quickly recognised the necessity of these evasion options to survive droug...

  18. Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection.

    Eun-Young Kim

    2014-07-01

    Full Text Available Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1 cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection.

  19. [Mitochondrial DNA polymorphisms shared between modern humans and neanderthals: adaptive convergence or evidence for interspecific hybridization?].

    Maliarchuk, B A

    2013-09-01

    An analysis of the variability of the nucleotide sequences in the mitochondrial genome of modern humans, neanderthals, Denisovans, and other primates has shown that there are shared polymorphisms at positions 2758 and 7146 between modern Homo sapiens (in phylogenetic cluster L2'3'4'5'6) and Homo neanderthalensis (in the group of European neanderthals younger than 48000 years). It is suggested that the convergence may be due to adaptive changes in the mitochondrial genomes of modern humans and neanderthals or interspecific hybridization associated with mtDNA recombination.

  20. High resolution mosaic image of capillaries in human retina by adaptive optics

    Ning Ling; Yudong Zhang; Xuejun Rao; Cheng Wang; Yiyun Hu; Wenhan Jiang

    2005-01-01

    Adaptive optics (AO) has been proved as a powerful means for high resolution imaging of human retina.Because of the pixel number of charge-coupled device (CCD) camera, the field of view is limited to 1°.In order to have image of capillaries around vivo human fovea, we use mosaic method to obtain high resolution image in area of 6°× 6°. Detailed structures of capillaries around fovea with resolution of 2.3μm are clearly shown. Comparison shows that this method has a much higher resolution than current clinic retina imaging methods.

  1. GH/IGF-I axis and matrix adaptation of the musculotendinous tissue to exercise in humans

    Heinemeier, K M; Mackey, Abigail; Doessing, S

    2012-01-01

    Exercise is not only associated with adaptive responses within skeletal muscle fibers but also with induction of collagen synthesis both in muscle and adjacent connective tissue. Additionally, exercise and training leads to activation of the systemic growth hormone/insulin-like growth factor I axis...... (GH/IGF-I), as well as increased local IGF-I expression. Studies in humans with pathologically high levels of GH/IGF-I, and in healthy humans who receive either weeks of GH administration or acute injection of IGF-I into connective tissue, demonstrate increased expression and synthesis of collagen...

  2. Adaptive interaction a utility maximization approach to understanding human interaction with technology

    Payne, Stephen J

    2013-01-01

    This lecture describes a theoretical framework for the behavioural sciences that holds high promise for theory-driven research and design in Human-Computer Interaction. The framework is designed to tackle the adaptive, ecological, and bounded nature of human behaviour. It is designed to help scientists and practitioners reason about why people choose to behave as they do and to explain which strategies people choose in response to utility, ecology, and cognitive information processing mechanisms. A key idea is that people choose strategies so as to maximise utility given constraints. The frame

  3. View-invariant human action recognition via robust locally adaptive multi-view learning

    Jia-geng FENG; Jun XIAO

    2015-01-01

    Human action recognition is currently one of the most active research areas in computer vision. It has been widely used in many applications, such as intelligent surveillance, perceptual interface, and content-based video retrieval. However, some extrinsic factors are barriers for the development of action recognition;e.g., human actions may be observed from arbitrary camera viewpoints in realistic scene. Thus, view-invariant analysis becomes important for action recognition algorithms, and a number of researchers have paid much attention to this issue. In this paper, we present a multi-view learning approach to recognize human actions from different views. As most existing multi-view learning algorithms often suffer from the problem of lacking data adaptiveness in the nearest neighborhood graph construction procedure, a robust locally adaptive multi-view learning algorithm based on learning multiple local L1-graphs is proposed. Moreover, an efficient iterative optimization method is proposed to solve the proposed objective function. Experiments on three public view-invariant action recognition datasets, i.e., ViHASi, IXMAS, and WVU, demonstrate data adaptiveness, effectiveness, and efficiency of our algorithm. More importantly, when the feature dimension is correctly selected (i.e.,>60), the proposed algorithm stably outperforms state-of-the-art counterparts and obtains about 6%improvement in recognition accuracy on the three datasets.

  4. Stomach (Gastric) Cancer Prevention

    ... Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... has stayed about the same since 2005. Stomach (gastric) cancer is a disease in which malignant (cancer) cells ...

  5. Ghrelin and gastric acid secretion.

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-11-07

    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.

  6. Ghrelin and gastric acid secretion

    Koji Yakabi; Junichi Kawashima; Shingo Kato

    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-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-in-duced 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 add 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.

  7. Tumour gastrin expression and serum gastrin concentrations in dogs with gastric carcinoma are poor diagnostic indicators

    Seim-Wikse, T.; Kolbjørnsen, Ø.; Jörundsson, E.;

    2014-01-01

    Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator...

  8. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting

  9. Amplification Analysis of Helicobacter pylori and Fungi Gene Fragments in Human Gastric Ulcer and Gastric Cancer Tissues%胃溃疡、胃癌组织中幽门螺杆菌及真菌基因片段的扩增分析

    张东生; 张少华; 李东海; 王平凡

    2012-01-01

    The possibility of simple and mixed infection with Helicobacter pylori (Hp) and fungi in human gastric ulcer and gastric cancer tissues was investigated, tested and verified. Specific gene fragments of Hp and fungi were amplified by polymerase chain reaction (PCR) and determined by sequencing in 8 FFPE specimens, including 4 gastric ulcer and 4 gastric cancer cases with accompanied infection by respective Hp and fungi simple and mixed Hp/fungi infection. Genomic DNA was successfully extracted from paraffin embedded tissues. Hp 16S rRNA gene and fungi ITS gene fragments were amplified by PCR. The size of the band was 114 bp and 375 bp respectively after sequencing. Comparison analysis through BLAST on line the amplified genes had high isogeny with Hp and fungal nulceotide. Therefore, simple and mixed Hp and fungi infection occurred in gastric ulcer and gastric cancer tissues, speculated that Hp/fungi mixed-infection might be another pathogenetic factors that aggravate gastric ulcer to develop and induce the occurrence of gastric cancer. Active treatment of Hp/fungi mixed-infection conduces to improve the cure rate of gastric ulcer and reduce the incidence of gastric cancer.%探讨胃溃疡、胃癌组织中幽门螺杆菌(Helicobacter pylori,Hp)、真菌(Fungi)单纯感染及混合感染的可能性并进行验证.应用聚合酶链反应( PCR)技术,分别自4例胃溃疡和4例胃癌并伴单纯幽门螺杆菌、真菌及其混合感染病例石蜡包埋组织(FFPE)中扩增Hp及fungi基因特异片段并进行测序分析.成功提取了FFPE胃组织基因组DNA,并扩增出Hp 16S rRNA及真菌内转录间隔区18S rDNA基因和28S rDNA之间的基因特异条带,测序大小分别为114 bp和357 bp,经在线BLAST比对分析表明所扩增基因与Hp及真菌核苷酸具有高度同源性.胃溃疡、胃癌组织中存在Hp和真菌单纯感染及混合感染.推测Hp与真菌混合感染可能是加重胃溃疡发展和诱发胃癌发生的又一致病因素.

  10. Gastric lymphoma

    Sravani Padala

    2016-06-01

    Full Text Available Gastrointestinal lymphomas represent 5-20% of extra nodal lymphomas and mainly occur in the stomach and small intestine. Clinical findings are not specific, thus often determining a delay in the diagnosis. Imaging features at conventional and cross-sectional imaging must be known by the radiologist since he/she plays a pivotal role in the diagnosis and disease assessment, thus assisting in the choice of the optimal treatment to patients. This review focuses on the wide variety of imaging presentation of esophageal, gastric, and small and large bowel lymphoma presenting their main imaging appearances at conventional and cross-sectional imaging, mainly focusing on computed tomography and magnetic resonance, helping in the choice of the best imaging technique for the disease characterization and assessment and the recognition of potential complications. Gastrointestinal tract is the most common extra nodal site involved by lymphoma. Although lymphoma can involve any part of the gastrointestinal tract .The most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. [Int J Res Med Sci 2016; 4(6.000: 2481-2486

  11. Expression and significance of Cystatin SN mRNA in human gastric cancer tissues%胃癌组织Cystatin SN mRNA表达及其临床意义的探讨

    徐大方; 陈平; 石磊; 赵群; 顾学文

    2012-01-01

    OBJECTIVE! To investigate the expression and clinical significance of Cystatin SN in human gastric cancer. METHODS; The Cystatin SNmRNA expression was examined quantitatively by using real-time quantitative polymer-ase chain reaction on a cohort of human gastric cancer tissues (n=40) and corresponding adjacent tissues (w=40). RESULTS: The expression levels of Cystatin SN mRNA in gastric cancer were 5. 370 0±3. 034 5 and adjacent tissues were 1. 705 0±0. 738 8 respectively; Cystatin SN expression was dramatically increased in gastric cancer tissues compared with the corresponding adjacent tissues (?=8. 297, P = 0. 000). The expression of Cystatin SN was significantly associated with tumor size (t = - 0. 646, P = 0. 001), lymphnode metastasis (t = 3. 393 ,-P = 0. 002), gastric cancer stage (I = - 3. 798,P = 0. 001) and infiltration (£=4. 904,P=0. 000). However.it was not related to gastric differentiation,age and grader of patients (P>0. 05). CONCLUSION: Cystatin SN is overexpressed in gastric cancer tissues and significantly correlates with clinical prognosis.%目的:研究半胱氨酸蛋白酶抑制剂1 (Cystatin SN)在胃癌组织中的表达及临床意义.方法:荧光定量PCR方法检测40例胃癌组织和40例癌旁组织中Cystatin SN的表达.结果:胃癌组织中Cystatin SN mRNA的表达水平为5.370 0±3.034 5,相应的癌旁组织为1.705 0±0.738 8,癌组织显著高于癌旁组织,t=8.297,P=0.000.Cystatin SN的表达与肿瘤大小(t=-0.646,P=0.001)、淋巴转移(t=3.393,P=0.002)、TNM分期(t=-3.798,P=0.001)和浸润程度(t=4.904,P=0.000)相关,与肿瘤的分化程度、患者年龄和性别无关,P>0.05.结论:Cystatin SN在胃癌组织中的高表达与胃癌的发生发展密切相关.

  12. [The regulatory-adaptive status in the evaluation of human stress-resistance].

    Pokrovskiĭ, V M; Mingalev, A N

    2012-01-01

    There was offered a method of human stress-resistance evaluation via the dynamics of the regulatory-adaptive status. The regulatory-adaptive status was being determined via the parameters of the cardiorespiratory synchronism in the original state and at the application of the stress factor. Individuals, whose regulatory-adaptive status didn't change or decreased by not more than 5-6% at the exposition to the stress factor formed the group with a high level of stress-resistance. The individuals, whose regulatory adaptive status at the exposition to the stress factor decreased by less than 50% formed a group with a moderate level of stress-resistance. The examinees, whose regulatory-adaptive status decreased by more than 50% in a response to the stress factor were set in a group with a low stress-resistance level. The method was tested in the three stress models: 1) exam stress-on 58 students; 2) parachute jump stress-on 35 beginner parachutists; 3) stress, caused by the relocation to the zone of the catastrophe on 30 rescuers. In all the three models the method is highly informative. At the same time the levels of the stress-resistance were being evaluated by the psychological methods. It was shown, that the evaluation of the stress-resistance level via the dynamics of the regulatory-adaptive status allows to objectively characterize the ability of an individual to resist stress and should be included in the test complex for the casting of the candidates for the extreme professions.

  13. Dealcoholized Korean Rice Wine (Makgeolli) Exerts Potent Anti-Tumor Effect in AGS Human Gastric Adenocarcinoma Cells and Tumor Xenograft Mice.

    Shin, Eun Ju; Kim, Sung Hee; Kim, Jae Ho; Ha, Jaeho; Hwang, Jin-Taek

    2015-09-01

    Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.

  14. 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.

    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.

  15. Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma

    Nicolai J. Wewer Albrechtsen

    2016-05-01

    Full Text Available Low-abundance regulatory peptides, including metabolically important gut hormones, have shown promising therapeutic potential. Here, we present a streamlined mass spectrometry-based platform for identifying and characterizing low-abundance regulatory peptides in humans. We demonstrate the clinical applicability of this platform by studying a hitherto neglected glucose- and appetite-regulating gut hormone, namely, oxyntomodulin. Our results show that the secretion of oxyntomodulin in patients with type 2 diabetes is significantly impaired, and that its level is increased by more than 10-fold after gastric bypass surgery. Furthermore, we report that oxyntomodulin is co-distributed and co-secreted with the insulin-stimulating and appetite-regulating gut hormone glucagon-like peptide-1 (GLP-1, is inactivated by the same protease (dipeptidyl peptidase-4 as GLP-1 and acts through its receptor. Thus, oxyntomodulin may participate with GLP-1 in the regulation of glucose metabolism and appetite in humans. In conclusion, this mass spectrometry-based platform is a powerful resource for identifying and characterizing metabolically active low-abundance peptides.

  16. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

    Matteo Fumagalli

    2011-11-01

    Full Text Available Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the

  17. Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

    Fumagalli, Matteo; Sironi, Manuela; Pozzoli, Uberto; Ferrer-Admetlla, Anna; Ferrer-Admettla, Anna; Pattini, Linda; Nielsen, Rasmus

    2011-11-01

    Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some

  18. Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

    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

    2016-03-03

    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.

  19. Lack of adaptation to human tetherin in HIV-1 Group O and P

    Haworth Kevin G

    2011-09-01

    Full Text Available Abstract Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread.

  20. A Conceptual Architecture for Adaptive Human-Computer Interface of a PT Operation Platform Based on Context-Awareness

    Qing Xue

    2014-01-01

    Full Text Available We present a conceptual architecture for adaptive human-computer interface of a PT operation platform based on context-awareness. This architecture will form the basis of design for such an interface. This paper describes components, key technologies, and working principles of the architecture. The critical contents covered context information modeling, processing, relationship establishing between contexts and interface design knowledge by use of adaptive knowledge reasoning, and visualization implementing of adaptive interface with the aid of interface tools technology.

  1. Colloquium paper: adaptive specializations, social exchange, and the evolution of human intelligence.

    Cosmides, Leda; Barrett, H Clark; Tooby, John

    2010-05-11

    Blank-slate theories of human intelligence propose that reasoning is carried out by general-purpose operations applied uniformly across contents. An evolutionary approach implies a radically different model of human intelligence. The task demands of different adaptive problems select for functionally specialized problem-solving strategies, unleashing massive increases in problem-solving power for ancestrally recurrent adaptive problems. Because exchange can evolve only if cooperators can detect cheaters, we hypothesized that the human mind would be equipped with a neurocognitive system specialized for reasoning about social exchange. Whereas humans perform poorly when asked to detect violations of most conditional rules, we predicted and found a dramatic spike in performance when the rule specifies an exchange and violations correspond to cheating. According to critics, people's uncanny accuracy at detecting violations of social exchange rules does not reflect a cheater detection mechanism, but extends instead to all rules regulating when actions are permitted (deontic conditionals). Here we report experimental tests that falsify these theories by demonstrating that deontic rules as a class do not elicit the search for violations. We show that the cheater detection system functions with pinpoint accuracy, searching for violations of social exchange rules only when these are likely to reveal the presence of someone who intends to cheat. It does not search for violations of social exchange rules when these are accidental, when they do not benefit the violator, or when the situation would make cheating difficult.

  2. Prehistoric Human Dispersal to the Tibetan Plateau and Adaptation to the High Altitude Environment

    Zhang, Dongju; Dong, Guanghui; Chen, Fahu

    2016-04-01

    Human history of the Tibetan Plateau and human adaptation to the high altitude environment is hotly debated in the past decade among archaeological, anthropological, genetic, and even past climate change studies. Based on previous studies on the Tibetan Plateau and our own archaeological studies in northeastern Tibetan Plateau (NETP), we propose that human migrated to the Tibetan Plateau from the last Deglacial period to late Holocene mainly from North China via Yellow River valley and its tributary valleys in NETP. This migration is constituted of four stages (Upper Paleolithic, Epi-Paleolithic, Neolithic and Bronze Age) when human adapted to the high altitude environment and climate change with different strategies and techniques. Particularly, the prevail of microlithic technology in North China provoked hunter-gatherers' first visit to the NETP in relatively ameliorated last Deglacial period, and the quick development of millet farming and subsequent mixed barley-wheat farming and sheep herding facilitated farmers and herders permanently settled in NETP, even above 3000 masl, during mid- and late Holocene.

  3. Adaptive optics OCT using 1060nm swept source and dual deformable lenses for human retinal imaging

    Jian, Yifan; Lee, Sujin; Cua, Michelle; Miao, Dongkai; Bonora, Stefano; Zawadzki, Robert J.; Sarunic, Marinko V.

    2016-03-01

    Adaptive optics concepts have been applied to the advancement of biological imaging and microscopy. In particular, AO has also been very successfully applied to cellular resolution imaging of the retina, enabling visualization of the characteristic mosaic patterns of the outer retinal layers using flood illumination fundus photography, Scanning Laser Ophthalmoscopy (SLO), and Optical Coherence Tomography (OCT). Despite the high quality of the in vivo images, there has been a limited uptake of AO imaging into the clinical environment. The high resolution afforded by AO comes at the price of limited field of view and specialized equipment. The implementation of a typical adaptive optics imaging system results in a relatively large and complex optical setup. The wavefront measurement is commonly performed using a Hartmann-Shack Wavefront Sensor (HS-WFS) placed at an image plane that is optically conjugated to the eye's pupil. The deformable mirror is also placed at a conjugate plane, relaying the wavefront corrections to the pupil. Due to the sensitivity of the HS-WFS to back-reflections, the imaging system is commonly constructed from spherical mirrors. In this project, we present a novel adaptive optics OCT retinal imaging system with significant potential to overcome many of the barriers to integration with a clinical environment. We describe in detail the implementation of a compact lens based wavefront sensorless adaptive optics (WSAO) 1060nm swept source OCT human retinal imaging system with dual deformable lenses, and present retinal images acquired in vivo from research volunteers.

  4. Adaptive potential of genomic structural variation in human and mammalian evolution.

    Radke, David W; Lee, Charles

    2015-09-01

    Because phenotypic innovations must be genetically heritable for biological evolution to proceed, it is natural to consider new mutation events as well as standing genetic variation as sources for their birth. Previous research has identified a number of single-nucleotide polymorphisms that underlie a subset of adaptive traits in organisms. However, another well-known class of variation, genomic structural variation, could have even greater potential to produce adaptive phenotypes, due to the variety of possible types of alterations (deletions, insertions, duplications, among others) at different genomic positions and with variable lengths. It is from these dramatic genomic alterations, and selection on their phenotypic consequences, that adaptations leading to biological diversification could be derived. In this review, using studies in humans and other mammals, we highlight examples of how phenotypic variation from structural variants might become adaptive in populations and potentially enable biological diversification. Phenotypic change arising from structural variants will be described according to their immediate effect on organismal metabolic processes, immunological response and physical features. Study of population dynamics of segregating structural variation can therefore provide a window into understanding current and historical biological diversification.

  5. Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo

    Da-Qiang Li; Zhi-Biao Wang; Jin Bai; Jie Zhao; Yuan Wang; Kai Hu; Yong-Hong Du

    2004-01-01

    AIM: To investigate the effects of mifepristone on the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 and its mechanisms.METHODS: After incubation with various concentrations of mifepristone (5, 10, 20 μmol/L), the adhesion to artificial basement membrane, Matrigel, and the migration of MKN-45cells were assayed using MTT assay and lranswell cell culture chambers, respectively. Enzyme- linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine the expression of vascular endothelial growth factor (VEGF)and integrin β3 in the cells. After subcutaneous transplantation of MKN-45 cells in nude mice, mifepristone (50 mg/kg.d)was administrated subcutaneously for 8 wk to assess its effects on tumor metastasis. Immunohistochemical analysis was used to detect the expression of VEGF and microvascular density (MVD) in xenografted tumors.RESULTS: Mifepristone dose-dependently inhibited the heterotypic adhesion to Matrigel of MKN-45 cells. The inhibition was accompanied by a significant down-regulation of integrin β3 expression in the cells. After incubation with 5, 10, 20 μmol/L mifepristone, the number of migrated MKN-45 cells was 72±8, 50±6, 41±5 in experiment group, and 94±16 in control group (P<0.01). Meanwhile, secreted VEGF protein of MKN-45 cells in mifepristone-treated group (14.2±2.9, 8.9±3.1, 5.4±2.1 ng/g per liter) was significantly lower than that in control group (22.7±4.3 ng/g per liter,P<0.01). In vivo, mifepristone decreased the number of metastatic foci in lungs of nude mice and down-regulated the expression of VEGF and MlVD in the xenograted tumors.CONCLUSION: Mifepristone can effectively inhibit the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45in vitro and in vivo through inhibition of heterotypic adhesion to basement membrane,cell migration and angiogenesis.

  6. Rate and adaptation effects on the auditory evoked brainstem response in human newborns and adults.

    Lasky, R E

    1997-09-01

    Auditory evoked brainstem response (ABR) latencies increased and amplitudes decreased with increasing stimulus repetition rate for human newborns and adults. The wave V latency increases were larger for newborns than adults. The wave V amplitude decreases were smaller for newborns than adults. These differences could not be explained by developmental differences in frequency responsivity. The transition from the unadapted to the fully adapted response was less rapid in newborns than adults at short (= 10 ms) inter stimulus intervals (ISIs). At longer ISIs (= 20 ms) there were no developmental differences in the transition to the fully adapted response. The newborn transition occurred in a two stage process. The rapid initial stage observed in adults and newborns was complete by about 40 ms. A second slower stage was observed only in newborns although it has been observed in adults in other studies (Weatherby and Hecox, 1982; Lightfoot, 1991; Lasky et al., 1996). These effects were replicated at different stimulus intensities. After the termination of stimulation the return to the wave V unadapted response took nearly 500 ms in newborns. Neither the newborn nor the adult data can be explained by forward masking of one click on the next click. These results indicate human developmental differences in adaptation to repetitive auditory stimulation at the level of the brainstem.

  7. Chemoprevention of gastric cancer: current status

    2003-01-01

    The development of gastric cancer is a multi-factor process. In addition to genetic factors, environmental factors including smoking, low gastric acidity, excessive intake of salt or salty food and low consumption of fresh fruits and vegetables all contribute to the development of gastric cancer. Of particular interest, epidemiological and experimental studies have demonstrated that Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. Most studies using micronutrient supplementation have failed to demonstrate any preventive effect against the development of gastric cancer. The use of non-steroidal anti-inflammatory drugs has been consistently observed to protect against the development of gastric cancer. Recently, eradication of H. pylori infection by a chemopreventative approach is being studied in a number of trials. Studies using precancerous lesions as an end point of the treatment have produced conflicting and mostly negative results. Trials using cancer as an end point are being cautiously carried out in high-risk populations, and will provide the definitive answer to this important question. In the end, vaccination may be proven to be the optimal strategy in human for the management of H. pylori infection and prevention of gastric cancer.

  8. Current practice of gastric cancer treatment

    Yoon Young Choi; Ji Yeong An; Hyung-Il Kim; Jae-Ho Cheong; Woo Jin Hyung; Sung Hoon Noh

    2014-01-01

    Objective The aim of this review was to overview the current practice of gastric cancer treatment including surgery and other adjuvant modalities.Data sources The review was based on data obtained from the published articles and main guidelines in the East and West.Study selection Articles with high level of evidence or current best evidence in each issue were selected to be reviewed.Results Although varied adjuvant modalities have been proved to be benefit for treating gastric cancer,surgery is still the most important treatment strategy against gastric cancer.Actively adapting to new technology is important but it should be balanced with an effort to establish sound scientific rationale that adheres to oncologic principles.Conclusions Future treatment of gastric cancer will be focused on tailored,personalized therapy.For achieving it,collaboration across disciplines is essential.Also the philosophy of caring for the patients with gastric cancer should be rooted in the realization of true patient benefit regardless of who is providing the care.With these philosophies,we can shift the scientific and technological advances toward triumph over gastric cancer.

  9. Completed Experiments in Human Adaptation: Roles for Social Science in Arctic Policy Development

    Jensen, A. M.

    2015-12-01

    The Arctic contains many sites with exquisite organic preservation, which can be used to inform policy decisions in two very different ways. Archaeological sites can be considered at the result of completed experiments in human adaptation. With proper analysis of the multiple types of data they contain, one can see how climate change affected arctic ecosystems (including the human components) and how successful human responses were. Secondly, archaeological finds can provide vivid illustrations of the effects of climate change effects and extreme climatic events at a particular place. These illustrations appear to be far easier for members of the public to relate to than other means of transmitting scientific information, and can be good means of motivating people to be proactive.

  10. A forskolin derivative, FSK88, induces apoptosis in human gastric cancer BGC823 cells through caspase activation involving regulation of Bcl-2 family gene expression, dissipation of mitochondrial membrane potential and cytochrome c release.

    Li, Zhonghai; Wang, Jingze

    2006-11-01

    FSK88, a forskolin derivative, was extracted and purified from cultured tropical plant roots, Coleus forskohlii. Our previous studies have demonstrated that FSK88 can inhibit HL-60 cell proliferation and induce the differentiation of HL-60 cells to monocyte macrophages. In this study, we showed that FSK88 can induce apoptotic death of human gastric cancer BGC823 cells in a dose- and time-dependent manner. Results showed that FSK88-induced apoptosis was accompanied by the mitochondrial release of cytochrome c and activation of caspase-3 in BGC823 cells. Furthermore, treatment with caspase-3 inhibitor (z-DEVD-fmk) was capable of preventing the FSK88-induced caspase-3 activity and apoptosis. FSK88-induced apoptosis in human gastric cancer BGC823 cells was also accompanied by the up-regulation of Bax, Bad and down-regulation of Bcl-2. Theses results clearly demonstrated that the induction of apoptosis by FSK88 involved multiple cellular and molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family genes, mitochondrial membrane potential (Deltapsi(m)), cytochrome c, and caspase-3, participate in the FSK88-induced apoptotic process in human gastric cancer BGC823 cells.

  11. Gastric stimulation for weight loss

    Meir Mizrahi; Ami Ben Ya'acov; Yaron Ilan

    2012-01-01

    The prevalence of obesity is growing to epidemic proportions,and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss.Behavior and lifestyle therapy are safe treatments for obesity in the short term,but the durability of the weight loss is limited.Although promising obesity drugs are in development,the currently available drugs lack efficacy or have unacceptable side effects.Surgery leads to long-term weight loss,but it is associated with morbidity and mortality.Gastric electrical stimulation (GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders.GES is a promising,minimally invasive,safe,and effective method for treating obesity.External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time.In addition,data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES.This may involve alteration of secretion of hormones associated with hunger or satiety.Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome.Here,we review the current status,potential mechanisms of action,and possible future applications of gastric stimulation for obesity.

  12. Human physiological adaptation to extended Space Flight and its implications for Space Station

    Kutyna, F. A.; Shumate, W. H.

    1985-01-01

    Current work evaluating short-term space flight physiological data on the homeostatic changes due to weightlessness is presented as a means of anticipating Space Station long-term effects. An integrated systems analysis of current data shows a vestibulo-sensory adaptation within days; a loss of body mass, fluids, and electrolytes, stabilizing in a month; and a loss in red cell mass over a month. But bone demineralization which did not level off is seen as the biggest concern. Computer algorithms have been developed to simulate the human adaptation to weightlessness. So far these paradigms have been backed up by flight data and it is hoped that they will provide valuable information for future Space Station design. A series of explanatory schematics is attached.

  13. How do precision medicine and system biology response to human body's complex adaptability?

    Yuan, Bing

    2016-12-01

    In the field of life sciences, although system biology and "precision medicine" introduce some complex scientifific methods and techniques, it is still based on the "analysis-reconstruction" of reductionist theory as a whole. Adaptability of complex system increase system behaviour uncertainty as well as the difficulties of precise identifification and control. It also put systems biology research into trouble. To grasp the behaviour and characteristics of organism fundamentally, systems biology has to abandon the "analysis-reconstruction" concept. In accordance with the guidelines of complexity science, systems biology should build organism model from holistic level, just like the Chinese medicine did in dealing with human body and disease. When we study the living body from the holistic level, we will fifind the adaptability of complex system is not the obstacle that increases the diffificulty of problem solving. It is the "exceptional", "right-hand man" that helping us to deal with the complexity of life more effectively.

  14. Detection of Human Impacts by an Adaptive Energy-Based Anisotropic Algorithm

    Manuel Prado-Velasco

    2013-10-01

    Full Text Available Boosted by health consequences and the cost of falls in the elderly, this work develops and tests a novel algorithm and methodology to detect human impacts that will act as triggers of a two-layer fall monitor. The two main requirements demanded by socio-healthcare providers—unobtrusiveness and reliability—defined the objectives of the research. We have demonstrated that a very agile, adaptive, and energy-based anisotropic algorithm can provide 100% sensitivity and 78% specificity, in the task of detecting impacts under demanding laboratory conditions. The algorithm works together with an unsupervised real-time learning technique that addresses the adaptive capability, and this is also presented. The work demonstrates the robustness and reliability of our new algorithm, which will be the basis of a smart falling monitor. This is shown in this work to underline the relevance of the results.

  15. Alterations in Gastric Microbiota After H. Pylori Eradication and in Different Histological Stages of Gastric Carcinogenesis

    Li, Tung Hiu; Qin, Youwen; Sham, Pak Chung; Lau, K.S.; Chu, Kent-Man; Leung, Wai K.

    2017-01-01

    The role of bacteria other than Helicobacter pylori (HP) in the stomach remains elusive. We characterized the gastric microbiota in individuals with different histological stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP negative controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominant H. pylori, we observed other Proteobacteria including Haemophilus, Serratia, Neisseria and Stenotrophomonas as the major components of the human gastric microbiota. Although samples were largely converged according to the relative abundance of HP, a clear separation of GC and other samples was recovered. Whilst there was a strong inverse association between HP relative abundance and bacterial diversity, this association was weak in GC samples which tended to have lower bacterial diversity compared with other samples with similar HP levels. Eradication of HP resulted in an increase in bacterial diversity and restoration of the relative abundance of other bacteria to levels similar to individuals without HP. In conclusion, HP colonization results in alterations of gastric microbiota and reduction in bacterial diversity, which could be restored by antibiotic treatment. PMID:28322295

  16. Upregulation of autophagy-related gene-5 (ATG-5 is associated with chemoresistance in human gastric cancer.

    Jie Ge

    Full Text Available Autophagy-related gene-5 (ATG-5 is one of the key regulators of autophagic cell death. It has been widely regarded as a protective molecular mechanism for tumor cells during the course of chemotherapy. In the present study, we investigated the expression pattern of ATG-5 and multidrug resistance-associated protein-1 (MRP-1 in 135 gastric cancers (GC patients who were treated with epirubicin, cisplatin and 5-FU adjuvant chemotherapy (ECF following surgical resection and explored their potential clinical significance. We found that both ATG-5 (77.78% and MRP-1 (79.26% were highly expressed in GC patients. ATG-5 expression was significantly associated with depth of wall invasion, TNM stages and distant metastasis of GC (P<0.05, whereas MRP-1 expression was significantly linked with tumor size, depth of wall invasion, lymph node metastasis, TNM stages and differentiation status (P<0.05. ATG-5 expression was positively correlated with MRP-1 (rp = 0.616, P<0.01. Increased expression of ATG-5 and MPR-1 was significantly correlated with poor overall survival (OS; P<0.01 and disease free survival (DFS; P<0.01 of our GC cohort. Furthermore, we demonstrated that ATG-5 was involved in drug resistant of GC cells, which was mainly through regulating autophagy. Our data suggest that upregulated expression of ATG-5, an important molecular feature of protective autophagy, is associated with chemoresistance in GC. Expression of ATG-5 and MRP-1 may be independent prognostic markers for GC treatment.

  17. Localization and translocation of RhoA protein in the human gastric cancer cell line SGC-7901

    2008-01-01

    AIM: To elucidate the localization of RhoA in gastric SGC-7901 cancer cells and its translocation by lysophosphatidic acid (LPA) and/or 8-chlorophenylthio cAMP (CPT-cAMP). METHODS: Immunofluorescence microscopy was used to determine the localization of RhoA. Western blotting was used to detect both endogenous and exogenous RhoA in different cellular compartments (membrane, cytosol, nucleus) and the translocation of RhoA following treatment with LPA, CPT-cAMP, or CPT-cAMP+LPA. RESULTS: Immunofluorescence staining revealed endogenous RhoA to be localized in the membrane, the cytosol, and the nucleus, and its precise localization within the nucleus to be the nucleolus. Western blotting identified both endogenous and exogenous RhoA within different cellular compartments (membrane, cytosol, nucleus, nucleolus). After stimulation with LPA, the amount of RhoA within membrane and nuclear extracts increased, while it decreased in the cytosol fractions. After treatment with CPT-cAMP the amount of RhoA within the membrane and the nuclear extracts decreased, while it increased within the cytosol fraction. Treatment with a combination of both substances led to a decrease in RhoA in the membrane and the nucleus but to an increase in the cytosol. CONCLUSION: In SGC-7901 cells RhoA was found to be localized within the membrane, the cytosol, and the nucleus. Within the nucleus its precise localization could be demonstrated to be the nucleolus. Stimulation with LPA caused a translocation of RhoA from the cytosol towards the membrane and the nucleus; treatment with CPT-cAMP caused the opposite effect. Furthermore, pre-treatment with CPT-cAMP was found to block the effect of LPA.

  18. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.

    Tulika Arora

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3, which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

  19. 生长激素受体在胃癌组织中的表达及其临床意义%Expression of Growth Hormone Receptor in Human Gastric Cancer Tissue and its clinical significance

    袁媛; 李苏宜; 卓士超; 宋永谦

    2012-01-01

    目的:研究人胃癌组织生长激素受体( GHR)的表达情况及其与肿瘤临床病理特点的关系. 方法:回顾性分析100例胃癌病人资料,采用免疫组化法检测组织的GHR表达,分析其与肿瘤分化程度、病理分期、Borrmann分型的关系.同时检测其中14例癌旁正常胃黏膜组织的GHR表达情况,分析正常胃黏膜与肿瘤组织GHR表达的差异. 结果:胃癌组织中GHR表达阳性率为55% (55/100),正常组织为85.7% (12/14).GHR表达与临床分期、组织分化程度显著相关(P<0.01),与Borrmann分型相关(P<0.05).GHR表达与肿瘤发生部位、性别和年龄均无相关性. 结论:胃癌组织中GHR的表达存在差异.%Objective:To investigate the expression of growth hormone receptor(GHR)in human gastric cancer tissue. Methods:The GHR was detected in samples of the human gastric cancer (100 cases) by immunohistochetnistry technique. In 14 of these cases, data of adjacent normal gastric tissue was similarly analyzed. Results-. The GHR expression positive rate was 55% (55/100)in the human gastric cancer tissue and 12/14 in normal tissue samples. There were statistic differences among the gastric cancer tissues of different clinical stage , different differentiation and Borrmann type and different tissue type( P 0.05 ). Conclusion:GHR expression in gastric cancer is differ.

  20. Studies on microsatellite instability in p16 gene and expression of hMSH2 mRNA in human gastric cancer tissues

    Qin-Xian Zhang; Yi Ding; Xiao-Ping Le; Peng Du

    2003-01-01

    AIM: To detect the loss of heterozygosity (LOH) frequency of microsatellite sites D9s171, D9s1604 of p16 gene and expression of hMSH2 mRNA in various differentiated types of gastric cancer, adjacent cancer tissues and normal gastric mucosa.METHODS: LOH was detected by polymerase chain reaction (PCR)-denaturing polyacrylamide gel electrophoresis-silver staining. The expression of hMSH2 mRNA was examined with in situ hybridization.RESULTS: The frequency rate of LOH was significantly higher in gastric cancers than that in adjacent cancer tissues (P=0.032). No significant difference was noted among various differentiated types and various clinical stages of gastric cancers. The significantly reduced expression of hMSH2mRNA positive signal cells exhibited in gastric cancers, in comparison with that in the adjacent cancer tissues and normal gastric mucosa, respectively (P=0.001). No significant difference was noted among various clinical stages of gastric cancers (P>0.05). The difference of positive signal cells in poorly differentiated cancers and those in well and moderately differentiated cancers were significant (P<0.001).CONCLUSION: The frequencies of LOH in two microsatellite sites, D9s171 and D9s1604, in p16 genome were associated with development of gastric cancer and no significant correlation was demonstrated between the LOH frequency and the cell differentiated types of tumor cells or clinical stages. There was a positive relationship between the expression of hMSH2 mRNA and the differentiated types of gastric cancer.

  1. Not My Problem: Vicarious Conflict Adaptation with Human and Virtual Co-actors

    Spapé, Michiel M.; Ravaja, Niklas

    2016-01-01

    The Simon effect refers to an incompatibility between stimulus and response locations resulting in a conflict situation and, consequently, slower responses. Like other conflict effects, it is commonly reduced after repetitions, suggesting an executive control ability, which flexibly rewires cognitive processing and adapts to conflict. Interestingly, conflict is not necessarily individually defined: the Social Simon effect refers to a scenario where two people who share a task show a conflict effect where a single person does not. Recent studies showed these observations might converge into what could be called vicarious conflict adaptation, with evidence indicating that observing someone else's conflict may subsequently reduce one's own. While plausible, there is reason for doubt: both the social aspect of the Simon Effect, and the degree to which executive control accounts for the conflict adaptation effect, have become foci of debate in recent studies. Here, we present two experiments that were designed to test the social dimension of the effect by varying the social relationship between the actor and the co-actor. In Experiment 1, participants performed a conflict task with a virtual co-actor, while the actor-observer relationship was manipulated as a function of the similarity between response modalities. In Experiment 2, the same task was performed both with a virtual and with a human co-actor, while heart-rate measurements were taken to measure the impact of observed conflict on autonomous activity. While both experiments replicated the interpersonal conflict adaptation effects, neither showed evidence of the critical social dimension. We consider the findings as demonstrating that vicarious conflict adaptation does not rely on the social relationship between the actor and co-actor. PMID:27199839

  2. Genomic Signatures for Avian H7N9 Viruses Adapting to Humans.

    Guang-Wu Chen

    Full Text Available An avian influenza A H7N9 virus emerged in March 2013 and caused a remarkable number of human fatalities. Genome variability in these viruses may provide insights into host adaptability. We scanned over 140 genomes of the H7N9 viruses isolated from humans and identified 104 positions that exhibited seven or more amino acid substitutions. Approximately half of these substitutions were identified in the influenza ribonucleoprotein (RNP complex. Although PB2 627K of the avian virus promotes replication in humans, 45 of the 147 investigated PB2 sequences retained the E signature at this position, which is an avian characteristic. We discovered 10 PB2 substitutions that covaried with K627E. An RNP activity assay showed that Q591K, D701N, and M535L restored the polymerase activity in human cells when 627K transformed to an avian-like E. Genomic analysis of the human-isolated avian influenza virus is crucial in assessing genome variability, because relationships between position-specific variations can be observed and explored. In this study, we observed alternative positions that can potentially compensate for PB2 627K, a well-known marker for cross-species infection. An RNP assay suggested Q591K, D701N, and M535L as potential markers for an H7N9 virus capable of infecting humans.

  3. Canine distemper virus associated with a lethal outbreak in monkeys can readily adapt to use human receptors.

    Sakai, Kouji; Yoshikawa, Tomoki; Seki, Fumio; Fukushi, Shuetsu; Tahara, Maino; Nagata, Noriyo; Ami, Yasushi; Mizutani, Tetsuya; Kurane, Ichiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Komase, Katsuhiro; Morikawa, Shigeru; Takeda, Makoto

    2013-06-01

    A canine distemper virus (CDV) strain, CYN07-dV, associated with a lethal outbreak in monkeys, used human signaling lymphocyte activation molecule as a receptor only poorly but readily adapted to use it following a P541S substitution in the hemagglutinin protein. Since CYN07-dV had an intrinsic ability to use human nectin-4, the adapted virus became able to use both human immune and epithelial cell receptors, as well as monkey and canine ones, suggesting that CDV can potentially infect humans.

  4. Human-pet interaction and loneliness: a test of concepts from Roy's adaptation model.

    Calvert, M M

    1989-01-01

    This research used two key concepts from Roy's adaptation model of nursing to examine the relationship between human-pet interaction and loneliness in nursing home residents. These concepts included (a) environmental stimuli as factors influencing adaptation and (b) interdependence as a mode of response to the environment. The hypothesis of this study asserted that the residents of a nursing home who had greater levels of interaction with a pet program would experience less loneliness than those who had lower levels of interaction with a pet. The study used an ex post facto nonexperimental design with 65 subjects. The simplified version of the revised UCLA loneliness scale was used to measure loneliness. Reported level of human-pet interaction was measured according to a four-point scale (1 = no interaction, 4 = quite a lot of interaction). The hypothesis was supported at the p less than 0.03 level of significance. Implications for practice through organizing pet programs in situations where loneliness exists are discussed. Recommendations for future research include replicating the study using a larger sample and developing a comprehensive human-pet interaction tool.

  5. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes

    Moon, Robert

    2012-12-24

    Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.

  6. Genotypic and phenotypic diversity of the noncapsulated Haemophilus influenzae: adaptation and pathogenesis in the human airways.

    Garmendia, Junkal; Martí-Lliteras, Pau; Moleres, Javier; Puig, Carmen; Bengoechea, José A

    2012-12-01

    The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes.

  7. Local Adaptation of Sun-Exposure-Dependent Gene Expression Regulation in Human Skin

    Kita, Ryosuke; Fraser, Hunter B.

    2016-01-01

    Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin. We then tested whether genetic variants may influence each individual’s gene expression response to sun-exposure. Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). The allele frequencies of the RASSF9 se-eQTL across diverse populations correlate with the magnitude of solar radiation experienced by these populations, suggesting local adaptation to varying levels of sunlight. These results provide the first examples of sun-exposure-dependent regulatory variation and suggest that this variation has contributed to recent human adaptation. PMID:27760139

  8. Demography-based adaptive network model reproduces the spatial organization of human linguistic groups

    Capitán, José A.; Manrubia, Susanna

    2015-12-01

    The distribution of human linguistic groups presents a number of interesting and nontrivial patterns. The distributions of the number of speakers per language and the area each group covers follow log-normal distributions, while population and area fulfill an allometric relationship. The topology of networks of spatial contacts between different linguistic groups has been recently characterized, showing atypical properties of the degree distribution and clustering, among others. Human demography, spatial conflicts, and the construction of networks of contacts between linguistic groups are mutually dependent processes. Here we introduce an adaptive network model that takes all of them into account and successfully reproduces, using only four model parameters, not only those features of linguistic groups already described in the literature, but also correlations between demographic and topological properties uncovered in this work. Besides their relevance when modeling and understanding processes related to human biogeography, our adaptive network model admits a number of generalizations that broaden its scope and make it suitable to represent interactions between agents based on population dynamics and competition for space.

  9. Coleusin factor exerts cytotoxic activity by inducing G0/G1 cell cycle arrest and apoptosis in human gastric cancer BGC-823 cells.

    Sun, Bo; Geng, Shuo; Huang, Xiaojia; Zhu, Jin; Liu, Shu; Zhang, Yajing; Ye, Jian; Li, Yongjin; Wang, Jingze

    2011-02-01

    Coleusin factor (CF), a kind of diterpenoids, is isolated and purified from the root of a Chinese tropical plant Coleus forskohlii by our laboratory. Our previous studies have demonstrated that CF significantly inhibits growth in some kinds of cancer cell lines. Here, we found that CF remarkably inhibited growth in human gastric cancer BGC-823 cells by decreasing cell proliferation, inducing G(0)/G(1) cell cycle arrest and apoptosis. CF also decreased the mitochondrial membrane potential in BGC-823 cells. Immunoblotting analysis revealed that CF significantly decreased the expressions of cyclinD1, Bcl-2, and Bcl-x(L), increased the expressions of cytosol cytochrome c, p53, p21, and Rb. In addition, CF significantly increased the expressions and activities of caspase-3 and -9. More importantly, CF potently inhibited the growth of BGC-823 cells xenografted in athymic nude mice with negligible body weight loss and damage towards the spleen. These results indicate that CF exerts a cytotoxic effect on BGC-823 cells by inducing cell cycle arrest and apoptosis.

  10. Effect of Human Milk Appetite Hormones, Macronutrients, and Infant Characteristics on Gastric Emptying and Breastfeeding Patterns of Term Fully Breastfed Infants.

    Gridneva, Zoya; Kugananthan, Sambavi; Hepworth, Anna R; Tie, Wan J; Lai, Ching T; Ward, Leigh C; Hartmann, Peter E; Geddes, Donna T

    2016-12-28

    Human milk (HM) components influence infant feeding patterns and nutrient intake, yet it is unclear how they influence gastric emptying (GE), a key component of appetite regulation. This study analyzed GE of a single breastfeed, HM appetite hormones/macronutrients and demographics/anthropometrics/body composition of term fully breastfed infants (n = 41, 2 and/or 5 mo). Stomach volumes (SV) were calculated from pre-/post-feed ultrasound scans, then repeatedly until the next feed. Feed volume (FV) was measured by the test-weigh method. HM samples were analyzed for adiponectin, leptin, fat, lactose, total carbohydrate, lysozyme, and total/whey/casein protein. Linear regression/mixed effect models were used to determine associations between GE/feed variables and HM components/infant anthropometrics/adiposity. Higher FVs were associated with faster (-0.07 [-0.10, -0.03], p whey protein concentration was associated with higher post-feed SVs (4.99 [0.84, 9.13], p = 0.023). Longer GE time was associated with higher adiponectin concentration (2.29 [0.92, 3.66], p = 0.002) and dose (0.02 [0.01, 0.03], p = 0.005), and lower casein:whey ratio (-65.89 [-107.13, -2.66], p = 0.003). FV and HM composition influence GE and breastfeeding patterns in term breastfed infants.

  11. Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87) Cell Line

    Atnip, Allison A.; Sigurdson, Gregory T.; Bomser, Joshua; Giusti, M. Mónica

    2017-01-01

    Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h), concentration (50–1500 µM), and pH (3.0, 5.0, 7.4) on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87