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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 eff...

  2. DBGC: A Database of Human Gastric Cancer

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

    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...

  3. 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.

  4. Global regulation of virulence and the stress response by CsrA in the highly adapted human gastric pathogen Helicobacter pylori

    Barnard, F.M.; Loughlin, M.F.; Fainberg, H.P.;

    2004-01-01

    Although successful and persistent colonization of the gastric mucosa depends on the ability to respond to changing environmental conditions and co-ordinate the expression of virulence factors during the course of infection, Helicobacter pylori possesses relatively few transcriptional regulators....... We therefore investigated the contribution of the regulatory protein CsrA to global gene regulation in this important human pathogen. CsrA was necessary for full motility and survival of H. pylori under conditions of oxidative stress. Loss of csrA expression deregulated the oxidant...... NapA protein was produced in the mutant strain. Finally, H. pylori strains deficient in the production of CsrA were significantly attenuated for virulence in a mouse model of infection. This work provides evidence that CsrA has a broad role in regulating the physiology of H. pylori in response to...

  5. Honey and Apoptosis in Human Gastric Mucosa

    Alireza Ostadrahimi

    2012-07-01

    Full Text Available Background: Gastric cancer is the fourth most common malignancy in the world. Honey is acomplex mixture of special biological active constituents. Honey possesses antioxidant and antitumorproperties. Nutritional studies have indicated that consumption of honey modulates therisk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisiverole in precancerous changes. Our chief study was conducted to assess the relationship betweenconsumption of honey and apoptosis in human gastric mucosa.Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred totwo hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire(FFQ and apoptosis was detected by TUNEL technique. We tested polynomial curve tofind the best fit between honey consumption and apoptosis.Results: A positive relation between honey consumption and apoptosis was found (P=0.024.Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honeyamount - 0.533(honey amount2 +1.833×10-5(honey amount7.Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis ingastric mucosa.

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

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

    2004-01-01

    The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess "enterogastrone" activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 +/- 3.3 yr, body mass....... 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 31 +/- 9 pmol/l for intact GIP during the administration of GIP and placebo, respectively (P Gastric half-emptying times were 120 +/- 9 and 120 +/- 18 min (P = 1...

  7. Evidence of cross-stressor - induced adaptive gastric cytoprotection

    Glavin, G.B.; Lockhart, L.K.; Rockman, G.E.; Hall, A.M.; Kiernan, K.M.

    1987-11-09

    Rats were given 7 days pre-treatment with either water (p.o.), 1 h immobilization or 20% ethanol (p.o.) with or without concomitant indomethacin injection. Following the pre-treatment phase, rats from each pre-treatment group were exposed to either 3 h cold-restraint stress or to 100% ethanol p.o. Results indicated that immobilization and 20% ethanol pre-treatment significantly reduce both cold-restraint stress ulcer formation and 100% ethanol-induced ulcers. Indomethacin co-treatment attenuated the reduction of ulcer formation of both pretreatments. These results suggest that cross-stressor adaptive cytoprotection occurs. Indomethacin abolished these effects, implicating the involvement of endogenous prostaglandins in the mediation of cross-stressor - induced gastric cytoprotection. 12 references, 2 figures.

  8. Expression of survivin in human gastric carcinoma and gastric carcinoma model of rats

    Xiao-Dong Zhu; Geng-Jin Lin; Li-Ping Qian; Zhong-Qing Chen

    2003-01-01

    AIM: To study the expression of survivin, an inhibitor of apoptosis protein, in human gastric carcinomas and gastric carcinoma models of rats.METHODS: With the method of immunohistochemical staining, we studied the expression of survivin in 20 cases of chronic gastritis and 56 cases of gastric carcinomas. We used N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and high dose sodium-chloride diet to induce rat gastric carcinomas. Survivin expression was studied in glandular stomachs of normal rats, adenocarcinomas and tissues adjacent to the tumor, as well as in rats during the induction period.RESULTS: Survivin was expressed in 27 of 56 (48.2 %)cases of human gastric carcinoma tissues and 1 of 20 (5 %)cases of chronic gastritis. It was found that the expression of survivin had no relation with the elements of age, tumor depth, tumor size, and disease stage, but was significantly related to histological type. The positive rate of survivin expression in cases of intestinal type was significantly higher than that in cases of diffuse type (P<0.05). In animal experiments, survivin expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and tissues adjacent to tumor were 0,40.0 %, 78.3 % and 38.9 %, respectively. Compared with the survivin expression in normal rats, the differences were significant.CONCLUSION: These data imply that survivin plays an important role in the onset of gastric carcinoma and that high survivin expression is an early event of gastric carcinoma.

  9. 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.

  10. Conjugation of 1-naphthol in human gastric epithelial cells.

    Déchelotte, P; Varrentrapp, M; Meyer, H.J.; Schwenk, M.

    1993-01-01

    The biotransformation of xenobiotics is essential to the maintenance of the body's integrity. Mucosal biotransformation has been well documented in the small and large intestine of animals and humans but whether the gastric mucosa plays a role in detoxifying ingested compounds remains largely unknown. The conjugation of the model phenolic compounds, 1-naphthol, by human gastric epithelial cells was assessed in vitro. Freshly isolated and cultured epithelial cells were prepared from surgical s...

  11. 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.

  12. Honey and Apoptosis in Human Gastric Mucosa

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

    2012-01-01

    Background: Gastric cancer is the fourth most common malignancy in the world. Honey is acomplex mixture of special biological active constituents. Honey possesses antioxidant and antitumorproperties. Nutritional studies have indicated that consumption of honey modulates therisk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisiverole in precancerous changes. Our chief study was conducted to assess the relationship betweenconsumption of honey and apop...

  13. Expression of pituitary tumor transforming gene in human gastric carcinoma

    Chun-Yang Wen; Ichiro Sekine; Toshiyuki Nakayama; Ai-Ping Wang; Masahiro Nakashima; Yi-Tao Ding; Masahiro Ito; Hiromi Ishibashi; Mutsumi Matsuu; Kazuko Shichijo

    2004-01-01

    AIM: Pituitary tumor transforming gene (PTTG1) is overexpressed in a variety of tumors, including carcinomas of the lung, breast, colon, as well as in leukemia, lymphoma and pituitary adenomas. However, there is little information on its expression in gastric carcinoma. We sought to investigate the expression of PTTG1 in gastric carcinoma and to explore the relationship between its expression and clinicopathological factors.METHODS: We studied 75 primary human gastric adenocarcinomas, including 17 mucosal carcinomas, 21 submucosal infiltrative carcinomas, 12 carcinomas invading proprial muscle layers, 6 carcinomas reaching the subserosa,and 19 carcinomas penetrating the serosal surface.Immunohistochemical analysis was performed using paraffin embedded sections of gastric adenocarcinomas.RESULTS: PTTG1 was expressed heterogeneously in carcinomas. Positive PTTG1 staining was observed in 65.3% of the carcinomas (49 of 75). Its expression did not correlate significantly with either the histological type or the depth of infiltration of the gastric carcinomas. However,a statistical analysis showed significant differences between the primary adenocarcinomas and the associated metastatic lymph nodes.CONCLUSION: The results of this study demonstrate that PTTG1 expression is enhanced in metastatic lymph nodes in comparison to that in primary carcinomas. We suggest that PTTG1 may contribute to lymph node metastases in gastric carcinoma.

  14. In vitro mucin biosynthesis by human gastric mucosa biopsies

    A method is described for the study of the in vitro biosynthesis of mucins by human gastric biopsy samples. 14C-glucose was incorporated in the biopsies obtained from the fundus and antral regions of four normal human donors during a four hours incubation period. Labelled glycoproteins (mucins) were released in the medium and were also retained in the tissue-residue. Neutral sugars, fucose, protein and DNA determinations carried out on the tissue homogenates indicated that significant information on mucin biosynthesis can be obtained by this biopsy procedure which is particularly suitable for the exploration of gastric pathology

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

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

  16. Human Adaptations: Free divers

    Tournat, Troy Z.

    2014-01-01

    Freediving has been around for thousands of years and was only way to dive until the inventionof oxygen tanks in the 19th century. Around the world, people dove for goods such as pearls, andtoday people freedive for sport. Divers stretch the limit of their body and mind’s capabilitiesthrough psychological adaptations from thermal, respiratory, and cardiovascular responses.Findings conclude that thermal adaptations are a similar process to cold adaptive response. Withthe implementation of wets...

  17. 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.

  18. 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

  19. Terahertz spectroscopic investigation of human gastric normal and tumor tissues

    Human dehydrated normal and cancerous gastric tissues were measured using transmission time-domain terahertz spectroscopy. Based on the obtained terahertz absorption spectra, the contrasts between the two kinds of tissue were investigated and techniques for automatic identification of cancerous tissue were studied. Distinctive differences were demonstrated in both the shape and amplitude of the absorption spectra between normal and tumor tissue. Additionally, some spectral features in the range of 0.2∼0.5 THz and 1∼1.5 THz were revealed for all cancerous gastric tissues. To systematically achieve the identification of gastric cancer, principal component analysis combined with t-test was used to extract valuable information indicating the best distinction between the two types. Two clustering approaches, K-means and support vector machine (SVM), were then performed to classify the processed terahertz data into normal and cancerous groups. SVM presented a satisfactory result with less false classification cases. The results of this study implicate the potential of the terahertz technique to detect gastric cancer. The applied data analysis methodology provides a suggestion for automatic discrimination of terahertz spectra in other applications. (paper)

  20. Magnetogastrographic detection of gastric electrical response activity in humans

    The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre- and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre- and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders

  1. 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

    2015-01-01

    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. PMID:25788149

  2. 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.

  3. Human whole body cold adaptation.

    Daanen, Hein A M; Van Marken Lichtenbelt, Wouter D

    2016-01-01

    Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced vasodilation in fingers and toes compared to Caucasians and Inuit. About 40,000 y after humans left Africa, natives in cold terrestrial areas seems to have developed not only behavioral adaptations, but also physiological adaptations to cold. Dedicated studies show that repeated whole body exposure of individual volunteers, mainly Caucasians, to severe cold results in reduced cold sensation but no major physiological changes. Repeated cold water immersion seems to slightly reduce metabolic heat production, while repeated exposure to milder cold conditions shows some increase in metabolic heat production, in particular non-shivering thermogenesis. In conclusion, human cold adaptation in the form of increased metabolism and insulation seems to have occurred during recent evolution in populations, but cannot be developed during a lifetime in cold conditions as encountered in temperate and arctic regions. Therefore, we mainly depend on our behavioral skills to live in and survive the cold. PMID:27227100

  4. 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

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

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

    2016-01-01

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

  6. 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...... 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...... 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...

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

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

    2007-11-01

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

  8. Gastric Helicobacters in domestic animals and nonhuman primates and their significance for human health

    Haesebrouck, Freddy; Pasmans, Frank; Flahou, Bram; Chiers, Koen; Baele, Margo; Meyns, Tom; Decostere, Annemie; Ducatelle, Richard

    2009-01-01

    Summary: Helicobacters other than Helicobacter pylori have been associated with gastritis, gastric ulcers, and gastric mucosa-associated lymphoid tissue lymphoma in humans. These very fastidious microorganisms with a typical large spiral-shaped morphology were provisionally designated “H. heilmannii,” but in fact they comprise at least five different Helicobacter species, all of which are known to colonize the gastric mucosa of animals. H. suis, which has been isolated from the stomachs of pi...

  9. 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

    gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.......BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans...

  10. 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. PMID:26632203

  11. Reduced amoxicillin uptake into human gastric mucosa when gastric juice pH is high.

    Cardaci, G; Lambert, J.R.; King, R. G.; Onishi, N; Midolo, P

    1995-01-01

    Amoxicillin when administered with gastric acid suppressors has been shown to be effective in eradication of Helicobacter pylori in 50 to 80% of subjects. The aim of this investigator-blind crossover study was to determine if gastric mucosal amoxicillin uptake was affected by increasing gastric juice pH. Fifteen male subjects (7 H. pylori positive and 8 H. pylori negative) were randomized to receive 150 mg of ranitidine twice a day, 300 mg of ranitidine twice a day, or no drug for 2 days prio...

  12. 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 gas...

  13. Down-Regulated MAC30 Expression Inhibits Proliferation and Mobility of Human Gastric Cancer Cells

    Xiao-Yan Xu

    2014-05-01

    Full Text Available Background: Gastric cancer is one of the most common cancers in the world. MAC30/Transmembrane protein 97 (TMEM97 is aberrantly up-regulated in many human carcinoma cells. However, the function of MAC30 in gastric carcinoma cells is not studied. Material and Methods: To investigate the function of MAC30 in gastric carcinoma, we used RNA silencing technology to knock down the expression of MAC30 in gastric cancer cells BGC-823 and AGS. Real-time quantitative PCR and Western blot were used to analyze the mRNA level and the related protein expression. The localization of MAC30 and lamellipodia was observed by immunofluorescence. The biological phenotypes of gastric cells were examined by cell proliferation assay, cell cycle analysis, apoptosis assay, cell migration and invasion assay. Results: We found that down-regulation of MAC30 expression efficiently inhibited the proliferation of gastric cancer cells. Furthermore, the mobility of gastric cancer cells was also inhibited by down-regulation of MAC30. Moreover, we found that MAC30 knockdown inhibited AKT phosphorylation and reduced the expression of cyclinB1 and WAVE2. Conclusion: To our knowledge, this is the first report investigating the effect of MAC30 on growth, cell cycle, migration, and invasion in gastric carcinoma cells via suppressing AKT signaling pathway. MAC30 may be a potential therapeutic target for treatment of gastric carcinoma.

  14. 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.

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

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

    2006-09-01

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

  16. Helicobacter pylori infection induced alteration of gene expression in human gastric cells

    Chiou, C.; Chan, C.; Sheu, D; Chen, K; Li, Y; Chan, E

    2001-01-01

    BACKGROUND—Helicobacter pylori, a human pathogen responsible for many digestive disorders, induces complex changes in patterns of gene expression in infected tissues. cDNA expression arrays provide a useful tool for studying these complex phenomena.
AIM—To identify genes that showed altered expression after H pylori infection of human gastric cells compared with uninfected controls.
METHODS—The gastric adenocarcinoma cell line AGS was cocultivated with H pylori. Growth of infected cells was d...

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

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

    2016-09-01

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

  18. Central oxytocin is involved in restoring impaired gastric motility following chronic repeated stress in mice

    Babygirija, Reji; Zheng, Jun; Ludwig, Kirk; Takahashi, Toku

    2009-01-01

    Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. The development of gastric symptoms may depend on how humans adapt to the stressful events in their daily lives. Although acute stress delays gastric emptying and alters upper gastrointestinal motility in rodents, the effects of chronic stress on gastric motility and its adaptation mechanism remains unclear. Central oxytocin has been shown to have antistress effects. We studied whether central oxytocin is i...

  19. Probing human vision with spatial adaptation

    Mark W. Greenlee; Magnussen, S.

    2014-01-01

    Adaptation to spatial displays has robust effects on the perception of visual stimuli presented after adaptation. Referred to as the ‘psychophysicist’s microelectrode’ (Frisby, 1979), spatial adaptation and aftereffects has proved to be a powerful technique in the investigation of the functional organization of the human visual system. Our 20 years of collaboration on spatial adaptation research in the hospitable atmosphere of Lothar Spillmann’s laboratory at the University of Freiburg has re...

  20. 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.

  1. Expression of human chorionic gonadotropin beta in gastric carcinoma: A retrospective immunohistochemical study

    Murhekar Kanchan; Anuratha Jayaram; Majhi Urmila; Rajkumar Thangarajan

    2009-01-01

    Context: Beta Human Chorionic Gonadotropin (βHCG), a marker of the trophoblastic neoplasm, is also secreted by non-trophoblastic neoplasms including gastric carcinomas. Its role in disease progression remains unclear. Aim: To investigate the incidence of βHCG positivity in gastric carcinomas and correlate its presence with the biological behavior of the tumor. Setting and Design: A hospital-based, immunohistochemical study. Materials and Methods: One hundred and fifty formali...

  2. HSulf-1 suppresses cell growth and down-regulates Hedgehog signaling in human gastric cancer cells

    MA, HUI-YAN; Zhang, Fang; Li, Jie; Mo, Min-Li; Chen, Zhao; Liu, Lili; Zhou, Hai-Meng; Sheng, Qing

    2011-01-01

    Gastric cancer is the second most lethal cancer worldwide. Despite the current surgical and adjuvant therapies, 5-year survival remains less than 20–25% in the US, Europe and China. Therefore, there is an urgent need to identify new therapeutic targets for treating this malignant disease. Accumulating evidence has supported that aberrant activation of the Hedgehog signaling pathway plays a crucial role in tumorigenesis and progression of gastric cancer. Human sulfatase-1 (HSulf-1) is a recent...

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

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

    2001-01-01

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

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

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

    2016-01-01

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

  6. 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. PMID:1733359

  7. Effect of low-dose X-ray radiation on adaptive response in gastric cancer cell

    Shukai Wang; Gang Jiang; Hongsheng Yu; Xiangping Liu; Chang Xu

    2013-01-01

    Objective: We aimed to study the effect and mechanism of low-dose radiation (LDR) on adaptive response of gastric cancer cell. Methods: SGC7901 cells were cultured in vitro, and divided into 4 groups: control group (D0 group), low-dose radiation group (D1 group, 75 mGy), high-dose radiation group (D2 group, 2 Gy), low-dose plus high-dose radiation group (D1 + D2 group, 75 mGy + 2 Gy, the interval of low and high-dose radiation being 8 h). Cell inhibition rate was detected by cytometry and CCK8 method; the proportion of cell cycle at different times after irradiation was determined by using a flow cytometry. The ATM mRNA levels were detected by using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results: There was no significant different between groups D0 and D1, groups D2 and D1 + D2 cell inhibition rate (P > 0.05). There was a significant increase G2/M arrest in groups D2 and D1 + D2 than groups D0 and D1 after 6 h of radiation and did not recover at 48 h (P 0.05). Conclusion: LDR cannot induce adaptive response in SGC7901 cells in vitro, which may be associated the regulation of cell cycle, and its ATM mRNA expression cannot be affected by 75 mGy X-ray radiation.

  8. Adaptive gain control during human perceptual choice

    Cheadle, Samuel; WYART, Valentin; Tsetsos, Konstantinos; Myers, Nicholas; de Gardelle, Vincent; Herce Castañón, Santiago; Summerfield, Christopher

    2014-01-01

    Neural systems adapt to background levels of stimulation. Adaptive gain control has been extensively studied in sensory systems, but overlooked in decision-theoretic models. Here, we describe evidence for adaptive gain control during the serial integration of decision-relevant information. Human observers judged the average information provided by a rapid stream of visual events (samples). The impact that each sample wielded over choices depended on its consistency with the previous sample, w...

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

    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

  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. Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma

    Du-Hu Liu; Yu-Bo Chai; Ming Jin; Xue-Yong Zhang; Dai-Ming Fan; Yu-Xin Huang; Jin-Shan Zhang; Wei-Quan Huang; Yuan-Qiang Zhang; Qing-Sheng Huang; Wen-Yu Ma

    2001-01-01

    AIM To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesisof human gastric carcinoma more directly. METHODS The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF165 complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or downregulated. RESULTS VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR,localized in both the cytoplasm and membrane.Introduction of VEGF165 antisense into human gastric cancer cells ( SGC-7901, immunofluorescence intensity,31.6%)) resulted in a significant reduction in VEGFspecific messenger RNA and total and cell surface VEGF protein ( immunofluorescence intensity, 8.9%)(P<0.05). Conversely, stable integration of VEGF165 in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity,75.4%) (P<0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tomor volume: 345.40 ± 136.31 mm3) (P<0.05 vs control SGC7901 group: 1534.40 ± 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tomor volume: 2350.50 ± 637.70mm3) (P<0.05 vs control SGC-7901 group). CONCLUSION This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.

  12. 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.

  13. 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.

  14. Alcoholic beverages produced by alcoholic fermentation but not by distillation are powerful stimulants of gastric acid secretion in humans.

    Teyssen, S; Lenzing, T; González-Calero, G; Korn, A.; Riepl, R. L.; Singer, M V

    1997-01-01

    BACKGROUND: The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown. AIM AND METHODS: In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini, and sherry) on gastric acid output and release of gastrin was studied. Gastric acid output was determined ...

  15. 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.

  16. OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

    Jun Shi; Guo-Jing Zheng; Xiao-Mei Su; Ya-Lin Chen; Yan-Fang Liu; Ling Xu; Pin-Kang Wei; Shen Zhang; Zhi-Feng Qin; Jun Li; Da-Zhi Sun; Yan Xiao; Zhi-Hong Yu; Hui-Ming Lin

    2008-01-01

    AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique.METHODS: Using OB glue paste technique,orthtopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice.Biological features,growth of the implanted tumors,the success rate of transplantation and the rate of auto-metastasis of the two models were observed.RESULTS: The success rates of orthotopic transplantation of the two models were 94.20% and 96%.The rates of hepatic metastasis,pulmonary metastasis,peritoneal metastasis,lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%,48.43% and 57.97%,30.83% and 36.96%,67.30% and 84.06%,and 59.75% and 10.53%,respectively.The occurrence of ascites was 47.80% and 36.96%.CONCLUSION: OB glue paste technique is easy to follow.The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer,and,therefore,can be used as an ideal model for experimental research of proliferative metastasis of tumors.

  17. Labelling of human gastric inhibitory polypeptide with 125I using conjunction method

    Human gastric inhibitory polypeptide (GIP) was labelled with the conjunction method. The results showed that the conjunction method succeeds in protecting the immunoactivity of human GIP. The 125I-GIP was able to combine with its GIP antibody specifically. The binding rate was 50% at an antiserum dilution of 1.3 x 104

  18. 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

  19. 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.

  20. 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.

  1. Adenoviral delivery of the EMX2 gene suppresses growth in human gastric cancer.

    Jie Li

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

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

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

    2012-01-01

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

  3. DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling

    Yu, Yuanzi; Yan, Wenji; Liu, Xuefeng; Jia, Yan; Cao, Baoping; YU, YINGYAN; Lv, Youyong; Brock, Malcolm V; Herman, Jame G; Licchesi, Julien; Yang, Yunsheng; Guo, Mingzhou

    2014-01-01

    Dapper, Dishevelled-associated antagonist of β-catenin (DACT), is a key regulator of Wnt signaling pathway. The purpose of this study is to explore the epigenetic changes and the function ofDACT2 in human gastric cancer (GC). Eight human gastric cancer cell lines, 167 cases of primary gastric cancer and 8 cases of normal gastric mucosa were involved in this study. In addition, methylation Specific PCR (MSP), semi-quantitative RT-PCR, colony formation assay, flow cytometry assay, siRNA, immuno...

  4. Intestinal adaptations in chronic kidney disease and the influence of gastric bypass surgery.

    Hatch, Marguerite

    2014-09-01

    Studies have shown that compensatory adaptations in gastrointestinal oxalate transport can impact the amount of oxalate excreted by the kidney. Hyperoxaluria is a major risk factor in the formation of kidney stones, and oxalate is derived from both the diet and the liver metabolism of glyoxylate. Although the intestine generally absorbs oxalate from dietary sources and can contribute as much as 50% of urinary oxalate, enteric oxalate elimination plays a significant role when renal function is compromised. While the mechanistic basis for these changes in the direction of intestinal oxalate movements in chronic renal failure involves an upregulation of angiotensin II receptors in the large intestine, enteric secretion/excretion of oxalate can also occur by mechanisms that are independent of angiotensin II. Most notably, the commensal bacterium Oxalobacter sp. interacts with the host enterocyte and promotes the movement of oxalate from the blood into the lumen, resulting in the beneficial effect of significantly lowering urinary oxalate excretion. Changes in the passive permeability of the intestine, such as in steatorrhoea and following gastric bypass, also promote oxalate absorption and hyperoxaluria. In summary, this report highlights the two-way physiological signalling between the gut and the kidney, which may help to alleviate the consequences of certain kidney diseases. PMID:24951497

  5. 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.

  6. 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

  7. 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

    characterization of the aspirates was conducted on a TA AR-G2 rheometer, using cone and plate geometry. Lipase activity was measured by continuous titration of released free fatty acid from tributyrate. Further, pH, osmolality, buffer capacity, and surface tension were measured and the total protein content.......8 and 5.4, respectively. pH, surface tension, buffer capacity, bile salt concentration, and osmolality were measured and compared with literature data. CONCLUSION: The rheological behavior and the mean apparent viscosity of HGA are significantly different from that of water and should therefore......SSGF and HCl pH 1.2 have no shear-thinning properties and showed lower viscosity (1.1 mPas at 50 s(-1)). The observed viscosity of the HGA will decrease the intrinsic dissolution rate of drugs. The activity of the gastric lipase was 7.4 ± 4.0 U/mL (N = 6, n = 3) and 99.0 ± 45.3 U/mL (N = 19, n = 3) at pH 2...

  8. Comments on: The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study

    Ekaterina A Pigarova

    2012-06-01

    Full Text Available Comments on: Stevens JE, Horowitz M, Deacon CF, Nauck M, Rayner CK, Jones KL. The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study. Aliment Pharmacol Ther. 2012 Jun 28. doi: 10.1111/j.1365-2036.2012.05198.x

  9. 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.

  10. Nuclear factor-κB1 expression levels in human gastric adenocarcinoma

    Razieh Ebrahimi-Askari

    2012-01-01

    Full Text Available NF-κB pathway is a link between inflammation and cancer and is involved in cellular responses to different stimuli. Gastrointestinal lumen is exposed to many inflammatory agents such as foods, free radicals and bacterial or viral antigens. The aim of the present study was to evaluate the possible role of NF-κB1in gastric adenocarcinoma. To detect the relative level of NF-κB1transcript, total RNA was extracted from tissue specimens, a cDNA library was generated, and quantitative RT-PCR was performed for thirty human gastric adenocarcinoma tissue samples and thirty matched normal gastric tissue samples. NF-κB1 expression showed two-sidedness, which means that a group of 11 sample pairs showed up-regulation and a group of 16 sample pairs showed down-regulation. No histopathologic characteristics of samples could justify the observed two-sidedness. The NF-κB1 two-sidedness expression indicates the involvement of NF-κB1 and in a larger scale, NF-κB signaling pathway in gastric carcinogenesis. Our results show the complexity of regulatory mechanisms involved in developing and controlling the process of gastric cancer pathogenesis.

  11. [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. PMID:14974895

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

    Madsen, Jan Lysgård; Søndergaard, S B; Fuglsang, Stefan; Rumessen, J J; Graff, J

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans....... 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...... gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION...

  13. Adaptive gain control during human perceptual choice

    Cheadle, Samuel; Wyart, Valentin; Tsetsos, Konstantinos; Myers, Nicholas; de Gardelle, Vincent; Castañón, Santiago Herce; Summerfield, Christopher

    2015-01-01

    Neural systems adapt to background levels of stimulation. Adaptive gain control has been extensively studied in sensory systems, but overlooked in decision-theoretic models. Here, we describe evidence for adaptive gain control during the serial integration of decision-relevant information. Human observers judged the average information provided by a rapid stream of visual events (samples). The impact that each sample wielded over choices depended on its consistency with the previous sample, with more consistent or expected samples wielding the greatest influence over choice. This bias was also visible in the encoding of decision information in pupillometric signals, and in cortical responses measured with functional neuroimaging. These data can be accounted for with a new serial sampling model in which the gain of information processing adapts rapidly to reflect the average of the available evidence. PMID:24656259

  14. Adenovirus-mediated p53 gene transfer increases radiosensitivity of human gastric carcinoma cells

    Objective: To evaluate the effect of adenovirus-mediated p53 gene (Adp53) on apoptosis and radiosensitivity of human gastric carcinoma cell lines. Methods: Recombinant adenovirus carrying 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 and Western blot assay. Cell survival was assessed using a clonogenic assay. TUNEL assay was used in determination of apoptosis. The four human gastric carcinoma cell line infected with Adp53 were irradiated with 4 Gy, and cell cycle distribution and apoptotic rate were assayed by flow cytometry. Nude mice xenograft models of W and M cell were intratumorally injected with Adp53 and 48 h later were irradiated with 6 Gy. Relative volume in growth curve of tumor was used to observe tumor regression. Results: G2/M arrest, apoptosis and inhibition of tumor cell proliferation were induced by infection with Adp53 at 100 MOI, which caused high transfer rate of wild-type p53 and strong expression of P53 protein in the four human gastric carcinoma cell line cells. When evaluating radio-biologic efficacy by apoptotic rate, the apoptotic enhancement ratio of Adp53 at 4 Gy was 3.0 for W cell, 3.6 for M cell, 2.2 for neo cell and 2.5 for 823 cell respectively, in vitro. The antitumor enhancement ratio of Adp53 at 6 Gy was 1.41 for cell-implanted tumor and 1.91 for M cell-implanted tumor in vivo. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and radiosensitivity of human gastric carcinoma

  15. Recent acceleration of human adaptive evolution

    Hawks, John; Wang, Eric T; Cochran, Gregory M.; Harpending, Henry C.; Moyzis, Robert K.

    2007-01-01

    Genomic surveys in humans identify a large amount of recent positive selection. Using the 3.9-million HapMap SNP dataset, we found that selection has accelerated greatly during the last 40,000 years. We tested the null hypothesis that the observed age distribution of recent positively selected linkage blocks is consistent with a constant rate of adaptive substitution during human evolution. We show that a constant rate high enough to explain the number of recently selected variants would pred...

  16. Computational adaptive optics of the human retina

    South, Fredrick A.; Liu, Yuan-Zhi; Carney, P. Scott; Boppart, Stephen A.

    2016-03-01

    It is well known that patient-specific ocular aberrations limit imaging resolution in the human retina. Previously, hardware adaptive optics (HAO) has been employed to measure and correct these aberrations to acquire high-resolution images of various retinal structures. While the resulting aberration-corrected images are of great clinical importance, clinical use of HAO has not been widespread due to the cost and complexity of these systems. We present a technique termed computational adaptive optics (CAO) for aberration correction in the living human retina without the use of hardware adaptive optics components. In CAO, complex interferometric data acquired using optical coherence tomography (OCT) is manipulated in post-processing to adjust the phase of the optical wavefront. In this way, the aberrated wavefront can be corrected. We summarize recent results in this technology for retinal imaging, including aberration-corrected imaging in multiple retinal layers and practical considerations such as phase stability and image optimization.

  17. β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis

    β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved. β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene. Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer

  18. 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

  19. 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.

  20. 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.

  1. Human gastric emptying and colonic filling of solids characterized by a new method

    Our first aim was to compare 111In-labeled Amberlite IR-12OP resin pellets and 131I-labeled fiber in the assessment of gastric and small bowel transit and colonic filling in healthy humans. Both radiolabels were highly stable for 3 h in an in vitro stomach model and remained predominantly bound to solid phase of stools collected over 5 days [90.5 +/- 2.1 (SE)% for 131I and 87.4 +/- 1.4% for 111In]. The lag phase of gastric emptying was shorter for 111In-pellets (30 +/- 11 min compared with 58 +/- 12 min for 131I-fiber, P less than 0.05). However, the slope of the postlag phase of gastric emptying and the half time of small bowel transit were not significantly different for 111In-pellets and 131I-fiber. Filling of the colon was characterized by bolus movements of the radiolabel (10-80% range, 26% mean) followed by plateaus (periods of no movement of isotope into colon lasting 15-120 min, range; 51 min, mean). Half of the bolus movements occurred within 1 h of the intake of a second meal. Thus 111In-labeled Amberlite pellets provide an excellent marker for the study of gastric and small bowel transit and colonic filling in humans. The ileum acts as a reservoir and transfers boluses of variable sizes into the colon, often soon after the intake of a subsequent meal

  2. 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.

  3. 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.

  4. Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

    2013-01-01

    AIM: To investigate human epidermal growth factor receptor 2 (HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.

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

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

    2002-01-01

    AIM: To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-α-tocopheryl succinate (VES), a derivative of natural Vitamin E, via inducing apoptosis and DNA synthesis arrest.

  6. Epstein-Barr virus-specific methylation of human genes in gastric cancer cells

    Coleman William B

    2010-12-01

    Full Text Available Abstract Background Epstein-Barr Virus (EBV is found in 10% of all gastric adenocarcinomas but its role in tumor development and maintenance remains unclear. The objective of this study was to examine EBV-mediated dysregulation of cellular factors implicated in gastric carcinogenesis. Methods Gene expression patterns were examined in EBV-negative and EBV-positive AGS gastric epithelial cells using a low density microarray, reverse transcription PCR, histochemical stains, and methylation-specific DNA sequencing. Expression of PTGS2 (COX2 was measured in AGS cells and in primary gastric adenocarcinoma tissues. Results In array studies, nearly half of the 96 human genes tested, representing 15 different cancer-related signal transduction pathways, were dysregulated after EBV infection. Reverse transcription PCR confirmed significant impact on factors having diverse functions such as cell cycle regulation (IGFBP3, CDKN2A, CCND1, HSP70, ID2, ID4, DNA repair (BRCA1, TFF1, cell adhesion (ICAM1, inflammation (COX2, and angiogenesis (HIF1A. Demethylation using 5-aza-2'-deoxycytidine reversed the EBV-mediated dysregulation for all 11 genes listed here. For some promoter sequences, CpG island methylation and demethylation occurred in an EBV-specific pattern as shown by bisulfite DNA sequencing. Immunohistochemistry was less sensitive than was western blot for detecting downregulation of COX2 upon EBV infection. Virus-related dysregulation of COX2 levels in vitro was not recapitulated in vivo among naturally infected gastric cancer tissues. Conclusions EBV alters human gene expression in ways that could contribute to the unique pathobiology of virus-associated cancer. Furthermore, the frequency and reversability of methylation-related transcriptional alterations suggest that demethylating agents have therapeutic potential for managing EBV-related carcinoma.

  7. Inhibitory Effect of Saponins and Polysaccharides from Radix Ranunculi Ternati on Human Gastric Cancer BGC823 Cells

    Niu, Lidan; Zhou, Yingfeng; Sun, Bing; Hu, Junling; Kong, Lingyu; Duan, Sufang

    2013-01-01

    The effects of different Radix ranunculi ternati extracts on human gastric cancer BGC823 cells were investigated, different methods were used to extract the saponins and polysaccharides from Radix ranunculi ternati, and MTT assay and colony formation assay were used to observe the effects of saponins and polysaccharides from Radix ranunculi ternati on in-vitro cultured human gastric cancer BGC823 cells. The results found that the saponins and polysaccharides from Radix Ranunculi Ternati had c...

  8. 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.

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

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

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

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

    2016-01-01

    Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detect...

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

    Cousin, Fabien,; Jouan-Lanhouet, Sandrine; Dimanche-Boitrel, Marie-Thérèse; Corcos, Laurent; Jan, Gwénaël

    2012-01-01

    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. [br/] Methodology/Principal Findings: A fermented milk, exclusiv...

  12. 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.

  13. Human Adaptive Mechatronics and Human-System Modelling

    Satoshi Suzuki; Hiroshi Igarashi; Harumi Kobayashi; Tetsuya Yasuda; Fumio Harashima

    2013-01-01

    Several topics in projects for mechatronics studies, which are ʹHuman Adaptive Mechatronics (HAM)ʹ and ʹHuman‐System Modelling (HSM)ʹ, 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...

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

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

    2016-01-01

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

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

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

    2016-01-01

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

  16. Evaluation of endoscopic laser Doppler flowmetry for measurement of human gastric blood flow

    Endoscopic measurement of gastric blood perfusion by laser Doppler flowmetry (LDF) has been evaluated in 28 patients and 15 healthy vounteers. During the recordings it was necessary to keep the probe in light contact with the mucosa to obtain stable curves and to avoid artificial Doppler signals caused by relative movements between the gastric wall and the probe. Gastric distention by air insufflation did not influence the recorded flow level significantly when air insufflation was moderate. The intravenous injection of 0.6 mg atropine did not cause any significant alteration in recorded blood flow, and this drug may be used as premedication before endoscopic blood flow measurements. Recordings with both 4 kHz and 12 kHz bandwidth of the LDF instruments showed a relative constant relationship for different flow levels, the flow values measured with 12 kHz being about twice the corresponding values measured with 4 kHz. With 12 kHz bandwith more of the disturbance signal is recorded, which makes analysis of endoscopic recorded flow curves difficult and inaccurate. It is therefore recommended to use 4 kHz bandwidth during endoscopic measurements in conscious humans. Blood flow measurements from both sides of the gastric wall were consistently of the same order of magnitude (r=0.91), and the endoscopically recorded output signal increased in three of five patients when a reflecting mirror was placed at the serosal side. The results indicate that endoscopic LDF usually represents blood perfusion in all layers of the gastric wall

  17. Adaptive human behavior in epidemiological models.

    Fenichel, Eli P; Castillo-Chavez, Carlos; Ceddia, M G; Chowell, Gerardo; Parra, Paula A Gonzalez; Hickling, Graham J; Holloway, Garth; Horan, Richard; Morin, Benjamin; Perrings, Charles; Springborn, Michael; Velazquez, Leticia; Villalobos, Cristina

    2011-04-12

    The science and management of infectious disease are entering a new stage. Increasingly public policy to manage epidemics focuses on motivating people, through social distancing policies, to alter their behavior to reduce contacts and reduce public disease risk. Person-to-person contacts drive human disease dynamics. People value such contacts and are willing to accept some disease risk to gain contact-related benefits. The cost-benefit trade-offs that shape contact behavior, and hence the course of epidemics, are often only implicitly incorporated in epidemiological models. This approach creates difficulty in parsing out the effects of adaptive behavior. We use an epidemiological-economic model of disease dynamics to explicitly model the trade-offs that drive person-to-person contact decisions. Results indicate that including adaptive human behavior significantly changes the predicted course of epidemics and that this inclusion has implications for parameter estimation and interpretation and for the development of social distancing policies. Acknowledging adaptive behavior requires a shift in thinking about epidemiological processes and parameters. PMID:21444809

  18. Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer

    Ding J

    2014-09-01

    Full Text Available Jian Ding,1,* Dan Li,2,* Minzhen Gong,1 Jinpo Wang,1 Xunru Huang,1 Ting Wu,1 Chengdang Wang11Digestive Department of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Digestive Department of Union Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workBackground: Highly sensitive markers are urgently needed for the diagnosis and grading of gastric cancer and for managing drug resistance. The recent identification of long-non-coding RNAs (lncRNAs has provided new approaches for resolving this challenge. The aim of this study was to screen and identify new biomarkers for human gastric cancer from lncRNAs.Methods: First, we used lncRNA microarrays to conduct a preliminary screening for candidate lncRNAs of gastric cancer biomarkers in both human gastric cancer tissues and in two gastric cancer cell lines, SGC7901 cells and paclitaxel-resistant SGC7901 cells. The lncRNA plasmacytoma variant translocation 1 (PVT1 was found to exhibit higher expression in both gastric cancer tissues and the SGC7901 paclitaxel-resistant cell line. Quantitative polymerase chain reaction was used for large-scale analysis in a large number of human gastric cancer tissues to verify the involvement of PVT1 in development of gastric cancer. The relationships between PVT1 expression and clinical features were also analyzed.Results: PVT1 showed higher expression in human gastric cancer tissues than in adjacent non-cancerous tissues and in SGC7901 paclitaxel-resistant cells compared with SGC7901 cells. PVT1 expression was correlated with lymph node invasion of gastric cancer.Conclusion: PVT1 is a new biomarker for human gastric cancer and may indicate lymph node invasion. Therefore, PVT1 shows potential as a novel therapeutic target for the treatment of gastric cancer and enhancement of paclitaxel sensitivity.Keywords: microarray analysis

  19. In vitro effects of recombinant human growth hormone on growth of human gastric cancer cell line BGC823 cells

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

    2004-01-01

    AIM: To study the effects of recombinant human growth hormone (rhGH) on growth of human gastric cancer cell line in vitro.METHODS: Experiment was divided into control group,rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cell inhibitory rate, cell cycle, cell proliferation index (PI) and DNA inhibitory rate of human gastric cancer line BGC823, at different concentrations of rhGH treatment were studied by cell culture, MTT assay and flow cytometry.RESULTS: The distinctly accelerated effects of rhGH on multiplication of BGC823 cell line were not found in vitro.There was no statistical significance between rhGH group and control group, or between rhGH+L-OHP group and LOHP group (P>0.05). The cell growth curve did not rise.Cell inhibitory rate and cells arrested in G0-G1 phase were obviously increased. Meanwhile, cells in S phase and PI were distinctly decreased and DNA inhibitory rate was obviously increased in rhGH+L-OHP group in comparison with control group and rhGH group, respectively (P<0.01).Cell inhibitory rate showed an increasing trend and PI showed a decreasing trend in rhGH+L-OHP group compared with L-OHP group.CONCLUSION: In vitro rhGH does not accelerate the multiplication of human gastric cancer cells. It may increase the therapeutic efficacy when it is used in combination with anticancer drugs.

  20. 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

  1. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia

    Meier, J J; Gallwitz, B; Siepmann, N; Holst, Jens Juul; Deacon, C F; Schmidt, W E; Nauck, M A

    2003-01-01

    AIMS/HYPOTHESIS: In the isolated perfused pancreas, gastric inhibitory polypeptide (GIP) has been shown to enhance glucagon secretion at basal glucose concentrations, but in healthy humans no glucagonotropic effect of GIP has yet been reported. Therefore, we studied the effect of GIP on glucagon...... (specific radioimmunoassays). In addition, 31 healthy subjects (16 men, 15 women; 42+/-11 years; BMI 24.4+/-2.7 kg/m(2)) were studied with 20 pmol GIP/kg. Statistics were done with RM-ANOVA and Duncan's post hoc tests. RESULTS: Gastric inhibitory polypeptide dose-dependently stimulated glucagon secretion......, glucagon concentrations increased over the baseline from 7.5+/-0.5 to 9.3+/-0.7 pmol/l ( p=0.0082). CONCLUSIONS/INTERPRETATION: Glucagon secretion is dose-dependently stimulated by GIP at basal glucose concentrations. The absence of a glucagonotropic GIP effect in previous studies could be due to the...

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

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

    2016-07-01

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

  3. 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.

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

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

    2011-12-01

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

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

    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

  6. Helicobacter pylori-Induced Disruption of Monolayer Permeability and Proinflammatory Cytokine Secretion in Polarized Human Gastric Epithelial Cells

    Fiorentino, Maria; Ding, Hua; Blanchard, Thomas G.; Czinn, Steven J.; Sztein, Marcelo B.; Fasano, Alessio

    2013-01-01

    Helicobacter pylori infection of the stomach is related to the development of diverse gastric pathologies. The ability of H. pylori to compromise epithelial junctional complexes and to induce proinflammatory cytokines is believed to contribute to pathogenesis. The purpose of this study was to use an in vitro human gastric epithelial model to investigate the ability of H. pylori to affect permeability and the extent and polarity of the host inflammatory response. NCI-N87 monolayers were cocult...

  7. 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.

  8. Effects of proximal gastric vagotomy and antrectomy on parietal cell function in humans

    Both proximal gastric vagotomy and antrectomy reduce maximal gastric acid secretion in vivo by about 60%. The combination of vagotomy and antrectomy reduces the maximal acid secretion by about 80%. This additive effect indicates that these surgical procedures differ in their mode of action. The function of isolated human oxyntic glands was studied before and after vagotomy and antrectomy, respectively, using radioactively labeled aminopyrine as a marker of parietal cell response. The basal accumulation increased after vagotomy, suggesting a vagally controlled inhibitory component. The carbachol response disappeared and the maximal response induced by histamine or dibutyryl-cyclic adenosine monophosphate was reduced by 60% (p less than 0.01) after vagotomy. This reduction could not be overcome by increasing the dose of dibutyryl-cyclic adenosine monophosphate. This indicates an intracellular effect of vagotomy peripheral to dibutyryl-cyclic adenosine monophosphate point of action. Antrectomy did not induce any statistically significant change at the glandular level, indicating that the reduced gastric acid secretion in vivo may be caused by a reduction in the number of oxyntic glands due to a removal of a trophic effect of antral gastrin

  9. 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...... to GLP-1. The aim of the present study was to assess the effect of IV administered GLP-2 on gastric emptying and feelings of hunger in human volunteers. In eight (five men) healthy subjects (age 31.1+/-2.9 years and BMI 24.1+/-1.0 kg m(-2)), scintigraphic solid gastric emptying, hunger ratings (VAS...... of GLP-2 on either the lag phase (29.5+/-4.4, 26.0+/-5.2 and 21.2+/-3.6 min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1), respectively) or the half emptying time (84.5+/-6.1, 89.5+/-17.8 and 85.0+/-7.0 min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1), respectively). The change in hunger...

  10. 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.

  11. Disorders of gastric emptying in humans and the use of radionuclide techniques

    Associated with the development of methods to quantify gastric emptying, there has been an increased understanding of the physiology of gastric emptying in normal subjects and the pathophysiology and pharmacological treatment of gastric emptying disorders. The measurement of gastric emptying, using radionuclide-labeled food markers and a scintillation camera, has widespread clinical and research applications

  12. Expression of human chorionic gonadotropin beta in gastric carcinoma: A retrospective immunohistochemical study

    Murhekar Kanchan

    2009-01-01

    Full Text Available Context: Beta Human Chorionic Gonadotropin (βHCG, a marker of the trophoblastic neoplasm, is also secreted by non-trophoblastic neoplasms including gastric carcinomas. Its role in disease progression remains unclear. Aim: To investigate the incidence of βHCG positivity in gastric carcinomas and correlate its presence with the biological behavior of the tumor. Setting and Design: A hospital-based, immunohistochemical study. Materials and Methods: One hundred and fifty formalin-fixed, paraffin-embedded tissue specimens from histopathologically confirmed cases of gastric carcinoma were immunostained using an indigenously developed antibody against βHCG. Tumors with diffuse reactivity to βHCG were considered as positive. Those with occasional, focal or no reactivity to βHCG were considered as negative. Statistical Analysis: Differences in βHCG staining were compared according to the histological grade and surgical stage using the χ2 test. Using the Cox proportional hazards model, the time till the onset of development of an adverse outcome after surgery (defined as death, local or distant metastasis was compared between the bHCG positive and negative tumors. Results: Twenty-eight (18.7% of the 150 specimens were βHCG positive. No association was found between the histological grade (P=0.49 and the surgical stage (P=0.19 with βHCG positivity. The median disease-free survival after surgery was not different among bHCG positive and negative tumors. Risk of an adverse outcome after surgery was significantly associated with the stage of the tumor (Hazard ratio=2.9, 95% confidence interval: 1.1-7.4. No association was observed with grade or βHCG positivity. Conclusion: βHCG immunoreactivity was observed in about one-fifth of the gastric cancers. bHCG reactivity, however, played no role in the biological behavior.

  13. Moleucle action mechunisms of NM-3 on human gastric cancer SGC-7901 Cells in vivo or in vitro

    Jin-Shui Zhu; Bo Shen; Jin-Lian Chen; Guo-Qiang Chen; Xiao-Hu Yu; Hua-Fang Yu; Zu-Ming Zhu

    2003-01-01

    AIM: To study the moleucle action mechunisms of NM-3 on the growth of human gastric cancer SGC-7901 cells in vivo or in vitro.METHODS: SGC-7901 from human non-differentiated gastric cancer cell line was cultured with NM-3 at 100 mg/ml for 24 h. We observed its inhibitory rate and the density of micro-vascular growth in grafted mice with human gastric cancer SGC-7901. The apoptosis of human gastric cancer SGC-7901 was revealed in NM-3 treatment group by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-fluorescene nick end labeling (TUNEL)method and flow cytometry analysis.RESULTS: The growth of SGC-7901 cells was markedly inhibited compared with control growp, which was smaller than that in normal saline control group (4.17 g±0.22 g VS 9.45 g±1.38 g, P<0.01). The level of apoptosis of human gastric cell line SGC-7901 was obviously increased in NM-3treatment group at 1 mg.L-1 for 24 h. NM-3 inducing apoptotic index in NM-3 plus carboplatin group was 3.5 times that of carboplatin control group (TUNEL: 27.98±6.12 % VS 12.94±2.12 %, FACScan: 26.86±5.69 % VS11.86±1.09 %,P<0.01). Western blot analysis showed that the apoptotic index of human gastric cancer was elevated for 12, 24 and 36 h with an evident time-effect relationship in groups at 100 mg.L-L. NM-3 enhanced the inhibitive effects and sensitivity of chemotherapy for human gastric cancer in nude mice. These results suggested that NM-3 played a key inhibitive role in the growth of grafted human gastric cancer in nude mice.CONCLUSION: NM-3 can inhibit the growth of human gastric cancer cell line SGC-7901, and enhance the sensitivity of carboplatin on SGC-7901 and induced its apoptosis.

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

    Sara eQuercia; Marco eCandela; Cristina eGiuliani; Silvia eTurroni; Donata eLuiselli; Simone eRampelli; Patrizia eBrigidi; Claudio eFranceschi; Maria Giulia eBacalini; Paolo eGaragnani; Chiara ePirazzini

    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. 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 i...

  16. 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.

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

    A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t1/2 for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis

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

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

    2016-05-01

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

  19. Genome sequence of Helicobacter suis supports its role in gastric pathology

    Vermoote Miet; Vandekerckhove Tom; Flahou Bram; Pasmans Frank; Smet Annemieke; De Groote Dominic; Van Criekinge Wim; Ducatelle Richard; Haesebrouck Freddy

    2011-01-01

    Abstract Helicobacter (H.) suis has been associated with chronic gastritis and ulcers of the pars oesophagea in pigs, and with gastritis, peptic ulcer disease and gastric mucosa-associated lymphoid tissue lymphoma in humans. In order to obtain better insight into the genes involved in pathogenicity and in the specific adaptation to the gastric environment of H. suis, a genome analysis was performed of two H. suis strains isolated from the gastric mucosa of swine. Homologs of the vast majority...

  20. 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. PMID:25729886

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

    Ziebarth, D; Schramm, T; Töppel, A

    1989-01-01

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

  2. Proliferative and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line

    LI Shu-guang; WANG Yuan-yu; YE Zai-yuan; SHAO Qing-shu; TAO Hou-quan; SHU Li-sha; ZHAO Yi-feng

    2013-01-01

    Background Andrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers.The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.Methods Cell proliferation and IC50 were evaluated using MTT assay,cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay,and morphologic structure with transmission electron microscopy.Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2,Bax,and caspase-3 expressions.Results Andrographolide showed a time-and concentration-dependent inhibitory effects on BGC-823 cell growth.Compared to controls,the number of cells in the G0-G1-phase increased significantly,S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide,and both early and late apoptotic rates increased significantly compared to the controls,all in a concentration-dependent manner.Bax and caspase-3 expressions were markedly increased,and Bcl-2 expression was decreased.Conclusions Andrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression.Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.

  3. 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.

  4. 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.

  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

    2012-09-01

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

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

    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 fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. 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. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

  7. Side population cells isolated from KATO Ⅲ human gastric cancer cell line have cancer stem cell-like characteristics

    Jun-Jun She; Peng-Ge Zhang; Xuan Wang; Xiang-Ming Che; Zi-Ming Wang

    2012-01-01

    AIM:To investigate whether the side population (SP)cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer.METHODS:We analyzed the presence of SP cells in different human gastric carcinoma cell lines,and then isolated and identified the SP cells from the KATO Ⅲ human gastric cancer cell line by flow cytometry.The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays.The related genes were determined by reverse transcription polymerase chain reaction.To compare tumorigenic ability,SP and non-side population (NSP) cells from the KATO Ⅲ human gastric cancer cell line were subcutaneously injected into nude mice.RESULTS:SP cells from the total population accounted for 0.57% in KATO Ⅲ,1.04% in Hs-746T,and 0.02% in AGS (CRL-1739).SP cells could grow clonally and have self-renewal capability in conditioned media.The expression of ABCG2,MDRI,Bmi-1 and Oct-4 was different between SP and NSP cells.However,there was no apparent difference between SP and NSP cells when they were injected into nude mice.CONCLUSION:SP cells have some cancer stem celllike characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.

  8. 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.

  9. 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.

  10. 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.

  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. 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

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

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

    2013-11-01

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

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

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

    2016-01-01

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

  15. Characterization of human gastric carcinoma-related methylation of 9 miR CpG islands and repression of their expressions in vitro and in vivo

    Many miR genes are located within or around CpG islands. It is unclear whether methylation of these CpG islands represses miR transcription regularly. The aims of this study are to characterize gastric carcinoma (GC)-related methylation of miR CpG islands and its relationship with miRNA expression. Methylation status of 9 representative miR CpG islands in a panel of cell lines and human gastric samples (including 13 normal biopsies, 38 gastritis biopsies, 112 pairs of GCs and their surgical margin samples) was analyzed by bisulfite-DHPLC and sequencing. Mature miRNA levels were determined with quantitative RT-PCR. Relationships between miR methylation, transcription, GC development, and clinicopathological characteristics were statistically analyzed. Methylation frequency of 5 miR CpG islands (miR-9-1, miR-9-3, miR-137, miR-34b, and miR-210) gradually increased while the proportion of methylated miR-200b gradually decreased during gastric carcinogenesis (Ps < 0.01). More miR-9-1 methylation was detected in 62%-64% of the GC samples and 4% of the normal or gastritis samples (18/28 versus 2/48; Odds ratio, 41.4; P < 0.01). miR-210 methylation showed high correlation with H. pylori infection. miR-375, miR-203, and miR-193b methylation might be host adaptation to the development of GCs. Methylation of these miR CpG islands was consistently shown to significantly decrease the corresponding miRNA levels presented in human cell lines. The inverse relationship was also observed for miR-9-1, miR-9-3, miR-137, and miR-200b in gastric samples. Among 112 GC patients, miR-9-1 methylation was an independent favourable predictor of overall survival of GC patients in both univariate and multivariate analysis (P < 0.02). In conclusion, alteration of methylation status of 6 of 9 tested miR CpG islands was characterized in gastric carcinogenesis. miR-210 methylation correlated with H. pylori infection. miR-9-1 methylation may be a GC-specific event. Methylation of miR CpG islands may

  16. 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.

  17. 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.

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

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

    2010-11-01

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

  19. 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.

  20. 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.

  1. Effects of the H(2)-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    Madsen, Jan Lysgård; Graff, J

    2008-01-01

    Objective. Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist...

  2. Effects of the H2-receptor antagonist ranitidine on gastric motor function after a liquid meal in healthy humans

    Madsen, J.L.; Graff, J.

    2008-01-01

    OBJECTIVE: Studies on animals have shown that histamine may be involved in the regulation of gastrointestinal smooth muscle tone. However, the role of histamine in the regulation of human gastric motor function is not clear. This study examined the effect of ranitidine, an H(2)-receptor antagonist...

  3. 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

  4. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

    Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection

  5. Intestinal Adaptations in Chronic Kidney Disease and the Influence of Gastric Bypass Surgery

    Hatch, Marguerite

    2014-01-01

    Studies have shown that compensatory adaptations in gastrointestinal oxalate transport can impact the amount of oxalate excreted by the kidney. Hyperoxaluria is a major risk factor in the formation of kidney stones and oxalate is derived from both the diet as well as from liver metabolism of glyoxylate. Although the intestine generally absorbs oxalate from dietary sources, and can contribute as much as 50% of urinary oxalate, enteric oxalate elimination plays a significant role when renal fun...

  6. 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.

  7. Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor

    Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone that stimulates insulin secretion in the presence of glucose. Complementary DNA clones encoding human GIP were isolated from a library prepared with RNA from duodenum. The predicted amino acid sequence indicates that GIP is derived by proteolytic processing of a 153-residue precursor, preproGIP. The GIP moiety is flanked by polypeptide segments of 51 and 60 amino acids at its NH2 and COOH termini, respectively. The former includes a signal peptide of about 21 residues and an NH2-terminal propeptide of 30 amino acids. GIP is released from the precursor by processing at single arginine residues. There is a region of nine amino acids in the COOH-terminal propeptide of the GIP precursor that has partial homology with a portion of chromogranin A as well as pancreastatin

  8. 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.

  9. 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.

  10. An in vitro adherence assay reveals that Helicobacter pylori exhibits cell lineage-specific tropism in the human gastric epithelium.

    Falk, P; Roth, K A; Borén, T; Westblom, T U; Gordon, J I; Normark, S

    1993-01-01

    Helicobacter pylori is a microaerophilic bacterium found in the stomach of asymptomatic humans as well as patients with acid peptic disease and gastric adenocarcinoma. We have developed an in situ adherence assay to examine the cell lineage-specific nature of binding of this organism and to characterize the nature of cell surface receptors that recognize its adhesin. Fluorescein isothiocyanate-labeled H. pylori strains were bound to surface mucous cells present in the pit region of human and ...

  11. Comparison of the low-density-lipoprotein receptor activity in human epithelioid gastric carcinoma cell lines and in human normal epithelioid cells

    In this experiment, the authors compared the LDLR activity in two human epithelioid gastric carcinoma cell lines (SGC-7901, NKM-45) and two human normal epithelioid cells (amniotic cell line, gastric mucosal cells derived from tissue culture) with the methods of saturation analysis. It was found that the uptake and degradation of 125I-LDL in carcinoma cell line (SGC-7901 and NKM-45) was obviously higher than that in normal cells. The maximum binding of LDL for the four different cell types were 412.02 (SGC-7901), 384.43 (NKM-45), 291.07 (gastric mucosal cell), and 291.42 μg/g cell protein (amniotic cell) respectively, which indicated that the LDLR level was increased in carcinoma cells. The results also showed that the equilibrium dissociation constant (Kd) value in carcinoma cells were similar to that in normal cells, demonstrating the LDLR affinity and specificity was similar in both carcinoma and normal cells

  12. 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.

  13. Aqueous extract from taxus baccata inhibits adenosine deaminase activity significantly in cancerous and noncancerous human gastric and colon tissues

    Zahide Esra Durak

    2014-01-01

    Full Text Available Objective: To investigate possible effects of aqueous taxus baccata extract on adenosine deaminase (ADA activity in cancerous and noncancerous human tissues and to clarify mechanism(s of its anticancer potential. Materials and Methods: Cancerous and noncancerous human gastric and colon tissues were used in the study. The extracts were prepared in distilled water. Before and after treatment with the extracts, ADA activities in the tissue homogenates were measured. Results: ADA activity was found to be higher in gastric tissue compared with colon tissue, but no differences were found between ADA activities of cancerous and noncancerous tissues for both as well. In the plant extract studies, it was found that taxus extract significantly inhibited ADA activity both in cancerous and noncancerous gastric and colon tissues. Conclusion: Our results suggest that aqueous extract from taxus baccata inhibits ADA activities in both gastric and colon tissues significantly. It is suggested that in addition to other proposed mechanisms, accumulated adenosine due to the inhibition of ADA enzyme might also play part in the anticancer properties of taxus species.

  14. 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 repres...... in genetic adaptation to high altitude....

  15. 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.

  16. 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.

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

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

    2016-08-01

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

  18. Nuclear factor kappa B: A marker of chemotherapy for human stage IV gastric carcinoma

    Sheng Ye; You-Ming Long; Jian Rong; Wen-Rui Xie

    2008-01-01

    AIM: To detect the nuclear factor kappa B (NF-κB) condition in human stage IV gastric carcinoma patients and to explore the correlation between NF-κB activation and survival of these patients after chemotherapy. METHODS: Expression of NF-κB-p65 was determined by immunohistochemical analysis.Activity of NF-κB DNA-binding in carcinoma tissue was detected by electrophoretic mobility shift assay.Kaplan-Meier survival analysis was performed to show the relation between NF-κB and progression-free survival (PFS) or overall survival (OS) of the patients.RESULTS: The positive expression rate of NF-κB-p65 in 60 gastric cancer tissue samples was 76.7%(46/60).The expression of NF-κB-p65 was reduced in adjacent carcinoma and normal tissue samples.Electrophoretic mobility shift assay (EMSA) analysis showed a strong activation of NF-κB in cancer tissue samples.A survival difference was found in NF-κB-p65 positive and negative patients.NF-κB-p65 expression was negative in cancer tissue samples(n = 14).PFS was 191.40 ±59.88 d and 152.93 ±16.99 d,respectively,in patients with positive NF-κB-p65 expression (n = 46) (P = 0.4028).The survival time of patients with negative and positive NF-κB-p65 expression was 425.16 ± 61.61 d and 418.85 ± 42.98 d,respectively (P = 0.7303).Kaplan-Meier analysis showed no significant difference in PFS or OS.The 46 patient tissue which positive NF-κB-p65 expression was found in the tissue samples from the 46 patients whose PFS and OS were 564.89± 75.94 d and s 352.37 ± 41.32 d,respectively (P =0.0165).CONCLUSION: NF-κB is activated in gastric carcinoma tissue,which is related to the OS after chemotherapy.

  19. Phylogenomic evidence of adaptive evolution in the ancestry of humans

    Goodman, Morris; Sterner, Kirstin N.

    2010-01-01

    In Charles Darwin’s tree model for life’s evolution, natural selection adaptively modifies newly arisen species as they branch apart from their common ancestor. In accord with this Darwinian concept, the phylogenomic approach to elucidating adaptive evolution in genes and genomes in the ancestry of modern humans requires a well supported and well sampled phylogeny that accurately places humans and other primates and mammals with respect to one another. For more than a century, first from the ...

  20. 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.

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

    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

  2. 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.

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

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

    2016-09-01

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

  4. 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.

    2010-01-01

    To compare the gastroesophageal junction of the human with the pig, M2 and M3 receptor densities and the potencies of M2 and M3 muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M2 receptors are higher in pig than human clasp and sling fibers. M3 receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M3 receptors than sling fibe...

  5. Cognitive adaptations for gathering-related navigation in humans

    Krasnow, Max M.; Truxaw, Danielle; Gaulin, Steven J.C.; New, Joshua; Ozono, Hiroki; Uono, Shota; Ueno, Taiji; Minemoto, Kazusa

    2013-01-01

    Current research increasingly suggests that spatial cognition in humans is accomplished by many specialized mechanisms, each designed to solve a particular adaptive problem. A major adaptive problem for our hominin ancestors, particularly females, was the need to efficiently gather immobile foods which could vary greatly in quality, quantity, spatial location and temporal availability. We propose a cognitive model of a navigational gathering adaptation in humans and test its predictions in samples from the US and Japan. Our results are uniformly supportive: the human mind appears equipped with a navigational gathering adaptation that encodes the location of gatherable foods into spatial memory. This mechanism appears to be chronically active in women and activated under explicit motivation in men. PMID:23833551

  6. 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...... omelette (310 kcal) or GH substitution in GH-deficient patients. MAIN OUTCOME MEASURES: Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. RESULTS: The emptying rate was significantly faster...... for ghrelin (1.26 +/- 0.1% per minute), compared with saline (0.83% per minute) (P emptying time (49.4 +/- 3.9 and 75.6 +/- 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P

  7. 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.

  8. Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway

    Li, Jing; Shen, Lin; Lu, Fu-rong; Qin, You; Chen, Rui; Li, Jia; Li, Yan; Zhan, Han-zi; He, Yuan-qiao

    2012-01-01

    Aim: To investigate the effects and underlying mechanisms of plumbagin, a naphthoquinone derived from medicinal plant Plumbago zeylanica, on human gastric cancer (GC) cells. Methods: Human gastric cancer cell lines SGC-7901, MKN-28, and AGS were used. The cell viability was examined using CCK-8 viability assay. Cell proliferation rate was determined using both clonogenic assay and EdU incorporation assay. Apoptosis was detected via Annexin V/propidium iodide double-labeled flow cytometry. Wes...

  9. The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase.

    Bernbäck, S; Bläckberg, L; Hernell, O

    1990-01-01

    Gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase all have potential roles in digestion of human milk triacylglycerol. To reveal the function of each lipase, an in vitro study was carried out with purified lipases and cofactors, and with human milk as substrate. Conditions were chosen to resemble those of the physiologic environment in the gastrointestinal tract of breast-fed infants. Gastric lipase was unique in its ability to initiate hydrolysis of milk t...

  10. Carnosine Inhibits the Proliferation of Human Gastric Carcinoma Cells by Retarding Akt/mTOR/p70S6K Signaling

    Zhang, Zhenwei; Miao, Lei; Wu, Xin; Liu, Guangze; Peng, Yuting; Xin, Xiaoming; Jiao, Binghua; Kong, Xiangping

    2014-01-01

    Carnosine (β-alanyl-L-histidine), described as an enigmatic peptide for its antioxidant, anti-aging and especially antiproliferation properties, has been demonstrated to play an anti-tumorigenic role in certain types of cancer. However, its function in human gastric carcinoma remains unclear. In this study, the effect of carnosine on cell proliferation and its underlying mechanisms were investigated in the cultured human gastric carcinoma cells. The mTOR signaling axis molecules were analyzed...

  11. Selective induction of apoptosis in human gastric cancer cells by Lactobacillus kefiri (PFT), a novel kefir product.

    Ghoneum, Mamdooh; Felo, Nouran

    2015-10-01

    The present study was undertaken to evaluate the effect of Lactobacillus kefiri (PFT), a novel kefir product, on apoptosis of gastric cancer cells (AGS), breast cancer cells (4T1), and human peripheral blood mononuclear cells (PBMCs). Cells were cultured with PFT and apoptosis was determined by flow cytometry using 7-AAD dye and cytospin preparation. Mitochondrial dysfunction and expression of Bcl2 were monitored by flow cytometry. Results showed that PFT induced apoptosis in AGS gastric cancer cells in a dose-dependent manner. Apoptosis was detected at a concentration of 0.3 mg/ml (20.8%), increased to 25.8% at 0.6 mg/ml, 37% at 1.2 mg/ml, 53.1% at 2.5 mg/ml, and peaked at 66.3% at 5.0 mg/ml. Apoptosis is associated with the decreased polarization of mitochondrial membrane potential (MMP) and decreased Bcl2 expression. PFT-treated AGS cells manifested membrane blebbing, nuclear condensation, and fragmentation as identified in cytospin cytocentrifuge Giemsa stained preparations. On the other hand, flow cytometry analysis showed that PFT did not induce apoptosis in 4T1 breast cancer cells nor in PBMCs. These results suggest that PFT is safe for white blood cells and selectively induces apoptotic effects in gastric cancer cells. Hence, it may have potential as a therapeutic agent for the treatment of gastric cancers. PMID:26251956

  12. Allitridi induces apoptosis by affecting Bcl-2 expression and caspase-3 activity in human gastric cancer cells

    Hong LAN; You-yong LU

    2004-01-01

    AIM: To investigate the mechanism of allitridi-induced apoptosis in human gastric cancer cell line BGC823.METHODS: Growth inhibition by allitridi was analyzed using cell growth curve and MTT assay. Apoptotic cells were detected using staining with Hoechst 33342, and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression affected by allitridi was determined using Western blot. The activity of caspase-3 was measured using a fluorescence assay. RESULTS: Allitridi induced apoptosis, and then inhibited cells proliferation in human gastric cancer cell line BGC823. The protein level of Bcl-2 was decreased dramatically,while Bax and p53 were not significantly affected by allitridi. The expression and activity of caspase-3 started to increase after allitridi treatment for 72 h. CONCLUSION: Allitridi induced apoptosis through down-regulation of Bcl-2, and increased caspase-3 expression and its activity.

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

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

    2014-01-01

    Helicobacter pylori infection of the human stomach is associated with inflammation that leads to the release of reactive oxygen and nitrogen species (RONs), eliciting DNA damage in host cells. Unrepaired DNA damage leads to genomic instability that is associated with cancer. Base excision repair (BER) is critical to maintain genomic stability during RONs-induced DNA damage, but little is known about its role in processing DNA damage associated with H. pylori infection of normal gastric epithe...

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

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

    2014-01-01

    Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvat...

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

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

  16. Gastric cancer and trastuzumab: first biologic therapy in gastric cancer

    Gunturu, Krishna S; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.; Saif, M. Wasif

    2013-01-01

    Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer.

  17. 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.

  18. Learning, menopause, and the human adaptive complex.

    Kaplan, Hillard; Gurven, Michael; Winking, Jeffrey; Hooper, Paul L; Stieglitz, Jonathan

    2010-08-01

    This paper presents a new two-sex learning- and skills-based theory for the evolution of human menopause. The theory proposes that the role of knowledge, skill acquisition, and transfers in determining economic productivity and resource distribution is the distinctive feature of the traditional human ecology that is responsible for the evolution of menopause. The theory also proposes that male reproductive cessation and post-reproductive investment in descendants is a fundamental characteristic of humans living in traditional foraging and simple horticultural economies. We present evidence relevant to the theory. The data show that whereas reproductive decline is linked to increasing risks of mortality in chimpanzees, human reproductive senescence precedes somatic senescence. Moreover under traditional conditions, most human males undergo reproductive cessation at the same time as their wives. We then present evidence that after ceasing to reproduce, both men and women provide net economic transfers to children and grandchildren. Given this pattern of economic productivity, delays in menopause would produce net economic deficits within families. PMID:20738273

  19. 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.

  20. 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. PMID:25408692

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

    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

  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. Expression of epidermal growth factor receptor in human gastric and colonic carcinomas

    The expression of epidermal growth factor (EGF) receptor was examined immunohistochemically in a total of 122 gastric and 61 colonic carcinomas, out of which 16 gastric and 8 colonic carcinomas were also examined by 125I-labeled EGF binding analysis and Western blotting. The values of EGF binding were 12.68 +/- 1.98 (SE; n = 16) fmol/mg protein in gastric carcinomas and 5.72 +/- 2.15 (n = 8) fmol/mg protein in nonneoplastic gastric mucosa, the difference being significant (P less than 0.01). In the colonic tissue, the binding capacities in carcinomas and nonneoplastic mucosa were 13.29 +/- 4.17 (n = 8) and 10.68 +/- 0.41 (n = 3) fmol/mg protein, respectively. Scatchard analysis of 125I-labeled EGF binding indicated a single class of receptors in gastric and colonic carcinomas with an apparent Kd value of from 111 to 277 (n = 4) and from 87.4 to 341 fM (n = 5), respectively, except for one gastric carcinoma having two classes of receptors (Kd = 15.9 and 896 fM). In Western blotting using monoclonal anti-EGF receptor antibody, various levels of EGF receptor expression were detected in 12 (85.7%) of the 14 gastric carcinomas and in 7 (87.5%) of the 8 colonic carcinomas. Immunohistochemically, EGF receptor immunoreactivity was detected in one (3.8%) of the 26 early gastric carcinomas, while it was observed in 33 (34.4%) of the 96 advanced gastric carcinomas, the incidence between the two being significantly different (P less than 0.01). In the colonic carcinomas, 47 (77.1%) of the 61 cases showed positive immunoreactivity to EGF receptor, which did not differ by histological type

  4. Robot path adaptation for shared human-robot workspaces

    Zube, Angelika; Jung, A.; Frese, Christian

    2014-01-01

    In shared human-robot workspaces, safety has to be ensured by monitoring humans and other obstacles in the robot’s environment and by performing suitable robot motions to avoid collisions. In this contribution, information from multiple depth sensors is fused in an octree representing the current obstacles in consideration of occlusions. Based on this octree, the previously planned robot path is adapted using elastic bands in order to prevent collisions with humans.

  5. Wavefront sensorless adaptive optics ophthalmoscopy in the human eye

    Hofer, Heidi; Sredar, Nripun; Queener, Hope; Li, Chaohong; Porter, Jason

    2011-01-01

    Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor ‘beacon’ can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in ...

  6. 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 < 1, indicating a synergistic effect. Co-treatment with lupeol and 5-Fu induced apoptosis through up-regulating the expressions of Bax and p53 and down-regulating the expressions of survivin and Bcl-2. Furthermore, co-treatment displayed more efficient inhibition of tumor weight and volume on BGC823 xenograft mouse model than single-agent treatment with 5-Fu or lupeol. Taken together, our findings highlight that lupeol sensitizes GC to 5-Fu treatment, and combination treatment with lupeol and 5-Fu would be a promising therapeutic strategy for human GC treatment. PMID:26892272

  7. 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.

  8. Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude mice

    Chun-Gen Xing; Bao-Song Zhu; Xiao-Qing Fan; Hui-Hui Liu; Xun Hou; Kui Zhao; Zheng-Hong Qin

    2009-01-01

    AIM: To investigate the effects of class Ⅰ phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice.METHODS: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment,the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were observed.RESULTS: In this study, we showed that treating the tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% ± 3.11%, 43.20% ± 3.27% and 63.28% ± 2.10% at 5, 10 and 15 d, respectively) along with apoptosis.The expression of MMP-2 was also downregulated (from 71.4% ± 1.6% to 47.9% ± 0.7%, 31.9% ± 0.9% and 7.9% ± 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% ± 1.5% to 36.9% ± 0.4%, 23.5% ± 0.9% and 7.7% ± 0.6%), the mean MVD (from 51.2% ± 3.1% to 41.9% ± 1.5%, 30.9% ± 1.7% and 14.9% ± 0.8%),and the expression of VEGF (from 47.2% ± 3.1% to 25.9% ± 0.5%, 18.6% ± 1.2% and 5.1% ± 0.9%) by immunohistochemical staining.CONCLUSION: The class Ⅰ PI3K inhibitor LY294002 could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

  9. Human Adaptation to the Control of Fire

    Wrangham, Richard W.; Carmody, Rachel Naomi

    2010-01-01

    Charles Darwin attributed human evolutionary success to three traits. Our social habits and anatomy were important, he said, but the critical feature was our intelligence, because it led to so much else, including such traits as language, weapons, tools, boats, and the control of fire. Among these, he opined, the control of fire was “probably the greatest ever [discovery] made by man, excepting language.” Despite this early suggestion that the control of fire was even more important than tool...

  10. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans

    Nauck, Michael A; Kemmeries, Guido; Holst, Jens Juul;

    2011-01-01

    OBJECTIVE: Glucagon-like peptide (GLP)-1 lowers postprandial glycemia primarily through inhibition of gastric emptying. We addressed whether the GLP-1-induced deceleration of gastric emptying is subject to rapid tachyphylaxis and if so, how this would alter postprandial glucose control. RESEARCH...... DESIGN AND METHODS: Nine healthy volunteers (25 ± 4 years old, BMI: 24.6 ± 4.7 kg/m(2)) were examined with intravenous infusion of GLP-1 (0.8 pmol · kg(-1) · min(-1)) or placebo over 8.5 h. Two liquid mixed meals were administered at a 4-h interval. Gastric emptying was determined, and blood samples were...... drawn frequently. RESULTS: GLP-1 decelerated gastric emptying significantly more after the first meal compared with the second meal (P = 0.01). This was associated with reductions in pancreatic polypeptide levels (marker of vagal activation) after the first but not the second meal (P

  11. 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

  12. Human Adaptation to Isolated and Confined Environments

    Evans, Gary W.; Stokols, Daniel; Carrere, Sybil

    1987-01-01

    A study was conducted over seven months in a winter Antarctic isolated and confined environment (ICE). Physiological and psychological data was collected several times a week. Information was collected on a monthly basis on behavior and the use of physical facilities. Adaptation and information indicated that there was a significant decrease in epinephrine and norepinephrine during the middle trimester of the winter. No vital changes were found for blood pressure. Self reports of hostility and anxiety show a linear increase. There were no significant changes in depression during ICE. The physiological and psychological data do not move in a synchronous fashion over time. The data also suggest that both ambient qualities of an ICE and discrete social environmental events, such as the arrival of the summer crew, have an impact on the outcome measures used. It may be most appropiate to develop a model for ICE's that incorporates not only global chronic stressors common to all ICE's but also the role of discrete environmental effects which can minimize or enhance the influence of more chronic stressors. Behavioral adjustment information highlight the importance of developing schedules which balance work and recreational activities.

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

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

    2015-11-01

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

  14. Helicobacter pylori Infection Induces Oxidative Stress and Programmed Cell Death in Human Gastric Epithelial Cells▿

    Ding, Song-Ze; Minohara, Yutaka; Fan, Xue Jun; Wang, Jide; Reyes, Victor E; Patel, Janak; Dirden-Kramer, Bernadette; Boldogh, Istvan; Ernst, Peter B.; Crowe, Sheila E.

    2007-01-01

    Helicobacter pylori infection is associated with altered gastric epithelial cell turnover. To evaluate the role of oxidative stress in cell death, gastric epithelial cells were exposed to various strains of H. pylori, inflammatory cytokines, and hydrogen peroxide in the absence or presence of antioxidant agents. Increased intracellular reactive oxygen species (ROS) were detected using a redox-sensitive fluorescent dye, a cytochrome c reduction assay, and measurements of glutathione. Apoptosis...

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

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

    2004-01-01

    Helicobacter pylori infects over half the world's population and is a leading cause of peptic ulcer and gastric cancer. H. pylori infection results in chronic inflammation of the gastric mucosa, and progression of chronic inflammation leads to glandular atrophy and intestinal metaplasia. However, how this chronic inflammation is induced or maintained is not well known. Here, we show that chronic inflammation caused by H. pylori infection is highly correlated with de novo synthesis of peripher...

  16. Epidermal growth factor receptor antibody plus recombinant human endostatin in treatment of hepatic metastases after remnant gastric cancer resection

    2007-01-01

    We report a 55-year-old male who developed advanced hepatic metastasis and peritoneal carcinomatosis after resection of remnant gastric cancer resection 3 mo ago. The patient only received epidermal growth factor (EGF) receptor antibody (Cetuximab) plus recombinant human endostatin (Endostar).Anti-tumor activity was assessed by 18F-fluorodeoxyglucose (18F-FDG)positron emission tomography/computer tomography (PET/CT) at baseline and then every 4 wk. The case illustrates that 18FDG-PET/CT could make an early prediction of the response to Cetuximab plus Endostar in such clinical situations. 18FDG-PET/CT is a useful molecular imaging modality to evaluate the biological response advanced hepatic metastasis and peritoneal carcinomatosis to Cetuximab plus Endostar in patients after remnant gastric cancer resection.

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

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

  19. 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.

  20. Therapeutic effects of lentivirus-mediated shRNA targeting of cyclin D1 in human gastric cancer

    Gastric cancer is the second most common cause of cancer-related death in males and the fourth in females. Traditional treatment has poor prognosis because of recurrence and systemic side effects. Therefore, the development of new therapeutic strategies is an important issue. Lentivirus-mediated shRNA stably inhibits target genes and can efficiently transduce most cells. Since overexpressed cyclin D1 is closely related to human gastric cancer progression, inhibition of cyclin D1 using specific targeting could be an effective treatment method of human gastric cancer. The therapeutic effect of lentivirus-mediated shRNA targeting of cyclin D1 (ShCCND1) was analyzed both in vitro and in vivo experiments. In vitro, NCI-N87 cells with downregulation of cyclin D1 by ShCCND1 showed significant inhibition of cell proliferation, cell motility, and clonogenicity. Downregulation of cyclin D1 in NCI-N87 cells also resulted in significantly increased G1 arrest and apoptosis. In vivo, stable NCI-N87 cells expressing ShCCND1 were engrafted into nude mice. Then, the cancer-growth inhibition effect of lentivirus was confirmed. To assess lentivirus including ShCCND1 as a therapeutic agent, intratumoral injection was conducted. Tumor growth of the lentivirus-treated group was significantly inhibited compared to growth of the control group. These results are in accordance with the in vitro data and lend support to the mitotic figure count and apoptosis analysis of the tumor mass. The lentivirus-mediated ShCCND1 was constructed, which effectively inhibited growth of NCI-N87-derived cancer both in vitro and in vivo. The efficiency of shRNA knockdown and variation in the degree of inhibition is mediated by different shRNA sequences and cancer cell lines. These experimental results suggest the possibility of developing new gastric cancer therapies using lentivirus-mediated shRNA

  1. 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.

  2. 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.

  3. Adaptive memory in humans from a comparative perspective

    Krause, Mark

    2015-01-01

    Testing hypotheses about evolved psychological adaptations is the purview of human evolutionary psychology (HEP). A basic tenet of HEP is that the brain is comprised of specialized modules that evolved in response to selection pressures present in ancestral environments, and these modules support domain specific behavioral and cognitive processes that promoted survival and reproductive fitness during human evolutionary history. One set of cognitive domains involves learning and memory, and HE...

  4. Genetic Evidence of Human Adaptation to a Cooked Diet

    Carmody, Rachel N.; Dannemann, Michael; Briggs, Adrian W; Nickel, Birgit; Groopman, Emily E.; Wrangham, Richard W.; Kelso, Janet

    2016-01-01

    Humans have been argued to be biologically adapted to a cooked diet, but this hypothesis has not been tested at the molecular level. Here, we combine controlled feeding experiments in mice with comparative primate genomics to show that consumption of a cooked diet influences gene expression and that affected genes bear signals of positive selection in the human lineage. Liver gene expression profiles in mice fed standardized diets of meat or tuber were affected by food type and cooking, but n...

  5. Wavefront sensorless adaptive optics ophthalmoscopy in the human eye

    Hofer, Heidi; Sredar, Nripun; Queener, Hope; Li, Chaohong; Porter, Jason

    2011-07-01

    Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor `beacon' can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in retinal image frames acquired with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). When imaging through natural, undilated pupils, both control methods resulted in comparable mean image intensities. However, when imaging through dilated pupils, image intensity was generally higher following wavefront sensor-based control. Despite the typically reduced intensity, image contrast was higher, on average, with sensorless control. Wavefront sensorless control is a viable option for imaging the living human eye and future refinements of this technique may result in even greater optical gains.

  6. 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.

  7. 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...

  8. Genomic signatures reveal geographic adaption and human selection in cattle

    We investigated geographic adaptation and human selection using high-density SNP data of five diverse cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-k...

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

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

    2016-01-01

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

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

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

    2016-01-01

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

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

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

    2014-01-01

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

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

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

    2016-01-01

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

  13. Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway

    Yiwen Li

    2012-11-01

    Full Text Available Rhein is a primary anthraquinone found in the roots of a traditional Chinese herb, rhubarb, and has been shown to have some anticancer effects. The aim of the present study was to investigate the effect of rhein on the apoptosis of the human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC-7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 µM for 24, 48, or 72 h. Relative cell viability assessed by the MTT assay after treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and 100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining at 48 h after 100, 200 and 300 µm rhein. The percentage of apoptotic cells was 7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and -9 using real-time PCR. Treatment with 100 µM rhein for 48 h significantly increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein-treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. We conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial pathway.

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

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

    2008-03-01

    The present study investigated proliferation of MKN28 and MKN45 human gastric cancer cells regulated by the N-methyl-d-aspartate (NMDA) receptor subunit. The NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (AP5) inhibited proliferation of MKN45 cells, but not MKN28 cells. Of the NMDA subunits such as NR1, NR2 (2A, 2B, 2C, and 2D), and NR3 (3A and 3B), all the NMDA subunit mRNAs except for the NR2B subunit mRNA were expressed in both MKN28 and MKN45 cells. MKN45 cells were characterized by higher expression of the NR2A subunit mRNA and lower expression of the NR1 subunit mRNA, but MKN28 otherwise by higher expression of the NR1 subunit mRNA and lower expression of the NR2A subunit mRNA. MKN45 cell proliferation was also inhibited by silencing the NR2A subunit-targeted gene. For MKN45 cells, AP5 or knocking-down the NR2A subunit increased the proportion of cells in the G(1) phase of cell cycling and decreased the proportion in the S/G(2) phase. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G(1) phase; in other words, the NR2A subunit promotes MKN45 cell proliferation by accelerating cell cycling. PMID:18178157

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

    The present study investigated proliferation of MKN28 and MKN45 human gastric cancer cells regulated by the N-methyl-D-aspartate (NMDA) receptor subunit. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) inhibited proliferation of MKN45 cells, but not MKN28 cells. Of the NMDA subunits such as NR1, NR2 (2A, 2B, 2C, and 2D), and NR3 (3A and 3B), all the NMDA subunit mRNAs except for the NR2B subunit mRNA were expressed in both MKN28 and MKN45 cells. MKN45 cells were characterized by higher expression of the NR2A subunit mRNA and lower expression of the NR1 subunit mRNA, but MKN28 otherwise by higher expression of the NR1 subunit mRNA and lower expression of the NR2A subunit mRNA. MKN45 cell proliferation was also inhibited by silencing the NR2A subunit-targeted gene. For MKN45 cells, AP5 or knocking-down the NR2A subunit increased the proportion of cells in the G1 phase of cell cycling and decreased the proportion in the S/G2 phase. The results of the present study, thus, suggest that blockage of NMDA receptors including the NR2A subunit suppresses MKN45 cell proliferation due to cell cycle arrest at the G1 phase; in other words, the NR2A subunit promotes MKN45 cell proliferation by accelerating cell cycling

  16. Downregulation of survivin by RNAi inhibits growth of human gastric carcinoma cells

    Guo-Ying Miao; Qi-Ming Lu; Xiu-Lan Zhang

    2007-01-01

    AIM: To investigate the inhibitory effect of a specific small survivin interfering RNA (siRNA) on cell proliferation and the expression of survivin in human gastric carcinoma cell line SGC-7901.METHODS: To knockdown survivin expression, a small interfering RNA targeting against survivin was synthesized and transfected into SGC-7901 cells with lipofectamineTM2000. The downregulation of survivin expression at both mRNA and protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Cell proliferation inhibition rates were determined by methyl thiazolyl tetrazolium (MTT) assay. The effect of survivin siRNA on cell cycle distribution and cell apoptosis was determined by flow cytometry (FCM).RESULTS: RNA interference could efficiently suppress the survivin expression in SGC-7901 cells. At 48 h after transfection, the expression inhibition rate was 44.52% at mRNA level detected by RT-PCR and 40.17% at protein level by Western blot analysis. Downregulation of survivin resulted in significant inhibition of tumor cell growth in vitro. The cell proliferation inhibition rates at 24, 48 and 72 h after survivin siRNA and non-siliencing siRNA transfection, were 34.06%, 47.61% and 40.36%,respectively. The apoptosis rate was 3.56% and the number of cells was increased in G0/G1 phase from 38.2% to 88.6%, and decreased in S and G2/M phase at 48 h after transfection.CONCLUSION: Downregulation of survivin results in significant inhibition of tumor growth in vitro. The inhibition of survivin expression can induce apoptosis of SGC-7901 cells. The use of survivin siRNA deserves further investigation as a novel approach to cancer therapy.

  17. 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.

  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. 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. PMID:23021757

  20. 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.

  1. Biodistribution and radioimmunoimage of iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts

    Objective: To investigate the biodistribution of Iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts. Methods: The anti-human ADAM15 polyclonal antibody was labeled with I-125 using Chloramine-T method. The labeling efficiency and radiochemical purity of 125I-anti-ADAM15 antibody were measured. The SPECT planar imaging of nude mice bearing gastric carcinoma xenografts were performed at 1, 4, 8, 24, and 48 h post-injection and the biodistribution of 125I-anti-ADAM15 antibody was measured at 48 h after injection. Results: The labeling efficiency of 125I-anti-ADAM15 antibody was (75.16±9.43)% and its radiochemical purity was (99.44±0.21)% . Tumors could be cleanly visualized in SPECT planar images, and the radioactivity ratio of tumor to non-tumor tissue was 3.84±0.43 at 48 h post-injection. Conclusion: 125I-anti-ADAM15 antibody can target the gastric carcinoma in vivo, and provide good radioimmunoimages. (authors)

  2. Treatment of gastric cancer

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

    2014-01-01

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

  3. 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 with......, 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, with...

  4. 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

    2014-01-01

    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 wa...

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

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

    2016-01-01

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

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

    Nie, Chao; Zhou, Jie; Qin, Xiaokang; Shi, Xianming; Zeng, Qingqi; Liu, Jia; Yan, Shihai; Zhang, Lei

    2016-02-01

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

  7. 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.

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

    Jiang, Zheng; Liu, Yao; Wang, Chuan

    2016-01-01

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

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

    Jiang Z

    2016-08-01

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

  10. Effect of hyperthermic CO2-treated dendritic cell-derived exosomes on the human gastric cancer AGS cell line

    Wang, Jinlin; Wang, Zhiyong; MO, YANXIA; Zeng, Zhaohui; Wei, Pei; Li, Tao

    2015-01-01

    The aim of the present study was to determine the antitumor effects of hyperthermic CO2 (HT-CO2)-treated dendritic cell (DC)-derived exosomes (Dex) on human gastric cancer AGS cells. Mouse-derived DCs were incubated in HT-CO2 at 43°C for 4 h. The exosomes in the cell culture supernatant were then isolated. Cell proliferation was analyzed using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was observed using flow cytometry, Hoechst 33258 staining and the analysis of caspase-3 activity....

  11. 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

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

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

    2016-01-01

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

  14. Trafficking and phosphorylation dynamics of AQP4 in histamine-treated human gastric cells.

    Carmosino, M.; Procino, G.; Tamma, G.; Mannucci, R.; Svelto, M.; Valenti, G.

    2007-01-01

    BACKGROUND INFORMATION: AQP4 (aquaporin 4) internalization and a concomitant decrease in the osmotic water permeability coefficient (Pf) after histamine exposure has been reported in AQP4-transfected gastric HGT1 cells. RESULTS: In the present study we report that AQP4 internalization is followed by

  15. 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.

  16. 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.

  17. 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

  18. 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.

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

    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

  20. 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

  1. 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.

  2. Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex.

    Masamichi J Hayashi

    Full Text Available Although psychological and computational models of time estimation have postulated the existence of neural representations tuned for specific durations, empirical evidence of this notion has been lacking. Here, using a functional magnetic resonance imaging (fMRI adaptation paradigm, we show that the inferior parietal lobule (IPL (corresponding to the supramarginal gyrus exhibited reduction in neural activity due to adaptation when a visual stimulus of the same duration was repeatedly presented. Adaptation was strongest when stimuli of identical durations were repeated, and it gradually decreased as the difference between the reference and test durations increased. This tuning property generalized across a broad range of durations, indicating the presence of general time-representation mechanisms in the IPL. Furthermore, adaptation was observed irrespective of the subject's attention to time. Repetition of a nontemporal aspect of the stimulus (i.e., shape did not produce neural adaptation in the IPL. These results provide neural evidence for duration-tuned representations in the human brain.

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

    Amodeo, Martín Raúl

    2014-01-01

    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 be...

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

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

    2016-01-01

    Helicobacter pylori infects ~50% of the world population, causing chronic gastritis and other forms of cellular damage. The present study assessed the influence of H. pylori on the mRNA expression levels of nuclear factor-κB1 (NFKB1), p38α and tumor necrosis factor-α (TNF-α) in human gastric mucosa in a southern Brazilian population. Human gastric tissue was collected by upper endoscopy and H. pylori diagnosis was performed using a rapid urease test and histological analysis. Total RNA was ex...

  5. Gastric giardiasis.

    Doglioni, C; De Boni, M.; Cielo, R.; Laurino, L.; Pelosio, P.; P. Braidotti; Viale, G

    1992-01-01

    AIMS: To assess the prevalence of gastric giardiasis in patients undergoing upper gastrointestinal endoscopy, and to define the clinicopathological correlates of gastric Giardia lamblia infection. METHODS: Consecutive gastric biopsy specimens (n = 15,023) from 11,085 patients, taken at Feltre City Hospital (north eastern Italy) from January 1986 to December 1991, were histologically and immunocytochemically examined for the occurrence of G lamblia trophozoites. Three gastric biopsy specimens ...

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

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

    2016-01-01

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

  7. Synergistic Effect of Zuo Jin Wan on DDP-Induced Apoptosis in Human Gastric Cancer SGC-7901/DDP Cells

    Qing-Feng Tang

    2014-01-01

    Full Text Available A traditional Chinese medicine (TCM formula, Zuo Jin Wan (ZJW, has been found as an anticancer drug in human cancer. In this study, we investigated the synergistic effect of ZJW extracts on DDP-induced apoptosis in human gastric cancer SGC-7901/DDP cells. Our results demonstrated that ZJW extracts could increase the sensitivity of SGC-7901/DDP cells to DDP by increasing the concentration of DDP in cytoplasm and enhance the proapoptosis of DDP by upregulating the JNK and Bax expression, downregulating the Bcl-2 expression, increasing the accumulation of Cytochrome C in cytoplasm, and promoting the activities of caspase-3 and caspase-9. In vivo, ZJW extracts enhanced the inhibiting effect of DDP on tumor growth in SGC-7901/DDP xenograft model and upregulated the expression of p-JNK and Bax but downregulated the Bcl-2 expression in xenograft tumors. In conclusion, in vitro and in vivo, ZJW extracts could enhance the proapoptotic effect of DDP by promoting the activation of JNK and the expression of Bcl-2, inhibiting the Bax expression, followed by increasing the release of Cytochrome C from mitochondria to cytoplasm, and finally activating the caspase cade reaction. Our results implied that ZJW might serve as a synergistic drug with chemotherapeutic drugs DDP in the treatment of gastric cancer.

  8. 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

  9. Helicobacter pylori Infection Promotes Methylation and Silencing of Trefoil Factor 2, Leading to Gastric Tumor Development in Mice and Humans

    Peterson, Anthony J.; Menheniott, Trevelyan R.; O’Connor, Louise; Walduck, Anna K.; James G Fox; Kawakami, Kazuyuki; Minamoto, Toshinari; Ong, Eng Kok; Timothy C Wang; Judd, Louise M.; Giraud, Andrew S.

    2010-01-01

    Background & Aims Trefoil factors (TFFs) regulate mucosal repair and suppress tumor formation in the stomach. Tff1 deficiency results in gastric cancer, whereas Tff2 deficiency increases gastric inflammation. TFF2 expression is frequently lost in gastric neoplasms, but the nature of the silencing mechanism and associated impact on tumorigenesis have not been determined. Methods We investigated the epigenetic silencing of TFF2 in gastric biopsy specimens from individuals with Helicoba...

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

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

  11. Radioimmunoscintigraphy of human gastric carcinoma xenografts with 131I-labeled antigastric carcinoma monoclonal antibody, GL013

    Monoclonal antibody GL013 with specific binding reactivity in vitro to human tumors of the gastrointestinal tract was radioiodinated and injected intraperitoneally into nude mice bearing human gastric carcinoma xenografts SY86B (moderately differentiated glandular adenocarcinoma) and SY86D (signet ring cell carcinoma). Wholebody scintigraphy demonstrated tumor localization with 131I-labeled MAb GL013, but not with 131I-labeled normal mice immunoglobulin. Best tumor contrast was obtained between days 3 and 7 after injection. In confirmation of imaging results, 131I-GL013 preferentially localized in tumor tissue compared with normal tissue and 131I-GL013 gave higher tumor uptake ratio than did control 131I-NMIgG (at day 9 after injection), as determined by tissue counting of radioactivity. These results demonstrate that MAb GL013 does localize to the xenografts SY86D and SY86D and suggest the possible clinical application of MAb GL013 in radioimmunolocalization

  12. 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.

  13. Depletion of G9a gene induces cell apoptosis in human gastric carcinoma.

    Lin, Xiaolei; Huang, Yiqun; Zou, Yong; Chen, Xingsheng; Ma, Xudong

    2016-05-01

    G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Evidence suggests that G9a is required to maintain the malignant phenotype, but little documentation show the role of G9a function in mediating tumor growth. We retrospectively analyzed the protein of G9a and monomethylated histone H3 lysine 9 (H3K9 me1), and dimethylated histone H3 lysine 9 (H3K9 me2) in 175 cases of gastric carcinoma by immunohistochemistry. RNAi-based inhibition of G9a in MGC803 cancer cell line was studied. G9a depletion was done by transient transfection using Lipofectamine 2000. Depletion efficiency of G9a was tested using real-time PCR and western blot analysis. Cell apoptosis and proliferation were detected by TUNEL assay and MTT, respectively. The proteins of H3K9 me1, me2, trimethylation of H3K9 (H3K9 me3), monomethylated histone H3 lysine 27 (H3K27 me1), dimethylated histone H3 lysine 27 (H3K27 me2) and histone acetylated H3, apoptotic proteins were studied by western blot analysis. G9a and H3K9 me2 expression was higher in gastric cancer cells compared to the control (pG9a and H3K9 me2 were positively correlated with the degree of differentiation, depth of infiltration, lymphatic invasions and tumor-node-metastasis stage in gastric carcinoma, (pG9a induced cell apoptosis and inhibited cell proliferation. Depletion of G9a reduced the levels of H3K9 me1 and me2, H3K27 me1 and me2. Nonetheless, it did not activate acetylation of H3 and H3K9 me3. These data suggest that G9a is required in tumorigenesis, and correlated with prognosis. Furthermore, G9a plays a critical role in regulating epigenetics. Depletion of G9a inhibits cell growth and induces cells apoptosis in gastric cancer. It might be of therapeutic benefit in gastric cancers. PMID:27081761

  14. Bone loss and human adaptation to lunar gravity

    Keller, T. S.; Strauss, A. M.

    1992-01-01

    Long-duration space missions and establishment of permanently manned bases on the Moon and Mars are currently being planned. The weightless environment of space and the low-gravity environments of the Moon and Mars pose an unknown challenge to human habitability and survivability. Of particular concern in the medical research community today is the effect of less than Earth gravity on the human skeleton, since the limits, if any, of human endurance in low-gravity environments are unknown. This paper provides theoretical predictions on bone loss and skeletal adaptation to lunar and other nonterrestrial-gravity environments based upon the experimentally derived relationship, density approximately (mass x gravity)(exp 1/8). The predictions are compared to skeletal changes reported during bed rest, immobilization, certrifugation, and spaceflight. Countermeasures to reduce bone losses in fractional gravity are also discussed.

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

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

    2011-01-01

    For robots to be able coexist with people in future everyday human environments, they must be able to act in a safe, natural and comfortable way. This work addresses the motion of a mobile robot in an environment, where humans potentially want to interact with it. The designed system consists of ...... wishes to interact, and that the system is capable of adapting to changing behaviours of the humans in the environment....

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

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

    2015-01-01

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

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

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

    2012-12-01

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

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

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

    2016-05-01

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

  19. Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells through both of the mitochondrial respiration and glycolysis pathways.

    Yao Shen

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

  20. Adaptations of human skeletal muscle fibers to spaceflight

    Day, M. Kathleen; Allen, David L.; Mohajerani, Laleh; Greenisen, Michael C.; Roy, Roland R.; Edgerton, V. Reggie

    1995-01-01

    Human skeletal muscle fibers seem to share most of the same interrelationships among myosin ATPase activity, myosin heavy chain (MHC) phenotype, mitochondrial enzyme activities, glycolytic enzyme activities, and cross-sectional area (CSA) as found in rat, cat, and other species. One difference seems to be that fast fibers with high mitochrondrial content occur less frequently in humans than in the rat or cat. Recently, we have reported that the type of MHC expressed and the size of the muscle fibers in humans that have spent 11 days in space change significantly. Specifically, about 8% more fibers express fast MHCs and all phenotypes atrophy in the vastus lateralis (VL) post compared to preflight. In the present paper we examine the relationships among the population of myonuclei, MHC type, and CSA of single human muscle fibers before and after spaceflight. These are the first data that define the relationship among the types of MHC expressed, myonuclei number, and myonuclei domain of single fibers in human muscle. We then compare these data to similar measures in the cat. In addition, the maximal torque that can be generated by the knee extensors and their fatigability before and after spaceflight are examined. These data provide some indication of the potential physiologica consequences of the muscle adaptations that occur in humans in response to spaceflight.

  1. 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.

  2. Human neutrophil elastase inhibitors in innate and adaptive immunity.

    Fitch, P M; Roghanian, A; Howie, S E M; Sallenave, J-M

    2006-04-01

    Recent evidence shows that human neutrophil elastase inhibitors can be synthesized locally at mucosal sites. In addition to efficiently targeting bacterial and host enzymes, they can be released in the interstitium and in the lumen of mucosa, where they have been shown to have antimicrobial activities, and to activate innate immune responses. This review will address more particularly the pleiotropic functions of low-molecular-mass neutrophil elastase inhibitors [SLPI (secretory leucocyte proteinase inhibitor) and elafin] and, more specifically, their role in the development of the adaptive immune response. PMID:16545094

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

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

    1998-01-01

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

  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. PMID:26733497

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

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

  8. 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...... healthy volunteers were studied with intravenous infusion of GLP-1-(7-36) amide, GLP-1-(9-36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements......-(7-36) amide administration]. GLP-1-(7-36) amide reduced fasting and postprandial glucose concentrations (P gastric emptying (P

  9. 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...

  10. Cardiovascular adaptations supporting human exercise-heat acclimation.

    Périard, Julien D; Travers, Gavin J S; Racinais, Sébastien; Sawka, Michael N

    2016-04-01

    This review examines the cardiovascular adaptations along with total body water and plasma volume adjustments that occur in parallel with improved heat loss responses during exercise-heat acclimation. The cardiovascular system is well recognized as an important contributor to exercise-heat acclimation that acts to minimize physiological strain, reduce the risk of serious heat illness and better sustain exercise capacity. The upright posture adopted by humans during most physical activities and the large skin surface area contribute to the circulatory and blood pressure regulation challenge of simultaneously supporting skeletal muscle blood flow and dissipating heat via increased skin blood flow and sweat secretion during exercise-heat stress. Although it was traditionally held that cardiac output increased during exercise-heat stress to primarily support elevated skin blood flow requirements, recent evidence suggests that temperature-sensitive mechanisms may also mediate an elevation in skeletal muscle blood flow. The cardiovascular adaptations supporting this challenge include an increase in total body water, plasma volume expansion, better sustainment and/or elevation of stroke volume, reduction in heart rate, improvement in ventricular filling and myocardial efficiency, and enhanced skin blood flow and sweating responses. The magnitude of these adaptations is variable and dependent on several factors such as exercise intensity, duration of exposure, frequency and total number of exposures, as well as the environmental conditions (i.e. dry or humid heat) in which acclimation occurs. PMID:26905458

  11. 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.

  12. 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.

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

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

    1999-01-01

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

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

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

    2010-03-01

    Full Text Available 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.

  15. Silencing of Bcl-XL Expression in Human MGC-803 Gastric Cancer Cells by siRNA

    Xiao-Yong LEI; Miao ZHONG; Lan-Fang FENG; Chun-Yan YAN; Bing-Yang ZHU; Sheng-Song TANG; Duan-Fang LIAO

    2005-01-01

    To investigate the inhibitory effect of the Bcl-XL small interfering RNA (siRNA) on Bcl-XL gene expression in the human gastric cancer cell line MGC-803, green fluorescent protein (GFP) siRNA was constructed and transfected into MGC-803 ceils, together with GFP expression vector pTrace SV40.GFP expression levels were observed using fluorescence microscopy. Bcl-XL siRNA and negative siRNA were then constructed and stably transfected into MGC-803 cells. RT-PCR and immunofluorescence were used to detect the expression of Bcl-XL. Spontaneous apoptosis was detected by acridine orange (AO) and flow cytometry. Results were as follows: (1) 48 h after GFP expression vector and GFP siRNA co-transfection, the expression level of GFP in the GFP siRNA group was much lower than the negative siRNA group,according to fluorescence microscopy results. The mRNA and protein levels of Bcl-XL in Bcl-XL siRNA stable transfectants were reduced to almost background level compared with negative siRNA transfectants or untreated cells. (2) Changes in nucleus morphology was observed by AO staining nucleic and flow cytometry analysis, which showed that stable Bcl-XL siRNA transfectants have an increased spontaneous apoptosis (21.17%± 1.26% vs. 1.19%±0.18% and 1.56%±0.15 % respectively, P<0.05 vs. negative siRNA or untreated control). siRNA targeting GFP or Bcl-XL genes can specifically suppress GFP or Bcl-XL expression in MGC-803 cells, and Bcl-XL siRNA can increase spontaneous apoptosis. Bcl-XL siRNA may be a beneficial agent against human gastric adenocarcinoma.

  16. Paris chinensis dioscin induces G2/M cell cycle arrest and apoptosis in human gastric cancer SGC-7901 cells

    Lin-Lin Gao; Fu-Rong Li; Peng Jiao; Ming-Feng Yang; Xiao-Jun Zhou; Yan-Hong Si; Wen-Jian Jiang; Ting-Ting Zheng

    2011-01-01

    AIM: To investigate the anti-tumor effects of Paris chinensis dioscin (PCD) and mechanisms regarding cell cycle regulation and apoptosis in human gastric cancer SGC-7901 cells.METHODS: Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Cell apoptosis was evaluated by flow cytometry and laser scanning confocal microscope (LSCM) using Annexin-V/propidium iodide (PI) staining, and the cell cycle was evaluated using PI staining with flow cytometry. Intracellular calcium ions were detected under fluorescence microscope. The expression of cell cycle and apoptosis-related proteins cyclin B1, CDK1, cytochrome C and caspase-3 was measured by immunohistochemical staining. RESULTS: PCD had an anti-proliferation effect on human gastric cancer SGC-7901 cells in a dose- and time-dependent manner. After treatment of SGC-7901 cells with PCD, apoptosis appeared in SGC-7901 cells. Morphological changes typical of apoptosis were also observed with LSCM by Annexin V/PI staining, and the cell number of the G0/G1 phase was decreased, while the number of cells in the G2/M phase was increased. Cell cycle-related proteins, such as cyclin B1 and CDK1, were all down-regulated, but caspase-3 and cytochrome C were up-regulated. Moreover, intracellular calcium accumulation occurred in PCD-treated cells. CONCLUSION: G2/M phase arrest and apoptosis induced by PCD are associated with the inhibition of CDK-activating kinase activity and the activation of Ca2+-related mitochondrion pathway in SGC-7901 cells.

  17. 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.

  18. Comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma and normal lung fibroblast cell lines

    Mohammad Ali Rashmezad; Elahe Ali Asgary; Farzaneh Tafvizi; Seyed Ataollah Sadat Shandiz; Amir Mirzaie

    2015-01-01

    Background: Biosynthesis of nanoparticles has attracted the attention of the scientific community in nanotechnology and biotechnology due to their extensive application in the area of material sciences and medicine. Nowadays, despite a various application of nanomaterial’s, there is a little information about their impact on human health. In this study, we investigated the comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma (...

  19. Background analysis and comparison of two solid food markers (DTPA and HSA) in the measurement of human gastric emptying

    The measurement of gastric emptying of radiolabelled solid food is described. A procedure enabling the assessment of background radiation, and connected with it corrections of the parameters characterizing gastric emptying curves are discussed in detail. Considering background radiation, /sup 99m/Tc/labelled DTPA and HSA are shown to be equivalent as solid meal markers in studying gastric emptying. Corrections for background radiation can be neglected, if the background to total count ratio has been sufficiently reduced. (author)

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

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

    2012-12-01

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

  1. Disorders of gastric emptying and the application of radionuclide techniques

    There has been a greatly increased understanding of the physiology of gastric emptying in normal subjects, and of the pathophysiology and pharmacological treatment of gastric empyting disorders associated with the development and application of methods to quantify gastric emptying in humans. The non-invasive measurement of gastric emptying by means of radionuclide-labelled food markers has widespread clinical and research applications

  2. 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.

  3. 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

    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...... and glycogen synthase activity were enhanced 12 months post-surgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4 and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC as well as insulin-induced changes in phosphorylation of Akt and TBC1D4 were...... enhanced 12 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...

  4. 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

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

    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

  7. 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. PMID:23381601

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

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

    2016-01-01

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

  9. Adaptive image contrast enhancement based on human visual properties

    Existing methods for image contrast enhancement focus mainly on the properties of the image to be processed while excluding any consideration of the observer characteristics. In several applications, particularly in the medical imaging area, effective contrast enhancement for diagnostic purposes can be achieved by including certain basic human visual properties. In this paper the authors present a novel adaptive algorithm that tailors the required amount of contrast enhancement based on the local contrast of the image and the observer's Just-Noticeable-Difference (JND). This algorithm always produces adequate contrast in the output image, and results in almost no ringing artifacts even around sharp transition regions, which is often seen in images processed by conventional contrast enhancement techniques. By separating smooth and detail areas of an image and considering the dependence of noise visibility on the spatial activity of the image, the algorithm treats them differently and thus avoids excessive enhancement of noise, which is another common problem for many existing contrast enhancement techniques. The present JND-Guided Adaptive Contrast Enhancement (JGACE) technique is very general and can be applied to a variety of images. In particular, it offers considerable benefits in digital radiography applications where the objective is to increase the diagnostic utility of images. A detailed performance evaluation together with a comparison with the existing techniques is given to demonstrate the strong features of JGACE

  10. Characterization of gastric adenocarcinoma cell lines established from CEA424/SV40 T antigen-transgenic mice with or without a human CEA transgene

    Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murine in vivo models which allow the stepwise improvement of immunotherapies for gastric cancer. Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2CEA, mGC4CEA, mGC11CEA). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements. The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTL in vitro. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts. Although

  11. Low antroduodenal pressure gradients are responsible for gastric emptying of a low-caloric liquid meal in humans

    Hausken, T; Mundt, M; Samsom, M

    2002-01-01

    The motor mechanisms responsible for transpyloric flow of gastric contents are still poorly understood. The aim of our study was to investigate the relationship between luminal pressures and gastric wall motion and between gastroduodenal pressure gradients and pressure waves, and ante- and retrograd

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

    Hutton, Emily A.; Pauliukaite, Rasa; Hocevar, Samo B. [Analytical Chemistry Laboratory, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana (Slovenia); Ogorevc, Bozidar, E-mail: bogorevc@ki.s [Analytical Chemistry Laboratory, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana (Slovenia); Smyth, Malcolm R. [National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Dublin 9 (Ireland)

    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{sub 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 {mu}M (n = 22, r = 0.999) with a calculated limit of detection of 1.0 {mu}M. 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 {mu}M AA. The long-term reproducibility, using the same microsensor for 112 consecutive measurements of 20 {mu}M 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 {mu}M (n = 14, r = 0

  13. Radioimmunolocalization of human gastric carcinoma xenografts SY 86 B and SY 86 D with 131I-labeled monoclonal antibody

    The suitability of individual MAb for application in vivo should be carefully confirmed. The monoclonal antibody GL-013, with specific binding reactivity in vitro to human tumors of the gastrointenstinal tract, was radioiodinated and injected intraperitoneally into nude mice bearing human gastric carcinoma xenografts SY 86 B (moderately differentiated glandular adenocarcinoma) and SY 86 D (signet ring cell carcinoma). Whole body scintigraphy indicated tumor localization with 131I-labeled MAb GL-013, but not with 131I-labeled normal mice immunoglobulin. The best tumor contrast was obtained between days 3 and 7 after injection. As confirmation of the imaging results, 131I-GL-013 preferentially localized in tumor tissue compared with normal tissue and 131I-GL-013 gave a higher tumor uptake ratio than the control 131I-NMIgG (at day 9 after injection), as determined by tissue counting of radioactivity. These results demonstrate that MAb GL-013 localizes in xenografts SY 86 B and SY 86 D and the possible clinical application of MAb GL-013 to radioimmunolocalization. (author)

  14. 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.

  15. 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

    2015-01-01

    Ganoderma lucidum is one of the most widely studied mushroom species, particularly in what concerns its medicinal properties. Previous studies (including those from some of us) have shown some evidence that the methanolic extract of G. lucidum affects cellular autophagy. However, it was not known if it induces autophagy or decreases the autophagic flux. The treatment of a gastric adenocarcinoma cell line (AGS) with the mushroom extract increased the formation of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular levels of LC3-II were also increased, and the cellular levels of p62 decreased, confirming that the extract affects cellular autophagy. Treating the cells with the extract together with lysossomal protease inhibitors, the cellular levels of LC3-II and p62 increased. The results obtained proved that, in AGS cells, the methanolic extract of G. lucidum causes an induction of autophagy, rather than a reduction in the autophagic flux. To our knowledge, this is the first study proving that statement. PMID:26426001

  16. 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

  17. Significantly increased expression of OCT4 and ABCG2 in spheroid body-forming cells of the human gastric cancer MKN-45 cell line

    LIU, Jianming; Wang, Lei; MA, LILIN; Xu, Junfei; Liu, Chun; Zhang, Jianguo; Liu, Jie; CHEN, RUIXIN

    2013-01-01

    The cancer stem cell (CSC) theory hypothesizes that CSCs are the cause of tumor formation, recurrence and metastasis. Key to the study of CSCs is their isolation and identification. The present study investigated whether spheroid body-forming cells in the human gastric cancer (GC) MKN-45 cell line are enriched for CSC properties, and also assessed the expression of the candidate CSC markers, octamer-binding transcription factor-4 (OCT4) and adenosine triphosphate-binding cassette transporter ...

  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. PMID:27203688

  19. Gastric cancer stem cells: A novel therapeutic target

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, ...

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

    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

  1. 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. PMID:26479830

  2. Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products.

    Manu, Kanjoormana A; Shanmugam, Muthu K; Li, Feng; Chen, Luxi; Siveen, Kodappully Sivaraman; Ahn, Kwang Seok; Kumar, Alan Prem; Sethi, Gautam

    2014-03-01

    Chemoresistance remains a major problem in the treatment of gastric cancer patients. Hence, novel pharmacological agents that can overcome drug resistance are urgently required. Whether simvastatin can sensitize the gastric cancer to the antitumor effects of capecitabine in vitro and in vivo was investigated. The effect of simvastatin on the proliferation of gastric cancer cells was examined by mitochondrial dye-uptake 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis by esterase staining, NF-κB activation by DNA binding assay, and protein expression by western blot analysis. The effect of simvastatin on the tumor growth in xenograft mouse model of human gastric cancer was also examined. Simvastatin suppressed the proliferation of gastric cancer cells, enhanced the apoptotic effects of capecitabine, suppressed the constitutive activation of NF-κB, and abrogated the expression of cyclooxygenase-2 (COX-2), cyclin D1, Bcl-2, survivin, CXC motif receptor 4, and MMP-9 proteins. In a xenograft mouse model, we observed that the administration of simvastatin alone (5 mg/kg body weight, intraperitoneal thrice/week) significantly suppressed the growth of the tumor and this effect was further potentiated by capecitabine treatment. As compared to the vehicle control, simvastatin also suppressed the expression of NF-κB-regulated gene products such as cyclin D1, COX-2, ICAM-1, MMP-9, survivin, Bcl-xL, and XIAP in tumor tissues. Overall, our results demonstrate that simvastatin can enhance the effects of capecitabine through suppression of NF-κB-regulated markers of proliferation, invasion, angiogenesis, and metastasis. PMID:24233024

  3. Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

    Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the MDR1 gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the MDR1 gene. Overexpression of MDR1 gene has often been reported in primary gastric adenocarcinoma. This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining. The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (MDR1) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and MDR1 expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy. Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line

  4. Gastric culture

    ... test or procedure preparation (3 to 6 years) School age test or procedure preparation (6 to 12 ... immune system. The final results of the gastric culture test may take several weeks. Your provider will ...

  5. Gastric Banding

    ... gastric banding before deciding to have the procedure. Advertisements for a device or procedure may not include ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  6. 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.

  7. 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.

  8. Apoptosis induced by farrerol in human gastric cancer SGC-7901 cells through the mitochondrial-mediated pathway.

    Liu, Enli; Liang, Taigang; Wang, Xiaojian; Ban, Shurong; Han, Lingge; Li, Qingshan

    2015-09-01

    Farrerol, a typical flavanone isolated from the Chinese medicinal plant Rhododendron dauricum L., has been found to show various biological activities. However, to the best of our knowledge, its inhibitory actions against cancer cells have not been reported as yet. Therefore, the present study aimed to investigate the cytotoxic and apoptotic effects of farrerol on human gastric cancer SGC-7901 cells. Farrerol showed a 50% inhibition of SGC-7901 cell growth at a concentration of 40.4 μmol/l for 24 h according to MTT assays. The cell morphology results indicated that SGC-7901 cells treated with farrerol showed several features of apoptotic cell death, which was also confirmed by the Annexin-V FITC/PI double-staining assay. Further studies showed that farrerol treatment induced the attenuation of mitochondrial membrane potential, accompanied by the release of Cyt-c and the activation of caspase-9 and caspase-3. Furthermore, farrerol decreased the gene expression of Bcl-2, whereas the gene expression level of Bax was found to increase after farrerol treatment. These combined results indicated that farrerol can induce apoptosis through a mitochondrial-mediated pathway. PMID:26061993

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

    Cui, Xinhui; Liang, Tong; Liu, Changsheng; Yuan, Yuan; Qian, Jiangchao

    2016-10-01

    Three types of hydroxyapatite nanoparticles (HAPNs) were synthesized employing a sonochemistry-assisted microwave method by changing microwave power (from 200 to 300W) or using calcination treatment: L200 (200W, lyophilization), L300 (300W, lyophilization) and C200 (200W, lyophilization & calcination). Their physiochemical properties were characterized and correlated with cytotoxicity to human gastric cancer cells (MGC80-3). The major differences among these HAPN preparations were their size and specific surface area, with the L200 showing a smaller size and higher specific surface area. Although all HAPNs inhibited cell proliferation and induced apoptosis of cancer cells, L200 exhibited the greatest toxicity. All types of HAPNs were internalized through energy-dependent pathways, but the L200 nanoparticles were more efficiently uptaken by MGC80-3 cells. Inhibitor studies with dynasore and methyl-β-cyclodextrin suggested that caveolae-mediated endocytosis and, to a much lesser extent, clathrin-mediated endocytosis, were involved in cellular uptake of the various preparations, whereas the inhibition of endocytosis was more obvious for L200. Using fluorescein isothiocyanate-labeled HAPNs and laser-scanning confocal microscopy, we found that all forms of nanoparticles were present in the cytoplasm, and some L200 HAPNs were even found within nuclei. Treatment with all HAPN preparations led to the increase in the intracellular calcium level with the highest level detected for L200. PMID:27287142

  10. 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.

  11. 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.

  12. MiR-503 regulates cisplatin resistance of human gastric cancer cell lines by targeting IGF1R and BCL2

    Wang Tongshan; Ge Gaoxia; Ding Yin; Zhou Xin; Huang Zebo; Zhu Wei; Shu Yongqian

    2014-01-01

    Background Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs (miRNAs).We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell lines.Methods MiR-503 expression was measured by quantitative real-time PCR.MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA.A dual-luciferase activity assay was used to verify target genes of miR-503.Immunohistochemistry,Western blotting analysis,and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer cells.Results MiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell lines.Additionally,downregulation of miR-503 in the cisplatin (DDP)-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor (IGF1R) and B-cell lymphoma 2 (BCL2) expression compared with the parental SGC7901 cell line.An in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to cisplatin.The luciferase activity of reporters driven by IGF1R and BCL2 3'-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of miR-503.Enforced miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins,inhibited proliferation,and sensitized the cells to DDP-induced apoptosis.Conclusion Our findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.

  13. Human-Computer adaptation for EEG based communication

    Garcia, G. N.; Ebrahimi, T.; Vesin, J.-M

    2003-01-01

    Brain-computer interface (BCI) systems allow the user to interact with a computer by merely thinking. Successful BCI operation depends on the continuous adaptation of the system to the user and on the user motivation. This paper presents a model of continuous adaptation using kernel based dynamic data characterization. Additionally, the adaptive capabilities of the brain are engaged by providing feedback to the user who can modulate her mental activity so as to make the BCI accomplish her int...

  14. The oxytocin/vasopressin receptor antagonist atosiban delays the gastric emptying of a semisolid meal compared to saline in human

    Ekberg Olle; Björgell Ola; Ohlsson Bodil; Darwiche Gassan

    2006-01-01

    Abstract Background Oxytocin is released in response to a meal. Further, mRNA for oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract. The aim of this study was therefore to examine whether oxytocin, or the receptor antagonist atosiban, influence the gastric emptying. Methods Ten healthy volunteers (five men) were examined regarding gastric emptying at three different occasions: once during oxytocin stimulation using a pharmacological dose; once during blockag...

  15. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma

    A previous report described the isolation of a directly transforming retrovirus, AKT8, from a spontaneous thymoma of an AKR mouse. The AKT8 provirus has now been molecularly cloned from a transformed, nonproducer cell line. The virus genome contains both viral and nonviral, cell-related sequences; the nonviral sequence has been designated v-akt, the presumed viral oncogene of the AKT8 virus. This gene lacks homology to the 16 other oncogenes tested. The cloned provirus has undergone a partial deletion, during cell passage in vitro, that prevents direct demonstration of the transforming ability of this molecular clone. Two human homologues of the v-akt oncogene, AKT1 and AKT2, were cloned. A survey of 225 human tumors for changes involving ATK1 led to the discovery of a 20-fold amplification of this gene in one of the five gastric adenocarcinomas tested. The results demonstrate that AKT8 has the characteristic structure of a directly transforming retrovirus and that it contains a gene derived from highly conserved cellular sequences that may be involved in the pathogenesis of some human malignancies

  16. Aquaporin-3 positively regulates matrix metalloproteinases via PI3K/AKT signal pathway in human gastric carcinoma SGC7901 cells

    Yang Li

    2011-09-01

    Full Text Available Abstract Background matrix metalloproteinases (MMPs are produced by tumor cells, so they may be associated with tumor progression including invasion, migration, angiogenesis and metastasis. Aquaporin-3 (AQP3 also plays a critical role in gastric cancer cell migration and proliferation. Methods In this study, AQP3 was silenced or over-expressed in SGC7901 cells. Results We found a significant decrease in MT1-MMP, MMP-2, and MMP-9 expression after AQP3 knockdown, and a significant increase in MT1-MMP, MMP-2, and MMP-9 expression after AQP3 over-expression in SGC7901 cells. We also found that AQP3 silence led to a significant decrease of phosphorylation of ser473 in AKT in SGC7901 cells. Conclusion Our findings showed that AQP3 might positively regulate MMPs proteins expression through PI3K/AKT signal pathway in human gastric carcinoma SGC7901 cells.

  17. Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery.

    Sterl, Karin; Wang, Songyan; Oestricker, Lauren; Wallendorf, Michael J; Patterson, Bruce W; Reeds, Dominic N; Wice, Burton M

    2016-08-01

    Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of enteroendocrine cells located in the proximal small intestine. Many effects of Xen are mediated by neurotensin receptor-1 on neurons. In healthy humans with normal glucose tolerance (NGT), Xen administration causes diarrhea and inhibits postprandial glucagon-like peptide-1 (GLP-1) release but not insulin secretion. This study determines (i) if Xen has similar effects in humans with Roux-en-Y gastric bypass (RYGB) and (ii) whether neural pathways potentially mediate effects of Xen on glucose homeostasis. Eight females with RYGB and no history of type 2 diabetes received infusions with 0, 4 or 12pmol Xen/kg/min with liquid meals on separate occasions. Plasma glucose and gastrointestinal hormone levels were measured and insulin secretion rates calculated. Pancreatic polypeptide and neuropeptide Y levels were surrogate markers for parasympathetic input to islets and sympathetic tone, respectively. Responses were compared to those in well-matched non-surgical participants with NGT from our earlier study. Xen similarly increased pancreatic polypeptide and neuropeptide Y responses in patients with and without RYGB. In contrast, the ability of Xen to inhibit GLP-1 release and cause diarrhea was severely blunted in patients with RYGB. With RYGB, Xen had no statistically significant effect on glucose, insulin secretory, GLP-1, glucose-dependent insulinotropic peptide, and glucagon responses. However, insulin and glucose-dependent insulinotropic peptide secretion preceded GLP-1 release suggesting circulating GLP-1 does not mediate exaggerated insulin release after RYGB. Thus, Xen has unmasked neural circuits to the distal gut that inhibit GLP-1 secretion, cause diarrhea, and are altered by RYGB. PMID:27288245

  18. Allicin induces apoptosis of the MGC-803 human gastric carcinoma cell line through the p38 mitogen-activated protein kinase/caspase-3 signaling pathway.

    Zhang, Xuecheng; Zhu, Yong; Duan, Wei; Feng, Chen; He, Xuan

    2015-04-01

    Gastric cancer is one of the most common forms of malignant tumor, and the development of anti‑gastric cancer drugs with minimal toxicity is of clinical importance. Allicin is extracted from Allium sativum (garlic). Recent research, including clinical experiments, has shown that garlic has anticancer and tumor suppressive effects. The present study aimed to investigate the effects of allicin on the MGC‑803 human gastric carcinoma cell line, and to further explore the possible mechanisms of its tumor suppressor effects. The effects of allicin on the MGC‑803 cells were initially examined using an 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Hoechst staining was also used, in order to demonstrate the impact of allicin on MGC‑803 cell apoptosis. In addition, western blot analysis was performed to determine the abnormal expression levels of apoptosis‑associated proteins, following the treatment of MGC‑803 cells with allicin. Western blotting was also used to investigate the specific mechanisms underlying allicin‑induced apoptosis of MGC‑803 cells. The rate of MGC‑803 apoptosis was significantly increased, when the concentration and treatment time of allicin were increased. Hoechst staining detected an enhanced rate of apoptosis, and enhanced expression levels of cleaved caspase 3 were determined by western blotting. Notably, the protein expression levels of p38 were increased when the MGC‑803 cells were treated with allicin. The results of the present study suggest that allicin may inhibit the proliferation and induce the apoptosis of MGC‑803 human gastric carcinoma cells, and this may partially be achieved through the enhanced expression of p38 and cleaved caspase 3. PMID:25523417

  19. 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.

    2016-01-01

    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. PMID:27114515

  20. Human population structure and the adaptive response to pathogen-induced selection pressures

    Novembre, John; Han, Eunjung

    2012-01-01

    The past few years of research in human evolutionary genetics have provided novel insights and questions regarding how human adaptations to recent selective pressures have taken place. Here, we review the advances most relevant to understanding human evolution in response to pathogen-induced selective pressures. Key insights come from theoretical models of adaptive evolution, particularly those that consider spatially structured populations, and from empirical population genomic studies of ad...

  1. Human Resources Development Review according to Identity, Integration, Achievement and Adaptation Model

    Sayyed Mohsen Allameh; Javad Shabani Naftchali; Javad Khazaei Pool; Sayyed Mohammad Reza Davoodi

    2012-01-01

    The concept of human resource development review has included two approaches: HRD as a function and HRD as a field. This paper is reviewed human resource development from view point of I-A model (Identity, Integration, Achievement, Adaptation) on the basis of functional and field models as well as general theory. The main goal of the research is to measure dimensions of human resource development including identity, integration, achievement adaptation- among employee of Nowsahr health and tre...

  2. 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.

  3. 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.

  4. (-)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells.

    Xie, Jianhui; Lin, Zhixiu; Xian, Yanfang; Kong, Songzhi; Lai, Zhengquan; Ip, Siupo; Chen, Haiming; Guo, Huizhen; Su, Zuqing; Yang, Xiaobo; Xu, Yang; Su, Ziren

    2016-06-01

    (-)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions. PMID:27017292

  5. 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.

  6. 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.

  7. 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.

  8. Gastric leptin and Helicobacter pylori infection

    Azuma, T; Suto, H.; Ito, Y.; Ohtani, M.; Dojo, M; Kuriyama, M; Kato, T.

    2001-01-01

    BACKGROUND—Leptin regulates feeding behaviour and therefore may be a mediator of anorexia associated with acute and chronic inflammation. Recently, leptin mRNA and leptin protein were found in the gastric epithelium.
AIM—The aim of the present study was to examine the effect of Helicobacter pylori infection on gastric leptin expression to investigate the pathophysiological role of gastric leptin.
METHODS—Surgically resected human stomach tissues were subjected to immunohistochemistry and reve...

  9. 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.

  10. 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

    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 gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were...... consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal....

  11. Adaptive perspectives on human-technology interaction methods and models for cognitive engineering and human-computer interaction

    Kirlik, Alex

    2009-01-01

    In everyday life, and particularly in the modern workplace, information technology and automation increasingly mediate, augment, and sometimes even interfere with how humans interact with their environment. How to understand and support cognition in human-technology interaction is both a practically and socially relevant problem. The chapters in this volume frame this problem in adaptive terms: How are behavior and cognition adapted, or perhaps ill-adapted, to the demands and opportunities of an environment where interaction is mediated by tools and technology? The authors draw heavily on the

  12. Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells

    PTEN is a tumor suppressor gene that is frequently mutated or deleted in a variety of human cancers including human gastric cancer. PTEN functions primarily as a lipid phosphatase and plays a key role in the regulation of the PI3 kinase/Akt pathway, thereby modulating cell proliferation and cell survival. On the other hand, the IGF system plays an important role in cell proliferation and cell survival via the PI3 kinase/Akt and MAP kinase pathways in many cancer cells. To characterize the impact of PTEN on the IGF-IGFR-IGFBP axis in gastric cancer, we overexpressed PTEN using an adenovirus gene transfer system in human gastric adenocarcinoma cells, SNU-484 and SNU-663, which lack PTEN. Overexpression of PTEN inhibited serum-induced as well as IGF-I-induced cell proliferation as compared to control cells. PTEN overexpression resulted in a significant decrease in the expression of IGF-I, -II, and IGF-IR. Interestingly, amongst the six IGFBPs, only IGFBP-3 was upregulated by PTEN, whereas IGFBP-4 and -6 were reduced. The IGFBP-3 promoter activity assay and Western immunoblotting demonstrate that PTEN regulates IGFBP-3 at the transcriptional level. In addition, the PI3 kinase inhibitor, LY294002, upregulates IGFBP-3 expression but downregulates IGF-I and IGF-II, indicating that PTEN controls IGFBP-3 and IGFs by an Akt-dependent pathway. These findings suggest that PTEN may inhibit antiapoptotic IGF actions not only by blocking the IGF-IGFR-induced Akt activity, but also by regulating expression of components of the IGF system, in particular, upregulation of IGFBP-3, which is known to exert antiproliferative effects through IGF-dependent and IGF-independent mechanisms in cancer cells

  13. ADENOVIRUS-MEDIATED P53 GENE TRANSFER INCREASES THE THERMOSENSITIVITY OF HUMAN GASTRIC CARCINOMA CELL LINES (IN VITRO AND IN VIVO)

    张珊文; 肖绍文; 吕有勇

    2003-01-01

    Objective: To investigate the effect of adenovirus- mediated p53 (Adp53) transfer on thermosensitivity of human gastric carcinoma cell lines (BGC823). Methods: Two human gastric carcinoma cell lines with different p53 status, BGC823-wtp53 cell (abbreviate W) bearing the wilt-type p53 and BGC823-mutp53 cell (abbreviate M) bearing the mutant p53, were cultured with DMEM medium and were infected with Adp53 at a viral multiplicity of infection of 100 (1:100MOI) for 48h before heating. Cell cycle redistribution and apoptosis of two human gastric carcinoma cell lines in 24h at 37℃ after heat treatment at 42℃ for 2h or 43℃ for 0.5h were analyzed by flow cytometry. Relative tumor volume growth curves were used in a nude mouse tumor model of the two cell lines following hyperthermia at 43℃ for 0.5h after 48h intratumoral injection of 1(108 pfu of Adp53 to evaluate thermoenhancemet effect in vivo. Results: In vitro study showed that both W and M cells infected with Adp53 and treated with heating had strong arrest in G2 (after heating at 42℃ for 2h, 34.0% of original population for W cells and 25.3% of original population for M cells) and produced obvious apoptotic response. The apoptosis rate showed 230% increased (for W cells) and 110% increase (for M cells) compared with heating only control. In vivo study showed that the growth of tumor of both W cells and M cells was significantly delayed by hyperthemia combining with Adp53 as compared to tumors receiving either treatment alone. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and thermo- sensitivity in vitro and tumor thermosensitivity in vivo independent of cellular intrinsic p53 status. These results support the combined used of p53 gene therapy with hyperthermia in clinical trials.

  14. 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.

  15. [Gastric Acid].

    Ruíz Chávez, R

    1996-01-01

    Gastric acid, a product of parietal cells secretion, full fills multiple biological roles which are absolutely necessary to keep corporal homeostasis. The production of the acid depends upon an effector cellular process represented in the first step by histamine, acetilcholine and gastrin, first messengers of the process. These interact with specific receptors than in sequence activate second messengers -cAMP and the calcium-calmodulin system- which afterwards activate a kinase. An specific protein is then phosphorilated by this enzyme, being the crucial factor that starts the production of acid. Finally, a proton bomb, extrudes the acid towards the gastric lumen. The secretion process mentioned above, is progressive lyactivated in three steps, two of which are stimulators -cephalic and gastric phases- and the other one inhibitor or intestinal phase. These stages are started by mental and neurological phenomena -thought, sight, smell or memory-; by food, drugs or other ingested substances; and by products of digestion. Changes in regulation of acid secretion, in the structure of gastro-duodenal mucosal barrier by a wide spectrum of factors and agents including food, drugs and H. pylori, are the basis of acid-peptic disease, entity in which gastric acid plays a fundamental role. From the therapeutic point of view, so at the theoretical as at the practical levels, t is possible to interfere with the secretion of acid by neutralization of some of the steps of the effector cellular process. An adequate knowledge of the basics related to gastric acid, allows to create strategies for the clinical handling of associated pathology, specifically in relation to peptic acid disease in all of the known clinical forms. PMID:12165790

  16. Preliminary study on guiding therapy of subcutaneous human hetero graft in nude mice by 211-At labelled monoclonal antibody against gastric cancer

    In short time, 211At labelled monoclonal antibody 3H11 inhibited the growth of human gastric cancer grafted in nude mice effectively. The most evident inhibition was observed at the 9th day after treatment, and the tumor inhibition rates were 80%, 93%, 48% in the groups of intravenous injection, internal tumor injection (both 211At-3H11 5 μCi per animal), Na211 At (5 μCi per animal) treatment respectively. On the 20th day, when animals were killed, the tumor inhibition rates were 66%, 81%, 6%, respectively. Inhibition treated with Na211At showed obviously lower than those at the 9th day

  17. 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;

  18. Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

    Sander L J Wijers; Schrauwen, Patrick; Saris, Wim H. M.; van Marken Lichtenbelt, Wouter D.

    2008-01-01

    Background Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupli...

  19. Experimental Investigation of Human Adaptation to Change in Agent's Strategy through a Competitive Two-Player Game

    Terada, Kazunori; Yamada, Seiji; Ito, Akira

    We conducted an experimental investigation on human adaptation to change in an agent's strategy through a competitive two-player game. Modeling the process of human adaptation to agents is important for designing intelligent interface agents and adaptive user interfaces that learn a user's preferences and behavior strategy. However, few studies on human adaptation to such an agent have been done. We propose a human adaptation model for a two-player game. We prepared an on-line experimental system in which a participant and an agent play a repeated penny-matching game with a bonus round. We then conducted experiments in which different opponent agents (human or robot) change their strategy during the game. The experimental results indicated that, as expected, there is an adaptation phase when a human is confronted with a change in the opponent agent's strategy, and adaptation is faster when a human is competing with robot than with another human.

  20. 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.

  1. Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas.

    Byun, Do-Sun; Cho, Kyucheol; Ryu, Byung-Kyu; Lee, Min-Goo; Kang, Min-Ju; Kim, Hak-Ryul; Chi, Sung-Gil

    2003-11-01

    events in gastric tumorigenesis. Collectively, our study suggests that epigenetic silencing of XAF1 by aberrant promoter methylation may contribute to the malignant progression of human gastric tumors. PMID:14612497

  2. 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...... consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal.......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 gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were...

  3. Acute effect of oral sensation of sweetness on celiac artery blood flow and gastric myoelectrical activity in humans.

    Eguchi, Kohei; Kashima, Hideaki; Yokota, Akiko; Miura, Kohei; Yamaoka Endo, Masako; Hirano, Harutoyo; Tsuji, Toshio; Fukuba, Yoshiyuki

    2016-05-01

    Little is known about the effect of sweet taste stimulus on gastrointestinal motility and splanchnic blood flow. We examined whether gastric myoelectrical activity and/or celiac artery blood flow (CABF), which perfuses the stomach, are increased following an oral sensation of sweetness. After overnight fasting, 11 subjects rested for 5min and sipped, but not swallowed, one of four solutions for 1min. The fluid was then spat out, and subjects remained at rest for a further 10min. Fluids were approximately 15ml of three glucose solutions (4, 16, or 48%) or distilled water. Subjects completed trials with all four solutions in a randomized order. During each trial, gastric myoelectrical activity and CABF were continuously measured using electrogastrography and pulsed Doppler ultrasonography, respectively. None of the four solutions affected gastric myoelectrical activity. CABF was significantly increased after oral stimuli by all three glucose solutions, but not by water. There were no significant differences in the increments in CABF among the three glucose solutions. These results suggest that a sweet taste stimulus above a certain level of intensity acutely increases CABF during cephalic phase, without augmentation of gastric myoelectrical activity. PMID:26987409

  4. Effect of ionizing radiation on gastric secretion and gastric motility in monkeys

    The prodromal syndrome of radiation sickness is characterized by nausea and vomiting but the pathophysiology and the treatment of this entity is largely unknown. The authors investigated this problem by determining the effects of ionizing radiation on gastric function with and without administration of the dopamine antagonist domperidone. They measured gastric electrical control activity (waves per minute), fractional emptying rate (percent per minute), acid output (microequivalents per minute), and plasma levels of immunoreactive beta-endorphin. Twelve conscious, chair-adapted rhesus monkeys were studied twice before, once immediately after, and once 2 days after a single 800-cGy (800 rads) 60Co total body irradiation. In addition to causing vomiting, total body irradiation transiently suppressed gastric electrical control activity, gastric emptying and gastric secretion, while increasing plasma levels of immunoreactive beta-endorphin. Domperidone had no effect on vomiting or gastric function either before or after irradiation, but it significantly increased plasma immunoreactive beta-endorphin

  5. Studying of the DNA DSBs repair in the adaptive response of human lymphocytes

    Human lymphocytes exposed to very low doses of DNA damaging agents may become less sensitive to subsequent higher doses of the DNA damaging agent. This phenomenon is called the adaptive response. The aim of this project was to study the significance of DNA double-strand break (DSBs) repair in the adaptive response of human lymphocytes exposed to ionizing radiation. Human lymphocytes isolated from whole blood and stimulated with hemagglutynin (PHA) were irradiated with adaptive dose (5 cGy of X-rays) and then challenge dose of 2 Gy in case of micronuclei assay and 10 Gy in case of comet assay. The frequency of micronuclei in adapted lymphocytes was about 30% lower than expected for an additive effect of both, adaptive and challenge doses, applied separately. Estimation of DSBs was carried out with the use of single cell gel electrophoresis assay (comet assay) in neutral pH and to complement these results with pulse-field gel electrophoresis (PFGE). The use of both PFGE and comet assay allowed us to suggest that lower damage revealed in the adapted lymphocytes at the chromosomal level was unrelated to initial level of DSBs in DNA. The differences between kinetics of DNA repair in the adapted and non-adapted lymphocytes were not significant. (author)

  6. 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.

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

    Tait, Peter W; Hanna, Elizabeth G

    2015-09-01

    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

  8. Comparative Genomics of Helicobacter pylori and the human-derived Helicobacter bizzozeronii CIII-1 strain reveal the molecular basis of the zoonotic nature of non-pylori gastric Helicobacter infections in humans

    Schott Thomas

    2011-10-01

    Full Text Available Abstract Background The canine Gram-negative Helicobacter bizzozeronii is one of seven species in Helicobacter heilmannii sensu lato that are detected in 0.17-2.3% of the gastric biopsies of human patients with gastric symptoms. At the present, H. bizzozeronii is the only non-pylori gastric Helicobacter sp. cultivated from human patients and is therefore a good alternative model of human gastric Helicobacter disease. We recently sequenced the genome of the H. bizzozeronii human strain CIII-1, isolated in 2008 from a 47-year old Finnish woman suffering from severe dyspeptic symptoms. In this study, we performed a detailed comparative genome analysis with H. pylori, providing new insights into non-pylori Helicobacter infections and the mechanisms of transmission between the primary animal host and humans. Results H. bizzozeronii possesses all the genes necessary for its specialised life in the stomach. However, H. bizzozeronii differs from H. pylori by having a wider metabolic flexibility in terms of its energy sources and electron transport chain. Moreover, H. bizzozeronii harbours a higher number of methyl-accepting chemotaxis proteins, allowing it to respond to a wider spectrum of environmental signals. In this study, H. bizzozeronii has been shown to have high level of genome plasticity. We were able to identify a total of 43 contingency genes, 5 insertion sequences (ISs, 22 mini-IS elements, 1 genomic island and a putative prophage. Although H. bizzozeronii lacks homologues of some of the major H. pylori virulence genes, other candidate virulence factors are present. In particular, we identified a polysaccharide lyase (HBZC1_15820 as a potential new virulence factor of H. bizzozeronii. Conclusions The comparative genome analysis performed in this study increased the knowledge of the biology of gastric Helicobacter species. In particular, we propose the hypothesis that the high metabolic versatility and the ability to react to a range of

  9. Adapt

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  10. Nutrition and human physiological adaptations to space flight

    Lane, H. W.; LeBlanc, A. D.; Putcha, L.; Whitson, P. A.

    1993-01-01

    Space flight provides a model for the study of healthy individuals undergoing unique stresses. This review focuses on how physiological adaptations to weightlessness may affect nutrient and food requirements in space. These adaptations include reductions in body water and plasma volume, which affect the renal and cardiovascular systems and thereby fluid and electrolyte requirements. Changes in muscle mass and function may affect requirements for energy, protein and amino acids. Changes in bone mass lead to increased urinary calcium concentrations, which may increase the risk of forming renal stones. Space motion sickness may influence putative changes in gastro-intestinal-hepatic function; neurosensory alterations may affect smell and taste. Some or all of these effects may be ameliorated through the use of specially designed dietary countermeasures.

  11. Adaptive Human aware Navigation based on Motion Pattern Analysis

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

    2009-01-01

    are based on run-time motion pattern analysis compared to stored experience in a database. Using a potential field centered around the person, the robot positions itself at the most appropriate place relative to the person and the interaction status. The system is validated through qualitative tests...... 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....

  12. Spatiotopic perceptual maps in humans: evidence from motion adaptation

    Turi, M.; Burr, D.

    2012-01-01

    How our perceptual experience of the world remains stable and continuous despite the frequent repositioning eye movements remains very much a mystery. One possibility is that our brain actively constructs a spatiotopic representation of the world, which is anchored in external—or at least head-centred—coordinates. In this study, we show that the positional motion aftereffect (the change in apparent position after adaptation to motion) is spatially selective in external rather than retinal coo...

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

    Levett, Denny Z; Fernandez, Bernadette O.; Riley, Heather L.; Martin, Daniel S; Kay Mitchell; Leckstrom, Carl A.; Can Ince; Brian J. Whipp; Mythen, Monty G; Montgomery, Hugh E.; Grocott, Mike P.; Martin Feelisch

    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 biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxide...

  14. Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas

    Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation. Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0. From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%). Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively

  15. 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

  16. 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...

  17. Human Adaptation in the Light of Ancient and Modern Genomes

    Key, Felix-Michael

    2016-01-01

    Modern humans originated in Africa around 200,000 years ago and today have settled in nearly every corner of earth. During migrations humans became exposed to new pathogens, food sources and have encountered vastly different environments. Natural selection likely contributed to the survival under such diverse conditions by promoting the raise in frequency of advantageous alleles. Thereby natural selection leaves genetic footprints that we can identify. The thesis at hand is about understandin...

  18. Human adaptive mechatronics methods for mobile working machines

    Tervo, Kalevi

    2010-01-01

    Despite the trend of increasing automation degree in control systems, human operators are still needed in applications such as aviation and surgery, or machines used in remote mining, forestry, construction, and agriculture, just to name a few. Although there are research results showing that the performance between the operators of working machines differ significantly, there are currently no means to improve the performance of the human-machine system automatically based on the skill and wo...

  19. Social Interactions Model and Adaptability of Human Behavior

    Kun eZhao; Ginestra eBianconi

    2011-01-01

    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 soc...

  20. Research on operation and maintenance support system adaptive to human recognition and understanding in human-centered plant

    As a human-centered plant, advanced nuclear power plant needs appropriate role sharing between human and mobile intelligent agents. Human-machine cooperation for plant operation and maintenance activities is also required with an advanced interface. Plant's maintenance is programmed using mobile robots working under the radiation environments instead of human beings. Operation and maintenance support system adaptive to human recognition and understanding should be developed to establish adequate human and machine interface so as to induce human capabilities to the full and enable human to take responsibility for plan's operation. Plant's operation and maintenance can be cooperative activities between human and intelligent automonous agents having surveillance and control functions. Infrastructure of multi-agent simulation system for the support system has been investigated and developed based on work plans derived from the scheduler. (T. Tanaka)

  1. The oxytocin/vasopressin receptor antagonist atosiban delays the gastric emptying of a semisolid meal compared to saline in human

    Ekberg Olle

    2006-03-01

    Full Text Available Abstract Background Oxytocin is released in response to a meal. Further, mRNA for oxytocin and its receptor have been found throughout the gastrointestinal (GI tract. The aim of this study was therefore to examine whether oxytocin, or the receptor antagonist atosiban, influence the gastric emptying. Methods Ten healthy volunteers (five men were examined regarding gastric emptying at three different occasions: once during oxytocin stimulation using a pharmacological dose; once during blockage of the oxytocin receptors (which also blocks the vasopressin receptors and thereby inhibiting physiological doses of oxytocin; and once during saline infusion. Gastric emptying rate (GER was assessed and expressed as the percentage reduction in antral cross-sectional area from 15 to 90 min after ingestion of rice pudding. The assessment was performed by real-time ultrasonography. At the same time, the feeling of satiety was registered using visual satiety scores. Results Inhibition of the binding of endogenous oxytocin by the receptor antagonist delayed the GER by 37 % compared to saline (p = 0.037. In contrast, infusion of oxytocin in a dosage of 40 mU/min did not affect the GER (p = 0.610. Satiation scores areas in healthy subjects after receiving atosiban or oxytocin did not show any significant differences. Conclusion Oxytocin and/or vasopressin seem to be regulators of gastric emptying during physiological conditions, since the receptor antagonist atosiban delayed the GER. However, the actual pharmacological dose of oxytocin in this study had no effect. The effect of oxytocin and vasopressin on GI motility has to be further evaluated.

  2. L-lysine dose dependently delays gastric emptying and increases intestinal fluid volume in humans and rats

    Baruffol, C; Jordi, J; Camargo, S.; RADOVIC, T; Herzog, B.; Fried, M; Schwizer, W; Verrey, F; Lutz, T. A.; Steingoetter, A

    2014-01-01

    BACKGROUND: Novel sensory inputs for the control of food intake and gastrointestinal (GI) function are of increasing interest due to the rapid increase in nutrition-related diseases. The essential amino acid L-lysine was demonstrated to have a selective impact on food intake, gastric emptying, and intestinal transit in rats, thus indicating a potential novel direct sensory input to assess dietary protein content and quality. The aim of this study was to assess translational aspects of this fi...

  3. 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.

  4. Stage-specific Dietary Factors Associated with the Correa Multistep and Multifactorial Process of Human Gastric Carcinogenesis.

    Hsiung, Hui-Yin; Fann, Jean Ching-Yuan; Yen, Amy Ming-Fang; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Ku, Tsung-Ho; Liu, Tzeng-Ying; Chen, Hsiu-Hsi; Lin, Ming-Wei

    2016-01-01

    We assessed how individual dietary intakes act at different points in the chain of sequential stage of the Correa model in an area of Taiwan with high incidence of gastric cancer (GC). Using data on 2,201 participants in a two-stage screening for gastric neoplasia with pepsinogen test, we identified 154 superficial gastritis (SG), 32 atrophic gastritis (AG), 117 intestinal metaplasia (IM), and 22 GC. Effects of individual item-based and construct-based dietary variables aggregated by factor analysis on each stage of gastric neoplasm were assessed. Based on 1,211 subjects with complete information on serological test and dietary questionnaire, SG was associated with positive quartile trend for the intake of meat (trend test P = 0.0014) and the intake of fruits and leafy vegetables (trend test P = 0.0177), but with the negative trend for the intake of shrimp sauce (trend test P = 0.039). A significant positive association was noted between milk and AG (trend test P = 0.014) and IM (P = 0.0087). A positive association between seafood and IM was noted (P = 0.011). Frequent leafy vegetable intake based on individual item was inversely associated with GC (P = 0.0084), whereas frequent intake of meat showed a high positive association (P<0.001). Stage-specific dietary factors underpinning the Correa model were identified. PMID:27042805

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

    Hanna, Elizabeth G.; Peter W. Tait

    2015-01-01

    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. Clim...

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

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

    and the concept of coupled human-environmental timelines. Secondly, with point of departure in a baseline characterization of Bellona Island derived from a comprehensive survey in the late 1960s and resent fieldwork in late 2006, we present the case of Bellona Island. Key issues addressed concern climatic events...

  7. Shear stress mediates endothelial adaptations to exercise training in humans.

    Tinken, T.M.; Thijssen, D.H.J.; Hopkins, N.; Dawson, E.A.; Cable, N.T.; Green, D.J.

    2010-01-01

    Although episodic changes in shear stress have been proposed as the mechanism responsible for the effects of exercise training on the vasculature, this hypothesis has not been directly addressed in humans. We examined brachial artery flow-mediated dilation, an index of NO-mediated endothelial functi

  8. Assessing employability capacities and career adaptability in a sample of human resource professionals

    Melinde Coetzee; Nadia Ferreira; Ingrid L. Potgieter

    2015-01-01

    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 fo...

  9. 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.

  10. 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.

  11. The spread of adaptation in human foveal and parafoveal cone vision.

    Cicerone, C M; Hayhoe, M M; MacLeod, D I

    1990-01-01

    We investigated the spread of bleaching adaptation for human cone vision in the central fovea and at an eccentricity of 5 deg in the nasal retina. Cone thresholds measured after adaptation to a grating bleach were compared to those measured after a uniform bleach. We conclude that the foveal and parafoveal cone systems show excellent localization of the effects of adaptation. For areas 2.5-5 min removed from the bleach, our measurement show only small sensitivity losses amounting to between 0.10 and 0.25 log unit elevation in threshold, after taking account of optical scatter. PMID:2288078

  12. Adaptive thermogenesis in human body weight regulation: more of a concept than a measurable entity?

    Dulloo, Abdul G; JACQUET, JEAN; Montani, Jean-Pierre; Schutz, Yves

    2012-01-01

    According to Lavoisier, ‘Life is combustion’. But to what extent humans adapt to changes in food intake through adaptive thermogenesis – by turning down the rate of heat production during energy deficit (so as to conserve energy) or turning it up during overnutrition (so as to dissipate excess calories) – has been one of the most controversial issues in nutritional sciences over the past 100 years. The debate nowadays is not whether adaptive thermogenesis exists or not, but rather about its q...

  13. Identification of Adaptation in Human Postural Control using GARCH Models

    Johansson, Rolf; Fransson, Per-Anders; Magnusson, Måns

    2001-01-01

    Human postural dynamics was investigated in twelve normal subjects by means of a force platform recording body sway induced by bipolar transmastoid galvanic stimulation of the vestibular nerve and labyrinth. We modeled the stabilizing forces actuated by the feet as resulting from complex muscular activity subject to feedback of body velocity and position. Time series analysis demonstrated that a transfer function from stimulus to sway-force response with specific parameters could be identifie...

  14. Molecular networks of human muscle adaptation to exercise and age.

    Phillips, Bethan E.; Williams, John P; Thomas Gustafsson; Claude Bouchard; Tuomo Rankinen; Steen Knudsen; Kenneth Smith; Timmons, James A.; Atherton, Philip J.

    2013-01-01

    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%),...

  15. Molecular networks of human muscle adaptation to exercise and age

    Phillips, Bethan E.; Williams, John P; Gustafsson, Thomas; Bouchard, Claude; Rankinen, Tuomo; Knudsen, Steen; Smith, Kenneth; Timmons, James A; Atherton, Philip J

    2013-01-01

    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%),...

  16. Molecular Networks of Human Muscle Adaptation to Exercise and Age

    Phillips, Bethan E.; Williams, John P; Gustafsson, Thomas; Bouchard, Claude; Rankinen, Tuomo; Knudsen, Steen; Smith, Kenneth; Timmons, James A; Atherton, Philip J

    2013-01-01

    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%),...

  17. The long non-coding RNA H19-derived miR-675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1

    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. Evidence for adaptive design in human gaze preference.

    Conway, C A; Jones, B C; DeBruine, L M; Little, A C

    2008-01-01

    Many studies have investigated the physical cues that influence face preferences. By contrast, relatively few studies have investigated the effects of facial cues to the direction and valence of others' social interest (i.e. gaze direction and facial expressions) on face preferences. Here we found that participants demonstrated stronger preferences for direct gaze when judging the attractiveness of happy faces than that of disgusted faces, and that this effect of expression on the strength of attraction to direct gaze was particularly pronounced for judgements of opposite-sex faces (study 1). By contrast, no such opposite-sex bias in preferences for direct gaze was observed when participants judged the same faces for likeability (study 2). Collectively, these findings for a context-sensitive opposite-sex bias in preferences for perceiver-directed smiles, but not perceiver-directed disgust, suggest gaze preference functions, at least in part, to facilitate efficient allocation of mating effort, and evince adaptive design in the perceptual mechanisms that underpin face preferences. PMID:17986435

  19. Human adaptive behavior in common pool resource systems.

    Gunnar Brandt

    Full Text Available Overexploitation of common-pool resources, resulting from uncooperative harvest behavior, is a major problem in many social-ecological systems. Feedbacks between user behavior and resource productivity induce non-linear dynamics in the harvest and the resource stock that complicate the understanding and the prediction of the co-evolutionary system. With an adaptive model constrained by data from a behavioral economic experiment, we show that users' expectations of future pay-offs vary as a result of the previous harvest experience, the time-horizon, and the ability to communicate. In our model, harvest behavior is a trait that adjusts to continuously changing potential returns according to a trade-off between the users' current harvest and the discounted future productivity of the resource. Given a maximum discount factor, which quantifies the users' perception of future pay-offs, the temporal dynamics of harvest behavior and ecological resource can be predicted. Our results reveal a non-linear relation between the previous harvest and current discount rates, which is most sensitive around a reference harvest level. While higher than expected returns resulting from cooperative harvesting in the past increase the importance of future resource productivity and foster sustainability, harvests below the reference level lead to a downward spiral of increasing overexploitation and disappointing returns.

  20. Concurrent genotyping of Helicobacter pylori virulence genes and human cytokine SNP sites using whole genome amplified DNA derived from minute amounts of gastric biopsy specimen DNA

    Borch Kurt

    2008-10-01

    Full Text Available Abstract Background Bacterial and cellular genotyping is becoming increasingly important in the diagnosis of infectious diseases. However, difficulties in obtaining sufficient amount of bacterial and cellular DNA extracted from the same human biopsy specimens is often a limiting factor. In this study, total DNA (host and bacterial DNA was isolated from minute amounts of gastric biopsy specimens and amplified by means of whole genome amplification using the multiple displacement amplification (MDA technique. Subsequently, MDA-DNA was used for concurrent Helicobacter pylori and human host cellular DNA genotyping analysis using PCR-based methods. Results Total DNA was isolated from gastric biopsy specimens of 12 subjects with gastritis and 16 control subjects having a normal mucosa. The DNA was amplified using a multiple displacement amplification (MDA kit. Next, concurrent genotyping was performed using H. pylori-specific virulence gene PCR amplification assays, pyrosequencing of bacterial 16S rDNA and PCR characterisation of various host genes. This includes Interleukin 1-beta (IL1B and Interferon-gamma receptor (IFNGR1 SNP analysis, and Interleukin-1 receptor antagonist (IL1RN variable tandem repeats (VNTR in intron 2. Finally, regions of the vacA-gene were PCR amplified using M13-sequence tagged primers which allowed for direct DNA sequencing, omitting cloning of PCR amplicons. H. pylori specific multiplex PCR assays revealed the presence of H. pylori cagA and vacA genotypic variations in 11 of 12 gastritis biopsy specimens. Using pyrosequencing, 16S rDNA variable V3 region signatures of H. pylori were found in 11 of 12 individuals with gastritis, but in none of the control subjects. Similarly, IL1B and IFNGR1-SNP and IL1RN-VNTR patterns could be established in all individuals. Furthermore, sequencing of M13-sequence tagged vacA-PCR amplicons revealed the presence of highly diverse H. pylori vacA-s/i/m regions. Conclusion The PCR

  1. Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway

    Jing LI; Lin SHEN; Fu-rong LU; You QIN; Rui CHEN; Jia LI; Yan LI; Han-zi ZHAN; Yuan-qiao HE

    2012-01-01

    Aim:To investigate the effects and underlying mechanisms of plumbagin,a naphthoquinone derived from medicinal plant Plumbago zeylanica,on human gastric cancer (GC) cells.Methods:Human gastric cancer cell lines SGC-7901,MKN-28,and AGS were used.The cell viability was examined using CCK-8 viability assay.Cell proliferation rate was determined using both clonogenic assay and EdU incorporation assay.Apoptosis was detected via Annexin V/propidium iodide double-labeled flow cytometry.Western blotting was used to assess the expression of both NF-κBregulated gene products and TNF-α-induced activation of p65,IKBα,and IKK.The intracellular location of NF-κB p65 was detected using confocal microscopy.Results:Plumbagin (2.5-40 μmol/L) concentration-dependently reduced the viability of the GC cells.The IC50 value of plumbagin in SGC-7901,MKN-28,and AGS cells was 19.12,13.64,and 10.12 μmol/L,respectively.The compound (5-20 μmol/L) concentrationdependently induced apoptosis of SGC-7901 cells,and potentiated the sensitivity of SGC-7901 cells to chemotherapeutic agents TNFαand cisplatin.The compound (10 μmol/L) downregulated the expression of NF-κB-regulated gene products,including lAP1,XlAP,Bcl2,Bcl-xL,tumor factor (TF),and VEGF.In addition to inhibition of NF-κB p65 nuclear translocation,the compound also suppressed TNF-α-induced phosphorylation of p65 and IKK,and the degradation of IκBα.Conclusion:Plumbagin inhibits cell growth and potentiates apoptosis in human GC cells through the NF-κB pathway.

  2. Human migration and displacement in the context of adaptation to climate change: the Cancun Adaptation Framework and potential for future action

    Koko Warner

    2012-01-01

    The first-time-ever agreed-upon text on migration, displacement, and planned relocation in the United Nations Framework Convention on Climate Change (UNFCCC) climate negotiations process was informed by recent empirical research, and will shape how human mobility is dealt with under adaptation. Migration, displacement, and planned relocation feature in the text of the Cancun Adaptation Framework as technical cooperation issues which highlight activities that help to guide adaptation funding. ...

  3. 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.

  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. Comparison of adaptive response to γ-radiation and nickel sulfate treatment in human cells

    The comparison of the adaptive response to the impact of the γ-irradiation and nickel sulfate treatment in human cells, as the adaptive factors relative to these mutagens in the challenging doses by the cells survival criterium, is carried out. The pretreatment of human fibroblasts (the rhabdomyosarcoma line) with the low dose γ-radiation (10-14 cGy) formed increased viability of human cells to the nickel sulfate high concentrations (10-5-10-3 M). The adaptive response observed was similar to the radioadaptive response in human fibroblasts pretreated with low doses of γ-radiation with subsequent impact of high dose radiation. The pretreatment of human cells with the nickel sulfate low concentrations induced the DNA increased stability by impact of challenging doses of the γ-radiation and stimulated the DNA reparative synthesis by impact of both NiSO4 and 4-nitroquinoline-1-oxide. These data confirm the existence of the cross-sectional adaptive response in the experiments with the nickel sulfate

  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. Molecular networks of human muscle adaptation to exercise and age.

    Phillips, Bethan E; Williams, John P; Gustafsson, Thomas; Bouchard, Claude; Rankinen, Tuomo; Knudsen, Steen; Smith, Kenneth; Timmons, James A; Atherton, Philip J

    2013-03-01

    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

  8. Primary Gastric Chorioadenocarcinoma.

    Baraka, Bahaaeldin A; Al Kharusi, Suad S; Al Bahrani, Bassim J; Bhathagar, Gunmala

    2016-09-01

    Primary gastric chorioadenocarcinoma (PGC) is a rare and rapidly invasive tumor. Choriocarcinoma is usually known to be of endometrial origin and gestational; however, it has been reported in other extragenital organs, such as the gall bladder, prostate, lung, liver, and the gastrointestinal tract. Human chorionic gonadotropin related neoplasms of the stomach are seldom discussed in the literature. We report a case of PGC in a 56-year-old man treated with a standard non-gestational choriocarcinoma chemotherapy regimen, EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), with a complete response and good tolerability. PMID:27602194

  9. 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. PMID:26715411

  10. 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.

  11. Gastric mucosal blood flow measurement

    Pertechnetate clearance (C/sub Tc/) by the stomach before and after betazole stimulation was compared to regional measurements of gastric blood flow utilizing nuclide (Chromium-51 and Cerium-141)-labeled microspheres in five piglets. Pertechnetate clearance closely correlated (correlation coefficient 0.926) with mucosal blood flow in the gastric corpus measured by the microsphere technique. Betazole increased blood flow in the corpus region by 100 percent but did not alter this relationship. Except in one experiment, microsphere blood flow valves in the antrum and fundus were unchanged by betazole and did not significantly correlate with pertechnetate clearance. Pertechnetate clearance appears to be a reliable method of determining gastric mucosal blood flow in experimental animals and may be considered as a noninvasive method for measuring such flow in humans. (U.S.)

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

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

    1991-01-01

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

  13. Expression of Telomerase Subunits in Gastric Cancer

    CHEN Fenghua; HU Lihua; LI Yirong; WANG Lin

    2005-01-01

    To detect the expression of telomerase subunits human telomerase reverse transcriptase, human telomerase associated protein 1 and human telomerase RNA) in gastric cancer and to examine the role that different telomerase subunits play in the gastric carcinogenesis, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect telomerase subunits messenger RNA in 24 samples of gastric cancer and corresponding non-cancerous tissue. The results showed that the positive rate of hTERT mRNA from gastric cancer and corresponding non-cancerous tissues was 100 % and 25 %, respectively. The former was significantly higher than the latter (χ2 =26.4, P<0.01). The positive rate of hTEP1 mRNA from gastric cancer and corresponding non-cancerous tissues was 100 % and 91.7 %, respectively and no significant difference was found between them (χ2 =2.1, P>0.05). The positive rates of hTR for gastric cancer and corresponding non-cancerous tissues were both 100 % and no significant difference existed between them. It is concluded that in contrast to hTEP1 and hTR, the up-regulation of hTERT mRNA expression may play a more important role in the development of gastric cancer.

  14. 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.

  15. Middle Holocene rapid environmental changes and human adaptation in Greece

    Lespez, Laurent; Glais, Arthur; Lopez-Saez, José-Antonio; Le Drezen, Yann; Tsirtsoni, Zoï; Davidson, Robert; Biree, Laetitia; Malamidou, Dimitra

    2016-03-01

    Numerous researchers discuss of the collapse of civilizations in response to abrupt climate change in the Mediterranean region. The period between 6500 and 5000 cal yr BP is one of the least studied episodes of rapid climate change at the end of the Late Neolithic. This period is characterized by a dramatic decline in settlement and a cultural break in the Balkans. High-resolution paleoenvironmental proxy data obtained in the Lower Angitis Valley enables an examination of the societal responses to rapid climatic change in Greece. Development of a lasting fluvio-lacustrine environment followed by enhanced fluvial activity is evident from 6000 cal yr BP. Paleoecological data show a succession of dry events at 5800-5700, 5450 and 5000-4900 cal yr BP. These events correspond to incursion of cold air masses to the eastern Mediterranean, confirming the climatic instability of the middle Holocene climate transition. Two periods with farming and pastural activities (6300-5600 and 5100-4700 cal BP) are evident. The intervening period is marked by environmental changes, but the continuous occurrence of anthropogenic taxa suggests the persistence of human activities despite the absence of archaeological evidence. The environmental factors alone were not sufficient to trigger the observed societal changes.

  16. Gastric cancer

    Although gastric cancers are localized and surgically resectable in approximately 50% of patients at the time of diagnosis, regional metastases and direct invasion of surrounding structures frequently preclude cure by surgery alone. With recurrent or metastatic disease, some palliation can be obtained by chemotherapy, surgery, or irradiation, but few patients can actually be cured. This chapter addresses the rationale for adjuvant treatment in resectable disease and discusses results with single or combined modalities in locally advanced disease. The chapter also discusses future possibilities for aggressive combined modality approaches in patients who have undergone resection but are at high risk, who have undergone resection but have residual disease, or who have locally unresectable or recurrent disease

  17. 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

  18. Edited Adaptive Hypermedia: Combining Human and Machine Intelligence to Achieve Filtered Information

    Höök, Kristina; Rudström, Åsa; Waern, Annika

    1997-01-01

    We discuss a novel approach to filtering of hypermedia information based on an information broker and user environment coupled together. The advantage of the proposed approach, edited adaptive hypermedia, is that it combines human expertise with machine intelligence in order to achieve high quality of the filtered information provided to the end users.

  19. Multivariate Dynamic Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

    Shelhamer, Mark; Mindock, Jennifer; Zeffiro, Tom; Krakauer, David; Paloski, William H.; Lumpkins, Sarah

    2014-01-01

    The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in integrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach.

  20. Multivariate Dynamical Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

    Shelhamer, Mark; Mindock, Jennifer; Zeffiro, Tom; Krakauer, David; Paloski, William H.; Lumpkins, Sarah

    2014-01-01

    The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in intergrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach.

  1. Immunohistochemical study on expression of cathepsin in gastric carcinoma

    Wan Long Lin; Cong Jia Chen; Han Gao Zhou

    2000-01-01

    AIM To study the expression of cathepsin B in gastric carcinoma and its relationship with pathologic type.METHODS The cathepsin B expression in 54 specimens of human gastric adenocarcinoma was studied byimmunohistochemistry.RESULTS The cathepsin B expression was detected in 33/54 (61.1%) specimens of human gastriccarcinoma and in 3/54 (5.6%) of normal tissue (P<0.01). There was no obvious correlation between theexpression of cathepsin B and pathologic type of gastric adenocarcinoma.CONCLUSION There is a high expression of cathepsin B in human gastric adenocarcinoma.

  2. Helicobacter pylori induces β3GnT5 in human gastric cell lines, modulating expression of the SabA ligand sialyl–Lewis x

    Marcos, Nuno T; Magalhães, Ana; Ferreira, Bibiana; Maria J Oliveira; Carvalho, Ana S.; Mendes, Nuno; Gilmartin, Tim; Head, Steven R; Figueiredo, Céu; David, Leonor; Santos-Silva, Filipe; Celso A Reis

    2008-01-01

    Chronic Helicobacter pylori infection is recognized as a cause of gastric cancer. H. pylori adhesion to gastric cells is mediated by bacterial adhesins such as sialic acid–binding adhesin (SabA), which binds the carbohydrate structure sialyl–Lewis x. Sialyl–Lewis x expression in the gastric epithelium is induced during persistent H. pylori infection, suggesting that H. pylori modulates host cell glycosylation patterns for enhanced adhesion. Here, we evaluate changes in the glycosylation-relat...

  3. 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

  4. 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

  5. Regenerating gene family member 4 promotes growth and migration of gastric cancer through protein kinase B pathway

    Huang, Jiamiao; Yang, Ya; Yang, Jian; LI, XIAN

    2014-01-01

    Regenerating gene family member 4 (REG4), a secreted protein, is overexpressed in several cancers, including gastric cancer. The present study was undertaken to determine the roles of REG4 in the growth of gastric cancer in the nude mice and in the proliferation and migration in human gastric cancer cell line and its downstream signaling pathway. Gastric cancer models were elicited by intraperitoneally injecting MKN45 human gastric cancer cells and the tumor size was measured every other day....

  6. 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.

  7. 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.

  8. Prevention of chemically induced urinary bladder cancers by naproxen: protocols to reduce gastric toxicity in humans do not alter preventive efficacy.

    Lubet, Ronald A; Scheiman, James M; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M Margaret; Boring, Daniel L; Steele, Vernon E; Grubbs, Clinton J

    2015-04-01

    The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2-specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder-specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN-treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN -: treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in palpable cancers in 27%, 22%, 19%, and 96% of rats (P Short-term naproxen treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols that should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials. PMID:25762530

  9. 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

    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...... adaption indicated that the psychological adaption mode can speed up the process of thermal adaption to the variation in the outdoor climate condition. This study presented a new insight into the feedback from the thermal adaption modes to occupant thermal comfort.......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...

  10. 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.

  11. Stomach (Gastric) Cancer Prevention

    ... Treatment Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Prevention (PDQ®)–Patient Version What is ... to keep cancer from starting. General Information About Stomach Cancer Key Points Stomach (gastric) cancer is a ...

  12. Hereditary Diffuse Gastric Cancer

    ... procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known ... gastric cancer before age 40 Personal or family history of both diffuse gastric cancer and lobular breast ...

  13. 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. PMID:26555860

  14. 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.

  15. 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.

  16. Human Resources Development Review according to Identity, Integration, Achievement and Adaptation Model

    Sayyed Mohsen Allameh

    2012-02-01

    Full Text Available The concept of human resource development review has included two approaches: HRD as a function and HRD as a field. This paper is reviewed human resource development from view point of I-A model (Identity, Integration, Achievement, Adaptation on the basis of functional and field models as well as general theory. The main goal of the research is to measure dimensions of human resource development including identity, integration, achievement adaptation- among employee of Nowsahr health and treatment center. (Nowshahr city The research is an applied one with regard to the kind , nature of the research and is conducted using a survey– descriptive method. The sample consisted of 75 employee of Nowshahr health center that were selected randomized classified sampling and they were completed 20 questions of researcher- made questionnaire. T-student , ANOVA test, SPSS Ver 16 were used for data analysis.The research results indicate that all four dimensions of HRD (Identity, Integration, Achievement and Adaptation with environment were necessary for all three groups( managers, doctors and employees. The results also revealed that, except for identity and integration, the importance of human resource development dimensions was different among three groups.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Programmable System on Chip Distributed Communication and Control Approach for Human Adaptive Mechanical System

    Ahmad A.M. Faudzi; Suzumori, K

    2010-01-01

    Problem statement: Communication and control are two main components in any Mechatronics system. They can be designed either by centralized or decentralized approach. Both approaches can be chosen based on application designed and specific requirements of the designer. In this study, decentralized or normally called distributed approach was selected to solved communication and control of a human adaptive mechanical system namely Intelligent Chair Tools (ICT). The ICT seating system is powered...

  2. Adapting Human Videofluoroscopic Swallow Study Methods to Detect and Characterize Dysphagia in Murine Disease Models

    Lever, Teresa E.; Braun, Sabrina M.; Brooks, Ryan T.; Harris, Rebecca A.; Littrell, Loren L.; Neff, Ryan M.; Hinkel, Cameron J.; Allen, Mitchell J.; Ulsas, Mollie A.

    2015-01-01

    This study adapted human videofluoroscopic swallowing study (VFSS) methods for use with murine disease models for the purpose of facilitating translational dysphagia research. Successful outcomes are dependent upon three critical components: test chambers that permit self-feeding while standing unrestrained in a confined space, recipes that mask the aversive taste/odor of commercially-available oral contrast agents, and a step-by-step test protocol that permits quantification of swallow physi...

  3. Natural Selection at the Brush-Border: Adaptations to Carbohydrate Diets in Humans and Other Mammals

    Pontremoli, Chiara; Mozzi, Alessandra; Forni, Diego; Cagliani, Rachele; Pozzoli, Uberto; Menozzi, Giorgia; Vertemara, Jacopo; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela

    2015-01-01

    Dietary shifts can drive molecular evolution in mammals and a major transition in human history, the agricultural revolution, favored carbohydrate consumption. We investigated the evolutionary history of nine genes encoding brush-border proteins involved in carbohydrate digestion/absorption. Results indicated widespread adaptive evolution in mammals, with several branches experiencing episodic selection, particularly strong in bats. Many positively selected sites map to functional protein reg...

  4. 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...

  5. Adaptive reconfiguration of fractal small-world human brain functional networks

    Bassett, Danielle S; Meyer-Lindenberg, Andreas; Achard, Sophie; Duke, Thomas; Bullmore, Edward

    2006-01-01

    Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, we describe the topology and synchronizability of frequency-specific brain functional networks using wavelet decomposition of magnetoencephalographic time series, followed by construction and analysis of undirected graphs. Magnetoencephalographic data were acquired from 22 subjects, half of whom performed a ...

  6. Adaptive control for wearable robots in human-centered rehabilitation tasks

    Rajasekaran, Vijaykumar

    2015-01-01

    Robotic rehabilitation therapies have been improving by providing the needed assistance to the patient, in a human-centered environment, and also helping the therapist to choose the necessary procedure. This thesis presents an adaptive "Assistance-as-needed" strategy which adheres to the specific needs of the patient and with the inputs from the therapist, whenever needed. The exertion of assistive and responsive behavior of the lower limb wearable robot is dedicated for the rehabilitation of...

  7. Spot the Odd Song Out: Similarity Model Adaptation and Analysis using Relative Human Ratings

    Wolff, D.

    2014-01-01

    Understanding how listeners relate and compare pieces of music is a fundamental challenge in music research as well as for commercial applications: Today’s large-scale applications for music recommendation and exploration utilise various models for similarity prediction to satisfy users’ expectations. Perceived similarity is specific to the individual and influenced by a number of factors such as cultural background and age. Thus, adapting a generic model to human similarity data is useful fo...

  8. An Insight into the Changes in Human Plasma Proteome on Adaptation to Hypobaric Hypoxia

    Ahmad, Yasmin; Sharma, Narendra K.; Garg, Iti; Ahmad, Mohammad Faiz; Sharma, Manish; Bhargava, Kalpana

    2013-01-01

    Adaptation to hypobaric hypoxia is required by animals and human in several physiological and pathological situations. Hypobaric hypoxia is a pathophysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. Identifying the molecular variables playing key roles in this process would be of paramount importance to shed light on the mechanisms known to counteract the negative effects of oxygen lack. To obtai...

  9. 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

  10. 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.

  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. HER2 testing in gastric cancer: An update

    Abrahao-Machado, Lucas Faria; Scapulatempo-Neto, Cristovam

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2) overexpression is increasingly recognized as a frequent molecular abnormality in gastric and gastroesophageal cancer. With the recent introduction of HER2 molecular targeted therapy for patients with advanced gastric cancer, determination of HER2 status is crucial in order to select patients who may benefit from this treatment. This paper provides an update on our knowledge of HER2 in gastric and gastroesophageal cancer, including the prognostic...

  13. 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...... uses observed information from a laser range finder to detect persons and their position relative to the robot. This information together with the motion of the robot itself is fed through a Kalman filter, which utilizes a model of the human kinematic movement to produce an estimate of the person......’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...

  14. Adaptive-Neuro Fuzzy Inference System for Human Posture Classification Using a Simplified Shock Graph

    Shahbudin, S.; Hussain, A.; El-Shafie, Ahmed; Tahir, N. M.; Samad, S. A.

    In this paper, a neuro-fuzzy technique known as the Adaptive-Neuro Fuzzy Inference System (ANFIS) has been used to highlight the application of ANFIS to perform human posture classification task using the new simplified shock graph (SSG) representation. Basically, a shock graph is a shape abstraction that decomposed a shape into a set of hierarchically organized primitive parts. The shock graph that represents the silhouette of an object in terms of a set of qualitatively defined parts and organized in a hierarchical, directed acyclic graph is used as a powerful representation of human shape in our work. The SSG feature provides a compact, unique and simple way of representing human shape and has been tested with several classifiers. As such, in this paper we intend to test its efficacy with another classifier, that is, the ANFIS classifier system. The result showed that the proposed ANFIS model can be used in classifying various human postures.

  15. HUMEX. A study on the survivability and adaptation of humans to long-duration exploratory missions

    Harris, Robert A.

    2003-11-01

    After the realisation of the International Space Station (ISS), human exploratory missions to the Moon or Mars, i.e. beyond low Earth orbit (LEO), are widely considered as the next logical step in worldwide peaceful cooperation in space. The HUMEX study has concentrated on human health related aspects: it provides a critical assessment of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis has been put on human health, well-being and performance care, such as radiation health issues, adaptation to microgravity and reduced gravity, psychology issues and health, well-being and performance care, such as radiation health issues, adaptation to microgravity and reduced gravity, psychology issues and health maintenance and on advanced life support developments. The overall study goals are: to define reference scenarios for European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; for selected mission scenarios, to critically assess the limiting factors for human health, well-being, and performance and to recommend relevant countermeasures; for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy for this field, including terrestrial applications; to critically assess the applicability of existing facilities and technologies on the ground and in space as test beds for human exploratory missions and to develop a test plan for ground and ISS campaigns; to develop a roadmap for future European activities, in preparation for human exploratory missions, including preparatory activities and terrestrial applications and benefits.

  16. 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

  17. Do calories or osmolality determine gastric emptying

    Recent animal studies suggest that gastric emptying is dependent on the caloric and osmotic content of the ingested food. These studies have involved intubation with infusion of liquid meals into the stomach. Scintigraphic methods, which are non-invasive and do not alter normal physiology, are now available for precise quantitation of gastric emptying. To study the role of calories and osmolality on gastric emptying, the authors employed a standardized /sup 99m/Tc-scrambled egg meal washed with 50 cc tap water in 10 normal human volunteers. A variety of simple and complex sugars, non-absorbable complex carbohydrate (polycose), medium chain fatty acid (MCFA) and gluten were dissolved in water and ingested with the test meal. Each subject acted as his own control. Coefficient of variation in control tests in each subject 12 weeks apart was 9.9%. Results showed that incremental glucose (25-66 gm) produced a linear increase in gastric emptying (T/2 control 50 +- 3, 25 gm 60 +- 3, 50 gm 79 +- 3 and 66 gm 102 +- 3 minutes). 25 gm fructose (T/2 59 +- 3 minutes) and 25 gm polycose (T/2 59 +- 3 minutes) had similar effects to glucose. 25 gm sucrose and 25 gm gluten did not significantly differ from controls. MCFA had an effect similar to 50 gm glucose - suggesting that calories are important in gastric emptying. However, 25 gm xylose markedly prolonged gastric emptying to 80 +- 5 minutes. The rank order for osmolality for substances tested MCFA = gluten < polycose < polycose < fructose < sucrose = glucose < xylose defined no relationship to gastric emptying. The authors' results suggest that neither calories nor osmolality alone determine gastric emptying. A specific food does not necessarily have the same effect on gastric emptying in different individuals

  18. Complementary PTM Profiling of Drug Response in Human Gastric Carcinoma by Immunoaffinity and IMAC Methods with Total Proteome Analysis

    Matthew P. Stokes

    2015-08-01

    Full Text Available Gaining insight into normal cellular signaling and disease biology is a critical goal of proteomic analyses. The ability to perform these studies successfully to extract the maximum value and discovery of biologically relevant candidate biomarkers is therefore of primary importance. Many successful studies in the past have focused on total proteome analysis (changes at the protein level combined with phosphorylation analysis by metal affinity enrichment (changes at the PTM level. Here, we use the gastric carcinoma cell line MKN-45 treated with the c-Met inhibitor SU11274 and PKC inhibitor staurosporine to investigate the most efficient and most comprehensive strategies for both total protein and PTM analysis. Under the conditions used, total protein analysis yielded few changes in response to either compound, while analysis of phosphorylation identified thousands of sites that changed differentially between the two treatments. Both metal affinity and antibody-based enrichments were used to assess phosphopeptide changes, and the data generated by the two methods was largely complementary (non-overlapping. Label-free quantitation of peptide peak abundances was used to accurately determine fold-changes between control and treated samples. Protein interaction network analysis allowed the data to be placed in a biologically relevant context, and follow-up validation of selected findings confirmed the accuracy of the proteomic data. Together, this study provides a framework for start-to-finish proteomic analysis of any experimental system under investigation to maximize the value of the proteomic study and yield the best chance for uncovering actionable target candidates.

  19. 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.

  20. 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.

  1. 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.

  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. 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.

  4. p53-Dependent Adaptive Responses in Human Cells Exposed to Space Radiations

    Purpose: It has been reported that priming irradiation or conditioning irradiation with a low dose of X-rays in the range of 0.02-0.1 Gy induces a p53-dependent adaptive response in mammalian cells. The aim of the present study was to clarify the effect of space radiations on the adaptive response. Methods and Materials: Two human lymphoblastoid cell lines were used; one cell line bears a wild-type p53 (wtp53) gene, and another cell line bears a mutated p53 (mp53) gene. The cells were frozen during transportation on the space shuttle and while in orbit in the International Space Station freezer for 133 days between November 15, 2008 and March 29, 2009. After the frozen samples were returned to Earth, the cells were cultured for 6 h and then exposed to a challenging X-ray-irradiation (2 Gy). Cellular sensitivity, apoptosis, and chromosome aberrations were scored using dye-exclusion assays, Hoechst33342 staining assays, and chromosomal banding techniques, respectively. Results: In cells exposed to space radiations, adaptive responses such as the induction of radioresistance and the depression of radiation-induced apoptosis and chromosome aberrations were observed in wtp53 cells but not in mp53 cells. Conclusion: These results have confirmed the hypothesis that p53-dependent adaptive responses are apparently induced by space radiations within a specific range of low doses. The cells exhibited this effect owing to space radiations exposure, even though the doses in space were very low.

  5. 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.

  6. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway.

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. PMID:27163639

  7. Construction of cDNA representational difference analysis based on two cDNA libraries and identification of garlic inducible expression genes in human gastric cancer cells

    Yong Li; Lin Yang; Jian-Tao Cui; Wen-Mei Li; Rui-Fang Guo; You-Yong Lu

    2002-01-01

    AIM: To elucidate molecular mechanism of chemopreventiveefficacies of garlic against human gastric cancer (HGC):METHODS: HGC cell line BGC823 was treated with Allitridi (akind of garlic extract) and Allitridi-treated and parentalBGC823 cDNA librarles were constructed respectively byusing λZAP Ⅱ vector. cDNA Representatinal DifferenceAnalysis (cDNA RDA) was perfonmed using BamH Ⅰ cutting-site and abundant ~DNA messages provided by the Iibrarles.Northern blot analysls was applied to identifythe obtaineddifference prnducts.RESULTS: Two specific cDNA fragments were obtained andcharacterized to be derived from homo sapiens folatereceptorα (FRα) gene and calcyclin gene respectively.Northern blot results showed a 4-fold increase in FRα geneexpression level and 9-fold increase in calcyclin mRNA levelin BGC823 cells after Allilridi treatment for 72 h.CONCLUSION: The method of cDNA RDA based on cDNAlibraries combines the high specificity of cDNA RDA withabundant cDNA messages in cDNA library; this expands theapplication of cDNA library and increases the specificity ofcDNA RDA. Up-regulstion of FRα gene and calcyclin geneexpressions induced by Allitridi provide valuable molecularevidence for theefficacy of garlic in treating HGC as well asother diseases.

  8. Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells.

    Takahashi, Katsuyuki; Tanaka, Masako; Yashiro, Masakazu; Matsumoto, Masaki; Ohtsuka, Asuka; Nakayama, Keiichi I; Izumi, Yasukatsu; Nagayama, Katsuya; Miura, Katsuyuki; Iwao, Hiroshi; Shiota, Masayuki

    2016-08-01

    Heat shock protein 72 (Hsp72) is a molecular chaperone that assists in the folding of nascent polypeptides and in the refolding of denatured proteins. In many cancers, Hsp72 is constitutively expressed at elevated levels, which can result in enhanced stress tolerance. Similarly, following treatment with anticancer drugs, Hsp72 binds to denatured proteins that may be essential for survival. We therefore hypothesized that Hsp72 client proteins may play a crucial role in drug resistance. Here, we aimed to identify proteins that are critical for oxaliplatin (OXA) resistance by analyzing human gastric cancer cell lines, as well as OXA-resistant cells via a mass spectrometry-based proteomic approach combined with affinity purification using anti-Hsp72 antibodies. Stromal cell-derived factor 2 (SDF-2) was identified as an Hsp72 client protein unique to OCUM-2M/OXA cells. SDF-2 was overexpressed in OXA-resistant cells and SDF-2 silencing promoted the apoptotic effects of OXA. Furthermore, Hsp72 prevented SDF-2 degradation in a chaperone activity-dependent manner. Together, our data demonstrate that Hsp72 protected SDF-2 to avoid OXA-induced cell death. We propose that inhibition of SDF-2 may comprise a novel therapeutic strategy to counteract OXA-resistant cancers. PMID:27157913

  9. Attenuated gastric distress but no benefit to performance with adaptation to octanoate-rich esterified oils in well-trained male cyclists

    Thorburn, M.S.; Vistisen, Bodil; Thorp, R.M.; Rockell, M.J.; Jeukendrup, A.E.; Xu, X.B.; Rowlands, D.S.

    2006-01-01

    We investigated the effects of modifying a normal dietary fatty acid composition and ingestion of high-fat exercise supplements on gastrointestinal distress, substrate oxidation. and endurance cycling performance. Nine well-trained male cyclists completed a randomized triple-crossover comprising a......-rich dietary condition (MC-MC, Intervention) and 2) after one of the LCFA-rich dietary conditions (LC-MC. Placebo) or 3) CHO only following a LCFA-rich diet (LC-CHO, Control). During the 3-h ride MCFA-adaptation decreased octanoic-acid oxidation by 24% (90% confidence interval: 14-34%). The CHO+MCFA-rich oil...

  10. Gastric emptying in patients with fundal gastritis and gastric cancer.

    Tatsuta, M.; Iishi, H.; Okuda, S

    1990-01-01

    Gastric emptying was compared in patients with gastric cancers and fundal gastritis to determine its value in identifying patients at high risk of gastric cancer. Gastric emptying was measured by the acetaminophen absorption method, and the extent of fundal gastritis was determined by the endoscopic Congo red test. The results showed that gastric emptying was significantly slower in patients with severe fundal gastritis than in those without. Gastric emptying in patients with differentiated a...

  11. Future temperature in southwest Asia projected to exceed a threshold for human adaptability

    Pal, Jeremy S.; Eltahir, Elfatih A. B.

    2016-02-01

    A human body may be able to adapt to extremes of dry-bulb temperature (commonly referred to as simply temperature) through perspiration and associated evaporative cooling provided that the wet-bulb temperature (a combined measure of temperature and humidity or degree of `mugginess’) remains below a threshold of 35 °C. (ref. ). This threshold defines a limit of survivability for a fit human under well-ventilated outdoor conditions and is lower for most people. We project using an ensemble of high-resolution regional climate model simulations that extremes of wet-bulb temperature in the region around the Arabian Gulf are likely to approach and exceed this critical threshold under the business-as-usual scenario of future greenhouse gas concentrations. Our results expose a specific regional hotspot where climate change, in the absence of significant mitigation, is likely to severely impact human habitability in the future.

  12. 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.

  13. HER2 testing in gastric cancer: An update.

    Abrahao-Machado, Lucas Faria; Scapulatempo-Neto, Cristovam

    2016-05-21

    Human epidermal growth factor receptor 2 (HER2) overexpression is increasingly recognized as a frequent molecular abnormality in gastric and gastroesophageal cancer. With the recent introduction of HER2 molecular targeted therapy for patients with advanced gastric cancer, determination of HER2 status is crucial in order to select patients who may benefit from this treatment. This paper provides an update on our knowledge of HER2 in gastric and gastroesophageal cancer, including the prognostic relevance of HER2, the key differences between HER2 protein expression interpretation in breast and gastric cancer, the detection methods and the immunohistochemistry scoring system. PMID:27217694

  14. Gastric emptying in patients with gastric ulcer

    The estimated volume of meal in the stomach 30 mins after sup(113m)In-DTPA administration was determined in patients with gastric ulcer and normal controls by 1) relating counts in the stomach to those in the whole field of view of the gamma camera and 2) aspirations. In the normal controls there was no significant difference between the two methods but in the gastric ulcer patients, the gamma camera method predicted significantly more meal in the stomach than was recovered by aspiration. It was suggested that the large low lying stomach found in gastric ulcer disease causes extensive overlap of the small bowel and invalidates measurements of gastric emptying made by a gamma camera. (U.K.)

  15. DNA repeat arrays in chicken and human genomes and the adaptive evolution of avian genome size

    Piontkivska Helen

    2005-02-01

    Full Text Available Abstract Background Birds have smaller average genome sizes than other tetrapod classes, and it has been proposed that a relatively low frequency of repeating DNA is one factor in reduction of avian genome sizes. Results DNA repeat arrays in the sequenced portion of the chicken (Gallus gallus autosomes were quantified and compared with those in human autosomes. In the chicken 10.3% of the genome was occupied by DNA repeats, in contrast to 44.9% in human. In the chicken, the percentage of a chromosome occupied by repeats was positively correlated with chromosome length, but even the largest chicken chromosomes had repeat densities much lower than those in human, indicating that avoidance of repeats in the chicken is not confined to minichromosomes. When 294 simple sequence repeat types shared between chicken and human genomes were compared, mean repeat array length and maximum repeat array length were significantly lower in the chicken than in human. Conclusions The fact that the chicken simple sequence repeat arrays were consistently smaller than arrays of the same type in human is evidence that the reduction in repeat array length in the chicken has involved numerous independent evolutionary events. This implies that reduction of DNA repeats in birds is the result of adaptive evolution. Reduction of DNA repeats on minichromosomes may be an adaptation to permit chiasma formation and alignment of small chromosomes. However, the fact that repeat array lengths are consistently reduced on the largest chicken chromosomes supports the hypothesis that other selective factors are at work, presumably related to the reduction of cell size and consequent advantages for the energetic demands of flight.

  16. A Bio-Guided Fractionation to Assess the Inhibitory Activity of Calendula officinalis L. on the NF-κB Driven Transcription in Human Gastric Epithelial Cells

    Elisa Colombo; Enrico Sangiovanni; Michele D’Ambrosio; Enrica Bosisio; Alexandru Ciocarlan; Marco Fumagalli; Antonio Guerriero; Petru Harghel; Mario Dell’Agli

    2015-01-01

    Calendula officinalis L. has been largely known for its topical anti-inflammatory properties; however, there are no experimental evidences about its antiphlogistic effect at the gastric level. To investigate whether marigold might exert an activity against gastric inflammation, a CH2Cl2 extract obtained from C. officinalis flowers was evaluated in vitro on the NF-κB pathway. The lipophilic extract demonstrated a significant inhibitory effect on the NF-κB driven transcription. The identificati...

  17. Nicotinamide pharmacokinetics in humans: effect of gastric acid inhibition, comparison of rectal vs oral administration and the use of saliva for drug monitoring.

    Stratford, M. R.; Dennis, M.F.; Hoskin, P; Phillips, H.; Hodgkiss, R. J.; A. Rojas

    1996-01-01

    The effect of inhibiting gastric acid secretion on nicotinamide pharmacokinetics was studied in five volunteers with the intent of reducing the large variations observed previously in the time to and magnitude of peak plasma concentrations. Plasma levels were determined using a standard high-performance liquid chromatography (HPLC) method after an oral dose of 3 g of nicotinamide either alone or preceded by pretreatment with omeprazole. Suppression of gastric acid production had no significan...

  18. IL-17A in Human Respiratory Diseases: Innate or Adaptive Immunity? Clinical Implications

    Dominique M. A. Bullens

    2013-01-01

    Full Text Available Since the discovery of IL-17 in 1995 as a T-cell cytokine, inducing IL-6 and IL-8 production by fibroblasts, and the report of a separate T-cell lineage producing IL-17(A, called Th17 cells, in 2005, the role of IL-17 has been studied in several inflammatory diseases. By inducing IL-8 production and subsequent neutrophil attraction towards the site of inflammation, IL-17A can link adaptive and innate immune responses. More specifically, its role in respiratory diseases has intensively been investigated. We here review its role in human respiratory diseases and try to unravel the question whether IL-17A only provides a link between the adaptive and innate respiratory immunity or whether this cytokine might also be locally produced by innate immune cells. We furthermore briefly discuss the possibility to reduce local IL-17A production as a treatment option for respiratory diseases.

  19. 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.

  20. Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels in human gastric cancer and colon cancer

    Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase gene expressions are reported to be valid predictive markers for 5-fluorouracil sensitivity to gastrointestinal cancer. For more reliable predictability, their expressions in cancer cells and stromal cells in the cancerous tissue (cancerous stroma) have been separately investigated using laser capture microdissection. Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase mRNA in cancer cells and cancerous stroma from samples of 47 gastric and 43 colon cancers were separately quantified by reverse transcription polymerase chain reaction after laser capture microdissection. In both gastric and colon cancers, thymidylate synthase and orotate phosphoribosyltransferase mRNA expressions were higher (p < 0.0001, p <0.0001 respectively in gastric cancer and P = 0.0002, p < 0.0001 respectively in colon cancer) and dihydropyrimidine dehydrogenase mRNA expressions were lower in cancer cells than in cancerous stroma (P = 0.0136 in gastric cancer and p < 0.0001 in colon cancer). In contrast, thymidine phosphorylase mRNA was higher in cancer cells than in cancerous stroma in gastric cancer (p < 0.0001) and lower in cancer cells than in cancerous stroma in colon cancer (P = 0.0055). By using this method, we could estimate gene expressions separately in cancer cells and stromal cells from colon and gastric cancers, in spite of the amount of stromal tissue. Our method is thought to be useful for accurately evaluating intratumoral gene expressions

  1. Robust adaptive control modeling of human arm movements subject to altered gravity and mechanical loads

    Tryfonidis, Michail

    It has been observed that during orbital spaceflight the absence of gravitation related sensory inputs causes incongruence between the expected and the actual sensory feedback resulting from voluntary movements. This incongruence results in a reinterpretation or neglect of gravity-induced sensory input signals. Over time, new internal models develop, gradually compensating for the loss of spatial reference. The study of adaptation of goal-directed movements is the main focus of this thesis. The hypothesis is that during the adaptive learning process the neural connections behave in ways that can be described by an adaptive control method. The investigation presented in this thesis includes two different sets of experiments. A series of dart throwing experiments took place onboard the space station Mir. Experiments also took place at the Biomechanics lab at MIT, where the subjects performed a series of continuous trajectory tracking movements while a planar robotic manipulandum exerted external torques on the subjects' moving arms. The experimental hypothesis for both experiments is that during the first few trials the subjects will perform poorly trying to follow a prescribed trajectory, or trying to hit a target. A theoretical framework is developed that is a modification of the sliding control method used in robotics. The new control framework is an attempt to explain the adaptive behavior of the subjects. Numerical simulations of the proposed framework are compared with experimental results and predictions from competitive models. The proposed control methodology extends the results of the sliding mode theory to human motor control. The resulting adaptive control model of the motor system is robust to external dynamics, even those of negative gain, uses only position and velocity feedback, and achieves bounded steady-state error without explicit knowledge of the system's nonlinearities. In addition, the experimental and modeling results demonstrate that

  2. Genetic adaptation to levels of dietary selenium in recent human history.

    White, Louise; Romagné, Frédéric; Müller, Elias; Erlebach, Eva; Weihmann, Antje; Parra, Genís; Andrés, Aida M; Castellano, Sergi

    2015-06-01

    As humans migrated around the world, they came to inhabit environments that differ widely in the soil levels of certain micronutrients, including selenium (Se). Coupled with cultural variation in dietary practices, these migrations have led to a wide range of Se intake levels in populations around the world. Both excess and deficiency of Se in the diet can have adverse health consequences in humans, with severe Se deficiency resulting in diseases of the bone and heart. Se is required by humans mainly due to its function in selenoproteins, which contain the amino acid selenocysteine as one of their constituent residues. To understand the evolution of the use of this micronutrient in humans, we surveyed the patterns of polymorphism in all selenoprotein genes and genes involved in their regulation in 50 human populations. We find that single nucleotide polymorphisms from populations in Asia, particularly in populations living in the extreme Se-deficient regions of China, have experienced concerted shifts in their allele frequencies. Such differentiation in allele frequencies across genes is not observed in other regions of the world and is not expected under neutral evolution, being better explained by the action of recent positive selection. Thus, recent changes in the use and regulation of Se may harbor the genetic adaptations that helped humans inhabit environments that do not provide adequate levels of Se in the diet. PMID:25739735

  3. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2

    Li, Wenhui; Zhang, Chengsheng; Sui, Jianhua; Kuhn, Jens H; Moore, Michael J; Luo, Shiwen; Wong, Swee-Kee; Huang, I-Chueh; Xu, Keming; Vasilieva, Natalya; Murakami, Akikazu; He, Yaqing; Marasco, Wayne A; Guan, Yi; Choe, Hyeryun; Farzan, Michael

    2005-01-01

    Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic. PMID:15791205

  4. Treatment of gastric cancer

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

    2014-01-01

    The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically...

  5. Attenuated gastric distress but no benefit to performance with adaptation to octanoate-rich esterified oils in well-trained male cyclists

    Thorburn, M.S.; Vistisen, Bodil; Thorp, R.M.;

    2006-01-01

    a 2-wk diet high in octanoate-rich esterified oil (MCFA) or twice long-chain fatty acids (LCFA). Following the diets, participants performed 3-h of cycling at 50% of peak power followed by 10 maximal sprints while ingesting either 1) a carbohydrate (CHO)+MCFA-rich oil emulsion after the 2-wk MCFA......We investigated the effects of modifying a normal dietary fatty acid composition and ingestion of high-fat exercise supplements on gastrointestinal distress, substrate oxidation. and endurance cycling performance. Nine well-trained male cyclists completed a randomized triple-crossover comprising......-rich dietary condition (MC-MC, Intervention) and 2) after one of the LCFA-rich dietary conditions (LC-MC. Placebo) or 3) CHO only following a LCFA-rich diet (LC-CHO, Control). During the 3-h ride MCFA-adaptation decreased octanoic-acid oxidation by 24% (90% confidence interval: 14-34%). The CHO+MCFA-rich oil...

  6. 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.

  7. 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.

  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. PMID:26764748

  9. The Genetic Diversity of Helicobacter pylori Virulence Genes Is Not Associated with Gastric Atrophy Progression

    Kita, Masahide; Yokota,Kenji; Okada, Hiroyuki; Take,Susumu; Takenaka, Ryuta; Kawahara, Yoshiro; Oguma, Keiji; Matsushita, Osamu; Yamamoto, Kazuhide

    2013-01-01

    Atrophy of the gastric mucosa is a precursor of intestinal-type gastric cancer, and Helicobacter pylori infection causes atrophic gastritis. The aim of this study was to determine whether the genetic diversity of H. pylori virulence genes is associated with the development and progression of gastric atrophy in humans. We isolated and cultured H. pylori strains from patients with gastric ulcer and duodenal ulcer accompanied by atrophic gastritis in background mucosa. H. pylori strains were sto...

  10. A test of maternal human chorionic gonadotropin during pregnancy as an adaptive filter of human gestations

    Bruckner, Tim A; Saxton, Katherine B.; Pearl, Michelle; Currier, Robert; Kharrazi, Martin

    2012-01-01

    The risk of abnormalities and morbidity among live births increases with advanced maternal age. Explanations for this elevated morbidity invoke several maternal mechanisms. The relaxed filter stringency (RFS) hypothesis asserts that mothers, nearing the end of their reproductive lifespan, reduce the stringency of a screen of offspring quality in utero based on life-history traits of parity and interbirth interval (IBI). A separate line of research implicates human chorionic gonadotropin (hCG)...

  11. Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy

    Butler, A. E.; Cao-Minh, L.; Galasso, R; Rizza, R. A.; Corradin, A.; Cobelli, C; Butler, P C

    2010-01-01

    Aims/hypothesis We sought to establish the extent and basis for adaptive changes in beta cell numbers in human pregnancy. Methods Pancreas was obtained at autopsy from women who had died while pregnant (n = 18), post-partum (n = 6) or were not pregnant at or shortly before death (controls; n = 20). Pancreases were evaluated for fractional pancreatic beta cell area, islet size and islet fraction of beta cells, beta cell replication (Ki67) and apoptosis (TUNEL), and indirect markers of beta cel...

  12. Regulation of pH in human skeletal muscle: adaptations to physical activity

    Juel, C

    2008-01-01

    Regulation of pH in skeletal muscle is the sum of mechanisms involved in maintaining intracellular pH within the normal range. Aspects of pH regulation in human skeletal muscle have been studied with various techniques from analysis of membrane proteins, microdialysis, and the nuclear magnetic...... describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....

  13. Adaptive response of human lymphocytes exposed to low dose of gamma radiation

    The main goals of the present work are: (a) to study the induction of radioadaptive response in human lymphocytes and to establish the experimental conditions for which this response is optimized; (b) to evidence the relationship between the observed effect and the phase of the cell cycle. The radioadaptive response was assessed by the chromosome aberration test. Human lymphocytes were pre-irradiated with 1 cGy or 5 cGy (1 cGy/min) either before stimulation by phytohemagglutinin (for G0 study) or 20 h after stimulation by PHA (for G1), followed by 1 Gy (1 Gy/min) irradiation 46 h after stimulation by PHA. After the irradiation with high dose, the cultures were kept for 2 h in the incubator and then the colcemide was added to the cultures (at 48 h). The cultures incubated 2 h with colcemide were exposed to potassium chloride and then fixed in acetic acid:methanol (1:3). The fixed cells were dropped onto wet glass slides and dried. Slides were stained with Giemsa for the scoring of chromatid aberrations. Fifty cells were scored from replicate cultures for each treatment. We considered only those metaphases that contained 46 chromosomes. The following results have been obtained: - the human lymphocytes pre-exposed in G0 to 1 cGy and 5 cGy exhibit an adaptive response to the subsequent exposure at 1 Gy; - the evolution of cytogenetic parameter chromosomal aberration in the case of lymphocytes pre-irradiated in G1 is similar with that obtained for lymphocytes pre-irradiated in G0; - the maximal expression of adaptive response was determined by delivering 1 cGy; - the time interval between both types of successive irradiations is optimal for the induction of the repair processes; - the lymphocytes respond adaptively at low doses of irradiation, regardless the stimulation by phytohemagglutinin. These results are in agreement with other reported data which prove that human lymphocytes are able to adapt to low dose irradiation so that they undergo less damages at the

  14. Impact, adaptation and vulnerability of natural and human systems in Europe

    This article analyses the observed and projected impacts of climate change on human and natural systems, their vulnerability and adaptation options. It provides insight into the main results related to hydrology, agriculture, natural ecosystems, transport, energy, tourism, infrastructures, health and social aspects. This article presents the main results concerning Europe that were compiled in the contribution of Working Group II to the IPCC fifth assessment report published in 2014. Several studies focused on mainland France are also presented, without claiming to be exhaustive. (authors)

  15. Resilience, human agency and climate change adaptation strategies in the Arctic

    Sejersen, Frank

    2009-01-01

      In the Arctic, indigenous peoples, researchers and governments are working to develop climate change adaptation strategies due to the rapid changes in sea ice extent, weather conditions and in the ecosystem as such. These strategies are often based on specific perceptions of vulnerability and w...... scales and the implications for resilience....... work with a number of barriers for resilience. The objective of the article is first to address the position of institutional barriers in the studies and strategies. Second the article analyses the role human agency is ascribed in proposed strategies and projects in Nunavut and Greenland. With a focus...

  16. Epstein-Barr Virus in Gastric Carcinoma

    The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation

  17. Epstein-Barr Virus in Gastric Carcinoma

    Nishikawa, Jun, E-mail: junnis@yamaguchi-u.ac.jp [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Yoshiyama, Hironori; Iizasa, Hisashi; Kanehiro, Yuichi [Department of Microbiology, Shimane University Faculty of Medicine, 89-1 Enyacho, Izumo City, Shimane 693-8501 (Japan); Nakamura, Munetaka; Nishimura, Junichi; Saito, Mari; Okamoto, Takeshi [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Sakai, Kouhei; Suehiro, Yutaka; Yamasaki, Takahiro [Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Oga, Atsunori [Department of Pathology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan); Yanai, Hideo [Department of Clinical Research, National Hospital Organization Kanmon Medical Center, 1-1 Sotoura, Chofu, Shimonoseki, Yamaguchi 752-8510 (Japan); Sakaida, Isao [Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan)

    2014-11-07

    The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation.

  18. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts

    Otto, Thomas D.

    2014-09-09

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host–parasite interface may have mediated host switching.

  19. An Insight into the Changes in Human Plasma Proteome on Adaptation to Hypobaric Hypoxia

    Ahmad, Yasmin; Sharma, Narendra K.; Garg, Iti; Ahmad, Mohammad Faiz; Sharma, Manish; Bhargava, Kalpana

    2013-01-01

    Adaptation to hypobaric hypoxia is required by animals and human in several physiological and pathological situations. Hypobaric hypoxia is a pathophysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. Identifying the molecular variables playing key roles in this process would be of paramount importance to shed light on the mechanisms known to counteract the negative effects of oxygen lack. To obtain a molecular signature, changes in the plasma proteome were studied by using proteomic approach. To enrich the low-abundance proteins in human plasma, two highly abundant proteins, albumin and IgG, were first removed. By comparing the plasma proteins of high altitude natives with those of a normal control group, several proteins with a significant alteration were found. The up-regulated proteins were identified as vitamin D-binding protein, hemopexin, alpha-1–antitrypsin, haptoglobin β-chain, apolipoprotein A1, transthyretin and hemoglobin beta chain. The down-regulated proteins were transferrin, complement C3, serum amyloid, complement component 4A and plasma retinol binding protein. Among these proteins, the alterations of transthyretin and transferrin were further confirmed by ELISA and Western blotting analysis. Since all the up- and down- regulated proteins identified above are well-known inflammation inhibitors and play a positive anti-inflammatory role, these results show that there is some adaptive mechanism that sustains the inflammation balance in high altitude natives exposed to hypobaric hypoxia. PMID:23844025

  20. An insight into the changes in human plasma proteome on adaptation to hypobaric hypoxia.

    Yasmin Ahmad

    Full Text Available Adaptation to hypobaric hypoxia is required by animals and human in several physiological and pathological situations. Hypobaric hypoxia is a pathophysiological condition triggering redox status disturbances of cell organization leading, via oxidative stress, to proteins, lipids, and DNA damage. Identifying the molecular variables playing key roles in this process would be of paramount importance to shed light on the mechanisms known to counteract the negative effects of oxygen lack. To obtain a molecular signature, changes in the plasma proteome were studied by using proteomic approach. To enrich the low-abundance proteins in human plasma, two highly abundant proteins, albumin and IgG, were first removed. By comparing the plasma proteins of high altitude natives with those of a normal control group, several proteins with a significant alteration were found. The up-regulated proteins were identified as vitamin D-binding protein, hemopexin, alpha-1-antitrypsin, haptoglobin β-chain, apolipoprotein A1, transthyretin and hemoglobin beta chain. The down-regulated proteins were transferrin, complement C3, serum amyloid, complement component 4A and plasma retinol binding protein. Among these proteins, the alterations of transthyretin and transferrin were further confirmed by ELISA and Western blotting analysis. Since all the up- and down- regulated proteins identified above are well-known inflammation inhibitors and play a positive anti-inflammatory role, these results show that there is some adaptive mechanism that sustains the inflammation balance in high altitude natives exposed to hypobaric hypoxia.

  1. Gastric immature teratoma

    Gastric teratoma (GT) is a rare neoplasm which accounts for less than 1% of all teratomas in children. Little more than 100 cases of GT are reported in the literature out of which, about a dozen cases are of immature variety. We present a case of immature gastric teratoma in a 7-month-old male baby. (author)

  2. Epidemiology of gastric cancer

    Katherine D Crew; Alfred I Neugut

    2006-01-01

    The incidence and mortality of gastric cancer have fallen dramatically in US and elsewhere over the past several decades. Nonetheless, gastric cancer remains a major public health issue as the fourth most common cancer and the second leading cause of cancer death worldwide. Demographic trends differ by tumor location and histology. While there has been a marked decline in distal, intestinal type gastric cancers, the incidence of proximal, diffuse type adenocarcinomas of the gastric cardia has been increasing, particularly in the Western countries. Incidence by tumor sub-site also varies widely based on geographic location, race, and socioeconomic status. Distal gastric cancer predominates in developing countries, among blacks, and in lower socioeconomic groups, whereas proximal tumors are more common in developed countries, among whites, and in higher socio-economic classes. Diverging trends in the incidence of gastric cancer by tumor location suggest that they may represent two diseases with different etiologies. The main risk factors for distal gastric cancer include Helicobacter pylori (H pylori) infection and dietary factors, whereas gastroesophageal reflux disease and obesity play important roles in the development of proximal stomach cancer. The purpose of this review is to examine the epidemiology and risk factors of gastric cancer, and to discuss strategies for primary prevention.

  3. Comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma and normal lung fibroblast cell lines

    Mohammad Ali Rashmezad

    2015-03-01

    Full Text Available Background: Biosynthesis of nanoparticles has attracted the attention of the scientific community in nanotechnology and biotechnology due to their extensive application in the area of material sciences and medicine. Nowadays, despite a various application of nanomaterial’s, there is a little information about their impact on human health. In this study, we investigated the comparative study on cytotoxicity effect of biological and commercial synthesized nanosilver on human gastric carcinoma (AGS and normal lung fibroblast (MRC-5 cell lines. Methods: The current experimental study was carried out in Islamic Azad University, East Tehran Branch, from April to November 2014. The biological synthesis of nanosilver was obtained from Eucalyptus plant extract as a reducing agent. Further to more analysis, morphological study on size and shape of developed biological nanosilver was characterized by performing scanning electron microscopy and dynamic light scattering. AGS and MCR-5 cell lines were treated with various concentration of nanosilver for 24, 48 and 72 hours. Finally, the cell viability was evaluated by using MTT assay. Results: The results show that the nanosilver exerts a dose-dependent inhibitory effect on viability of cells. At 100µg/mL of commercial and biological synthesized nanosilver, the viability of AGS was reduced to 7.47±0.002% (P=0.002 and 3.65±0.01% (P=0.003 after 72 hours, respectively. In addition, the viability of MRC-5 at the same condition was reduced to 10.27±0.19% (P=0.001 and 9.16±1.53% (P=0.002, respectively. Conclusion: Based on a thorough literature surveys, the present study is the first research about biosynthesis of nanosilver using Eucalyptus plant extract. This eco-friendly and cost effective method can be used for large scale production of silver nanoparticle. In addition, based on the current obtained data, commercial and biological synthesized nanosilver can more inhibitory effect on cancer cells compared

  4. "Gastric bascule": an unusual form of gastric volvulus.

    Menezes, Amber; Sowerby, Leigh; Malthaner, Richard A; Parry, Neil G

    2010-03-01

    Gastric volvulus can occur along the organoaxial axis or the mesenteroaxial axis. We present a patient with a gastric bascule: a gastric volvulus due to two lead points. A 17-year-old boy with dextrogastria, asplenia, and left diaphragmatic eventration presented with acute onset of nonbilious emesis, jaundice, and diffuse abdominal tenderness. Surgical exploration demonstrated a gastric volvulus, with lead points of torsion at the gastroesophageal junction and the second part of the duodenum, causing biliary obstruction. After decompression, reduction, and gastropexy, the patient recovered well. Gastric bascule is a subtype of gastric volvulus, whereby two lead points cause gastric rotation and folding of the stomach upon itself. PMID:20172106

  5. Benign gastric filling defect

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  6. Shared and Unique Proteins in Human, Mouse and Rat Saliva Proteomes: Footprints of Functional Adaptation

    Robert C. Karn

    2013-12-01

    Full Text Available The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6 and the genome rat (BN/SsNHsd/Mcwi. Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.

  7. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  8. Gastric protein hydrolysis of raw and roasted almonds in the growing pig.

    Bornhorst, Gail M; Drechsler, Krista C; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J; Singh, R Paul

    2016-11-15

    Gastric protein hydrolysis may influence gastric emptying rate and subsequent protein digestibility in the small intestine. This study examined the gastric hydrolysis of dietary protein from raw and roasted almonds in the growing pig as a model for the adult human. The gastric hydrolysis of almond proteins was quantified by performing tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent image analysis. There was an interaction between digestion time, stomach region, and almond type for gastric protein hydrolysis (pGastric emptying rate of protein was a significant (pgastric protein hydrolysis. In general, greater gastric protein hydrolysis was observed in raw almonds (compared to roasted almonds), hypothesized to be related to structural changes in almond proteins during roasting. Greater gastric protein hydrolysis was observed in the distal stomach (compared to the proximal stomach), likely related to the lower pH in the distal stomach. PMID:27283660

  9. Human adaptation to isolated and confined environments: Preliminary findings of a seven month Antarctic winter-over human factors study

    Evans, Gary W.; Stokols, Daniel; Carrere, Sybil

    1988-01-01

    This field study was conducted during the last decade of an austral winter-over at Palmer Station in the Antarctic. The purpose of the study was to understand temporal patterns in physiological arousal and psychological mood over the course of the mission. The investigators were principally interested in how people adapted over time to chronic and acute stressors, and how people use and modify their built environment. Physiological and psychological data were collected several times a week, and information on behavior and the use of physical facilities was collected monthly. Physiological and psychological data were compared with social changes in the setting toward the development of a sequential model of human-environment transactional relationships. Based on the study results, guidelines for design of future isolated and confined environments (ICEs) included: plan space for items which make people feel at home, provide materials to allow people to personalize their environment, allow for flexible environments, provide areas for visual and auditory privacy, equip areas for socializing and remove them from private areas, and provide facilities for exercise and for projects involving physical activity. The study offers guidelines about patterns of adaption that could be expected in an ICE, discusses how these settings can be programmed to facilitate successful adjustment, and provides information about how to design future ICE habitats to maximize a healthy living environment.

  10. Gastric acid inhibitory and gastric protective effects of Cannabis and cannabinoids.

    Abdel-Salam, Omar

    2016-05-01

    Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this 'endocannabinoid system' in different pathophysiologic processes is beginning to be delineated. There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in Δ(9)-tetrahydrocannabinol inhibit gastric acid secretion in humans and experimental animals. This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2-deoxy-d-glucose. Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress-induced mucosal damage. Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties. PMID:27261847

  11. Effects of Recombinant Human Growth Hormone on Growth of Human Gastric Cancer Cell Line in Vitro%重组人类生长激素对胃癌细胞的体外增殖研究

    费哲为; 欧敬明; 董谦; 刘颖斌; 方国恩

    2011-01-01

    Objective: To investigate the effects of recombinant human growth hormone (rhGH) on growth of human gastric cancer cell line in vitro. Methods: Cells were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cell inhibitory rate, cell cycle and DNA inhibitory rate of human gastric cancer line SGC-7901, at different concentrations of rhGH treatment were detected by cell culture, MTT assay and flow cytometry. Results: There was not distinctly accelerated effect of rhGH on multiplication of SGC-7901 cell line in vitro. There was no statistical significance between rhGH group and control group, or between rhGH+L-OHP group and L-OHP group (P>0.05). Cell inhibitory rate and cell arrested in G0-G1 phase increased. Meanwhile, cells in S phase distinctly decreased and DNA inhibitory rate increased in rhGH+L-OHP group in comparison with L-OHP group (P< 0.01). Conclusion: rhGH does not accelerate the multiplication of human gastric cancer cells. It may increase the therapeutic efficacy when used in combination with anticancer drugs.%目的:通过体外实验,研究重组人类生长激素对胃癌细胞的增殖的影响.方法:实验分为空白组,重组人类生长激素组,奥沙利铂组和重组人类生长激素+奥沙利铂组.用不同浓度的重组人类生长激素处理SGC-7901细胞,采用MTT法和流式细胞仪检测人胃癌细胞株的细胞抑制率,细胞周期和DNA抑制率.结果:体外实验结果表明,重组人类生长激素对SGC-7901细胞株增殖没有明显的促进作用,重组人类生长激素组和空白组以及重组人类生长激素+奥沙利铂组和奥沙利铂组之间没有统计显著性(P>0.05),细胞抑制率和停止生长的细胞在G0-GI期明显增加(P<0.01),同时重组人类生长激素+奥沙利铂组和空白组以及奥沙利铂组在S期,细胞数依次下降,DNA抑制率依次增加.重组人类生长激素+奥沙利铂组与奥沙利铂组相比,细胞抑制率有明显上升

  12. Gastric Lipase Secretion in Children with Gastritis

    Krystyna Sztefko

    2013-07-01

    Full Text Available 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, the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14 and the control group including healthy adolescents (n = 14. Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK, glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic peptide (GIP were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005 and the control group (p < 0.005. Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003 and the HPG group (p < 0.01. We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

  13. The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia.

    Deng, Lian; Hoh, Boon Peng; Lu, Dongsheng; Fu, Ruiqing; Phipps, Maude E; Li, Shilin; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Ismail, Endom; Mokhtar, Siti Shuhada; Jin, Li; Zilfalil, Bin Alwi; Marshall, Christian R; Scherer, Stephen W; Al-Mulla, Fahd; Xu, Shuhua

    2014-09-01

    Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations--especially indigenous populations--inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N(e)) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000--6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration

  14. Gastric Necrosis due to Acute Massive Gastric Dilatation

    Ibrahim Aydin

    2013-01-01

    Full Text Available Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

  15. DNA损伤修复基因在胃癌组织中的异常甲基化改变%Promoter region methylation of DNA damage repair genes in human gastric cancer

    郭贺; 闫文姬; 杨云生; 郭明洲

    2014-01-01

    目的 联合检测7个DNA损伤修复基因在胃癌组织中的异常甲基化改变.方法 收集解放军总医院胃癌手术标本70例,酚-氯仿法提取DNA后,经亚硫酸氢盐处理,甲基化特异性聚合酶链反应(MSP)方法检测标本中MLH1,CHFR,MGMT,FANCF,Rassf1A,BRCA1和GSTpi基因启动子区CpG岛的甲基化状况.结果 7个DNA损伤修复基因的甲基化率分别如下:MLH1 22.9%(16/70),CHFR 47.1% (33/70),MGMT 34.3% (24/70),FANCF 11.4%(8/70),RASSF1A 7.1%(5/70),BRCA1 1.4% (1/70),GSTpi 0% (0/70).临床资料分析显示CHFR的甲基化与患者年龄、胃癌肿瘤大小和分化程度相关.基因间相关性分析显示CHFR的甲基化分别与MLH1和MGMT基因的甲基化相关.结论 MLH1,CHFR和MGMT基因在胃癌组织中频繁甲基化,而FANCF、RASSF1A、BRCA1和GSTpi基因在胃癌组织中甲基化率低,MLH1,CHFR和MGMT基因在胃癌的发生发展中可能起重要作用.联合检测上述3个基因的甲基化可能对胃癌的诊断提供帮助.%Objective To detect the status of promoter region methylation of damage repair genes in gastric cancer and analyze its association with clinicopathologic characteristics.Methods A total of 70 human gastric cancer tissue samples representing all stages of disease were obtained from surgical resection specimens.DNA was extracted with the phenol-chloroform method.The technique of methylation specific polymerase chain reaction (MSP) was used to examine the methylation status of MLH1,CHFR,MGMT,FANCF,Rassf1A,BRCA1 and GSTpi in gastric cancer specimens.And MSP products were analyzed with 2% agarose gel electrophoresis.Results The methylation rates of DNA damage related genes in human gastric cancer were as follows:MLH1 22.9% (16/70),CHFR 47.1% (33/70),MGMT 34.3% (24/70),FANCF 11.4% (8/70),RASSF1A 7.1% (5/70),BRCA1 1.4% (1/70) and GSTpi0% (0/70).And CHFR methylation was correlated with patient age (< 60 year) (P =0.035),tumor size (diameter ≥5 cm) (P =0

  16. The effect of ω-fatty acids on the expression of phospholipase A 2 group 2A in human gastric cancer patients

    Mahboube Shariati

    2016-01-01

    Full Text Available Background: Studies show that polyunsaturated fatty acids (PUFAs may have an inhibitory role in carcinogenesis. It was previously shown that PLA2 group 2A (PLA2G2A messenger RNA (mRNA expression is associated with less frequent metastasis and longer survival in gastric adenocarcinoma. This study intends to investigate the effect of PUFAs on the expression of PLA2G2A in patients with gastric cancer. Materials and Methods: Thirty-four patients with gastric cancer (GC were randomly divided into two groups. The first group received cisplatin medication. The second group received cisplatin medication and supplements of ω-fatty acids for three courses. The total RNA was extracted from the tissues and cDNA was synthesized. The gene expression of PLA2G2A was evaluated by the real-time polymerase chain reaction (PCR method. To confirm the changes in gene expression, frozen section was utilized. The frozen tissue samples were sectioned and stained using the immunohistochemistry technique. Results: After chemotherapy and chemotherapy plus supplement, the relative mean of PLA2G2A gene expression increased 1.5 ± 0.5-fold and 7.4 ± 2.6-fold, respectively (P = 0.006. The relative mean of gene expression in patients who received cisplatin and ω-fatty acids supplement increased more significantly (7.5 ± 3.3-fold than in patients who received only cisplatin (P = 0.016. Conclusion: It was found that PUFAs increased the gene and protein expression of PLA2G2A in gastric cancer. Concerning the fact that studies reveal protective function of PLA2G2A in gastric cancer, it is suggested that increased expression of PLA2G2A is helpful. Furthermore, PUFAs can be considered as a useful therapeutic supplement for patients with gastric cancer.

  17. Gastric emptying in morbid obesity

    Weight loss following gastroplasty had no correlation with gastric emptying rate. Patients who showed transient prolongation of gastric emptying returned to normal one year later and showed no significant difference in weight loss from those who did not have temporary delayed gastric emptying. Perhaps gatroplasty (at least temporarily) reduces the gastric volume producing early satiation without affecting the gastric emptying rate as tested by a small volume radiolabelled test meal. Longer follow-up is indicated to see if delayed weight gain occurs because of gastric pouch stretching and if this has any correlation with gastric emptying rate. (Author)

  18. Tests of gastric neuromuscular function.

    Parkman, Henry P; Jones, Michael P

    2009-05-01

    Tests of gastric neuromuscular function are used to evaluate patients with symptoms referable to the upper digestive tract. These symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical function and contractility. Management of gastric neuromuscular disorders requires an understanding of pathophysiology and treatment options as well as the appropriate use and interpretation of diagnostic tests. These tests include measures of gastric emptying; contractility; electrical activity; regional gastric motility of the fundus, antrum, and pylorus; and tests of sensation and compliance. Tests are also being developed to improve our understanding of the afferent sensory pathways from the stomach to the central nervous system that mediate gastric sensation in health and gastric disorders. This article reviews tests of gastric function and provides a basic description of the tests, the methodologies behind them, descriptions of the physiology that they assess, and their clinical utility. PMID:19293005

  19. HUMEX, a study on the survivability and adaptation of humans to long- duration exploratory missions

    Horneck, G.

    for terrestrial applications. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnistic systems become essential especially for the long-term Mars scenario. A roadmap for a future European strategy leading to a potential European participation in a cooperative human exploratory mission, either to the Moon or to Mars, was produced. Ref. Horneck et al. HUMEX, study on the Survivability and Adaptation of Humans to Long-Duration Exploratory Missions, ESA SP (in press)

  20. Searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes

    Sazzini, M; Schiavo, G; Fanti, S.; Martelli, P. L.; Casadio, R.; D. Luiselli

    2014-01-01

    Adaptation to low temperatures has been reasonably developed in the human species during the colonization of the Eurasian landmass subsequent to Out of Africa migrations of anatomically modern humans. In addition to morphological and cultural changes, also metabolic ones are supposed to have favored human isolation from cold and body heat production and this can be hypothesized also for most Neandertal and at least for some Denisovan populations, which lived in geographical areas that strongl...