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Sample records for chief cells gastric

  1. Novel insights of the gastric gland organization revealed by chief cell specific expression of moesin

    OpenAIRE

    Zhu, Lixin; Hatakeyama, Jason; Zhang, Bing; Makdisi, Joy; Ender, Cody; Forte, John G.

    2008-01-01

    ERM (ezrin, radixin, and moesin) proteins play critical roles in epithelial and endothelial cell polarity, among other functions. In gastric glands, ezrin is mainly expressed in acid-secreting parietal cells, but not in mucous neck cells or zymogenic chief cells. In looking for other ERM proteins, moesin was found lining the lumen of much of the gastric gland, but it was not expressed in parietal cells. No significant radixin expression was detected in the gastric glands. Moesin showed an inc...

  2. Novel insights of the gastric gland organization revealed by chief cell specific expression of moesin

    Science.gov (United States)

    Zhu, Lixin; Hatakeyama, Jason; Zhang, Bing; Makdisi, Joy; Ender, Cody; Forte, John G.

    2009-01-01

    ERM (ezrin, radixin, and moesin) proteins play critical roles in epithelial and endothelial cell polarity, among other functions. In gastric glands, ezrin is mainly expressed in acid-secreting parietal cells, but not in mucous neck cells or zymogenic chief cells. In looking for other ERM proteins, moesin was found lining the lumen of much of the gastric gland, but it was not expressed in parietal cells. No significant radixin expression was detected in the gastric glands. Moesin showed an increased gradient of expression from the neck to the base of the glands. In addition, the staining pattern of moesin revealed a branched morphology for the gastric lumen. This pattern of short branches extending from the glandular lumen was confirmed by using antibody against zonula occludens-1 (ZO-1) to stain tight junctions. With a mucous neck cell probe (lectin GSII, from Griffonia simplicifolia) and a chief cell marker (pepsinogen C), immunohistochemistry revealed that the mucous neck cells at the top of the glands do not express moesin, but, progressing toward the base, mucous cells showing decreased GSII staining had low or moderate level of moesin expression. The level of moesin expression continued to increase toward the base of the glands and reached a plateau in the base where chief cells and parietal cells abound. The level of pepsinogen expression also increased toward the base. Pepsinogen C was located on cytoplasmic granules and/or more generally distributed in chief cells, whereas moesin was exclusively expressed on the apical membrane. This is a clear demonstration of distinctive cellular expression of two ERM family members in the same tissue. The results provide the first evidence that moesin is involved in the cell biology of chief cells. Novel insights on gastric gland morphology revealed by the moesin and ZO-1 staining provide the basis for a model of cell maturation and migration within the gland. PMID:19074636

  3. Novel insights of the gastric gland organization revealed by chief cell specific expression of moesin.

    Science.gov (United States)

    Zhu, Lixin; Hatakeyama, Jason; Zhang, Bing; Makdisi, Joy; Ender, Cody; Forte, John G

    2009-02-01

    ERM (ezrin, radixin, and moesin) proteins play critical roles in epithelial and endothelial cell polarity, among other functions. In gastric glands, ezrin is mainly expressed in acid-secreting parietal cells, but not in mucous neck cells or zymogenic chief cells. In looking for other ERM proteins, moesin was found lining the lumen of much of the gastric gland, but it was not expressed in parietal cells. No significant radixin expression was detected in the gastric glands. Moesin showed an increased gradient of expression from the neck to the base of the glands. In addition, the staining pattern of moesin revealed a branched morphology for the gastric lumen. This pattern of short branches extending from the glandular lumen was confirmed by using antibody against zonula occludens-1 (ZO-1) to stain tight junctions. With a mucous neck cell probe (lectin GSII, from Griffonia simplicifolia) and a chief cell marker (pepsinogen C), immunohistochemistry revealed that the mucous neck cells at the top of the glands do not express moesin, but, progressing toward the base, mucous cells showing decreased GSII staining had low or moderate level of moesin expression. The level of moesin expression continued to increase toward the base of the glands and reached a plateau in the base where chief cells and parietal cells abound. The level of pepsinogen expression also increased toward the base. Pepsinogen C was located on cytoplasmic granules and/or more generally distributed in chief cells, whereas moesin was exclusively expressed on the apical membrane. This is a clear demonstration of distinctive cellular expression of two ERM family members in the same tissue. The results provide the first evidence that moesin is involved in the cell biology of chief cells. Novel insights on gastric gland morphology revealed by the moesin and ZO-1 staining provide the basis for a model of cell maturation and migration within the gland. PMID:19074636

  4. Expression and phosphorylation of a MARCKS-like protein in gastric chief cells: further evidence for modulation of pepsinogen secretion by interaction of Ca2+/calmodulin with protein kinase C.

    Science.gov (United States)

    Raufman, J P; Malhotra, R; Xie, Q; Raffaniello, R D

    1997-03-01

    In gastric chief cells, agents that activate protein kinase C (PKC) stimulate pepsinogen secretion and phosphorylation of an acidic 72-kDa protein. The isoelectric point and molecular mass of this protein are similar to those for a common PKC substrate; the MARCKS (for Myristoylated Alanine-Rich C Kinase Substrate) protein. We examined expression and phosphorylation of the MARCKS-like protein in a nearly homogeneous suspension of chief cells from guinea pig stomach. Western blotting of fractions from chief cell lysates with a specific MARCKS antibody resulted in staining of a myristoylated 72-kDA protein (pp72), associated predominantly with the membrane fraction. Using permeabilized chief cells, we examined the effect of PKC activation (with the phorbol ester PMA), in the presence of basal (100 nM) or elevated cellular calcium (1 microM), on pepsinogen secretion and phosphorylation of the 72-KDa MARCKS-like protein. Secretion was increased 2.3-, 2.6-, and 4.5-fold by incubation with 100 nM PMA, 1 microM calcium, and PMA plus calcium, respectively. A PKC inhibitor (1 microM CGP 41 251) abolished PMA-induced secretion, but did not alter calcium-induced secretion. This indicates that calcium-induced secretion is independent of PKC activation. Chief cell proteins were labeled with 32P-orthophosphate and phosphorylation of pp72 was detected by autoradiography of 2-dimensional polyacrylamide gels. In the presence of basal calcium, PMA (100 nM) caused a > two-fold increase in phosphorylation of pp72. Without PMA, calcium did not alter phosphorylation of pp72. However, 1 microM calcium caused an approx. 50% attenuation of PMA-induced phosphorylation of pp72. Experiments with a MARCKS "phosphorylation/calmodulin binding domain peptide" indicated that calcium/calmodulin inhibits phosphorylation of pp72 by binding to the phosphorylation/calmodulin binding domain and not by inhibiting PKC activity. These observations support the hypothesis that, in gastric chief cells

  5. The origin of pre-neoplastic metaplasia in the stomach: Chief cells emerge from the Mist

    Energy Technology Data Exchange (ETDEWEB)

    Goldenring, James R., E-mail: jim.goldenring@vanderbilt.edu [Nashville Department of Veterans Affairs Medical Center, Nashville, TN (United States); Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN (United States); Nam, Ki Taek [Nashville Department of Veterans Affairs Medical Center, Nashville, TN (United States); Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN (United States); Mills, Jason C. [Divison of Gastroenterology, Departments of Medicine, Pathology, and Developmental Biology, Washington University School of Medicine, St. Louis, MO (United States)

    2011-11-15

    The digestive-enzyme secreting, gastric epithelial chief (zymogenic) cell is remarkable and underappreciated. Here, we discuss how all available evidence suggests that mature chief cells in the adult, mammalian stomach are postmitotic, slowly turning over cells that arise via a relatively long-lived progenitor, the mucous neck cell, The differentiation of chief cells from neck cells does not involve cell division, and the neck cell has its own distinct pattern of gene expression and putative physiological function. Thus, the ontogeny of the normal chief cell lineage exemplifies transdifferentiation. Furthermore, under pathophysiogical loss of acid-secreting parietal cell, the chief cell lineage can itself trasndifferentiate into a mucous cell metaplasia designated Spasmolytic Polypeptide Expressing Metaplasia (SPEM). Especially in the presence of inflammation, this metaplastic lineage can regain proliferative capacity and, in humans may also further differentiate into intestinal metaplasia. The results indicate that gastric fundic lineages display remarkable plasticity in both physiological ontogeny and pathophysiological pre-neoplastic metaplasia.

  6. Gastric Cancer Stem Cells

    OpenAIRE

    Takaishi, Shigeo; Okumura, Tomoyuki; Timothy C Wang

    2008-01-01

    Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony format...

  7. Erythropoietin -induced proliferation of gastric mucosal cells

    OpenAIRE

    Itoh, Kazuro; Sawasaki, Yoshio; Takeuchi, Kyoko; Kato, Shingo; Imai, Nobuhiro; Kato, Yoichiro; Shibata, Noriyuki; KOBAYASHI, MAKIO; Moriguchi, Yoshiyuki; Higuchi, Masato; Ishihata, Fumio; Sudoh, Yushi; Miura, Soichiro

    2006-01-01

    AIM: To analyze the localization of erythropoietin receptor on gastric specimens and characterize the effects of erythropoietin on the normal gastric epithelial proliferation using a porcine gastric epithelial cell culture model.

  8. Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas

    Directory of Open Access Journals (Sweden)

    Roth Sanford I

    2007-10-01

    Full Text Available Abstract Background The potential pathogenetic significance of mitochondrial DNA (mtDNA mutations in tumorigenesis is controversial. We hypothesized that benign tumorigenesis of a slowly replicating tissue like the human parathyroid might constitute an especially fertile ground on which a selective advantage conferred by mtDNA mutation could be manifested and might contribute to the oxyphilic phenotype observed in a subset of parathyroid tumors. Methods We sought acquired mitochondrial DNA mutations by sequencing the entire 16.6 kb mitochondrial genome of each of thirty sporadic parathyroid adenomas (18 chief cell and 12 oxyphil cell, eight independent, polyclonal, parathyroid primary chief cell hyperplasias plus corresponding normal control samples, five normal parathyroid glands, and one normal thyroid gland. Results Twenty-seven somatic mutations were identified in 15 of 30 (9 of 12 oxyphil adenomas, 6 of 18 chief cell parathyroid adenomas studied. No somatic mutations were observed in the hyperplastic parathyroid glands. Conclusion Features of the somatic mutations suggest that they may confer a selective advantage and contribute to the molecular pathogenesis of parathyroid adenomas. Importantly, the statistically significant differences in mutation prevalence in oxyphil vs. chief cell adenomas also suggest that mtDNA mutations may contribute to the oxyphil phenotype.

  9. Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice.

    Science.gov (United States)

    Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

    2016-07-01

    The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5(+) stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5(+) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5(+) stem cells and their progeny with Cre-reporter Rosa26(tdTomato). Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5(+) stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5(+) chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5(+) cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5(+) stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression. PMID:27091432

  10. Gastric Large Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    Case: A 63-year-old male presented with unintentional weight loss of 20 pounds over a 4-month duration. He reported loss of appetite, intermittent post-prandial nausea, bloating and early satiety. He also complained of dyspepsia and had been treated for reflux during the previous 2 years. He denied vomiting, dysphagia, odynophagia, abdominal pain, melena, hematochezia, or alterations in bowel habits. Additionally, he denied fevers, night sweats, cough, or dyspnea. He quit smoking 25 years ago, and denied alcohol use. His past medical history was significant for basal cell carcinoma treated with local curative therapy and he was without recurrence on surveillance. Pertinent family history included a paternal uncle with lung cancer at the age of 74. Physical examination was unremarkable except for occult heme-positive stools. Laboratory evaluation revealed elevated liver enzymes (ALT-112, AST-81, AlkPhos-364). CT scan of the chest, abdomen and pelvis showed diffuse heterogeneous liver with extensive nodularity, raising the concern for metastases. Serum tumor-markers: PSA, CEA, CA 19-9, and AFP were all within normal limits. Screening colonoscopy was normal, but esophagogastroduodenoscopy revealed a malignant-appearing ulcerative lesion involving the gastro-esophageal junction and gastric cardia. Pathology confirmed an invasive gastric large cell neuroendocrine carcinoma. Ultrasound-guided fine needle aspiration of a hepatic lesion revealed malignant cells with cytologic features consistent with large-cell type carcinoma and positive immunostaining for synaptophysin favoring neuroendocrine differentiation. A PET-CT demonstrated intense diffuse FDG uptake of the liver, suggesting diffuse hepatic parenchymal infiltration by tumor. There were multiple foci of intense osseous FDG uptake with corresponding osteolytic lesions seen on CT scan. The remaining intra-abdominal and intra-thoracic structures were unremarkable. The patient will receive palliative systemic therapy

  11. Gastric cancer stem cells: A novel therapeutic target

    OpenAIRE

    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, ...

  12. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    Science.gov (United States)

    Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

    2016-01-01

    Bruton’s tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer. PMID:27508020

  13. Erythropoietin-induced proliferation of gastric mucosal cells

    Institute of Scientific and Technical Information of China (English)

    Kazuro Itoh; Masato Higuchi; Fumio Ishihata; Yushi Sudoh; Soichiro Miura; Yoshio Sawasaki; Kyoko Takeuchi; Shingo Kato; Nobuhiro Imai; Yoichiro Kato; Noriyuki Shibata; Makio Kobayashi; Yoshiyuki Moriguchi

    2006-01-01

    AIM: To analyze the localization of erythropoietin receptor on gastric specimens and characterize the effects of erythropoietin on the normal gastric epithelial proliferation using a porcine gastric epithelial cell culture model.METHODS: Erythropoietin receptor was detected by RT-PCR, Western blotting and immunohistochermistry.Growth stimulation effects of erythropoietin on cultured gastric mucosal cells were determined by ELISA using bromodeoxyuridine (BrdU).RESULTS: Erythropoietin receptor was detected on cultured porcine gastric mucosal epithelial cells.Erythropoietin receptor was also detected histochemically at the base of gastric mucosal epithelium. BrdU assay demonstrated a dose-dependent increase in growth potential of cultured porcine gastric mucosal epithelial cells by administration of erythropoietin, as well as these effects were inhibited by administration of antierythropoietin antibody (P< 0.01).CONCLUSION: These findings indicate that erythropoietin has a potential to proliferate gastric mucosal epithelium via erythropoietin receptor.

  14. Expression of Telomerase Activity in Gastric Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    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. Cytotoxic T Cells in H. pylori-Related Gastric Autoimmunity and Gastric Lymphoma

    Directory of Open Access Journals (Sweden)

    Mathijs P. Bergman

    2010-01-01

    Full Text Available Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop gastric B-cell lymphoma, gastric autoimmunity, or other life threatening diseases, as gastric cancer or peptic ulcer. The type of host immune response against H. pylori, particularly the cytolytic effector functions of T cells, is crucial for the outcome of the infection. T cells are potentially able to kill a target via different mechanisms, such as perforins or Fas-Fas ligand interaction. In H. pylori-infected patients with gastric autoimmunity cytolytic T cells, that cross-recognize different epitopes of H. pylori proteins and H+K+-ATPase autoantigen, infiltrate the gastric mucosa and lead to gastric atrophy via long-lasting activation of Fas ligand-mediated appotosis and perforin-induced cytotoxicity. On the other hand, gastric T cells from MALT lymphoma exhibit defective perforin- and Fas-Fas ligand-mediated killing of B cells, with consequent abnormal help for B-cell proliferation, suggesting that deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support both the onset and the promotion of low-grade B-cell lymphoma.

  16. Gastric hyperplastic polyps coexisting with early gastric cancers, adenoma and neuroendocrine cell hyperplasia.

    Science.gov (United States)

    Karpińska-Kaczmarczyk, K; Lewandowska, M; Białek, A; Ławniczak, M; Urasińska, E

    2016-03-01

    Gastric hyperplastic polyps (GHP) constitute up to 93% of all benign epithelial polyps of the stomach. The average probability of malignant transformation in GHP is 0.6-22% in large series. The aim of the study was to present the coexistence of GHP with early gastric cancer (EGC), gastric adenoma (GA), neuroendocrine cell hyperplasia (NH) and well-differentiated neuroendocrine tumour (NET G1). Three cases were studied to reveal clinical data and morphological changes and to assess the relationship between GHP and accompanying gastric neoplastic lesions. PMID:27179272

  17. Expression and Clinical Significance of REGy in Gastric Cancer Tissue and Variously Differentiated Gastric Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Jia Li; Tian Tian; Xiaoyi Wang; Fan Li; Guosheng Ren

    2009-01-01

    OBJECTIVE To evaluate the REGy expression in gastric cancer tissue and gastric cancer cell lines of various differentiation levels and its clinical significance.METHODS Immunohistochemistry was used to detect the expression of REGy protein in 70 specimens of gastric cancer and 30 specimens of normal gastric mucosa. The relationship between the expression of REGy protein and the biological behaviors of gastric cancer was analyzed. RT-PCR and Western blot were used to detect the mRNA level and the protein expression of REGγ in normal gastric cell line GES-1, well differentiated gastric cancer cell line MKN-28, moderately differentiated gastric cancer cell line SGC-7901 and poorly differentiated gastric cancer cell line BGC-823.RESULTS The expression rate of REGγprotein in gastric cancer tissue (52/70, 74.29%) was significantly higher than that in normal gastric tissue (12/30, 40%) (P<0.01). The expression rate of REGywas correlated with tumor size (P<0.01), lymph node metastasis (P<0.05), differentiation degree (P<0.01), infiltration depth (P<0.01)and distant metastasis (P<0.05). RT-PCR analysis showed that theexpression of REGγ mRNA was 0.459±0.079 in the normal gastric mucosa cell line, 0.588±0.118 in the well differentiated gastric cancer cell line, 0.715±0.066 in the moderately differentiated gastric cancer cell line, and 0.873±0.099 in the poorly differentiated gastric cancer cell line, showing a negative correla- tion between REGγmRNA expression and differentiation level (P <0.05). Western blot analysis showed that the expression of REGy protein was 0.712±0.065 in the normal gastric mucosa cell line, 1.176±0.185 in the well differentiated gastric cancer cell line, 1.533 ±0.127 in the moderately differentiated gastric cancer cell line, and 2.061±0.398 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγprotein expression and differentiation level (P<0.05).CONCLUSION REGγ is expressed in gastric cancer

  18. Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium.

    Science.gov (United States)

    Moore, Benjamin D; Khurana, Shradha S; Huh, Won Jae; Mills, Jason C

    2016-08-01

    We have previously shown that the sequential transcription factors Xbp1→Mist1 (Bhlha15) govern the ultrastructural maturation of the secretory apparatus in enzyme-secreting zymogenic chief cells (ZCs) in the gastric unit. Here we sought to identify transcriptional regulators upstream of X-box binding protein 1 (XBP1) and MIST1. We used immunohistochemistry to characterize Hnf4α(flox/flox) adult mouse stomachs after tamoxifen-induced deletion of Hnf4α We used qRT-PCR, Western blotting, and chromatin immunoprecipitation to define the molecular interaction between hepatocyte nuclear factor 4 alpha (HNF4α) and Xbp1 in mouse stomach and human gastric cells. We show that HNF4α protein is expressed in pit (foveolar) cells, mucous neck cells, and zymogenic chief cells (ZCs) of the corpus gastric unit. Loss of HNF4α in adult mouse stomach led to reduced ZC size and ER content, phenocopying previously characterized effects of Xbp1 deletion. However, HNF4α(Δ/Δ) stomachs also exhibited additional phenotypes including increased proliferation in the isthmal stem cell zone and altered mucous neck cell migration, indicating a role of HNF4α in progenitor cells as well as in ZCs. HNF4α directly occupies the Xbp1 promoter locus in mouse stomach, and forced HNF4α expression increased abundance of XBP1 mRNA in human gastric cancer cells. Finally, as expected, loss of HNF4α caused decreased Xbp1 and Mist1 expression in mouse stomachs. We show that HNF4α regulates homeostatic proliferation in the gastric epithelium and is both necessary and sufficient for the upstream regulation of the Xbp1→Mist1 axis in maintenance of ZC secretory architecture. PMID:27340127

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  20. Establishment of novel in vitro mouse chief cell and SPEM cultures identifies MAL2 as a marker of metaplasia in the stomach.

    Science.gov (United States)

    Weis, Victoria G; Petersen, Christine P; Mills, Jason C; Tuma, Pamela L; Whitehead, Robert H; Goldenring, James R

    2014-10-15

    Oxyntic atrophy in the stomach leads to chief cell transdifferentiation into spasmolytic polypeptide expressing metaplasia (SPEM). Investigations of preneoplastic metaplasias in the stomach are limited by the sole reliance on in vivo mouse models, owing to the lack of in vitro models for distinct normal mucosal lineages and metaplasias. Utilizing the Immortomouse, in vitro cell models of chief cells and SPEM were developed to study the characteristics of normal chief cells and metaplasia. Chief cells and SPEM cells isolated from Immortomice were cultured and characterized at both the permissive (33°C) and the nonpermissive temperature (39°C). Clones were selected on the basis of their transcriptional expression of specific stomach lineage markers (named ImChief and ImSPEM) and protein expression and growth were analyzed. The transcriptional expression profiles of ImChief and ImSPEM cells were compared further by using gene microarrays. ImChief cells transcriptionally express most chief cell markers and contain pepsinogen C and RAB3D-immunostaining vesicles. ImSPEM cells express the SPEM markers TFF2 and HE4 and constitutively secrete HE4. Whereas ImChief cells cease proliferation at the nonpermissive temperature, ImSPEM cells continue to proliferate at 39°C. Gene expression profiling of ImChief and ImSPEM revealed myelin and lymphocyte protein 2 (MAL2) as a novel marker of SPEM lineages. Our results indicate that the expression and proliferation profiles of the novel ImChief and ImSPEM cell lines resemble in vivo chief and SPEM cell lineages. These cell culture lines provide the first in vitro systems for studying the molecular mechanisms of the metaplastic transition in the stomach.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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

  3. Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Holck, Susanne; Holm, I.L.; Holck, P.P.;

    2007-01-01

    Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load...

  4. RNA interference targeting raptor inhibits proliferation of gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, William Ka Kei; Lee, Chung Wa [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Cho, Chi Hin [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Chan, Francis Ka Leung [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Yu, Jun, E-mail: junyu@cuhk.edu.hk [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Sung, Joseph Jao Yiu, E-mail: joesung@cuhk.edu.hk [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)

    2011-06-10

    Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G{sub 0}/G{sub 1}-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D{sub 3} and p21{sup Waf1}, which stabilizes cyclin D/cdk4 complex for G{sub 1}-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.

  5. Astragalus extract inhibits destruction of gastric cancer cells to mesothelial cells by anti-apoptosis

    Institute of Scientific and Technical Information of China (English)

    Di Na; Fu-Nan Liu; Zhi-Feng Miao; Zong-Min Du; Hui-Mian Xu

    2009-01-01

    AIM: To determine the inhibitory effect of Astragalus memebranaceushas on gastric cancer cell supernatantinduced apoptosis of human peritoneal mesothelial cells. METHODS: Human peritoneal mesothelial cell (HPMC) line HMrSV5 was co-incubated with gastric cancer cell supernatant (MKN45) and/or Astragalus memebranaceushas. Morphological changes in gastric cancer cells were observed under phase-contrast microscope. Quantitative cell damage was determined by MTT assay. Apoptosis was determined under transmission electron microscope and quantified by detecting acridine orange/ethidium bromide-stained (AO/EB) condensed nuclei under fluorescent microscope or by flow cytometry. Expressions of Bcl-2 and Bax were evaluated with immunostaining. RESULTS: Morphological changes and exfoliation occurred and naked areas appeared in cultured HMrSV5 cells 24 h after they were treated with gastric cancer cell supernatant. Cell supernatant from MKN45 gastric cancer cells induced apoptosis of HMrSV5 cells in a time-dependent manner. Obvious morphological changes were observed in cell apoptosis, such as condensation of chromatin, nuclear fragmentations and apoptotic bodies. Astragalus memebranaceus could partly suppress these changes and regulate the expressions of Bcl-2 and Bax in HMrSV5 cells. CONCLUSION: Gastric cancer cells induce apoptosis of HPMCs through the supernatant. Astragalus memebranaceushas inhibits this phenomenon and can be used an adjuvant chemothera-peutic agent in gastric cancer therapy.

  6. Adrenomedullin Expression by Gastric Epithelial Cells in Response to Infection

    OpenAIRE

    Robert P. Allaker; Kapas, Supriya

    2003-01-01

    Many surface epithelial cells express adrenomedullin, a multifunctional peptide found in a wide number of body and cell systems. Recently, we and others have proposed that adrenomedullin has an important novel role in host defense. This peptide has many properties in common with other cationic antimicrobial peptides, including the human β-defensins. Upon exposure of human gastric epithelial cells to viable cells of invasive or noninvasive strains of Helicobacter pylori, Escherichia coli, Salm...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Current Status on Stem Cells and Cancers of the Gastric Epithelium

    Directory of Open Access Journals (Sweden)

    Werner Hoffmann

    2015-08-01

    Full Text Available Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.

  9. Paclitaxel induces apoptosis in human gastric carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    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.

  10. SUZ12 Depletion Suppresses the Proliferation of Gastric Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yingjun Cui

    2013-05-01

    Full Text Available Background/Aims: SUZ12 and EZH2 are two main components of polycomb repressive complex 2 (PRC2 that is known to be of great importance in tumorigenesis. EZH2 has been reported to play a vital role in pathogenesis of human cancer. However, whether SUZ12 has equivalent roles in tumorigenesis has not been demonstrated. Here, we investigated a possible role of SUZ12 for the proliferation of gastric cancer cells. Methods: Western-blot analysis was used to detected the levels of SUZ12, H3K27me3, EZH2 and p27 in ten gastric cell lines. SUZ12 was depleted by RNA interference. Cell cycle was detected by flow cytometry. Luciferase assays was to analyze whether miR-200b directly regulate SUZ12. Results: We found that SUZ12 depletion mediated by RNA interference (RNAi led to a reduction of gastric cell numbers and arrested the cell cycle at G1/S point. As an important G1/S phase inhibitory gene, p27 is re-induced to some extent by SUZ12 knockdown. Furthermore, we demonstrated that SUZ12 was directly downregulated by miR-200b. Conclusion: We provide evidence suggesting that SUZ12 may be a potential therapeutic target for gastric cancer.

  11. Altered expression of a putative progenitor cell marker DCAMKL1 in the rat gastric mucosa in regeneration, metaplasia and dysplasia

    Directory of Open Access Journals (Sweden)

    Watanabe Hiromitsu

    2010-06-01

    Full Text Available Abstract Background Doublecortin and calcium/calmodulin-dependent protein kinase-like-1 (DCAMKL1 is a candidate marker for progenitor cells in the gastrointestinal mucosa. Lineage cells in the gastric mucosa are derived from progenitor cells, but this process can be altered after injury. Therefore, we explored DCAMKL1 expression under pathological conditions. Methods An immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia. Results DCAMKL1 was exclusively expressed in immature quiescent cells in the isthmus of normal fundic glands, where putative progenitor cells are thought to reside. DCAMKL1-positive cells and proliferating cells shed into the lumen after superficial injury and re-appeared during the regenerative process, mainly in the superficial mucosa. In the marginal mucosa around the active ulcer, parietal and chief cells diminished, foveolar hyperplasia was evident, and trefoil factor family 2 (TFF2/spasmolytic polypeptide-expressing metaplasia (SPEM emerged at the gland base. DCAMKL1 cells re-emerged in the deep mucosa juxtaposed with SPEM and proliferating cells. In the healing ulcer, the TFF2 cell population expanded and seemed to redifferentiate to chief cells, while proliferating cells and DCAMKL1 cells appeared above and below the TFF2 cells to promote healing. SPEM appeared and PCNA cells increased in the intestinalized mucosa, and DCAMKL1 was expressed in the proximity of the PCNA cells in the deep mucosa. DCAMKL1, PCNA and TFF2 were expressed in different dysplastic cells lining dilated glands near SPEM. Conclusion The ultrastructural appearance of DCAMKL1-positive cells and the expression patterns of DCAMKL1 in normal and pathological states indicate that the cells belong to a progenitor cell population. DCAMKL1 expression is closely associated with TFF2/SPEM cells after injury. DCAMKL1 cells repopulate close to proliferating, hyperplastic

  12. Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    William L Riles; Jason Erickson; Sanjay Nayyar; Mary Jo Atten; Bashar M Attar; Oksana Holian

    2006-01-01

    AIM: To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-Ⅲ) with deleted p53.METHODS: Nuclear fragmentation was used to quantitate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression.RESULTS: Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARP, Resveratrol, however, has no effect on mitochondria-associated apoptotic proteins Bcl-2, Bclxl, Bax, Bid or Smac/Diablo, and did not promote subcellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines.SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO-Ⅲ cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities.CONCLUSION: These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells.

  13. Function of chloride intracellular channel 1 in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Peng-Fei Ma; Jun-Qiang Chen; Zhen Wang; Jin-Lu Liu; Bo-Pei Li

    2012-01-01

    AIM:To investigate the effect of chloride intracellular channel 1 (CLIC1) on the cell proliferation,apoptosis,migration and invasion of gastric cancer cells.METHODS:CLIC1 expression was evaluated in human gastric cancer cell lines SGC-7901 and MGC-803 by real time polymerase chain reaction (RT-PCR).Four segments of small interference RNA (siRNA) targeting CLIC1 mRNA and a no-sense control segment were designed by bioinformatics technology.CLIC1 siRNA was selected using Lipofectamine 2000 and transfected transiently into human gastric cancer SGC-7901 and MGC-803 cells.The transfected efficiency was observed under fluorescence microscope.After transfection,mRNA expression of CLIC1 was detected with RT-PCR and Western blotting was used to detect the protein expression.Proliferation was examined by methyl thiazolyl tetrazolium and apoptosis was detected with flow cytometry.Polycarbonate membrane transwell chamber and Matrigel were used for the detection of the changes of invasion and migration of the two cell lines.RESULTS:In gastric cancer cell lines SGC-7901 and MGC-803,CLIC1 was obviously expressed and CLIC1 siRNA could effectively suppress the expression of CLIC1 protein and mRNA.Proliferation of cells transfected with CLIC1 siRNA3 was enhanced notably,and the highest proliferation rate was 23.3% (P =0.002) in SGC-7901 and 35.55% (P =0.001) in MGC-803 cells at 48 h.The G2/M phase proportion increased,while G0/G1 and S phase proportions decreased.The apoptotic rate of the CLIC1 siRNA3 group obviously decreased in both SGC-7901 cells (62.24%,P =0.000) and MGC-803 cells (52.67%,P =0.004).Down-regulation of CLIC1 led to the inhibition of invasion and migration by 54.31% (P =0.000) and 33.62% (P =0.001) in SGC-7901 and 40.74% (P =0.000) and 29.26% (P =0.002) in MGC-803.However,there was no significant difference between the mock group cells and the negative control group cells.CONCLUSION:High CLIC1 expression can efficiently inhibit proliferation and

  14. Apoptotic cell death and its relationship to gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Ferda Bir; Nese Calli-Demirkan; A Cevik Tufan; Metin Akbulut; N Lale Satiroglu-Tufan

    2007-01-01

    AIM: To investigate the apoptotic process of cells within the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis.METHODS: Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, colocalizing either to gastric carcinoma or chronic gastritis,were counted and converted to apoptotic indices.In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry.RESULTS: Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas.64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14),respectively; P≤0.05]. The mean apoptotic index in tumor cells was 0.70±0.08. The mean apoptotic index in intestinal metaplasias co-localizing to tumors was significantly higher than that of intestinal metaplasias co-localizing to chronic gastritis (0.70±0.03 vs 0.09±0.01, respectively; P≤0.05). P53 positivity was not observed in areas of intestinal metaplasia adjacent to tumors or chronic gastritis. Intestinal metaplasia areas adjacent to tumors showed lower cytoplasmic bcl-2 positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [55.5% (15/27) vs 70.5%(12/17), respectively]. On the other hand, intestinal metaplasia areas adjacent to tumors showed significantly higher cytoplasmic bax positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [44.4%(12/27) vs 11.7% (2/17), respectively; P≤0

  15. Gastric Marginal Zone B Cell Lymphoma of the Duodenum

    Directory of Open Access Journals (Sweden)

    A. Ndzengue

    2011-10-01

    Full Text Available Small bowel lymphomas of the extranodal type occur in the young and are characteristically associated with malabsorption syndrome. We present the case of an elderly in whom there was no malabsorption and the duodenal tumor was a gastric type marginal zone B cell lymphoma also known as gastric mucosa-associated lymphoid tissue (MALT lymphoma. A 73-year-old woman presented to the emergency room with 2 weeks of general weakness, recurrent vomiting containing food particles and abdominal distension. She had been diagnosed with diabetic gastroparesis 4 years prior. CT of the abdomen and pelvis was suggestive of gastric outlet obstruction but no evidence of pancreatic or duodenal mass. Endoscopy and biopsy of the tumor obstructing the distal first part of the duodenum confirmed a gastric marginal MALT lymphoma. The patient’s symptoms improved with radiotherapy. Gastric MALT lymphoma, an extranodal lymphoma primarily described in the stomach, can also present in the small bowel and is not associated with malabsorption.

  16. Correlation between myeloid-derived suppressor cells and gastric cancer begin with chronic gastritis

    Institute of Scientific and Technical Information of China (English)

    朱立宁

    2012-01-01

    Objective To investigate the correlation between the ratio change of circulating myeloid-derived suppressor cells(MDSCs) and cellular immune function in healthy volunteers,chronic gastritis patients,gastric intraepithelial neoplasia patients and gastric cancer patients

  17. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Céu; Seruca, Raquel;

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA...... of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  18. Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness

    Science.gov (United States)

    Wu, Xiao Yu; Liu, Wen Tao; Wu, Zhen Feng; Chen, Che; Liu, Jia Yun; Wu, Guan Nan; Yao, Xue Quan; Liu, Fu Kun; Li, Gang

    2016-01-01

    Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment. PMID:27725900

  19. CO-029 is overexpressed in gastric cancer and mediates the effects of EGF on gastric cancer cell proliferation and invasion.

    Science.gov (United States)

    Zhu, Hongyu; Wu, Yulian; Zheng, Wen; Lu, Shiliu

    2015-03-01

    Tetraspanins are cell-surface glycoproteins and have received attention recently as both suppressors and promoters of metastasis. CO-029 is a member of the tetraspanin family and is implicated to be a metastasis-promoting tetraspanin in some cancers. However, the role of CO-029 in gastric cancer remains unexplored. The present study aimed to investigate the expression of CO-029 in gastric cancer tissues and to determine whether CO-029 is involved in the effects of epidermal growth factor (EGF) on gastric cancer cell proliferation and invasion. We collected clinical samples and found that the expression of CO-029 was increased both at the mRNA level and protein level in gastric cancer tissues in comparison to normal and tumor-adjacent tissues, as demonstrated by RT-qPCR and western blot analysis, respectively. Furthermore, we performed an in vitro experiment using AGS cells and observed that EGF promoted AGS cell proliferation and enhanced the invasion ability of the AGS cells, as shown by MTT assay and cell invasion assay, respectively. To the best of our knowledge, our results reveal for the first time, that CO-029 expression was affected by EGF in a concentration- time-dependent manner. The knockdown of CO-029 attenuated the effects of EGF on gastric cancer cell proliferation and invasion. These findings suggest that CO-029 is an oncogene in human gastric cancer and that CO-029 at least partially mediates the effects of EGF on gastric cancer cell proliferation and invasion. Our data may provide a novel target for therapeutic intervention in human gastric cancer. PMID:25592989

  20. Changes of G cells and D cells in the antral mucosa in rat experimental gastric ulcer

    Institute of Scientific and Technical Information of China (English)

    SUN Feng-peng; SONG Yu-gang; CHENG Wei; ZHAO Tong

    2002-01-01

    Objective: To investigate the association of changes in G and D cells in the antral mucosa with the production of gastrin and somatostatin during gastric ulcer and the healing process. Methods: Experimental gastric ulcer was induced with acetic acid in 42 Wistar rats and another 7 normal rats served as control.Changes in the production of gastrin and somatostatin in the plasma, gastric fluid and the antral tissues of the rats were measured by radio immunoassay, and the number and distribution of G and D cells were respectively determined by immunochemistry and Quantimet500 image analysis system. Results: In rats with gastric ulcer, the gastrin levels in the plasma, gastric fluid and the antral tissues increased while somatostatin levels were reduced, which were corrected in the healing process. Immunochemistry demonstrated the increase in the number of G cells in the antral tissues with decrease in D cell number, and the area covered by both cells shrank. The G cell to D cell number and area ratios were both decreased after the onset of the ulcer and returned to the normal when the healing process took place. Conclusion: Secretion of gastrin by G cells increases and that of somatostatin by D cells declines during gastric ulcer in rats, and imbalance of G and D cells may be restponsible for gastrointestinal dysfunction.

  1. Survivin is a Key Factor in the Differential Susceptibility of Gastric Endothelial and Epithelial Cells to Alcohol-Induced Injury

    OpenAIRE

    Jones, Michael K.; Padilla, Oscar R.; Zhu, Ercheng

    2010-01-01

    We previously demonstrated that the anti-apoptosis protein, survivin, plays a protective role against alcohol-induced gastric injury. Since the endothelium is a primary target of alcohol-induced gastric damage, we investigated whether survivin expression is a key factor in the greater susceptibility of gastric endothelial vs. epithelial cells to alcohol-induced injury. Here, we demonstrate that rat gastric epithelial cells (RGM1 cells, an epithelial cell line derived from normal rat gastric m...

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

    Science.gov (United States)

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

    2014-04-01

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

  3. Characteristic gene expression profiles in the progression from normal gastric epithelial cells to moderate gastric epithelial dysplasia and to gastric cancer

    Institute of Scientific and Technical Information of China (English)

    LI Mao-lan; DING Qi-chen; WU Xiang-song; MU Jia-sheng; YANG Jia-hua; ZHANG Wen-jie; CHEN Lei; LIU Ying-bin; ZHANG Jing-cheng; LI Song-gang; WU Wen-guang; RAO Long-hua; DONG Ping; GU Jun; LU Jian-hua; ZHANG Lin

    2012-01-01

    Background Gastric cancer ranks high among the most common causes of cancer-related death worldwide.This study was designed to explore key genes involved in the progression of normal gastric epithelial cells to moderate gastric epithelial dysplasia (mGED) and to gastric cancer.Methods Twelve pairs of mGED tissues,gastric cancer tissues,and normal gastric tissues were collected by gastroscopy.Total RNA was then extracted and purified.After the addition of fluorescent tags,hybridization was carried out on a Gene chip microarray slide.Significance analysis of microarrays was performed to determine significant differences in gene expression between the different tissue types.Results Microarray data analysis revealed totally 34 genes that were expressed differently:18 highly expressed (fold change>2; P<0.01) and 16 down-regulated (fold change >2; P <0.01).Of the 34 genes,24 belonged to several different functional categories such as structural molecule activity,extracellular regions,structural formation,cell death,biological adhesion,developmental processes,locomotion,and biological regulation that were associated with cancer.The remaining 10 genes were not involved in cancer research.Of these genes,the expression levels of Matrix metalloproteinase-12 (MMP12),Caspase-associated recruitment domain 14 (CARD14),and Chitinase 3-like 1 (CHI3L1)were confirmed by semi-quantitative RT-PCR.A two-way clustering algorithm divided the 36 samples into three categories and the overall correct classification efficiency was 80.6% (29/36).Almost all of these genes (31/34) showed constant changes in the process of normal gastric epithelial cells to mGED to gastric cancer.Conclusions The results of this study provided global gene expression profiles during the development and progression from normal gastric epithelial cells to mGED to gastric cancer.These data may provide new insights into the molecular pathology of gastric cancer which may be useful for the detection

  4. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    International Nuclear Information System (INIS)

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer

  5. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

  6. Cannabinoids enhance gastric X/A-like cells activity.

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    Bogusław Sawicki

    2008-06-01

    Full Text Available It has been reported that cannabinoids may cause overeating in humans and in laboratory animals. Although, endogenous cannabinoids and their receptors (CB1 have been found in the hypothalamus, and recently also in gastrointestinal tract, the precise mechanism of appetite control by cannabinoids remains unknown. Recently, ghrelin--a hormone secreted mainly from the stomach X/A-like cells was proposed to be an appetite stimulating agent. The aim of this study was the evaluation of the influence of a single ip injection of a stable analogue of endogenous cannabinoid--anandamide, R-(+-methanandamide (2.5 mg/kg and CP 55,940 (0.25 mg/kg, an exogenous agonist of CB1 receptors, on ghrelin plasma concentration and on ghrelin immunoreactivity in the gastric mucosa of male Wistar rats. Four hours after a single injection of both cannabinoids or vehicle, the animals were anaesthetized and blood was taken from the abdominal aorta to determinate plasma ghrelin concentration by RIA. Subsequently, the animals underwent resection of distal part of stomach. Immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antibodies against ghrelin was performed. The intensity of ghrelin immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. The attenuation of ghrelin-immunoreactivity of gastric mucosa, after a single injection of R-(+-methanandamide and CP 55,940 was accompanied by a significant increase of ghrelin plasma concentration. These results indicate that stimulation of appetite exerted by cannabinoids may be connected with an increase of ghrelin secretion from gastric X/A-like cells.

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

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    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.

  8. NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells.

    Science.gov (United States)

    Chang, Xiaojing; Xu, Xiaoyang; Ma, Jinguo; Xue, Xiaoying; Li, Zhenhua; Deng, Peng; Zhang, Shuanglong; Zhi, Yu; Chen, Jing; Dai, Dongqiu

    2014-09-01

    N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.

  9. Destruction of Gastric Cancer Cells to Mesothelial Cells by Apoptosis in the Early Peritoneal Metastasis

    Institute of Scientific and Technical Information of China (English)

    Di NA; Funan LIU; Zhifeng MIAO; Zongmin DU; Huimian XU

    2009-01-01

    This study examined the mechanism by which the gastric cancer cells lead to early peritoneal metastasis.HMrSV5 cells,a human peritoneal mesothelial cell line,were co-incubated with the supernatants of gastric cancer cells.Morphological changes of HMrSV5 cells were observed.The cell damage was quantitatively determined by MTT assay.The apoptosis of HMrSV5 cells was observed under transmission electron microscope.Acridine orange/ethidium bromidestained condensed nuclei was detected by fluorescent microscopy and flow cytometry.The expressions of Bcl-2 and Bax was immunochemically evaluated.The results showed that conspicuous morphological changes of apoptosis were observed in HMrSV5 cells 24 h after treatment with the supematants of gastric cancer cells.The supernatants could induce apoptosis of HMrSV5 cells in a time-dependent manner.Th esupematants could up-regulate the expression of Bax and suppress that of Bcl-2 in HMrSV5 cells.These findings demonstrated that gastric cancer cells can induce the apoptosis of HPMCs through supernatants in the early peritoneal metastasis.The abnormal expressions of Bcl-2 and Bax may contribute to the apoptosis.Anti-apoptosis drugs promise to be adjuvant chemotherapeutic agents in the treatment of peritoneal metastasis of gastric cancer.

  10. Effects of different Helicobacter pylori culture filtrates on growth of gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Yan-Guo Yan; Gang Zhao; Jin-Ping Ma; Shi-Rong Cai; Wen-Hua Zhan

    2008-01-01

    AIM: To study the effects of different Helicobacter pylori (H py/orl) culture filtrates on growth of gastric epithelial cells.METHODS: Broth culture filtrates of H pylori were prepared. Gastric epithelial cells were treated with the filtrates, and cell growth was determined by growth curve and flow cytometry. DNA damage of gastric epithelial cells was measured by single-cell microgel electrophoresis.RESULTS: Gastric epithelial cells proliferated actively when treated by CagA-gene-positive broth culture filtrates, and colony formation reached 40%. The number of cells in S phase increased compared to controls. Comet assay showed 41.2% comet cells in GES-1 cells treated with CagA-positive filtrates (P<0.05).CONCLUSION: CagA-positive filtrates enhance the changes in morphology and growth characteristics of human gastric epithelial tumor cells. DNA damage maybe one of the mechanisms involved in the growth changes.

  11. Paclitaxel sensitizes gastric cancer cells to TRAIL-induced apoptosis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promise for cancer therapy as it has unique capacity to selectively trigger apoptosis in cancer cells. We reported here that paclitaxel sensitized gastric cancer cells to TRAIL-induced apoptosis.Methods: After drug exposure, apoptosis rate and caspase activation were examined. Various proteins were detected by western blot. Several interventions, including pharmacological inhibitors and siRNA transfection were used. hTe growth inhibition of tumors was evaluated in SGC-7901-implanted nude mice model.Results:We found gastric cancer cellsshowed a mixed response to TRAIL. Combined treatment with paclitaxel markedly enhanced TARIL-induced apoptosis in vitro and in vivo. The underlying mechanisms involved in synergistical activation of caspase proteins, up-regulation of receptors, down-regulation of antiapoptotic proteins and inactivation of MAPKs.Conclusion:TRAIL-induced cytotoxicity and apoptosis can be synergistically enhanced by paclitaxel, suggesting the therapeutic potential of combining TARIL plus paclitaxel in gastric cancer treatment.

  12. Gastrointestinal hormone abnormalities and G and D cells in functional dyspepsiapatients with gastric dysmotility

    Institute of Scientific and Technical Information of China (English)

    Mei-Rong He; Yu-Gang Song; Fa-Chao Zhi

    2005-01-01

    AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT)were measured by radioimmunoassay in all the subjects.G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis.RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying.CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.

  13. Genome-wide gene copy number and expression analysis of primary gastric tumors and gastric cancer cell lines

    International Nuclear Information System (INIS)

    Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer related death. Gene copy number alterations play an important role in the development of gastric cancer and a change in gene copy number is one of the main mechanisms for a cancer cell to control the expression of potential oncogenes and tumor suppressor genes. To highlight genes of potential biological and clinical relevance in gastric cancer, we carried out a systematic array-based survey of gene expression and copy number levels in primary gastric tumors and gastric cancer cell lines and validated the results using an affinity capture based transcript analysis (TRAC assay) and real-time qRT-PCR. Integrated microarray analysis revealed altogether 256 genes that were located in recurrent regions of gains or losses and had at least a 2-fold copy number- associated change in their gene expression. The expression levels of 13 of these genes, ALPK2, ASAP1, CEACAM5, CYP3A4, ENAH, ERBB2, HHIPL2, LTB4R, MMP9, PERLD1, PNMT, PTPRA, and OSMR, were validated in a total of 118 gastric samples using either the qRT-PCR or TRAC assay. All of these 13 genes were differentially expressed between cancerous samples and nonmalignant tissues (p < 0.05) and the association between copy number and gene expression changes was validated for nine (69.2%) of these genes (p < 0.05). In conclusion, integrated gene expression and copy number microarray analysis highlighted genes that may be critically important for gastric carcinogenesis. TRAC and qRT-PCR analyses validated the microarray results and therefore the role of these genes as potential biomarkers for gastric cancer

  14. Cancer stem cells in Helicobacter pylori infection and aging: Implications for gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Edi; Levi; Paula; Sochacki; Nabiha; Khoury; Bhaumik; B; Patel; Adhip; PN; Majumdar

    2014-01-01

    AIM: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells(CSCs) of gastric mucosa in an animal model. METHODS: In this study we investigated the effects of aging and Helicobacter pylori(H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old(young) with 22 mo(aged) old Fischer-344 rats. For human studies, gastric biop-sies and resection specimens representing normal mucosa or different stages of H. pylori gastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells. RESULTS: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylori gastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylori gastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia. CONCLUSION: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pylori infection may have additive effects in progression to neoplasia.

  15. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

    Directory of Open Access Journals (Sweden)

    Yan-fei Liu

    Full Text Available Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2, which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.

  16. Sonic hedgehog pathway contributes to gastric cancer cell growth and proliferation.

    Science.gov (United States)

    Wan, Jianhua; Zhou, Ji; Zhao, Hailong; Wang, Mei; Wei, Zhuanqin; Gao, Hongyan; Wang, Yongzhong; Cui, Hongjuan

    2014-04-01

    The Sonic Hedgehog (Shh) signaling pathway is commonly activated in gastrointestinal cancer. However, our understanding of the Shh pathway in gastric cancer remains limited. Here we examined the effects of cyclopamine, a specific inhibitor of the Shh signaling pathway, on cell growth and proliferation in gastric primary cancer cells GAM-016 and the MKN-45 cell line. The results showed that the Shh signaling molecules SHH, PTCH, SMO, GLI1, and GLI2 were intact and activated in both types of cells. Furthermore, we observed that cyclopamine inhibited gastric cancer cell proliferation through cell cycle arrest and apoptosis. An in vivo study using NOD/SCID mouse xenografts demonstrated that cyclopamine significantly prevented tumor growth and development. Our study indicated that Shh signaling pathway could promote gastric cancer cell proliferation and tumor development, and blocking this pathway may be a potential strategy in gastric cancer treatment.

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

    Science.gov (United States)

    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

  18. Development of representative models for the study of gastric cancer and evaluation of potential antitumor agents in primary gastric cancer cells and gastric metastasis in liver

    International Nuclear Information System (INIS)

    Gastric cancer has been the sixth most common malignancy worldwide and the leading cause of death by tumors in Costa Rica, the survival of patients is limited by difficulties in diagnosis and the lack of therapeutic options to improve life expectancy. The study has conducted a number of research models that will allow in the future to better understand the pathology of this tumor and it has evaluated the therapeutic action of naturally occurring in gastric cancer cells. A vivo model of carcinogenesis in stomachs of Wistar rats, has achieved to establish by means of chemical induction with MNNG, in which it has been possible to observe the appearance of tumors in the stratified epithelium flat keratinized starting from week 22 of experiment; while for the 40th week adenomas were observed in the simple cylindrical epithelium. Additionally, the role of Helicobacter pylori was inquired in the development of gastric cancer by inoculation of two strains of bacteria (CagA + and CagA-) in the stomach of Wistar rats, as well as the effect of his administration together with MNNG. However, the results of these models have been limited due to the lack of detection of the bacteria in the stomachs of rats inoculated. In addition, it has established an in vitro model of threedimensional cell culture, which has allowed to reproduce some of the characteristics observed in vivo in the tumors, in this case it was determined that the two gastric cancer cell lines have showed a different behavior, since the cells NCI-N87 from a in metastasis gastric liver were able to form steroids compact whereas AGS cells have been originate from a primary tumor that has formed easily dispersible structures and not compact spheroids. Finally, the effect of natural retinoids ATRA and retinoic acid 13-cis were evaluated, as well as retinamide synthetic retinoid on the viability of the cells AGS and NCI-N87. Cytotoxicity assays using MTT have allowed to observe the reduction of a variation in the

  19. Monitoring the cytoskeletal EGF response in live gastric carcinoma cells.

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    Marco Felkl

    Full Text Available Altered cell motility is considered to be a key factor in determining tumor invasion and metastasis. Epidermal growth factor (EGF signaling has been implicated in this process by affecting cytoskeletal organization and dynamics in multiple ways. To sort the temporal and spatial regulation of EGF-dependent cytoskeletal re-organization in relation to a cell's motile behavior time-lapse microscopy was performed on EGF-responsive gastric carcinoma-derived MKN1 cells co-expressing different fluorescently labeled cytoskeletal filaments and focal adhesion components in various combinations. The experiments showed that EGF almost instantaneously induces a considerable increase in membrane ruffling and lamellipodial activity that can be inhibited by Cetuximab EGF receptor antibodies and is not elicited in non-responsive gastric carcinoma Hs746T cells. The transient cell extensions are rich in actin but lack microtubules and keratin intermediate filaments. We show that this EGF-induced increase in membrane motility can be measured by a simple image processing routine. Microtubule plus-ends subsequently invade growing cell extensions, which start to accumulate focal complexes at the lamellipodium-lamellum junction. Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. These adhesions then serve as nucleation sites for keratin filaments which are used to enlarge the neighboring peripheral keratin network. Focal adhesions are either disassembled or give rise to stable zyxin-rich fibrillar adhesions which disassemble in the presence of EGF to support formation of new focal adhesion sites in the cell periphery. Taken together the results serve as a basis for modeling the early cytoskeletal EGF response as a tightly coordinated and step-wise process which is relevant for the prediction of the effectiveness of anti-EGF receptor-based tumor therapy.

  20. Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: A case report

    Institute of Scientific and Technical Information of China (English)

    Takayoshi; Fujita; Takafumi; Ando; Masatoshi; Sakakibara; Waki; Hosoda; Hidemi; Goto

    2010-01-01

    We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which led us to suspect IgG4-related sclerosing disease.To the best of our knowledge,this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.

  1. Gastric Carcinoma with Osteoclast-Like Giant Cells Coexisting with Gastrointestinal Spindle Cell Tumor

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    Christos Poulios

    2013-01-01

    Full Text Available Reactive multinucleated osteoclast-like giant cells (OGCs have been described in a variety of neoplasms but rarely in gastric carcinomas. Reported herein is a case of an 81-year-old Caucasian male presented with upper abdominal pain and dysphagia. Esophagogastroscopy revealed an ulcerative mass and a specimen of subtotal gastrectomy and lower esophagectomy was sent for histologic examination. At the gastroesophageal junction an exophytic tumor, measured 2.2 cm in greatest diameter, was observed. Sections from the tumor showed gastric adenocarcinoma, stage pT1bpN0. Diffusely among the neoplastic cells multinucleated giant cells, resembling osteoclasts, were observed, which were positive for CD68, lysozyme, and vimentin and negative for AE1/AE3, CK8/18, hHCG, and LMP1. Moreover, in a random section from the gastric fundus, a spindle cell lesion, sized 0.6 cm, was revealed, which was positive for CD117 and CD34 antigens and was diagnosed as gastrointestinal stromal tumor (GIST. The presence of OGCs is an uncommon finding in gastric carcinomas and by analogy to breast and pancreatic carcinomas it could characterize a rare distinct morphological variant of gastric adenocarcinoma. Due to the limited number of the reported cases, the prognostic value of OGCs is under discussion. Furthermore, pathologists should be aware that incidental GIST may accompany any tumor.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  3. Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor growth

    Institute of Scientific and Technical Information of China (English)

    Gang Zhao; Li-Li Guo; Jing-Yong Xu; Hua Yang; Mei-Xiong Huang; Gang Xiao

    2011-01-01

    AIM: To investigate the effects of integrin-linked kinase (ILK) on gastric cancer cells both in vitro and in vivo . METHODS: ILK small interfering RNA (siRNA) was transfected into human gastric cancer BGC-823 cells and ILK expression was monitored by real-time quantitative polymerase chain reaction, Western blotting analysis and immunocytochemistry. Cell attachment, proliferation, invasion, microfilament dynamics and the secretion of vascular endothelial growth factor (VEGF) were also measured. Gastric cancer cells treated with ILK siRNA were subcutaneously transplanted into nude mice and tumor growth was assessed. RESULTS: Both ILK mRNA and protein levels were significantly down-regulated by ILK siRNA in human gastric cancer cells. This significantly inhibited cell attachment, proliferation and invasion. The knockdown of ILK also disturbed F-actin assembly and reduced VEGF secretion in conditioned medium by 40% (P < 0.05). Four weeks after injection of ILK siRNA-transfected gastric cancer cells into nude mice, tumor volume and weight were significantly reduced compared with that of tumors induced by cells treated with non-silencing siRNA or by untreated cells (P < 0.05). CONCLUSION: Targeting ILK with siRNA suppresses the growth of gastric cancer cells both in vitro and in vivo . ILK plays an important role in gastric cancer progression.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  6. Therapeutic potential of highly cytotoxic natural killer cells for gastric cancer.

    Science.gov (United States)

    Mimura, Kousaku; Kamiya, Takahiro; Shiraishi, Kensuke; Kua, Ley-Fang; Shabbir, Asim; So, Jimmy; Yong, Wei-Peng; Suzuki, Yoshiyuki; Yoshimoto, Yuya; Nakano, Takashi; Fujii, Hideki; Campana, Dario; Kono, Koji

    2014-09-15

    To develop more effective therapies for patients with advanced gastric cancer, we examined the potential of ex vivo expanded natural killer (NK) cells. We assessed the expression of ligands for NK Group 2 Member D (NKG2D, an important NK activation molecule) in primary tumors from 102 patients with gastric cancer by immunohistochemistry and determined their prognostic value. We then examined the in vitro and in vivo cytotoxicity of NK cells from healthy donors and patients with gastric cancer. The cytotoxicity of resting and of interleukin (IL)-2-activated NK cells was compared to that of NK cells expanded for 7 days by coculture with the K562-mb15-4.1BBL cell line. As a result, the expression of NKG2D ligands in primary tumors was correlated with favorable presenting features and outcomes, suggesting that gastric cancer may be sensitive to NK cell cytotoxicity. Although resting NK cells showed minimal cytotoxicity against gastric cancer cells, K562-mb15-4.1BBL-expanded NK cells were highly cytotoxic and significantly more powerful than IL-2-activated NK cells. Cytotoxicity was correlated with NKG2D ligand expression and could be modulated by mitogen-activated protein kinase and AKT-PI3 kinase inhibitors. The cytotoxicity of expanded NK cells against HER2-positive gastric cancer cells could be increased by Herceptin and further augmented by Lapatinib. Finally, expanded NK cells exhibited strong antitumor activity in immunodeficient mice engrafted with a gastric cancer cell line. In conclusion, gastric cancer tumors express NKG2D ligands and are highly susceptible to killing by NK cells stimulated by K562-mb15-4.1BBL. These results provide a strong rationale for clinical testing of these NK cells in patients and suggest their use to augment the effects of antibody therapy. PMID:24615495

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Induction of apoptosis by arsenic trioxide and hydroxycamptothecin in gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jie Zhong; JI Hong Tan; Xiao Hua Jiang; Min Min Qiao; Yu Xin Wu; Shi Hu Jiang; ShuiPing Tu

    2000-01-01

    AIM To study the effects of arsenic trioxide and HCPT on different degrees of differentiated gastric cancer cells (SGC-7901, MKN-45, MKN-28)with respect to both cytotoxicity and induction of apoptosis in vitro. ~ODS The cytotoxicity of As2O3 and HCPT on gastric cancer cells was determined by MTTassay. Morphologic changes of apoptosis of gastric cancer cells were observed by light microscopy and transmission electron microscopy. Apoptosis and cell cycle changes of gastric cancer cells induced by HCPT and As2O3 were investigated by TUNEL method and flow cytometry. RESULTS As2O3 and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells. The IC50 of As2O3 on well differentiated gastric cancer cell MKN-28, moderately differentiated gastric cancer cell SGC-7901, and poorly differentiated gastric cancer cell MKN-28 were 8. 91 μmol/L, 10. 57 μmol/L, and 11.65 μmol/L, respectively. The IC50 of HCPT on MKN-28, SGC-7901, and MKN-45 were 9. 35 rg/L, 10. 21 rg/L, and 12. 63 mg/L respectively after 48 h treatment. After 12 h of exposure to both drugs, gastric cancer cells exhibited morphologic features of apoptosis, including cell shrinkage, nuclear condensation,and formation of apoptotic bodies. A typical subdiploid peak before G0/G1 phase was observed by flow cytometry. The apoptotic rates of SGC7901, MKN-45, and MKN-28 were 13. 84%, 22.52%, and 9. 68%, respectively after 48 h exposure to 10 μmol/L As2O3. The apoptotic rates of SGC-7901, MKN-45, and MKN-28 were 21.88%, 12.35%, and 30. 26%, respectively after 48 h exposure to 10 mg/L HCPT. The apoptotic indice were 7% - 15% as assessed by TUNEL method. The effect of As2O3 on SGC-7901 showed remarkable cell cycle specificity, which induced cell death in G1 phase, and blocked G2/M phase. HCPT also showed a remarkable cell cycle specificity, by inducing cell death and apoptosis in G1 phase and arrest of proliferation at S phase. CONCLUSION AS2O3 and HCPT exhibit significant

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

    OpenAIRE

    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...

  14. Modeling Murine Gastric Metaplasia Through Tamoxifen-Induced Acute Parietal Cell Loss.

    Science.gov (United States)

    Saenz, Jose B; Burclaff, Joseph; Mills, Jason C

    2016-01-01

    Parietal cell loss represents the initial step in the sequential progression toward gastric adenocarcinoma. In the setting of chronic inflammation, the expansion of the mucosal response to parietal cell loss characterizes a crucial transition en route to gastric dysplasia. Here, we detail methods for using the selective estrogen receptor modulator tamoxifen as a novel tool to rapidly and reversibly induce parietal cell loss in mice in order to study the mechanisms that underlie these pre-neoplastic events. PMID:27246044

  15. Effect of carbenoxolone on the synthesis of glycoproteins and DNA in rat gastric epithelial cells.

    OpenAIRE

    van Huis, G A; Kramer, M.F.

    1981-01-01

    The influence of carbenoxolone on the synthesis of glycoproteins in the surface mucous cells and the production of new cells in the rat gastric mucosa was studied by means of a vascular perfusion system. The rate of incorporation of tritiated galactose, glucosamine, serine, and sulphate in surface mucous cells, studied by autoradiography, was not affected by the addition of carbenoxolone to the drinking water. The sugar composition (determined by gas-liquid chromatography) of the gastric glyc...

  16. Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

    OpenAIRE

    Weifeng Huang; Chunpeng Wan; Qicong Luo; Zhengjie Huang; Qi Luo

    2014-01-01

    Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere f...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  18. Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

    Institute of Scientific and Technical Information of China (English)

    Kun Zhang; Peng-Fen Gao; Pei-Wu Yu; Yun Rao; Li-Xin Zhou

    2006-01-01

    AIM: To detect the biological characters of the SGC7901 gastric cancer cell-dendritic cell fusion vaccines.METHODS: The suspending living SGC7901 gastric cancer cells and dendritic cells were induced to be fusioned by polyethylene glycol. Pure fusion cells were obtained by selective culture with the HAT/HT culture systems.The fusion cells were counted at different time points of culture and their growth curves were drawn to reflect their proliferative activities. The fusion cells were also cultured in culture medium to investigate whether they could grow into cell clones. MTT method was used to test the stimulating abilities of the fusion cells on T lymphocytes' proliferations. Moreover, the fusion cells were planted into nude mice to observe whether they could grow into new planted tumors in this kind of immunodeficiency animals.RESULTS: The fusion cells had weaker proliferative activity and clone abilities than their parental cells. When they were cultured, the counts of cells did not increase remarkably, nor could they grow into cell clones in culture medium. The fusion cells could not grow into new planted tumors after planted into nude mice. The stimulating abilities of the fusion cells on T lymphocytes' proliferations were remarkably increased than their parental dendritic cells.CONCLUSION: The SGC7901 gastric cancer cell-dendritic cell fusion vaccines have much weaker proliferative abilities than their parental cells, but they keep strong abilities to irritate the T lymphocytes and have no abilities to grow into new planted tumors in immunodeficiency animals. These are the biological basis for their antitumor biotherapies.

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

    Science.gov (United States)

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

    2015-08-01

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

  20. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2.

    Science.gov (United States)

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-Yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic

  1. Urokinase plasminogen activator receptor on invasive cancer cells: A prognostic factor in distal gastric adenocarcinoma

    DEFF Research Database (Denmark)

    Alpizar, Warner Enrique Alpizar; Christensen, Ib Jarle; Santoni-Rugiu, Eric;

    2012-01-01

    Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation...... by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. u...... association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

  2. Mitochondrial aldehyde dehydrogenase 2 protects gastric mucosa cells against DNA damage caused by oxidative stress.

    Science.gov (United States)

    Duan, Yantao; Gao, Yaohui; Zhang, Jun; Chen, Yinan; Jiang, Yannan; Ji, Jun; Zhang, Jianian; Chen, Xuehua; Yang, Qiumeng; Su, Liping; Zhang, Jun; Liu, Bingya; Zhu, Zhenggang; Wang, Lishun; Yu, Yingyan

    2016-04-01

    Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a member of the aldehyde dehydrogenase superfamily and is involved with the metabolic processing of aldehydes. ALDH2 plays a cytoprotective role by removing aldehydes produced during normal metabolism. We examined the cytoprotective role of ALDH2 specifically in gastric mucosa cells. Overexpression of ALDH2 increased the viability of gastric mucosa cells treated with H2O2, while knockdown of ALDH2 had an opposite effect. Moreover, overexpression of ALDH2 protected gastric mucosa cells against oxidative stress-induced apoptosis as determined by flow cytometry, Hoechst 33342, and TUNEL assays. Consistently, ALDH2 knockdown had an opposite effect. Additionally, DNA damage was ameliorated in ALDH2-overexpressing gastric mucosa cells treated with H2O2. We further identified that this cytoprotective role of ALDH2 was mediated by metabolism of 4-hydroxynonenal (4-HNE). Consistently, 4-HNE mimicked the oxidative stress induced by H2O2 in gastric mucosa cells. Treatment with 4-HNE increased levels of DNA damage in ALDH2-knockdown GES-1 cells, while overexpression of ALDH2 decreased 4-HNE-induced DNA damage. These findings suggest that ALDH2 can protect gastric mucosa cells against DNA damage caused by oxidative stress by reducing levels of 4-HNE.

  3. HERG K+ channels expression in gastric cancers and analysis of its regulation in tumor cell proliferation and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Qing Lü; Huiyu Li; Xiaoming Lu; Guobin Wang

    2009-01-01

    Objective: To investigate the expression of herg 1 gene in tumor tissues from gastric carcinomas and gastric carcinoma cell lines, and study the relationship between HERG K+ channel expressions and tumor cell proliferation and apoptosis. Methods: RT-PCR and PCR assays were used to detect the expression of herg 1 gene in 64 gastric carcinomas and the gastric cancer cell line SGC-7901. Blocking the HERG K+ channels was used to evaluate their effects on tumor cell proliferation and apoptosis. Results:The statistically significant expression of herg 1 gene was detected in all the gastric cancers and SGC-7901 cells, but not in normal tissues. The HERG K+ channel blocker, E-4031, increased the cell population in G0/G1 (P<0.05) and the number of apoptotic tumor cells(P<0.05). Conclusion: HERG K+ channels were expressed in all gastric carcinomas tested and these channels appear to modulate tumor cell proliferation and apoptosis.

  4. HMGCR is up-regulated in gastric cancer and promotes the growth and migration of the cancer cells.

    Science.gov (United States)

    Chushi, Li; Wei, Wu; Kangkang, Xie; Yongzeng, Feng; Ning, Xie; Xiaolei, Chen

    2016-08-01

    Alteration of metabolic profile is one of the hallmarks of cancer cells. Statin, the inhibitors for synthesis of cholesterol, has shown anti-cancer effects on the gastric cancer cells. However, the functions of its target, HMGCR, in the progression of gastric cancer remain unknown. In the present study, we investigated the expression profile and the biological functions of HMGCR in gastric cancer. It was found that the expression of HMGCR was increased in gastric cancer tissues. Over-expression of HMGCR promoted the growth and migration of gastric cancer cells, while knocking down the expression of HMGCR inhibited the growth, migration and tumorigenesis of gastric cancer cells. In the further molecular mechanism study, HMGCR was shown to activate Hedgehog/Gli1 signaling and promoted the expression of Gli1 target genes. Taken together, this study demonstrated the tumor-promoting effects of HMGCR in gastric cancer and suggested HMGCR as a promising therapeutic target. PMID:27085483

  5. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, C.; Seruca, R.;

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...

  6. Gastrin, somatostatin, G and D cells of gastric ulcer in rats

    Institute of Scientific and Technical Information of China (English)

    Feng-Peng Sun; Yu-Gang Song; Wei Cheng; Tong Zhao; Yong-Li Yao

    2002-01-01

    AIM: To investigate the relationship among gastrin,somatostatin, G and D calls in gastric ulcer and in its healing process in rats.METHODS: Fourty-nine Wistar rats were divided into 7groups. The gastric ulcer model was induced by acetic acid successfully. The gastrin and the somatostatin in rat plasma, gastric fluid and antral tissue were measured by radioimmunoassay(RIA). G and D cells in antral mucosa were analyzed with polyclonal antibody of gastrin and somatostatin by immunohistochemical method and Quantimet 500 image analysis systemRESULTS: In gastric ulcer, the level of gastrin in plasma,gastric fluid, and antral tissue increased, that ofsomatostatin declined, and the disorder gradually recoveredto the normal level in the healing process.Immunohistochemical technique of G and D cells in antralmucosa demonstrated that the number of G cells increasedand that of D cells decreased, both areas of G and D cellsdeclined, the ratio of number and area of G/D increased ingastric ulcer, and the disorder gradually recovered in thehealing process.CONCLUSION: In gastric ulcer, the increased gastrinsecreted by G cells, the declined somatostatin secreted by Dcells, and the disordered G/D cell ratio can lead togastrointestinal dysfunction.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Helicobacter pylori infection and stem cells at the origin of gastric cancer.

    Science.gov (United States)

    Bessède, E; Dubus, P; Mégraud, F; Varon, C

    2015-05-14

    Helicobacter pylori infection is now recognized as the main and specific infectious cause of cancer in the world. It is responsible for gastric adenocarcinomas of both intestinal and diffuse types, which are the long-term consequences of the chronic infection of the gastric mucosa. Case-control studies have shown an association between the two, recognized as early as 1994 and further substantiated by interventional studies in which H. pylori eradication has led to the prevention of at least part of the gastric cancers. Experimental studies have highlighted the role of bone marrow-derived cells (BMDCs) and particularly mesenchymal stem cells, in the neoplastic process in about a quarter of the cases and possibly an epithelial-mesenchymal transition (EMT) in the other cases. Different studies have confirmed that chronic infection with H. pylori induces a chronic inflammation and subsequent damage of the gastric epithelial mucosa, leading to BMDC recruitment. Once recruited, these cells home and differentiate by cell-cell fusion with local gastric epithelial cells, bearing local stem cell failure and participating in tissue regeneration. The context of chronic infection and inflammation leads to an EMT and altered tissue regeneration and differentiation from both local epithelial stem cells and BMDC. EMT induces the emergence of CD44+ cells possessing mesenchymal and stem cell properties, resulting in metaplastic and dysplastic lesions to give rise, after additional epigenetic and mutational events, to the emergence of cancer stem cells (CSCs) and adenocarcinoma. PMID:25043305

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

    Institute of Scientific and Technical Information of China (English)

    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.

  10. BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhi-Xin; Liu, Zhi-Qiang; Jiang, Biao; Lu, Xin-Yang; Ning, Xiao-Fei [Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining 272029 (China); Yuan, Chuan-Tao [Department of Pathology, Affiliated Hospital of Jining Medical University, Jining 272029 (China); Wang, Ai-Liang, E-mail: wang_ailiang@126.com [Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining 272029 (China)

    2015-09-18

    Background and objective: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. Methods: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. Results: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. Conclusion: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis. - Highlights: • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823. • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis. • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression. • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth. • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth.

  11. Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi [State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237 (China); Liu, Jianwen, E-mail: liujian@ecust.edu.cn [State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, #268, 130 Meilong Road, Shanghai 200237 (China); Ni, Lei, E-mail: nilei625@yahoo.com [Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road II, Shanghai 200025 (China)

    2014-07-18

    Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.

  12. Treatment of gastric cancer cells with non-thermal atmospheric plasma generated in water

    CERN Document Server

    Chen, Zhitong; Cheng, Xiaoqian; Gjika, Eda; Keidar, Michael

    2016-01-01

    Non-thermal atmospheric plasma (NTAP) can be applied to living tissues and cells as a novel technology for cancer therapy. Even though studies report on the successful use of NTAP to directly irradiate cancer cells, this technology can cause cell death only in the upper 3-5 cell layers. We report on a NTAP argon solution generated in DI water for treating human gastric cancer cells (NCl-N87). Our findings showed that the plasma generated in DI water during a 30-minute treatment had the strongest affect in inducing apoptosis in cultured human gastric cancer cells. This result can be attributed to presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced in water during treatment. Furthermore, the data showed that elevated levels of RNS may play an even more significant role than ROS in the rate of apoptosis in gastric cancer cells.

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

    Directory of Open Access Journals (Sweden)

    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

  14. Structural and functional development of rat and mouse gastric mucous cells in relation to their proliferative activity

    International Nuclear Information System (INIS)

    An investigation has been carried out to find a relation between the differentiation and the mitotic activity of gastric mucous cells of the rat and the mouse. It is shown that the bulk mucous production is carried out by the older, non-proliferative, surface mucous cells that line the foveolae and the gastric surface. One experiment describes the renewal of mouse gastric mucous cells following fast neutron irradiation. (C.F.)

  15. H pylori stimulates proliferation of gastric cancer cells through activating mitogen-activated protein kinase cascade

    Institute of Scientific and Technical Information of China (English)

    Yong-Chang Chen; Ying Wang; Jing-Yan Li; Wen-Rong Xu; You-Li Zhang

    2006-01-01

    AIM: To explore the mechanism by which H pylori causes activation of gastric epithelial cells.METHODS: A VacA (+) and CagA (+) standard Hpyloriline NCTC 11637 and a human gastric adenocarcinoma derived gastric epithelial cell line BGC-823 were applied in the study. MTT assay and 3H-TdR incorporation test were used to detect the proliferation of BGC-823 cells and Western blotting was used to detect the activity and existence of related proteins.RESULTS: Incubation with Hpylori extract increased the proliferation of gastric epithelial cells, reflected by both live cell number and DNA synthesis rate. The activity of extracellular signal-regulated protein kinase (ERK) signal transduction cascade increased within 20 min after incubation with Hpylori extract and appeared to be a sustained event. MAPK/ERK kinase (MEK) inhibitor PD98059abolished the action of H pylori extract on both ERK activity and cell proliferation. Incubation with H pyloriextract increased c-Fos expression and SRE-dependentgene expression. H pylori extract caused phosphorylation of several proteins including a protein with molecular size of 97.4 kDa and tyrosine kinase inhibitor genistein inhibited the activation of ERK and the proliferation of cells caused by H pylori extract.CONCLUSION: Biologically active elements in H pylori extract cause proliferation of gastric epithelial cells through activating tyrosine kinase and ERK signal transduction cascade.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  18. Suppression of local immune response by GrB expression in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    周业江; 熊玉霞; 李昌平; 时德

    2004-01-01

    Little information is available so far on local anti-tumour immune response in gastric cancer (GC). Moreover, studies in malignant lymphomas demonstrated that neoplastic cells expressed cytotoxic proteins GrB.1,2 Studies here were designed to detect by immunohistochemistry the density of dendritic cells labelled by S-100 protein (S-100+DCs) and activated cytotoxic T lymphocyte and nature killer cells labelled by GrB (GrB+CTL, NK) and observe whether benign/malignant gastric epithelium cells also express GrB.

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

    Institute of Scientific and Technical Information of China (English)

    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. Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein.

    Science.gov (United States)

    Liang, Jie; Luo, Guanhong; Ning, Xiaoxuan; Shi, Yongquan; Zhai, Huihong; Sun, Shiren; Jin, Haifeng; Liu, Zhenxiong; Zhang, Faming; Lu, Yuanyuan; Zhao, Yunping; Chen, Xiong; Zhang, Hongbo; Guo, Xuegang; Wu, Kaichun; Fan, Daiming

    2007-06-01

    The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein. PMID:17612632

  1. FOXO3a promotes gastric cancer cell migration and invasion through the induction of cathepsin L

    Science.gov (United States)

    Zhang, Wen; Yuan, Wei; Zhao, Naiqing; Li, Qian; Cui, Yuehong; Wang, Yan; Li, Wei; Sun, Yihong; Liu, Tianshu

    2016-01-01

    Forkhead box O3A (FOXO3a) is an important transcription factor involved in various human cancers. However, the role of FOXO3a in regulating the invasion and metastasis of gastric cancer cells has not been clarified. Here, we report that FOXO3a overexpression promoted migration and invasion of gastric cancer cells by upregulating cathepsin L. FOXO3a knockdown suppressed migration and invasion and also downregulated cathepsin L expression in gastric cancer cells. Silencing cathepsin L in these cells suppressed FOXO3a overexpression-induced cell migration and invasion. Mechanistic studies revealed that FOXO3a increased cathepsin L promoter activation, and cathepsin L overexpression repressed E-cadherin expression, causing gastric cancer cells to undergo epithelial-mesenchymal transition (EMT). Our data reveal a previously unexplored function of FOXO3a in gastric cancer invasion by regulating proteins involved in extracellular matrix (ECM) degradation and EMT. We suggest that FOXO3a may be of prognostic value and a potential therapeutic target in blocking tumor metastasis. PMID:27127880

  2. The effect pathway of retinoic acid through regulation of retinoic acid receptor in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Qiao Wu; Zheng-Ming Chen; Wen-Jin Su

    2001-01-01

    AIM To evaluate the role of RARa gene in mediating the growth inhibitory effect of ail-trans retinoic acid (ATRA)on gastric cancer cells.``METHODS The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of β retinoic acid response element (βRARE) and AP-l activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418.``RESULTS ATRA could induce expression level of RARα in MGC80-3, BGCC8823 and SGC-7901 cells obviously,resulting in growth inhibition of these cell lines. After sense RARa gene was transfected into MKN-45 cells that expressed rather Iow level of RARα and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARα gene was transfected into BGC-825 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823cells. In transient transfection assay, ATRA effectively induced transcriptional activity of βRARE in MGC80-3,BGC.823, SGC-7902 and MKN/RARa cell lines, but not in MKN-45 and BGC/aRARa cell lines. Similar results were observed in measuring anti-AP-l activity by ATRA in these cancer cell lines.``CONCLUSION ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARa; RARa is the major mediator of ATRA action in gastric cancer cells; and adequate level of RAPa is required for ATRA effect on gastric cancer cells.``

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

    Institute of Scientific and Technical Information of China (English)

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

    2001-01-01

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

  4. Effects of resistin-like molecule β over-expression on gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Li-Duan Zheng; Chun-Lei Yang; Teng Qi; Meng Qi; Ling Tong; Qiang-Song Tong

    2012-01-01

    AIM:To investigate the effects of resistin-like molecule β (RELMβ) over-expression on the invasion,metastasis and angiogenesis of gastric cancer cells.METHODS:Human RELMβ encoding expression vector was constructed and transfected into the RELMβ lowly-expressed gastric cancer cell lines SGC-7901 and MKN-45.Gene expression was measured by Western blotting,reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR.Cell proliferation was measured by 2-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetry,colony formation and 5-ethynyl-20-deoxyuridine incorporation assays.The in vitro migration,invasion and metastasis of cancer cells were measured by cell adhesion assay,scratch assay and matrigel invasion assay.The angiogenic capabilities of cancer cells were measured by tube formation of endothelial cells.RESULTS:Transfection of RELMβ vector into SGC-7901 and MKN-45 cells resulted in over-expression of RELMβ,which did not influence the cellular proliferation.However,over-expression of RELMβ suppressed the in vitro adhesion,invasion and metastasis of cancer cells,accompanied by decreased expression of matrix metalloproteinase-2 (MMP-2) and MMP-9.Moreover,transfection of RELMβ attenuated the expression of vascular endothelial growth factor and in vitro angiogenic capabilities of cancer cells.CONCLUSION:Over-expression of RELMβ abolishes the invasion,metastasis and angiogenesis of gastric cancer cells in vitro,suggesting its potentials as a novel therapeutic target for gastric cancer.

  5. Non-invasive exploration of neonatal gastric epithelium by using exfoliated epithelial cells.

    Directory of Open Access Journals (Sweden)

    Bertrand Kaeffer

    Full Text Available BACKGROUND & AIMS: In preterm infants, exfoliated gastric epithelial cells can be retrieved from aspirates sampled through the naso-gastric feeding tube. Our aims were to determine (1 whether the recovery of exfoliated cells is feasible at any time from birth through the removal of the nasogastric tube, (2 whether they can be grown in culture in vitro, and (3 whether the physiological state of exfoliated cells expressing H+/K+ -ATPases reflects that of their counterparts remaining in situ at the surface of the gastric epithelium in neonatal rat pups. METHODS: In infants, gastric fluid aspirates were collected weekly after birth or every 3 hours over 24-h periods, and related to clinical parameters (Biocollection PROG/09/18. In rat pups submitted to a single fasting/refeeding cycle, we explored circadian exfoliation with the cellular counter-parts in the gland. All samples were analyzed by confocal imaging and Enzyme-Linked Immunosorbent Assay. RESULTS: Epithelial cells were identified by microscopy using membrane-bound anti-H+/K+ ATPases antibody, assessed for nucleus integrity, and the expression of selected proteins (autophagy, circadian clock. On 34 infants, the H+/K+-ATPase-positive cells were consistently found quiescent, regardless of gestational age and feeding schedule from day-5 of life to the day of removal of the naso-gastric tube. By logistic regression analysis, we did find a positive correlation between the intensity of exfoliation (cellular loss per sample and the postnatal age (p<0.001. The H+/K+ ATPase-positive cells established in culture retained the expression of a biomarker of progenitor status (Pouf5F1-Oct4. In rat pups, the expression pattern of Survivin in H+/K+ ATPase-positive exfoliated cells paralleled that observed in cells remaining at the surface of the gastric gland. CONCLUSIONS: Tracking parietal cells can improve clinical monitoring and understanding of the autophagic death via the phosphatidylinositol 3-kinase

  6. The Relationship between Apoptosis and the Expression of Proliferating Cell Nuclear Antigen and the Clinical Stages in Gastric Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5±3.7) % and (49.8±15.9) % respectively, and the rate of AI/PI was 0.13±0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer (P<0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage Ⅱ to Ⅳ (P<0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.

  7. RhoC regulates the proliferation of gastric cancer cells through interaction with IQGAP1.

    Directory of Open Access Journals (Sweden)

    Yan Wu

    Full Text Available Our previous research results showed that both Ras homolog family member C (RhoC and IQ-domain GTPase-activating protein 1 (IQGAP1 were over-expressed in gastric cancer tissues and cells, but their role in tumorigenensis has not been addressed clearly. Herein we reported the proliferation stimulating effect of RhoC and IQGAP1 on gastric cancer cells and the interaction between two proteins in regulating the proliferation of gastric cancer cells. Plasmids and viral constructs encoding target siRNA and DNA were used to alter the expression of RhoC and IQGAP1. MTT method and BrdU incorporation assay were used for analyzing the effect of RhoC and different structures of IQGAP1 on proliferation. Protein levels of IQGAP1 and RhoC in cell lines were detected by Western blotting. Immunofluorescence and Co-Immunoprecipitation assays were applied to investigate the localization and binding between RhoC and IQGAP1. The results showed that RhoC, IQGAP1 and the C-terminal fragment of IQGAP1 significantly stimulated the proliferation of gastric cancer cells, and enhanced the expression of cyclin E and cyclin D1. By contrast, reduction of endogenous IQGAP1 or RhoC by siRNA attenuated cell proliferation. The depletion of IQGAP1 expression by siRNA significantly blocked the proliferative activity of constitutively active RhoC, while RhoC silencing by siRNA had no effect on IQGAP1-induced proliferation in gastric cancer cells. Co-immunoprecipitation and Immunofluorescence assays showed that RhoC and IQGAP1 bound each other. In conclusion, our results suggest that RhoC stimulates the proliferation of gastric cancer cells through recruiting IQGAP1 as an effector.

  8. Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ling Xu; Xiu-Juan Qu; Yun-Peng Liu; Ying-Ying Xu; Jing Liu; Ke-Zuo Hou; Ye Zhang

    2011-01-01

    Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell proliferation was measured using MTT assay, and apoptosis was determined by flow cytometry. Protein expression was detected by Western blot. Autophagy was observed using fluorescent microscopy. Our results showed that the rate of apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20 μg/mL oxaliplatin for 24 h, respectively. In addition, caspase activation and poly ADP-ribose polymerase (PARP)cleavage were detected. Furthermore, when MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate LC3 and an increase of LC3-Ⅱ protein were also detected, indicating the activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of cell proliferation and the induction of cell apoptosis. In conclusion, oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may be a new therapeutic option for gastric cancer.

  9. Characterization and functional properties of gastric tissue-resident memory T cells from children, adults and the elderly

    Directory of Open Access Journals (Sweden)

    Jayaum S. Booth

    2014-06-01

    Full Text Available T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell isolation method that yielded high numbers of viable lamina propria mononuclear cells (LPMC from gastric biopsies. Classic memory T (TM subsets were identified in gastric LPMC and compared to peripheral blood mononuclear cells (PBMC obtained from children, adults and the elderly using an optimized 14 color flow cytometry panel. A dominant effector memory (TEM phenotype was observed in gastric LPMC CD4+ and CD8+ T cells in all age groups. We then evaluated whether these cells represented a population of gastric tissue-resident memory T (TRM cells by assessing expression of CD103 and CD69. The vast majority of gastric LPMC CD8+ T cells either co-expressed CD103/CD69 (>70% or expressed CD103 alone (~20%. Gastric LPMC CD4+ T cells also either co-expressed CD103/CD69 (>35% or expressed at least one of these markers. Thus, gastric LPMC CD8+ and CD4+ T cells had the characteristics of TRM cells. Gastric CD8+ and CD4+ TRM cells produced multiple cytokines (IFN-γ, IL-2, TNF-α, IL-17A, MIP-1β and up-regulated CD107a upon stimulation. However, marked differences were observed in their cytokine and multi-cytokine profiles when compared to their PBMC TEM counterparts. Furthermore, gastric CD8+ TRM and CD4+ TRM cells demonstrated differences in the frequency, susceptibility to activation and cytokine/multi-cytokine production profiles among the age groups. Most notably, children’s gastric TRM cells responded differently to stimuli than gastric TRM cells from adults or the elderly. In conclusion, we demonstrate the presence of gastric TRM which exhibit diverse functional characteristics in children, adults and the elderly.

  10. Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection

    DEFF Research Database (Denmark)

    Holck, Susanne; Holm, I.L.; Holck, P.P.;

    2007-01-01

    Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load...... and cytokines which may improve knowledge concerning the outcome of gastric diseases caused by H. pylori. Antral biopsies from 42 dyspeptic patients including 27 H. pylori-positive and 15 H. pylori-negative patients were tested for apoptotic activity by the TUNEL assay, and immuno-histochemically for p53...... and the proliferative marker Ki-67. H. pylori infection, bacteria load and inflammatory activity were associated with increased cell turnover as judged by enhanced activities of TUNEL, p53 and Ki-67. Only p53 was significantly correlated to IFN-gamma, IL-8 and IL-10. The H. pylori-positive state was furthermore...

  11. Isocitrate Dehydrogenase 2 Dysfunction Contributes to 5-hydroxymethylcytosine Depletion in Gastric Cancer Cells.

    Science.gov (United States)

    Chou, Nan-Hua; Tsai, Chung-Yu; Tu, Ya-Ting; Wang, Kuo-Chiang; Kang, Chi-Hsiang; Chang, Po-Min; Li, Guan-Cheng; Lam, Hing-Chung; Liu, Shiuh-Inn; Tsai, Kuo-Wang

    2016-08-01

    The isocitrate dehydrogenase (IDH) family of enzymes comprises of the key functional metabolic enzymes in the Krebs cycle that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG). α-KG acts as a cofactor in the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). However, the relationship between 5hmC and IDH in gastric cancer remains unclear. Our study revealed that the 5hmC level was substantially lower and 5mC level was slightly higher in gastric cancer tissues; however, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels did not change significantly in these tissues. We further examined the expression levels of IDH1 and IDH2 in gastric cancer tissues and observed that IDH2 levels were significantly lower in gastric cancer tissues than in the adjacent normal tissues. The ectopic expression of IDH2 can increase 5hmC levels in gastric cancer cells. In conclusion, our results suggested that IDH2 dysfunction is involved in 5hmC depletion during gastric cancer progression. PMID:27466503

  12. Effect of p27KIP1 on cell cycle and apoptosis in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Zheng; Wei-Zhong Wang; Kai-Zong Li; Wen-Xian Guan; Wei Yan

    2005-01-01

    AIM: To elucidate the effect of p27KIP1 on cell cycle and apoptosis regulation in gastric carcinoma cells.METHODS: The whole length of p27KIP1 cDNA was transfected into human gastric cancer cell line SCG7901by lipofectamine. Expression of p27KIP1 protein or mRNA was analyzed by Western blot and RNA dot blotting,respectively. Effect of p27KIP1 on cell growth was observed by MTT assay and anchorage-independent growth in soft agar. Tumorigenicity in nude mice was used to assess the in vivo biological effect of p27KIP1. Flow cytometry,TUNEL, and electron microscopy were used to assess the effect of p27KIP1 on cell cycle and apoptosis.RESULTS: Expression of p27KIP1 protein or mRNA increased evidently in SCG7901 cells transfected with p27KIP1. The cell growth was reduced by 31% at 48 h after induction with zinc determined by cell viability assay. The alteration of cell malignant phenotype was evidently indicated by the loss of anchorage-independent growth ability in soft agar. The tumorigenicity in nude mice was reduced evidently (0.55±0.14 cm vs 1.36±0.13crn, P<0.01). p27KIP1 overexpression caused cell arrest with 36% increase (from 33.7% to 69.3%,P<0.01) in G1 population. Prolonged p27KIP1 expression induced apoptotic cell death reflected by pre-G1 peak in the histogram of FACS, which was also confirmed by TUNEL assay and electron microscopy.CONCLUSION: p27KIP1 can prolong cell cycle in G1phase and lead to apoptosis. p27KIP1 may be a good candidate for cancer gene therapy.

  13. Curcumin combined FOLFOX induced cell apoptosis of gastric cancer and its mechanism

    Institute of Scientific and Technical Information of China (English)

    周香

    2013-01-01

    Objective To observe the effect of curcumin combined folinic acid fluorouracil oxaliplatin (FOLFOX) on the gastric adenocarcinoma cell line BGC-823 and to explore its possible mechanisms.Methods Cells were divided into five groups,i.e.the blank control group,the

  14. Raman spectroscopic investigations on the interactions of gastric cancer cells with 5-fluorouracil

    Institute of Scientific and Technical Information of China (English)

    Jianyu Guo; Weiying Cai; Jipeng Yang; Zhenrong Sun

    2008-01-01

    To study the efficacy and side effects of antitumor drug by the method of Raman spectroscopy, the cancerous (SGC-7901) and normal (GES-1) gastric cells were treated with 0, 25-, 100-, and 200-mg/L 5-fluorouracil (5-Fu) for 24 h, respectively, then Raman spectra of cells were recorded. The excitation wavelength was 514.5 nm and the Raman spectra in the region of 500 - 1800 cm-1 were recorded. For the gastric cancer cells, as the concentration of 5-Fu increases, the band at 1094 cm-1 attributed to the symmetric stretching vibration mode of PO2- in the DNA backbone gradually decreases, and the intensity ratio of the band at 1315 cm-1 to that at 1340 cm-1 (I1315/I1340) shows the ascending trend, and the ratio of the band area at 1655 cm-1 to that at 1450 cm-1 (A1655/A1450) shows the slight ascending trend. For the normal gastric cells, these peaks also appear changes, however, the changes are weaker than those for the cancer cells. In SGC-7901 cells, 5-Fu can interfere with the DNA synthesis and result in the reduction of the DNA content. Besides, it can affect the unsaturation degree of the hydrocarbon chains and alter the external environment of guanine and adenine residues in cancer cells. The changes of Raman spectra for normal gastric cells reveal the side effect of 5-Fu.

  15. Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell

    Institute of Scientific and Technical Information of China (English)

    WU Zhi-qun; ZHANG Rui; Connie Chao; ZHANG Ji-feng; ZHANG Yuan-qiang

    2007-01-01

    Background Histone deacetylase inhibitors (HDACIs) have been reported to induce apoptosis in cancer cells.The effects of trichostatin A (TSA) on gastric cancer cells have not been well characterized.This study was aimed to explore the effects and mechanisms of TSA on human gastric cancer SGC-7901 cells.Methods The cells were treated with TSA and analyzed by cell proliferation assay,Western blot,TUNEL assay,flow cytometry by fluorescein isothiocyanate (FITC) conjugated with Annexin V and PI staining,immunofluorescence analysis,analysis of subcellular fractionation,gene chips and real time polymerase chain reaction (PCR).Results TSA could inhibit cell growth and induced apoptosis in gastric cancer SGC-7901 cells through the regulation of apoptosis-related genes,such as Bcl-2,Bax and survivin.Further study indicated that the pan-caspase inhibitor z-VAD-fmk did not inhibit the apoptosis induced by TSA,and we did not observe the cleavage of poly ADP ribose polymerase(PARP)after TSA treatment too.In addition,apoptosis inducing factor (AIF) and EndoG were found to translocate from mitochondria to nucleus in the immunofluorescence assay and the Western analysis of subcellular fractionation confirmed the result of immunofluorescence assay.Conclusions The apoptosis induced by TSA in gastric cancer SGC-7901 cells involves a caspase-independent pathway.

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

    Institute of Scientific and Technical Information of China (English)

    廉超

    2014-01-01

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

  17. Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Liang-Hui Shi; Xiao-Qun Zhu; Guo-Hai Zhao; Ya-Bin Xia; Yi-Sheng Zhang

    2006-01-01

    AIM: To investigate the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in gastric carcinoma and its clinical significance and to explore its relationship with cell proliferation.METHODS: Expressions of IGFBP-2 and Ki-67 in 118cases of gastric carcinoma and 40 cases of normal gastric mucosa were detected by EnVision immunohistochemical technique.RESULTS: Expression of IGFBP-2 in gastric carcinoma was higher than that in normal gastric mucosa (P 0.05). Fxpression of IGFBP-2 in aclvancecl gastric carcinoma was higher than that in early gastric carcinoma (P < 0.05). Expression of IGFBP-2 in gastric carcinoma with lymph node metastasis was higher than that without lymph node metastasis (P < 0.01).IGFBP-2 expression was a positively related to the clinical stage of gastric carcinoma (P < 0.01). There was a positive correlation between IGFBP-2 and Ki-67 (P < 0.05).CONCLUSION: IGFBP-2 may be involved in carcinogenesis and progression of gastric carcinoma by promoting cell proliferation.

  18. 胃癌干细胞研究概况%Advanced in Gastric Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    武慧军; 欧阳晓晖; 苏秀兰

    2014-01-01

    Gastric cancer stem cells in gastric cancer tissues, the stomach may originate from adult stem cells, bone marrow cells or by other stem cells transformed. At present, gastric cancer stem cell identification, separation methods mainly depend on gastric cancer stem cell markers, side group cells (side population cells, sP cells). Greater omentum milk spot and epithelial interstitial transformation helps to gastric cancer cell identification separation. Gastric cancer stem cells and gastric cancer treatment and prognosis were significantly related. in this paper the origin of gastric cancer stem cells, the identification of separation and the treatment of gastric cancer were summarized in this review.%胃癌干细胞(gastric cancer stem cell)存在于胃癌组织中,可能来源于胃成体干细胞、骨髓细胞或由其他干细胞转化而来。目前胃癌干细胞的鉴定、分离方法主要依靠胃癌干细胞标志物,侧群细胞(side population cells,sP)细胞。大网膜乳斑及上皮间质转化有助于胃癌细胞的鉴定分离。胃癌干细胞与胃癌的治疗和预后明显相关。本文就胃癌干细胞的起源、鉴定分离与胃癌的治疗作一综述。

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

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

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

  20. Homeostatic Mass Control in Gastric Non-Neoplastic Epithelia under Infection of Helicobacter pylori: An Immunohistochemical Analysis of Cell Growth, Stem Cells and Programmed Cell Death

    International Nuclear Information System (INIS)

    We evaluated homeostatic mass control in non-neoplastic gastric epithelia under Helicobacter pylori (HP) infection in the macroscopically normal-appearing mucosa resected from the stomach with gastric cancer, immunohistochemically analyzing the proliferation, kinetics of stem cells and programmed cell death occurring in them. Ki67 antigen-positive proliferating cells were found dominantly in the elongated neck portion, sparsely in the fundic areas and sporadically in the stroma with chronic infiltrates. CD117 could monitor the kinetics of gastric stem cells and showed its expression in two stages of gastric epithelial differentiation, namely, in transient cells from the gastric epithelial stem cells to the foveolar and glandular cells in the neck portion and in what are apparently progenitor cells from the gastric stem cells in the stroma among the infiltrates. Most of the nuclei were positive for ssDNA in the almost normal mucosa, suggesting DNA damage. Cleaved caspase-3-positive foveolar cells were noted under the surface, suggesting the suppression of apoptosis in the surface foveolar cells. Besides such apoptosis of the foveolar cells, in the severely inflamed mucosa apoptotic cells were found in the neck portion where most of the cells were Ki67 antigen-positive proliferating cells. Beclin-1 was recognized in the cytoplasm and in a few nuclei of the fundic glandular cells, suggesting their autophagic cell death and mutated beclin-1 in the nuclei. Taken together, the direct and indirect effects of HP infection on the gastric epithelial proliferation, differentiation and programmed cell death suggested the in-situ occurrence of gastric cancer under HP infection

  1. In vivo transplantation of bone marrow mesenchymal stem cells accelerates repair of injured gastric mucosa in rats

    Institute of Scientific and Technical Information of China (English)

    CHANG Qing; YAN Li; WANG Chang-zheng; ZHANG Wen-hui; HU Ya-zhuo; WU Ben-yan

    2012-01-01

    Background Adult stem cells provide a promising alternative for the treatment of injured tissues.We aimed to investigate the effect of in vivo transplantation of bone marrow mesenchymal stem cells (BMMSCs) on injured gastric mucosa in rats.Methods The gastric ulcer in rats was induced by indomethacin.BMMSCs from male rats,labeled with the fluorescent cell linker 5,6-carboxyfluorescein diacetate succinimidyl ester (CFDA SE),were transplanted into the female rats via tail vein injection.The healing process of gastric ulcers was monitored by HE staining.The protein levels of vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) in the injured gastric mucosa were determined by immunohistochemistry.Results At 48 and 72 hours after BMMSCs transplantation,the CFDA SE labeled cells were found scattered in the injured gastric mucosa,but not in the gastric mucosa of control rats.At 72 hours after BMMSCs transplantation,the mean ulcer index was 12.67±2.16 in the BMMSCs transplanted group and 17.33±1.97 in vehicle-treated controls (P <0.01).Both VEGF and EGFR protein expression levels were significantly higher in the gastric section from the rats that received BMMSCs transplantation as compared to rats without BMMSCs transplantation.Conclusion Autologous BMMSCs transplantation can accelerate gastric ulcer healing in injured gastric mucosa in a rodent model.

  2. Lectin Histochemical Study of Cell Surface Glycoconjugate in Gastric Carcinoma Using Helix Pomatia Agglutinin

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Arab

    2010-07-01

    Full Text Available "nAltered glycosylation of proteins in cancer cells is one of the main processes responsible for anaplasia, invasion and metastatic potential of neoplastic cells. Lectins are nonimmunogenetic compounds which specifically detect certain terminal sugars of glycoconjugates. The aim of the present study was to identify the N-acetylgalactosamine (GalNac containing glycoconjugates in cancer cells in all grades of gastric carcinoma. Paraffin blocks belong to 30 patients of gastric carcinoma (10 cases from each grade was collected from pathology file of Ali-Ebn-Abitaleb Hospital in Zahedan during 2005-2007. Prepared sections (5-7μm in thickness were stained by Alcian Blue, hematoxylin and eosin (H&E and helix pomatia agglutinin (HPA conjugated lectin. Lectin diluted up to 10μg/ml in PBS (0.1M, pH=6.8. Lectin reactivity was visualized by 0.03% diaminobenzidine (DAB solution. Sections were graded according to staining intensity to lectin (0-4+. Although there was some difference for lectin staining intensity between cancer cells in different grades of gastric carcinoma, statistical analysis showed that there was only a significant difference for cancer cells reactivity between histopathological grades of II and III. The pattern of reactivity to HPA lectin were also different from all histopathological grades. It seems that in cancer cells, the amount and distribution of GalNac containing glycoconjugate differ from neoplastic cells of different histopathological grades in gastric carcinoma.

  3. Lectin Histochemical Study of Cell Surface Glycoconjugate in Gastric Carcinoma Using Helix Pomatia Agglutinin

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Arab

    2010-08-01

    Full Text Available Altered glycosylation of proteins in cancer cells is one of the main processes responsible for anaplasia, invasion and metastatic potential of neoplastic cells. Lectins are nonimmunogenetic compounds which specifically detect certain terminal sugars of glycoconjugates. The aim of the present study was to identify the N-acetylgalactosamine (GalNac containing glycoconjugates in cancer cells in all grades of gastric carcinoma. Paraffin blocks belong to 30 patients of gastric carcinoma (10 cases from each grade was collected from pathology file of Ali-Ebn-Abitaleb Hospital in Zahedan during 2005-2007. Prepared sections (5-7μm in thickness were stained by Alcian Blue, hematoxylin and eosin (H&E and helix pomatia agglutinin (HPA conjugated lectin. Lectin diluted up to 10μg/ml in PBS (0.1M, pH=6.8. Lectin reactivity was visualized by 0.03% diaminobenzidine (DAB solution. Sections were graded according to staining intensity to lectin (0-4+. Although there was some difference for lectin staining intensity between cancer cells in different grades of gastric carcinoma, statistical analysis showed that there was only a significant difference for cancer cells reactivity between histopathological grades of II and III. The pattern of reactivity to HPA lectin were also different from all histopathological grades. It seems that in cancer cells, the amount and distribution of GalNac containing glycoconjugate differ from neoplastic cells of different histopathological grades in gastric carcinoma.

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

    Science.gov (United States)

    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

  5. Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens.

    Science.gov (United States)

    Chang, Xiaojing; Zhang, Shuanglong; Ma, Jinguo; Li, Zhenhua; Zhi, Yu; Chen, Jing; Lu, Yao; Dai, Dongqiu

    2013-05-01

    NDRG1 (N-myc downstream-regulated gene 1) plays a role in cell differentiation and suppression of tumor metastasis. This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression. Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real-time PCR and Western blot. High-resolution melting analysis (HRM) and methylation-specific PCR (MSP) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples. Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues. Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein. HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples. Moreover, treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A-treated HGC27 cells. In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter. Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer.

  6. Isobavachalcone induces the apoptosis of gastric cancer cells via inhibition of the Akt and Erk pathways

    OpenAIRE

    JIN, XIAOHONG; Shi, Yi

    2015-01-01

    In the present study, the MGC803 gastric cancer cell line was used as an experimental model to evaluate the potential role of isobavachalcone (IBC) in cell apoptosis, migration and invasion. The inhibitory effects of IBC on cell proliferation were determined using a methylthiazolyltetrazolium assay. Cellular morphological changes were assessed using Wright-Giemsa staining, and cell apoptosis was evaluated by flow cytometric analysis. The results of the present study demonstrated that IBC inhi...

  7. Extracellular galectin-3 counteracts adhesion and exhibits chemoattraction in Helicobacter pylori-infected gastric cancer cells.

    Science.gov (United States)

    Subhash, Vinod Vijay; Ling, Samantha Shi Min; Ho, Bow

    2016-08-01

    Galectin-3 (Gal-3) is a β-galactoside lectin that is upregulated and rapidly secreted by gastric epithelial cells in response to Helicobacter pylori infection. An earlier study reported the involvement of H. pylori cytotoxin-associated gene A (cagA) in the expression of intracellular Gal-3. However, the role of extracellular Gal-3 and its functional significance in H. pylori-infected cells remains uncharacterized. Data presented here demonstrate secretion of Gal-3 is an initial host response event in gastric epithelial cells during H. pylori infection and is independent of CagA. Previously, Gal-3 was shown to bind to H. pylori LPS. The present study elaborates the significance of this binding, as extracellular recombinant Gal-3 (rGal-3) was shown to inhibit the adhesion of H. pylori to the gastric epithelial cells. Interestingly, a decrease in H. pylori adhesion to host cells also resulted in a decrease in apoptosis. Furthermore, the study also demonstrated a chemoattractant role of extracellular rGal-3 in the recruitment of THP-1 monocytes. This study outlines the previously unidentified roles of extracellular Gal-3 where it acts as a negative regulator of H. pylori adhesion and apoptosis in gastric epithelial cells, and as a chemoattractant to THP-1 monocytes. Our findings could contribute to the better understanding of how Gal-3 acts as a modulator under H. pylori-induced pathological conditions. PMID:27283429

  8. Active Components of Fungus Shiraia bambusiscola Can Specifically Induce BGC823 Gastric Cancer Cell Apoptosis

    Science.gov (United States)

    Zhang, Shubing; Qiu, Dewen; Liu, Jingjiang; Li, Zhijian

    2016-01-01

    Objective Gastric cancer is a major health issue worldwide. Using a therapeutic approach, with minor side-effects, is very essential for the treatment of the gastric cancer. Shiraia bambusicola is a parasitic fungus which is widely used in China for curing several diseases with little side-effects. However, the mechanisms are not well understood yet. The aim of this study was to further understand the pharmacological mechanisms of Shiraia bambusicola and investigate whether it can be used for curing gastric cancer. Materials and Methods In this experimental study, we mainly tested the effect of active components extracted from Shiraia bambusicola on BGC823, A549 and HepG2 cells. We used MTT assay to test cell viability. We also analyzed morphologic changes caused by apoptosis using Hoechst 33342 fluorescence staining, as well as cell cycle status and apoptosis ratio using flow-cytometer. In addition, protein expression level was tested by Western-blotting assay. Results BGC-823 cell proliferation was specifically inhibited by active components of Shiraia bambusicola. Meanwhile, these active components could induce BGC-823 cells apoptosis and retard the cell cycle in S/G2 phase. We also determined that two critical protein markers cleaved Poly(ADP-ribose) polymerase-1 (PARP-1) and FLICE-inhibitory protein (FLIP), involved in apoptosis process, were regulated by these active components. Conclusion These data shed light on the treatment of human gastric cancer and conclude that Shiraia bambusicola can be a good therapeutic candidate for treatment of this malignancy.

  9. Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Madsen, Claus Desler; Bøggild, Cecilie Sisse Line;

    2013-01-01

    Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear...... and mitochondrial DNA of gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear DNA is known to be a consequence, in part, of a down-regulation of expression and activity of major DNA repair pathways. In this study, we demonstrate that H. pylori infection of gastric adenocarcinoma cells....... pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection....

  10. EXPERIMENTAL STUDY ON APOPTOSIS OF GASTRIC CANCER CELLS INDUCED BY TRICHOSANTHIN

    Institute of Scientific and Technical Information of China (English)

    张曙; 胡梅洁; 吴裕圻; 吴云林

    2001-01-01

    Objective To investigate whether the apoptosis is involved in the mechanism of cytotoxicity of trichosanthin to gastric cancer cells. Methods Morphologic studies and TUNEL stainning were used to explore qualitatively and quantitatively the apoptotic status of gastric cancer cells before and after treatment with trichosanthin. Results In the experiment in vitro , when gastric cancer cells SGC-7901 were treated by trichosanthin (0.1μg /ml , 36h ), some typical apoptotic morphologic changes occured. A significant increase of apoptotic index ( AI ) was from (3.78±1.11 )%, (3.98±1.12)% and (3.85±1.08)% at 36, 42, 48h to (11.30 ±2.33)%, (10.22±2.00)% and (11.18±1.85)%, respectively ( P <0.01 ). In the experiment in vivo , nude mice with SGC-7901 xenografted tumor were treated by trichosanthin (0.3mg· kg-1·d-1 ,× 5d, intraperitoneal injection ), some typical apoptotic morphologic changes were observed. These apoptotic cells were limited only in xenografted tumor. AI increased significantly from (4.95±1.94 )% to (8.75± 1.38)%, (P<0.01). Conclusion The apoptosis would be involved in the mechanism of cytotoxicity of trichosanthin to gastric cancer cells.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  12. Matrix metalloproteinase gene expressions might be oxidative stress targets in gastric cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Salih Gencer; Anil Cebeci; Meliha Burcu Irmak-Yazicioglu

    2013-01-01

    Objective:Oxidative stress is linked to increased risk of gastric cancer and matrix metalloproteinases (MMPs) are important in the invasion and metastasis of gastric cancer.We aimed to analyze the effect of the accumulation of oxidative stress in the gastric cancer MKN-45 and 23132/87 cells following hydrogen peroxide (H2O2) exposure on the expression patterns of MMP-1,MMP-3,MMP-7,MMP-9,MMP-10,MMP-11,MMP-12,MMP-14,MMP-15,MMP-17,MMP-23,MMP-28,and β-catenin genes.Methods:The mRNA transcripts in the cells were determined by RT-PCR.Following H2O2 exposure,oxidative stress in the viable cells was analyzed by 2',7'-dichlorofluorescein diacetate (DCFH-DA).Caffeic acid phenethyl ester (CAPE) was used to eliminate oxidative stress and the consequence of H2O2 exposure and its removal on the expressions of the genes were evaluated by quantitative real-time PCR.Results:The expressions of MMP-1,MMP-7,MMP-14,MMP-15,MMP-17 and β-catenin in MKN-45 cells and only the expression of MMP-15 in 23132/87 cells were increased.Removal of the oxidative stress resulted in decrease in the expressions of MMP genes of which the expressions were increased after H2O2 exposure.β-catenin,a transcription factor for many genes including MMPs,also displayed decreased levels of expression in both of the cell lines following CAPE treatment.Conclusions:Our data suggest that there is a remarkable link between the accumulation of oxidative stress and the increased expressions of MMP genes in the gastric cancer cells and MMPs should be considered as potential targets of therapy in gastric cancers due to its continuous exposure to oxidative stress.

  13. Transcriptional profiling of gastric epithelial cells infected with wild type or arginase-deficient Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Kim Songhee H

    2012-08-01

    Full Text Available Abstract Background Helicobacter pylori causes acute and chronic gastric inflammation induced by proinflammatory cytokines and chemokines secreted by cells of the gastric mucosa, including gastric epithelial cells. Previous studies have demonstrated that the bacterial arginase, RocF, is involved in inhibiting T cell proliferation and CD3ζ expression, suggesting that arginase could be involved in a more general dampening of the immune response, perhaps by down-regulation of certain pro-inflammatory mediators. Results Global transcriptome analysis was performed on AGS gastric epithelial cells infected for 16 hours with a wild type Helicobacter pylori strain 26695, an arginase mutant (rocF- or a rocF+ complemented strain. H. pylori infection triggered altered host gene expression in genes involved in cell movement, death/growth/proliferation, and cellular function and maintenance. While the wild type strain stimulates host inflammatory pathways, the rocF- mutant induced significantly more expression of IL-8. The results of the microarray were verified using real-time PCR, and the differential levels of protein expression were confirmed by ELISA and Bioplex analysis. MIP-1B was also significantly secreted by AGS cells after H. pylori rocF- mutant infection, as determined by Bioplex. Even though not explored in this manuscript, the impact that the results presented here may have on the development of gastritis, warrant further research to understand the underlying mechanisms of the relationship between H. pylori RocF and IL-8 induction. Conclusions We conclude that H. pylori arginase modulates multiple host signaling and metabolic pathways of infected gastric epithelial cells. Arginase may play a critical role in anti-inflammatory host responses that could contribute to the ability of H. pylori to establish chronic infections.

  14. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Geng-Qiu Luo; Jing-He Li; Ji-Fang Wen; Yan-Hong Zhou; Yong-Bin Hu; Jian-Hua Zhou

    2008-01-01

    AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved.METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique.RT-PCR,Western blotting, ENSA, gelatin zymography assay, and in vitro invasion and migration assays were performed.Nude mice metastasis models were established by the abdominal cavity transfer method.RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained.Compared with MKN28 and pcDNA3-MKN28 cells, adherence,migration and invasion ability of TwistS-MKN28 cells were clearly raised.The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells.Overexpression of Twist in MKN28 cells increased Tcf-4/Lef DNA binding activity, and promoted expression of Tcf-4's downstream target genes cyclin Dt and HMP-2.However, suppression of Twist (TwistAS-NKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced.The activity of MMP-2 was also decreased.CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/Tcf-4 signaling.

  15. Macrophage migration inhibitory factor stimulated by Helicobacter pyloriincreases proliferation of gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Harry Hua-Xiang Xia; Shiu Kum Lam; Annie O.O. Chan; Marie Chia Mi Lin; Hsiang Fu Kung; Keiji Ogura; Douglas E. Berg; Benjamin Chun-Yu Wong

    2005-01-01

    AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cay pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro.METHODS: A cytotoxic wild-type H pylori strain (TN2),its three isogenic mutants (TN2△cag, TN2△cagA and TN2△cagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45,were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter.RESULTS: The wild-type strain and the isogenic mutants,TN2△cagA and TN2△cagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2△cag did not increase the release of MIF at any of the four ratios.3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2△cagA and TN2△cagE, but not from the mutant TN2△cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared.CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H pylori

  16. Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Park, Won-Mee; Sakata, Ichiro;

    2013-01-01

    The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro,...

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

  19. Detection of free gastric cancer cell in peripheral and portal blood

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ho Yoon; Lee, Jong Inn [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    In fact, there is no definite treatment modality after liver or hematogenous metastasis in the gastric cancer. So it is important to develop a new method to predict the high risk patients for systemic recurrence. If we can detect metastatic cell in circulation, it may be beneficial in assessing tumor progression, metastatic potential and prognosis. To establish the RT-PCR methodology for detection of CEA expressing cancer cells in peripheral and portal blood and to define the relationship between peripheral and portal blood detection rate of gastric cancer patients, we performed RT-PCR analysis with peripheral and portal blood samples from 24 patients with gastric cancer (stage Ia,b, n=3; stage II, n=2; stage IIIa, n=9; stage IIIb, n=7; stage IV, n=3) and checked serum CEA level preoperatively. Mean age was 49.2 years old and male : female was 1.2 : 2 (13:11 patients). The mean serum CEA level was 10.4 ng/ml and that was higher than normal in only 2 cases. There was no positive case of tumor cell in portal and peripheral blood using RT-PCR and CEA gene specific primer. Our results indicate that the incidence of circulating cancer cells is unexpectedly very low even in advanced gastric cancer patients. (author). 20 refs.

  20. miR-449 inhibits cell proliferation and is down-regulated in gastric cancer

    Directory of Open Access Journals (Sweden)

    Federspiel Birgitte

    2011-03-01

    Full Text Available Abstract Background Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets. Results Invitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN, MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN, MET, CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues. Conclusions In this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its

  1. Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

    Institute of Scientific and Technical Information of China (English)

    Davide; Leopardo; Giuseppe; Di; Lorenzo; Amalia; De; Renz

    2010-01-01

    AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[schedule...

  2. Cyclooxygenase-2 Mediated Regulation of E-Cadherin Occurs in Conventional But Not Early-Onset Gastric Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    R. Sitarz

    2009-01-01

    Full Text Available Background: COX-2 and E-cadherin, involved in invasion and metastasis, are molecules critical for gastric carcinogenesis. A relationship between them is documented in non-small cell lung and prostate cancer. We present novel evidence of a relationship between COX-2 and E-cadherin expression in gastric cancer.

  3. Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line

    Directory of Open Access Journals (Sweden)

    H.F. Ribeiro

    2010-08-01

    Full Text Available Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG-100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95% of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85% presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.

  4. EXPRESSION OF MATRIX METALLOPROTEINASE-7 AND FAS LIGAND: THEIR APOPTOSIS-INDUCING EFFECT ON GASTRIC CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    郑华川; 杨雪飞; 孙晋民; 李晓晗; 姜卫国; 张荫昌; 辛彦

    2003-01-01

    Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren's classification, histological classification (P0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  6. Gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Ismail Gomceli; Baris Demiriz; Mesut Tez

    2012-01-01

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

  7. Sensitivity of gastric adenocarcinoma and normal cell lines against combined or conjugated antimetabolites.

    Science.gov (United States)

    Weinreich, Jürgen; Struller, Florian; Küper, Markus; Hack, Anita; Königsrainer, Alfred; Schott, Timm C

    2013-04-01

    The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth inhibition of the human gastric adenocarcinoma cell lines 23132/87 and MKN-45 in comparison with normal gastric intestinal CCL-241 and the dermal fibroblast cell line NHDF was evaluated using CASY technology. The cell lines were incubated with an equimolar mixture of 5-fluoro-2'-deoxyuridine (5FdU)+3'-C-ethynylcytidine (ECyd) or the covalently linked duplex drug 5FdU(5'→5')ECyd. The drug and metabolites of the assays and medium were determined semiquantitatively using high-performance liquid chromatography. The sensitivity of cancer and nonmalignant cell lines was clearly different against the duplex drug. A measure of 0.65 µmol/l 5FdU(5'→5')ECyd, for example, reduced the growth of MKN-45 or 23132/87 gastric cancer cells from 100% on day 0 to about 50 or 20% on day 10, respectively. However, under the same conditions, the growth of the nonmalignant NHDF and CCL-241 cell lines was not markedly inhibited. The cytostatic activity of the duplex drug is based on the active metabolites in and outside the cell formed by the degradation of 5FdU(5'→5')ECyd. The sensitivity of cell lines against the duplex drug depended on its ability to metabolize the duplex drug. 5FdU(5'→5')ECyd should be more advantageous for specific and efficient polychemotherapy of gastric cancer than the corresponding equimolar mixture of 5FdU+ECyd or a standard combination regime of single drugs.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Effects of tubeimoside-1 on the proliferation and apoptosis of BGC823 gastric cancer cells in vitro

    OpenAIRE

    Zhang, Yi; XU, XIAO-MAN; Zhang, Meng; Qu, Dan; NIU, HUI-YAN; Bai, Xue; KAN, LIANG; He, Ping

    2013-01-01

    Natural products isolated from Chinese medicinal herbs are useful sources of new drugs for cancer therapy. Tubeimoside-1 (TBMS1) is a natural compound isolated from the Chinese medicinal herb Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae). Studies have shown that TBMS1 has anticancer effects in various human cancer cell lines. However, the effect of TBMS1 on human gastric cancer cells is unknown. In the present study, it was observed that TBMS1 inhibited BGC823 gastric cancer cell ...

  11. Treatment of gastric cancer cells with nonthermal atmospheric plasma generated in water.

    Science.gov (United States)

    Chen, Zhitong; Lin, Li; Cheng, Xiaoqian; Gjika, Eda; Keidar, Michael

    2016-01-01

    Nonthermal atmospheric plasma (NTAP) can be applied to living tissues and cells as a novel technology for cancer therapy. The authors report on a NTAP argon solution generated in deionized (DI) water for treating human gastric cancer cells (NCI-N87). Our findings show that the plasma generated in DI water with 30-min duration has the strongest effect on apoptosis in precultured human gastric cancer cells. This result can be attributed to the presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced in water during treatment. Furthermore, the data show that the elevated levels of RNS may play a more significant role than ROS in the rate of cell death. PMID:27604078

  12. Macroscopic extent of gastric mucosal atrophy: increased risk factor for esophageal squamous cell carcinoma in Japan

    Directory of Open Access Journals (Sweden)

    Kobayashi Noritoshi

    2009-05-01

    Full Text Available Abstract Background We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection. Methods Two hundred and fifty-three patients who were diagnosed as having esophageal squamous cell carcinoma, and 253 sex- and age-matched controls were enrolled in the present study. The macroscopic extent of gastric mucosal atrophy was evaluated based on the Kimura and Takemoto Classification. A conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations. Results Body gastritis, defined endoscopically, was independently associated with an increased risk for esophageal squamous cell carcinoma. Conclusion Our findings suggest that macroscopic body gastritis may be a risk factor for esophageal squamous cell carcinoma in Japan. Further studies are needed to confirm these findings.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  15. 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth

    OpenAIRE

    WANG, TING-AN; Zhang, Xiao-Dong; GUO, XING-YU; XIAN, SHU-LIN; Lu, Yun-Fei

    2015-01-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor mod...

  16. Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

    Institute of Scientific and Technical Information of China (English)

    Kamran Ghaffarzadehgan; Mostafa Jafarzadeh; Hamid Reza Raziee; Harold Reza Sima; Ehsan Esmaili-Shandiz; Hanieh Hosseinnezhad; Ail Taghizadeh Kermani; Omeed Moaven; Maryam Bahrani

    2008-01-01

    AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was used for histological evaluation, including the type (Lauren's classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P=0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients.

  17. Diagnostic accuracy of circulating tumor cells detection in gastric cancer: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Circulating tumor cells (CTCs) detection has previously been used for diagnosing gastric cancer. However, the previous studies failed to make an agreement whether the detection of CTCs contributes to the diagnosis of gastric cancer. A systematic review and meta-analysis was performed to evaluate the overall accuracy of CTCs detection for diagnosing gastric cancer. PubMed, Embase and the Wanfang database were searched in all languages published up to Oct 2012. The pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR) and summary receiver operating characteristic (sROC) curve were calculated to evaluate the overall test performance. Twenty studies were included in this systematic review and meta-analysis. The diagnostic value of CTCs detection for the gastric cancer was calculated to evaluate the overall test performance. The summary estimates of The pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio were 0.42 (95% confidence interval (CI), 0.21-0.67), 0.99 (95% CI, 0.96-1.00), 58.2 (95% CI, 9.8-345.9), 0.58 (95% CI, 0.38-0.89), and 100 (95% CI, 15–663), respectively. The summary receiver operating characteristic curve was 0.97 (95% CI, 0.95–0.98). Deek’s funnel plot asymmetry test found no evidence of study publication bias in the current study (P = 0.49). This systematic review suggests that CTCs detection alone cannot be recommended as a screening test for gastric cancer. However, it might be used as a noninvasive method for the confirmation of the gastric cancer diagnosis

  18. Expression of vascular cell adhesion molecule-1 facilitates angiogenesis in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yongbin Ding; Tianson Xia; Guoyu Chen; Jianguo Xia

    2006-01-01

    Objective: To investigate the relationship between the expression of VCAM-1 and oncogenesis, tumor angiogenesis and metastasis in gastric carcinoma. Methods: Using RT-PCR and immunohistochemistry technique, the expression of VCAM-1 were detected in specimens from 44 patients with gastric cancer, 8 with ulcer. Microvessel density (MVD) was also counted by endothelial cells immunostained with monoclonal antibodies CD34. In addition, Circulating sVCAM-1 concentrations were measured by an enzyme linked immunosorbent assay. Results:Of 44 gastric cancer tumor tissues, 36were detected the ex pressions of VCAM-1 mRNA. The rates of VCAM-1 mRNA in the primary gastric cancer tissues were significantly higher than those in the para-cancerous tissues and benign ulcer tissues (P < 0.05). The VCAM-1 posithoseive isolates had more lymph node metastases than that of VCAM-l-negative ones (P < 0.05). MVD of positive VCAM-1 expression tissues were higher than those of negative VCAM-1 (P < 0.05). Circulating sVCAM-1 levels decreased significantly after operation (P < 0.05). Furthermore, the levels of sVCAM-1 were positively correlated with the expressions of VCAM-1 in the tumor tissues (r = 0.64, P <0.05). Conclusion: Expressions of VCAM-1 mRNA was closely related to oncogenesis, tumor angiogenesis and metastasis in gastric carcinoma. The concentration of sVCAM-1 may be considered as an effective mark of tumor burden of gastric cancer.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2012-04-01

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

  1. The RARgamma selective agonist CD437 inhibits gastric cell growth through the mechanism of apoptosis.

    Science.gov (United States)

    Jiang, S Y; Lin, D Y; Shyu, R Y; Reichert, U; Yeh, M Y

    1999-04-01

    Retinoids are differentiation-inducing agents that exhibit multiple functions. Their activities are mediated through interaction with nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). We have investigated the activities of synthetic retinoids on the growth of five gastric cancer cell lines. The effects of agonists selective for RARalpha, RARbeta and RARgamma (AM580, CD2019 and CD437, respectively) on cell growth were determined, in comparison to all-trans retinoic acid, by measuring total cellular DNA. AM580 and CD2019 had little or no effect on the growth of all five cell lines. In contrast, the RARgamma agonist CD437 inhibited cell growth up to 90-99% in both retinoic acid sensitive and resistant gastric cancer cells at a concentration of 1 microM. The growth suppression caused by CD437 was accompanied by the induction of apoptosis as judged by morphological criteria and DNA ladder formation. However, the extent of CD437-induced growth suppression was not correlated with RARgamma mRNA levels, which indicates that CD437 induces apoptosis in gastric cancer cells via an RARgamma independent pathway.

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

    Directory of Open Access Journals (Sweden)

    Emma C Skoog

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  5. Inhibitory effect of Polo-like kinase 1 depletion on mitosis and apoptosis of gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xue-Hua Chen; Bin Lan; Ying Qu; Xiao-Qing Zhang; Qu Cai; Bing-Ya Liu; Zheng-Gang Zhu

    2006-01-01

    AIM: Polo-like kinase 1 (PLK1) serine/threonine kinase plays a vital role in multiple phases of mitosis in gastric cancer cells. To investigate the effect of PLK1 depletion on mitosis and apoptosis of gastric cancer cells.METHODS: PLK1 expression was blocked by small RNA interference(siRNA). The expression levels of PLK1, cdc2, cyclin B and caspase 3 were detected by Western blotting. Then, PLK1 depletion, cdc2 activity,cell proliferation, cell cycle phase distribution, mitotic spindle structure, and the rate of apoptosis of the PLK1knockdown cells were observed.RESULTS: PLK1 gene knockdown was associated with increased cyclin B expression, increased cdc2 activity (but not with the expression levels), accumulation of gastric cancer cells at G2/M, improper mitotic spindle formation,delayed chromosome separation and delayed or arrested cytokinesis. Moreover, PLK1 depletion in gastric cancer cells was associated with decreased proliferation,attenuated pro-caspase 3 levels and increased apoptosis.CONCLUSION: Blockage of PLK1 expression may lead to decreased mitosis or even apoptosis in gastric cancer cells, indicating that PLK1 may be a valuable therapeutic target for gastric cancer.

  6. A Rare Case of Gastric Variceal Hemorrhage Secondary to Infiltrative B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Adrienne Lenhart

    2016-10-01

    Full Text Available Portal hypertension commonly arises in the setting of advanced liver cirrhosis and is the consequence of increased resistance within the portal vasculature. Less commonly, left-sided noncirrhotic portal hypertension can develop in a patient secondary to isolated obstruction of the splenic vein. We present a rare case of left-sided portal hypertension and isolated gastric varices in a patient with large B-cell lymphoma, who was treated with splenic artery embolization. The patient is a 73-year-old male with no previous history of liver disease, who presented with coffee ground emesis and melena. On admission to hospital, he was found to have a hemoglobin level of 3.4 g/l. Emergent esophagogastroduodenoscopy showed isolated bleeding gastric varices (IGV1 by Sarin classification in the fundus and cardia with subsequent argon plasma coagulation injection. He was transferred to our tertiary center where work-up revealed normal liver function tests, and abdominal ultrasound showed patent hepatic/portal vasculature without cirrhosis. MRI demonstrated a large heterogeneously enhancing mass in the pancreatic tail, with invasion into the spleen and associated splenic vein thrombosis. Surgery consultation was obtained, but urgent splenectomy was not recommended. The patient instead underwent splenic artery embolization to prevent future bleeding from his known gastric varices. Pathology from a CT-guided biopsy was consistent with diffuse large B-cell lymphoma. PET imaging showed uptake in the splenic hilum/pancreatic tail region with no additional metastatic involvement. He was evaluated by the Hematology Department to initiate R-CHOP chemotherapy. During his outpatient follow-up, he reported no further episodes of melena or hematemesis. To the best of our knowledge, there have only been two published case reports of large B-cell lymphoma causing upper gastrointestinal bleeding from isolated gastric varices. These cases were treated with splenectomy or

  7. Helicobacter pylori Infection Induces Genetic Instability of Nuclear and Mitochondrial DNA in Gastric Cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel; Figueiredo, Ceu; Touati, Eliette;

    2009-01-01

    Purpose: Helicobacter pylori is a major cause of gastric carcinoma. To investigate a possible link between bacterial infection and genetic instability of the host genome, we examined the effect of H. pylori infection on known cellular repair pathways in vitro and in vivo. Moreover, various types...... of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. Experimental Design: We observed the effects of H pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. Results: Following H pylori infection, the activity and expression of base excision repair...

  8. Glycomic and sialoproteomic data of gastric carcinoma cells overexpressing ST3GAL4

    Directory of Open Access Journals (Sweden)

    Stefan Mereiter

    2016-06-01

    Full Text Available Gastric carcinoma MKN45 cells stably transfected with the full-length ST3GAL4 gene were characterised by glycomic and sialoproteomic analysis. Complementary strategies were applied to assess the glycomic alterations induced by ST3GAL4 overexpression. The N- and O-glycome data were generated in two parallel structural analyzes, based on PGC-ESI-MS/MS. Data on glycan structure identification and relative abundance in ST3GAL4 overexpressing cells and respective mock control are presented. The sialoproteomic analysis based on titanium-dioxide enrichment of sialopeptides with subsequent LC-MS/MS identification was performed. This analysis identified 47 proteins with significantly increased sialylation. The data in this article is associated with the research article published in Biochim Biophys Acta “Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer” [1].

  9. Glycomic and sialoproteomic data of gastric carcinoma cells overexpressing ST3GAL4.

    Science.gov (United States)

    Mereiter, Stefan; Magalhães, Ana; Adamczyk, Barbara; Jin, Chunsheng; Almeida, Andreia; Drici, Lylia; Ibáñez-Vea, Maria; Larsen, Martin R; Kolarich, Daniel; Karlsson, Niclas G; Reis, Celso A

    2016-06-01

    Gastric carcinoma MKN45 cells stably transfected with the full-length ST3GAL4 gene were characterised by glycomic and sialoproteomic analysis. Complementary strategies were applied to assess the glycomic alterations induced by ST3GAL4 overexpression. The N- and O-glycome data were generated in two parallel structural analyzes, based on PGC-ESI-MS/MS. Data on glycan structure identification and relative abundance in ST3GAL4 overexpressing cells and respective mock control are presented. The sialoproteomic analysis based on titanium-dioxide enrichment of sialopeptides with subsequent LC-MS/MS identification was performed. This analysis identified 47 proteins with significantly increased sialylation. The data in this article is associated with the research article published in Biochim Biophys Acta "Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer" [1].

  10. Dendritic Cells as Vectors for Immunotherapy of Tumor and Its Application for Gastric Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    YugangWu; LiangWang; YanyunZhang

    2004-01-01

    Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells (APCs) with the ability to stimulate naive resting T cells and initiate primary immune responses. DCs are poised to capture antigen (Ag),migrate to draining lymphoid organs, and, after a process of maturation, select Ag-specific lymphocytes to which they present the processed Ag, thereby inducing immune responses. Numerous studies indicated that immunotherapies utilizing DC-presenting tumor-associated antigens can safely be administered to cancer patients and induce significant immunologic and clinical responses. Moreover, it has been demonstrated that DCs are related to clinical stage, invasion, metastasis and prognosis of gastric cancer. DC-based tumor vaccines become a new effective immunoadjuvant therapy for gastric cancer. Cellular & Molecular Immunology. 2004;1(5):351-356.

  11. Dendritic Cells as Vectors for Immunotherapy of Tumor and Its Application for Gastric Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Yugang Wu; Liang Wang; Yanyun Zhang

    2004-01-01

    Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells (APCs) with the ability to stimulate na(i)ve resting T cells and initiate primary immune responses. DCs are poised to capture antigen (Ag),migrate to draining lymphoid organs, and, after a process of maturation, select Ag-specific lymphocytes to which they present the processed Ag, thereby inducing immune responses. Numerous studies indicated that immunotherapies utilizing DC-presenting tumor-associated antigens can safely be administered to cancer patients and induce significant immunologic and clinical responses. Moreover, it has been demonstrated that DCs are related to clinical stage, invasion, metastasis and prognosis of gastric cancer. DC-based tumor vaccines become a new effective immunoadjuvant therapy for gastric cancer. Cellular & Molecular Immunology. 2004;1(5):351-356.

  12. Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Ceu; Touati, Eliette;

    2009-01-01

    PURPOSE: Helicobacter pylori is a major cause of gastric carcinoma. To investigate a possible link between bacterial infection and genetic instability of the host genome, we examined the effect of H. pylori infection on known cellular repair pathways in vitro and in vivo. Moreover, various types...... of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. EXPERIMENTAL DESIGN: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. RESULTS: Following H. pylori infection, the activity and expression of base excision repair...

  13. The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo.

    Science.gov (United States)

    Kato, Kiyohito; Gong, Jian; Iwama, Hisakazu; Kitanaka, Akira; Tani, Joji; Miyoshi, Hisaaki; Nomura, Kei; Mimura, Shima; Kobayashi, Mitsuyoshi; Aritomo, Yuuichi; Kobara, Hideyuki; Mori, Hirohito; Himoto, Takashi; Okano, Keiichi; Suzuki, Yasuyuki; Murao, Koji; Masaki, Tsutomu

    2012-03-01

    Recent studies suggest that metformin, which is commonly used as an oral anti-hyperglycemic agent of the biguanide family, may reduce cancer risk and improve prognosis, but the mechanisms by which metformin affects various cancers, including gastric cancer, remains unknown. The goal of the present study was to evaluate the effects of metformin on human gastric cancer cell proliferation in vitro and in vivo and to study microRNAs (miRNA) associated with antitumor effect of metformin. We used MKN1, MKN45, and MKN74 human gastric cancer cell lines to study the effects of metformin on human gastric cancer cells. Athymic nude mice bearing xenograft tumors were treated with or without metformin. Tumor growth was recorded after 4 weeks, and the expression of cell-cycle-related proteins was determined. In addition, we used miRNA array tips to explore the differences among miRNAs in MKN74 cells bearing xenograft tumors treated with or without metformin in vitro and in vivo. Metformin inhibited the proliferation of MKN1, MKN45, and MKN74 in vitro. Metformin blocked the cell cycle in G(0)-G(1)in vitro and in vivo. This blockade was accompanied by a strong decrease of G(1) cyclins, especially in cyclin D1, cyclin-dependent kinase (Cdk) 4, Cdk6 and by a decrease in retinoblastoma protein (Rb) phosphorylation. In addition, metformin reduced the phosphorylation of epidermal growth factor receptor and insulin-like growth factor-1 receptor in vitro and in vivo. The miRNA expression was markedly altered with the treatment of metformin in vitro and in vivo. Various miRNAs altered by metformin also may contribute to tumor growth in vitro and in vivo. PMID:22222629

  14. Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Chaudhary Prakash

    2010-10-01

    Full Text Available Abstract Background The National Comprehensive Cancer Network (NCCN guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells. Methods Human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823 were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB, vascular endothelial growth factor (VEGF, cyclooxygenase 2 (COX-2, and epidermal growth factor receptor (EGFR were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR. Results Propranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression. Conclusions Taken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway.

  15. The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Highlights: ► Zebularine inhibited cell growth of gastric cancer in a time- and dose-dependent manner. ► Chromatin condensation and nuclear fragmentation were induced. ► Zebularine promoted apoptosis via mitochondrial pathways. ► Tumorigenicity was inhibited by zebularine. -- Abstract: DNA methyltransferase (DNMT) inhibitor zebularine has been reported to potentiate the anti-tumor effect by reactivating the expression of tumor suppressor genes and apoptosis-related genes in various malignant cells. However, the apoptotic signaling pathway in gastric cancer cells induced by zebularine is not well understood. In the study, the effects of zebularine on the growth and apoptosis of gastric cancer cells were investigated by MTT assay, Hoechst assay, Western blot analysis, flow cytometric analysis of annexin V-FITC/PI staining, and TUNEL assay. Zebularine was an effective inhibitor of human gastric cancer cells proliferation in vitro and in vivo. The effects were dose dependent. A zebularine concentration of 50 μM accounted for the inhibition of cell proliferation of 67% at 48 h. The treatment with zebularine upregulated Bax, and decreased Bcl-2 protein. Caspase-3 was activated, suggesting that the apoptosis is mediated by mitochondrial pathways. Moreover, zebularine injection successfully inhibited the tumor growth via apoptosis induction which was demonstrated by TUNEL assay in xenograft tumor mouse model. These results demonstrated that zebularine induced apoptosis in gastric cancer cells via mitochondrial pathways, and zebularine might become a therapeutic approach for the treatment of gastric cancer.

  16. Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro

    International Nuclear Information System (INIS)

    The National Comprehensive Cancer Network (NCCN) guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because gastric cancer demonstrates limited sensitivity to radiotherapy, a radiosensitizer might therefore be useful to enhance the radiosensitivity of patients with advanced gastric carcinoma. In this study, we evaluated if propranolol, a β-adrenoceptor (β-AR) antagonist, could enhance radiosensitivity and explored its precise molecular mechanism in gastric cancer cells. Human gastric adenocarcinoma cell lines (SGC-7901 and BGC-823) were treated with or without propranolol and exposed to radiation. Cell viability and clonogenic survival assays were performed, and cell apoptosis was evaluated with flow cytometry. In addition, the expression of nuclear factor κB (NF-κB), vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and epidermal growth factor receptor (EGFR) were detected by western blot and real-time reverse transcription polymerase chain reaction (PCR). Propranolol combined with radiation decreased cell viability and clonogenic survivability. Furthermore, it also induced apoptosis in both cell lines tested, as determined by Annexin V staining. In addition, treatment with propranolol decreased the level of NF-κB and, subsequently, down-regulated VEGF, COX-2, and EGFR expression. Taken together, these results suggested that propranolol enhanced the sensitivity of gastric cancer cells to radiation through the inhibition of β-ARs and the downstream NF-κB-VEGF/EGFR/COX-2 pathway

  17. The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Wei, E-mail: polo5352877@163.com [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan (China); Zhou, Wei; Yu, Hong-gang; Luo, He-Sheng; Shen, Lei [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan (China)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Zebularine inhibited cell growth of gastric cancer in a time- and dose-dependent manner. Black-Right-Pointing-Pointer Chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Zebularine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by zebularine. -- Abstract: DNA methyltransferase (DNMT) inhibitor zebularine has been reported to potentiate the anti-tumor effect by reactivating the expression of tumor suppressor genes and apoptosis-related genes in various malignant cells. However, the apoptotic signaling pathway in gastric cancer cells induced by zebularine is not well understood. In the study, the effects of zebularine on the growth and apoptosis of gastric cancer cells were investigated by MTT assay, Hoechst assay, Western blot analysis, flow cytometric analysis of annexin V-FITC/PI staining, and TUNEL assay. Zebularine was an effective inhibitor of human gastric cancer cells proliferation in vitro and in vivo. The effects were dose dependent. A zebularine concentration of 50 {mu}M accounted for the inhibition of cell proliferation of 67% at 48 h. The treatment with zebularine upregulated Bax, and decreased Bcl-2 protein. Caspase-3 was activated, suggesting that the apoptosis is mediated by mitochondrial pathways. Moreover, zebularine injection successfully inhibited the tumor growth via apoptosis induction which was demonstrated by TUNEL assay in xenograft tumor mouse model. These results demonstrated that zebularine induced apoptosis in gastric cancer cells via mitochondrial pathways, and zebularine might become a therapeutic approach for the treatment of gastric cancer.

  18. Gastric adenocarcinoma of fundic gland type: Endoscopic and clinicopathological features.

    Science.gov (United States)

    Tohda, Gen; Osawa, Takeshi; Asada, Yasuyuki; Dochin, Masaki; Terahata, Shintarou

    2016-02-25

    Gastric adenocarcinoma of fundic gland type (GA-FG) with chief cell differentiation was recently proposed as an extremely rare type of gastric adenocarcinoma. Here, we report 4 cases of GA-FG with chief cell differentiation. Endoscopic features included a submucosal tumor shape or a flat shape, whitish discoloration and dilated vessels on the surface. The tumors were located in the upper or middle third of the stomach. All cases were preoperatively diagnosed as GA-FG by biopsy, and endoscopic submucosal dissection was performed. Resected specimens revealed well-differentiated adenocarcinomas resembling chief cells. Tumor cells were diffusely positive for pepsinogen-I, but partially positive for H(+)/K(+)-ATPase in scattered locations around the tumor margin. Despite the presence of minimal invasion of the carcinoma into the submucosal layer, which was observed in two cases, neither lymphatic nor venous invasion was detected in any of the cases. Finally, all cases showed less aggressive clinical behavior with low grade malignancy. PMID:26962407

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

    Institute of Scientific and Technical Information of China (English)

    张珊文; 肖绍文; 吕有勇

    2003-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Ming [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Department of Oncology, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu (China); Gao, Wen; Xu, Jing; Wang, Ping [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Shu, Yongqian, E-mail: shuyongqian39000@163.com [Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China)

    2014-06-06

    Graphical abstract: - Highlights: • H19 regulates gastric cancer cell proliferation phenotype via miR-675. • MiR-675 modulates cell proliferation of gastric cancer cells by targeting tumor suppressor RUNX1. • The H19/miR-675/RUNX1 axis plays an important role in the tumorigenesis of gastric cancer. - Abstract: The lncRNA H19 has been recently shown to be upregulated and play important roles in gastric cancer tumorigenesis. However, the precise molecular mechanism of H19 and its mature product miR-675 in the carcinogenesis of gastric cancer remains unclear. In this study, we found that miR-675 was positively expressed with H19 and was a pivotal mediator in H19-induced gastric cancer cell growth promotion. Subsequently, the tumor suppressor Runt Domain Transcription Factor1 (RUNX1) was confirmed to be a direct target of miR-675 using a luciferase reporter assay and Western blotting analyses. A series of rescue assays indicated that RUNX1 mediated H19/miR-67-induced gastric cancer cell phenotypic changes. Moreover, the inverse relationship between the expression of RUNX1 and H19/miR-675 was also revealed in gastric cancer tissues and gastric cancer cell lines. Taken together, our study demonstrated that the novel pathway H19/miR-675/RUNX1 regulates gastric cancer development and may serve as a potential target for gastric cancer therapy.

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

    International Nuclear Information System (INIS)

    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

  2. Isolation of melittin from bee venom and evaluation of its effect on proliferation of gastric cancer cells

    OpenAIRE

    Mahmoodzadeh A; Morady A; Zarrinnahad H; Pooshang Bagheri K; Ghasemi-Dehkordi P; Mahdavi M; Shahbazzadeh D; Shahmorady H

    2013-01-01

    Background: Gastric cancer (GC) is one of the most common cancers worldwide and in Iran. Conventional therapies are surgery and chemotherapy. Current studies are evaluating natural compounds in inhibiting growth of cancer cell. In this study isolated peptide melittin with 26 amino acids from bee venom and its impact on the viability and proliferation of gastric cancer cells was investigated. Methods: At first melittin was purified from honeybee venom using a reversed-phase high performance li...

  3. A Case of Successful Remission of Extensive Primary Gastric Diffuse Large B Cell Lymphoma: Radiologic, Endoscopic and Pathologic Evidence

    Directory of Open Access Journals (Sweden)

    Mike M. Bismar

    2014-04-01

    Full Text Available Though rare amongst stomach neoplasms, primary gastric diffuse large B cell lymphoma is one of the commonest extranodal non-Hodgkin lymphomas. If left untreated, it can have a devastating progression and life-threatening consequences. We present the case of a successfully treated large antral ulcer confirmed to be large B cell lymphoma as evidenced by radiologic, endoscopic and histopathologic findings. A brief discussion about the types of gastric lymphoma, their Helicobacter pylori relation and therapeutic modalities follows.

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

    OpenAIRE

    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...

  5. Aldehyde dehydrogenase 3A1 is robustly upregulated in gastric cancer stem-like cells and associated with tumorigenesis.

    Science.gov (United States)

    Wu, Di; Mou, Yi-Ping; Chen, Ke; Cai, Jia-Qin; Zhou, Yu-Cheng; Pan, Yu; Xu, Xiao-Wu; Zhou, Wei; Gao, Jia-Qi; Chen, Ding-Wei; Zhang, Ren-Chao

    2016-08-01

    Enhanced aldehyde dehydrogenase (ALDH) activity has been shown to serve as a hallmark for cancer stem cells (CSCs). Recent evidence suggests that its role as a stem cell-related marker has come down to the specific isoform. However, little is known about the specific ALDH isoform contributing to aldefluor activity in gastric cancer. In this study, we isolated ALDHbright cells from 2 human gastric cancer cell lines MKN-45 and SGC‑7901 by using an Aldefluor assay and found elevated self-renewal, differentiation and tumorigenicity, as demonstration of stemness characteristics. We also found that ALDHbright cells expressed decreased levels of E-cadherin but increased levels of Snail and Vimentin, indication of an epithelial-mesenchymal transition (EMT) phenotype which may be responsible for the enhanced metastatic potential. Since further research and prognostic application based on ALDH prevalence require the quantification of the specific ALDH isoform, we characterized the expression of all 19 ALDH isoforms in the sorted gastric cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Compared with the non-stem counterparts, robust upregulation of ALDH-3A1 was observed in these gastric cancer stem-like cells. Furthermore, we performed immunohistological analysis on 93 fixed patient gastric tumor samples and found that ALDH-3A1 expression correlated well with gastric cancer dysplasia and grades, differentiation, lymph node metastasis and cancer stage. Our data, therefore, provide strong evidence that ALDH-3A1 is a novel gastric cancer stem cell related marker with potential prognostic values and demonstrate a clear association between ALDH-3A1 prevalence and gastric cancer progression. PMID:27279633

  6. Phenotypic classification of gastric signet ring cell carcinoma and its relationship with clinicopathologic parameters and prognosis

    Institute of Scientific and Technical Information of China (English)

    Meng-Meng Tian; Ai-Lian Zhao; Zhong-Wu Li; Ji-You Li

    2007-01-01

    AIM: To distinguish subtypes of gastric signet ring cell(SRC) carcinoma by investigating the expression of gastric and intestinal phenotypic markers, and to study the significance of phenotypic classification in predicting tumor progression and outcome.METHODS: Immunohistochemistry was performed in 66 cases of SRC carcinoma with MUC2. VILLIN, CDX2, Licadherin antibodies as intestinal phenotype markers and MUC5AC, HGM, MUC6 antibodies as gastric phenotype markers, and the relationship was analyzed between the phenotypic expression pation and clinicopathologic parameters, as well as the 3-year survival rate.RESULTS: Expression of intestinal phenotypic markers was positively associated with tumor size, wall invasion,vascular invasion, lymph node metastasis and tumornode-metastasis (TNM) stage. Cases expressing one or more intestinal markers had a significant lower survival rate than cases expressing none of the intestinal markers.CONCLUSION: The SRC carcinomas expressing intestinal phenotype markers exhibited a high proliferative potential, bad biological behaviors and poor prognosis. Examination of phenotype expression may be useful in distinguishing histological type and in prediciting the prognosis of gastric SRC carcinoma.

  7. Mast cell density and the context of clinicopathological parameters and expression of p185,estrogen receptor,and proliferating cell nuclear antigen in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying-AnJiang; You-YuanZhang; He-ShengLuo; Shou-FuXing

    2002-01-01

    AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.

  8. Crosstalk between EGFR and integrin affects invasion and proliferation of gastric cancer cell line, SGC7901

    Directory of Open Access Journals (Sweden)

    Dan L

    2012-10-01

    Full Text Available Li Dan,1,* Ding Jian,2,* Lin Na,1 Wang Xiaozhong,1 1Digestive Department, the Union Hospital of Fujian Medical University, Fujian, People’s Republic of China; 2Digestive Department, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workBackground/objective: To investigate the crosstalk between epidermal growth factor receptor (EGFR and integrin-mediated signal transduction pathways in human gastric adenocarcinoma cells.Methods: EGF was used as a ligand of EGFR to stimulate the gastric adenocarcinoma cell, SGC7901. Signal molecules downstream of the integrin, FAK(Y397 and p130cas(Y410 phosphorylation, were measured by immunoprecipitation and western blot. Fibronectin (Fn was used as a ligand of integrin to stimulate the same cell line. Signal molecules downstream of EGFR and extracellular signal-regulated kinase (ERK general phosphorylation were also measured. Focal adhesion kinase (FAK small-interfering RNA was designed and transfected into SGC7901 cells to decrease the expression of FAK. Modified Boyden chambers and MTT assay were used to examine the effect of FAK inhibition on the invasiveness and proliferation of SGC7901.Results: EGF activated FAK(Y397 and p130cas(Y410 phosphorylation, while Fn activated ERK general phosphorylation. Inhibition of FAK expression decreased p130cas(Y410 phosphorylation activated by EGF and ERK general phosphorylation activated by Fn, also decreased the invasiveness and proliferation of SGC7901 cells activated by EGF or Fn.Conclusion: There is crosstalk between EGFR and integrin signal transduction. FAK may be a key cross point of the two signal pathways and acts as a potential target for human gastric cancer therapy.Keywords: gastric adenocarcinoma, epidermal growth factor receptor, integrin, focal adhesion kinase, crosstalk

  9. Oxaliplatin triggers necrosis as well as apoptosis in gastric cancer SGC-7901 cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Ping; Zhu, Xueping [Department of Immunology, Anhui Medical University, Hefei 230032 (China); Jin, Wei [Department of Otolaryngology, Chaohu Hospital of Anhui Medical University, Chaohu 238000 (China); Hao, Shumei; Liu, Qi [Department of Immunology, Anhui Medical University, Hefei 230032 (China); Zhang, Linjie, E-mail: zlj33@ahmu.edu.cn [Department of Immunology, Anhui Medical University, Hefei 230032 (China)

    2015-05-01

    Intrinsic apoptotic pathway is considered to be responsible for cell death induced by platinum anticancer drugs. While in this study, we found that, necrosis is an indispensable pathway besides apoptosis in oxaliplatin-treated gastric cancer SGC-7901 cells. Upon exposure to oxaliplatin, both apoptotic and necrotic features were observed. The majority of dead cells were double positive for Annexin V and propidium iodide (PI). Moreover, mitochondrial membrane potential collapsed and caspase cascades were activated. However, ultrastructural changes under transmission electron microscope, coupled with the release of cellular contents, demonstrated the rupture of the plasma membrane. Oxaliplatin administration did not stimulate reactive oxygen species (ROS) production and autophagy, but elevated the protein level of Bmf. In addition, receptor interacting protein 1 (RIP1), but not receptor interacting protein 3 (RIP3) and its downstream components participated in this death process. Necrostatin-1 (Nec-1) blocked oxaliplatin-induced cell death nearly completely, whereas z-VAD-fmk could partially suppress cell death. Oxaliplatin treatment resulted in poly(ADP-ribose) polymerase-1 (PARP-1) overactivation, as indicated by the increase of poly(ADP-ribose) (PAR), which led to NAD{sup +} and ATP depletion. PARP-1 inhibitor, olaparib, could significantly block oxaliplatin-induced cell death, thus confirming that PARP-1 activation is mainly responsible for the cytotoxicity of oxaliplatin. Phosphorylation of H2AX at Ser139 and translocalization of apoptosis-inducing factor (AIF) are critical for this death process. Taken together, these results indicate that oxaliplatin can bypass canonical cell death pathways to kill gastric cancer cells, which may be of therapeutic advantage in the treatment of gastric cancer. - Highlights: • Oxaliplatin induces apoptotic and necrotic cell death. • Nec-1 can inhibit oxaliplatin-induced cell death nearly completely. • RIP3 and its

  10. Effects of transforming growth interacting factor on biological behaviors of gastric carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Zhong-Liang Hu; Ji-Fang Wen; De-Sheng Xiao; Hui Zhen; Chun-Yan Fu

    2005-01-01

    AIM:Transforming growth interacting factor (TGIF) is an inhibitor of both transforming growth factor β (TGF-β) and retinoid signaling pathways. Moreover, the activation of MAPK pathway can prolong its half-life. However, its role in carcinogenesis is still unknown. Thus we attempted to investigate the effect of TGIF on biologic behaviors of gastric carcinoma cells.METHODS: Gastric carcinoma cell line, SGC-7901, was stably transfected with plasmid PcDNA3.1-TGIF. Western blotting and cell immunohistochemistry screening for the highly expressing clone of TGIF were employed. The growth of transfected cells was investigated by MTT and colonyformation assays, and apoptosis was measured by flow cytometry (FCM) and transmission electron microscopy.Tumorigenicity of the transfectant cells was also analyzed.RESULTS: TGIF had no effect on the proliferation, cell cycle and apoptosis of SGC-7901 cells, but cellular organelles of cells transfected with TGIF were richer than those of vector control or parental cells. Its clones were smaller than the control ones in plate efficiency, and its tumor tissues also had no obvious necrosis compared with the vector control or parental cells. Moreover, TGIF could resist TGF-β mediated growth inhibition.CONCLUSION: TGIF may induce differentiation of stomach neoplastic cells. In addition, TGIF can counteract the growth inhibition induced by TGF-β.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  12. SKI-II reverses the chemoresistance of SGC7901/DDP gastric cancer cells.

    Science.gov (United States)

    Liu, Ying; Zhu, Zuan; Cai, Hongxing; Liu, Qinghua; Zhou, Honglian; Zhu, Zhengqiu

    2014-07-01

    Cisplatin is frequently used in treating gastric cancers; however, acquired resistance to the drug often reduces the efficacy of therapy. The present study analyzed the efficacy of the combination of 4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol (SKI-II) and cisplatin [cis-diamminedichloroplatinum (II); DDP] on the gastric cancer SGC7901/DDP cell line. The results revealed that SKI-II and DDP had a clear synergistic effect. Glutathione (GSH) and glutathione S-transferase (GST) levels decreased significantly subsequent to the cells being treated with the combination of DDP and SKI-II compared with the cells that were treated with DDP or SKI-II alone. Phosphorylated extracellular-signal-regulated kinase (p-ERK) and phosphorylated c-Jun N-terminal kinase (p-JNK) expression levels also decreased following treatment with SKI-II. The results suggested that SKI-II is able to reverse the drug resistance in human gastric carcinoma cells and enhance the antitumor effect of DDP through the ras/mitogen-activated protein kinase (MAPK) proliferation pathway.

  13. Citrus Reticulata blanco induces apoptosis in human gastric cancer cells SNU-668.

    Science.gov (United States)

    Kim, Mi-Ja; Park, Hae Jeong; Hong, Mee Suk; Park, Hi-Joon; Kim, Min-Su; Leem, Kang-Hyun; Kim, Jeung-Beum; Kim, Youn Jung; Kim, Hye Kyung

    2005-01-01

    Citrus fruits have been known to reduce the proliferation of many cancer cells. The antiproliferative effects of Citrus reticulata Blanco (CR) extract, the immature tangerine peel, on human gastric cancer cell line SNU-668 were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidineo-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, reverse transcription-polymerase chain reaction expressions of BCL-2, BAX and CASP-3 genes, caspase-3 activity, and immunocytochemistry of caspase-3. From the results of the morphological and biochemical assays, CR (50 microg/ml) increased the apoptosis of human gastric cancer cells with typical apoptotic characteristics, including morphological changes of chromatin condensation and apoptotic body formation. CR (50 microg/ml) reduced the expression of BCL-2, whereas the expression of BAX and CASP-3 was increased compared with the control group. Furthermore, caspase-3 activity and caspase-3 protein expression in the CR-treated group was significantly increased compared with that in control group. These results suggest that CR may induce the apoptosis through the caspase-3 pathway in human gastric cancer cells. PMID:15749633

  14. Gastric Small-Cell Carcinoma Found on Esophagogastroduodenoscopy: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Natassja Frances

    2013-01-01

    Full Text Available Introduction. Characterized as an undifferentiated, neuroendocrine tumor arising from totipotent stem cells, small-cell carcinoma (SCC most commonly arises from the lung. Extrapulmonary small-cell carcinomas (ESCC are rare and account for only four percent of SCC. Gastric ESCC, more commonly seen in Japanese male patients in their seventh decade of life, accounts for approximately 0.1 percent of ESCC. Case Presentation. A 75-year-old Hispanic male presented with a several week history of worsening epigastric pain with nausea and vomiting. Computer tomography (CT of the abdomen and pelvis showed a large heterogeneous mass involving the posterior gastric wall with diffuse extension into the gastric cardia. Esophagogastroduodenoscopy (EGD revealed a large fungating mass in the lesser curvature of the stomach. Biopsy of the mass revealed small-cell carcinoma of the stomach. The patient was diagnosed with extensive/stage 4 disease and started on chemoradiation. Discussion. Our case, of a very rare condition highlights, the importance of recognizing atypical pathologic diagnoses. More research will need to be conducted with GSCC patients in order to better characterize disease pathogenesis, genetic mutations, and optimal disease management. The hope is to identify biomarkers that will identify patients earlier in their disease course when cure is possible.

  15. Efficacy of a Hypotonic Treatment for Peritoneal Dissemination from Gastric Cancer Cells: An In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Atsushi Shiozaki

    2014-01-01

    Full Text Available The aim of the present study was to determine the efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells using an in vivo model. We firstly evaluated the toxicity of a peritoneal injection of distilled water (DW (2 mL for 3 days in mice. Macroscopic and microscopic examinations revealed that the peritoneal injection of DW did not severely damage the abdominal organs of these mice. MKN45 gastric cancer cells preincubated with NaCl buffer or DW for 20 minutes in vitro were then intraperitoneally injected into nude mice, and the development of dissemination nodules was analyzed. The total number, weight, and volume of the dissemination nodules were significantly decreased by the DW preincubation. We then determined whether the peritoneal injection of DW inhibited the establishment of peritoneal dissemination. After a peritoneal injection of MKN45 cells into nude mice, NaCl buffer or DW was injected into the abdominal cavity for 3 days. The total volume of dissemination nodules was significantly lower in DW-injected mice than in NaCl-injected mice. In conclusion, we demonstrated the safeness of a peritoneal injection of DW. Furthermore, the development of dissemination nodules from gastric cancer cells was prevented by a preincubation with or peritoneal injection of DW.

  16. Detection of cancer cells and tumor markers in gastric lavage of patients with gastric cancer: Do these findings have a clinicopathological significance and oncological implication?

    Science.gov (United States)

    Virgilio, Edoardo; Giarnieri, Enrico; Montagnini, Monica; D'Urso, Rosaria; Proietti, Antonella; Mesiti, Alessandra; Giovagnoli, Maria Rosaria; Mercantini, Paolo; Cavallini, Marco; Balducci, Genoveffa

    2016-09-01

    Although decreasing in the incidence over the last years, currently gastric adenocarcinoma represents the second cause of cancer related-death worldwide. Further knowledge and novel therapies are desperately needed in order to make the prognosis of these patients more acceptable. Infact, even though in recent years numerous staging parameters have been largely studied and unanimously recognized for their clinical and prognostic value, today too many shadows still exist around the capacity to predict exactly the natural history or post-treatment behavior of this cancer even among patients of the same stage. This study has identified the presence of isolated cancer cells as well as tumor markers (CEA, Ca 19.9, Ca 72.4 and Ca 50) from the gastric lavage of patients affected by gastric adenocarcinoma. Such findings led to the hypothesis that endoluminal exfoliation of neoplastic cells and the release of their products (tumor markers) into the gastric juice might be an expression of neoplastic behavior as well as aggressive malignancy. Should this hypothesis become a reality, some important progress could be made in the knowledge, staging, prediction as well as management and follow-up of this inauspicious type of cancer. PMID:27515187

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    OpenAIRE

    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....

  20. Extrapulmonary small cell gastric carcinoma. A case report and review of the literature

    International Nuclear Information System (INIS)

    The described case of small cell gastric carcinoma, limited in stage at the time of diagnosis, had an excellent response to ACE chemotherapy resulting in a complete remission. Elevated calcitonin levels, detected at diagnosis, fell to normal with treatment. He remained without evidence of disease until relapse at 11 months and, with second line cytotoxic agents and subsequent palliative radiotherapy, survived a further 11 months. (orig./MG)

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

    OpenAIRE

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

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 μM) for 24 hr induced...

  2. Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer

    OpenAIRE

    Pengfei Kong; Ruiyan Wu; Chenlu Yang; Qirong Geng; Jianjun Liu; Shangxiang Chen; Xuechao Liu; Minting Ye; Wenzhuo He; Qiong Yang; Liangping Xia; Dazhi Xu

    2016-01-01

    Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC p...

  3. Aberrant expression of nuclear matrix proteins during HMBA-induced differentiation of gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the aberrant expression of nuclear matrix proteins in human gastric cancer cells before and after hexamethylene bisacetamide (HMBA) treatment.METHODS: Proteomics analysis of differential nuclear matrix proteins was performed by two dimensional electrophoresis polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.The expression levels of three nuclear matrix proteins were further confirmed by Western blotting and their location...

  4. Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin.

    Science.gov (United States)

    Shi, Rongliang; Yang, Zhen; Liu, Weiyan; Liu, Bingya; Xu, Ziping; Zhang, Ziping

    2014-02-01

    We previously showed that Slit2 was highly expressed in gastric cancer tissues that exhibit less advanced clinicopathological features, suggesting a tumor suppressor role for Slit2. In the present study, we investigated the effects of Slit2 knockdown on gastric cancer cells. Slit2-specific shRNAs were used to generate Slit2-knockdown SGC-7901 gastric cancer cells. Cell proliferation assay, Annexin V/PI double staining and cell cycle analysis were used to investigate the role of Slit2 knockdown in cell growth. Wound-healing and in vitro migration/invasion assays were performed. Subcutaneous tumor formation and peritoneal spreading in nude mice were employed to examine the in vivo effects of Slit2 knockdown. Cell signaling changes induced by Slit2 knockdown were analyzed by immunoblotting. Slit2 knockdown increased gastric cancer cell growth in monolayer and soft agar/Matrigel 3D culture. Slit2 knockdown inhibited apoptosis but did not alter cell cycle progression. Slit2-knockdown cells formed larger tumors and produced more peritoneal metastatic nodules in nude mice. Slit2 knockdown increased AKT phosphorylation, activated anti-apoptotic signaling, suppressed GSK3β activity and induced β-catenin activation. Blocking the effects of PI3K/AKT using pharmacological inhibitors abolished the ability of Slit2 knockdown to induce apoptosis resistance and cell migration/invasion. These results indicate that Slit2 knockdown promotes gastric cancer growth and metastasis through activation of the AKT/β‑catenin-mediated signaling pathway.

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

    Institute of Scientific and Technical Information of China (English)

    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

  6. 15d-PGJ2 inhibits cell growth and induces apoptosis of MCG-803 human gastric cancer cell line

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  7. Effects of H pylori infection on gap-junctional intercellular communication and proliferation of gastric epithelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To explore the effects of H pylori infection on gap-junctional intercellular communication (GJIC) and proliferation of gastric epithelial cells in vitro. METHODS: A human gastric epithelial cell line (SGC-7901) cultured on coverslips was exposed overnight to intact H pylori (CagA+ or CagA- strains) and sonicated extracts, respectively. GJIC between the cells was detected by fluorescence redistribution after photobleaching (FRAP) technique. Proliferation of SGC cells was determined by methylthiazolyl tetrazolium (MTT)assay.RESULTS: When compared with control in which cells were cultured with simple medium alone, both CagA+ and CagA- H pylori isolates could inhibit GJIC (CagA+:F = 57.98, P < 0.01; CagA-: F = 29.59, P < 0.01) and proliferation (CagA+: F = 42.65, P < 0.01; CagA-: F =58.14, P < 0.01) of SGC-7901 cells. Compared with CagA- strains, CagA+ H pylori more significantly downregulated GJIC of gastric cells (intact H pylori: t = 13.86,P < 0.01; sonicated extracts: t = 11.87, P < 0.01) and inhibited proliferation gastric cells to a lesser extent in vitro (intact H pylori: t = 3.06, P < 0.05; sonicated extracts: t = 3.94, P < 0.01).CONCLUSION: Compared with CagA- H pylori strains,CagA+ strains down-regulate GJIC of gastric epithelial cells more significantly and inhibit proliferation of gastric cells to a lesser extent in vitro. H pylori, especially CagA+ strains, may play an important role in gastric carcinogenesis.

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

    Science.gov (United States)

    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

  9. Comparison of peritoneal free gastric cancer cells' detecting rates between laparoscopically assisted and open radical gastrectomy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To compare laparoscopic gastrectomy and conventional surgery on the dissemination and seeding of tumor cells. Methods:Intraoperative peritoneal lavage cytologic examination was performed in 65 patients with gastric cancer, during laparoscopic gastrectomy (n=34) and conventional surgery (n=31). Cytology was examined twice, immediately after opening the peritoneal cavity and just before closing the abdomen. Saline was poured into the peritoneal cavity, and 100 ml fluid was retrieved after irrigation. Laparoscopic instruments were lavaged after surgery with 100 ml saline. Carbon dioxide (CO2) was derived through the trocar side orifice after pneumoperitoneum during laparoscopic gastrectomy and filtered through 100 ml saline. Cytologic examination of the filtrate was performed after the filtration process. Results: The incidence of positive cytology during laparoscopic surgery was 32.26% in the preoperative lavage and 22.58% in the postoperative lavage. The incidence of positive cytology during conventional surgery was 41.18% before lavage and 26.47% after lavage. Only one positive cytology was detected in the CO2 filtrate gas. The incidence of positive cytology in the lavage of the instruments during laparoscopic surgery was 6.45%. Conclusion: During gastric laparoscopic surgery, CO2 pneumoperitoneum does not affect tumor cell dissemination and seeding. In this study, laparoscopic techniques used in gastric cancer surgery were not associated with a higher risk for intraperitoneal dissemination of cancer cells than the conventional surgery.

  10. Ursolic Acid Inhibits the Proliferation of Gastric Cancer Cells by Targeting miR-133a.

    Science.gov (United States)

    Xiang, Fenfen; Pan, Chunying; Kong, Qianqian; Wu, Rong; Jiang, Jiemin; Zhan, Yueping; Xu, Jian; Gu, Xingang; Kang, Xiangdong

    2014-01-01

    Ursolic acid (UA), a potential chemotherapeutic agent, has the properties of inhibition of the growth of many human cancer cell lines. Whether UA can inhibit the growth and metastasis of human gastric cancer cells remains unknown. In this study, it was found that UA inhibited the growth and metastasis of human gastric cancer cells in vitro. Our results showed the increase of the percent of apoptotic cells and G1 phase, the inhibition of cell migrations well as the decrease of the expression of Bax, caspase 3 and Bcl-2 in BGC-823 cells after the treatment with UA. Real-time quantitative PCR analysis showed that UA treatment upregulated the level of miR-133a in BGC-823 cells. Overexpression of miR-133a increased the G1 phase of cell cycle and decreased Akt1 expression in BGC-823 cells. These outcomes might be secondary to the increased expression of miR-133a after the treatment with UA. PMID:26629938

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Yinxue Song; Jun Gong

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Characterization of gastric cancer models from different cell lines orthotopically constructed using improved implantation techniques

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Bo Li; Chun-Ping Xiang; Yu Zhang; Yuan-Yuan Li; Xiao-Ling Wu

    2012-01-01

    AIM: To develop orthotopic gastric cancer mouse models from different cell lines and characterize the tumor features to assist further in preclinical trials and clinical treatment strategies. METHODS: Human gastric cancer SGC-7901 and BGC- 823 cell suspensions were injected subcutaneously into nude mice to develop solid tumors, and tumor tissue pieces were then implanted under the serous coat of the stomach. An autopsy was performed on all animals of the SGC-7901 and BGC-823 models to observe the primary tumor growth and metastases using pathological and immunohistochemical methods. RESULTS: Both models showed large tumors in situ resulting in pressure and infiltration of the adjacent organs. The gastric cavity became smaller, along with stenosis of the cardia or pylorus. There were biological and statistical differences between the two models. The metastasis rate in involved organs (lymph nodes, kidney, spleen, testis) was significantly higher in the BGC-823 model compared to the SGC-7901 model (P < 0.05 or P < 0.01). The median survival of the BGC-823 model was shorter than that of SGC-7901 (23 d vs 84 d, P < 0.05). Histopathologically, the primary tumor and metastatic lesions of the two models showed obvious atypia and mucus in the cytoplasm. Compared with the SGC-7901 model, BGC-823 appeared more poorly differentiated (absence of adenoid structure), had a smaller volume, and richer capillary structure. Immunohistochemical staining revealed cytokeratin 20 and epithelial membrane antigen expression was positive in the SGC-7901 tumors, while negative in BGC-823 ones. CONCLUSION: Models using the SGC-7901 and BGC-823 cell lines were established which could function in gastric cancer research on carcinogenesis mechanism and drug discovery. The two models showed different tumor behavior and the latter was more malignant than the former.

  15. Angiostatin up-regulation in gastric cancer cell SGC7901 inhibits tumorigenesis in nude mice

    Institute of Scientific and Technical Information of China (English)

    Jing Wu; Yong-Quan Shi; Kai-Chun Wu; De-Xin Zhang; Jing-Hua Yang; Dai-Ming Fan

    2003-01-01

    AIM: To explore the influence of angiostatin up-regulationon the biologic behavior of gastric cancer cells in vitro andin vivo, and the potential of angiostatin gene therapy in thetreatment of human gastric cancer.METHODS: Mouse angiostatin cDNA was subcloned intothe eukaryotic expression vector pcDNA3.1(+) and identifiedby restriction endonucleases digestion and sequencing. Therecombinant vector pcDNA3. 1(+)-angio was transfected intohuman gastric cancer cells SGC7901 with liposome andparalleled with the vector control and the mock control.Angiostatin transcription and protein expression wereexamined by RT-PCR and Western blot in the stable celllines selected by G418. Cell proliferation and growth in vitroof the three groups were observed respectively undermicroscope, cell number counting and FACS. The cellsoverexpressing angiostatin, vector transfected and untreatedwere respectively implanted subcutaneously into nude mice.After 30days the size of tumors formed was measured, andmicrovessel density count (MVD) in the tumor tissues wasassessed by immunohistochemistry with the primary anti-vWF antibody.RESULTS: The recombinant vector pcDNA3.1(+)-angio wasconfirmed with the correct sequence of mouse angiostatinunder the promoter CMV. After 30 d of transfection andselection with G418, macroscopic resistant cell clones wereformed in the experimental group transfected with pcDNA3.1(+)-angio and the vector control. But no untreated cellssurvived in the mock control. Angiostatin mRNAtranscription and protein expression were detected in theexperimental group. No significant differences wereobserved among the three groups in cell morphology, cellgrowth curves and cell cycle phase distributions in vitro.However, in nude mice model, markedly inhibitedtumorigenesis and slowed tumor expansion were observedin the experimental group as compared with the controls,which was paralleled with decreased microvessel density inand around tumor tissues (P<0. 05).CONCLUSION: Angiostatin

  16. NR4A2 is regulated by gastrin and influences cellular responses of gastric adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kristine Misund

    Full Text Available The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2 expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1, suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    LIU Shao-ping; QIAN Wen-jun; MAO Wei-dong

    2014-01-01

    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 lfow cytometry. Results:In 0.01~30.00μg/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 30μg/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 0.01~30.00μg/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.

  20. Receptors for short-chain fatty acids in brush cells at the gastric groove

    Directory of Open Access Journals (Sweden)

    Julia Anna-Maria Eberle

    2014-04-01

    Full Text Available In the stomach of rodents clusters of brush cells are arranged at the gastric groove, immediately at the transition zone from the non-glandular reservoir compartment to the glandular digestive compartment. Based on their taste cell-like molecular phenotype it has been speculated that the cells may be capable to sense constituents of the ingested food, however, searches for nutrient receptors have not been successful. In this study, it was hypothesized that the cells may express receptors for short-chain fatty acids, metabolites generated by microorganisms during the storage of ingested food in the murine forestomach, which lacks the acidic milieu of more posterior regions of the stomach and is colonized with numerous microbiota. Experimental approaches, including RT-PCR analysis and immunohistochemical studies, revealed that the majority of these brush cells express the G-protein coupled receptor types GPR41 (FFAR3 and GPR43 (FFAR2, which are activated by short-chain fatty acids. Both, the GPR41 receptor proteins as well as an appropriate G-protein, α-gustducin, were found to be segregated at the apical brush border of the cells, indicating a direct contact with the luminal content of this gastric region. The exposure of microvillar processes with appropriate receptors and signaling elements to the gastric lumen suggests that the brush cells may in fact be capable to sense the short-chain fatty acids which originate from fermentation processes during the retention of ingested food in the anterior part of the stomach.

  1. Activation of JNK by TPA promotes apoptosis via PKC pathway in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yan Chen; Qiao Wu; Si-Yang Song; Wen-Jin Su

    2002-01-01

    AIM: JNK cascade plays an important role in cell proliferation, differentiation and apoptosis. However, the exact function of JNK cascade for apoptosis induction remains largely unknown. In this study, the role of JNK activation stimulated by TPA in the process of apoptosis induction and its signaling transduction pathway in gastric cancer cells were investigated and determined.METHODS: Expressions of mRNA and protein were detected by Northern blot and Western blot. Transcription activity was measured by transient transfection and CAT assay. Apoptotic cells were displayed through staining the nucleus with DAPI and were observed under fluorescence microscope. The apoptotic index was determined by counting 1000 cells randomly.RESULTS: JNK protein was stimulated rapidly by TPA, and reached its highest peak within 3 hr, then decreased in a time-dependent manner, but the expression level of JNK protein induced by TPA was always keeping higher than that in untreated cells. Similar pattern was seen in c-jun mRNA level induced by TPA. TPA significantly activated the transcriptional activity of activator protein-1 with a TPA-closedependent manner. Furthermore, activation of JNK was mediated through PKC pathway. Treatment of cells with PKC specific inhibitor, Wortmannin, led to repression of JNK even in the presence of TPA. More importantly, all these effects were associated with induction of apoptosis in gastric cancer cells. TPA inducted apoptosis obviously in gastric cancer cells. The apoptotic cells became smaller and rounded, and their nuclei became condensation and fragmentation with brightly stained chromatin. However, suppression of JNK by PKC specific inhibitor, Wortmannin, resulted in the decrease of apoptosis induced by TPA in a time-dependent manner, apoptotic index dramatically decreased from 32.56 % to 8.71%.CONCLUSION: TPA stimulates JNK cascade, including upregulation of JNK protein expression level and c-jun mRNA expression level, and activation of activator

  2. Secondary oesophageal or gastric cancer in patients treated for head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Anja Rosenlund; Bjerring, Ole Steen; Godballe, Christian;

    2016-01-01

    SPM. CONCLUSION: In this study, we confirm that there is an elevated risk of developing oesophageal and gastric cancer in the Danish population of patients with a cancer in the supraglottic or hypopharyngeal region. Therefore, we recommend close follow-up of these patients and a low threshold......INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) are at an elevated risk of developing second primary malignancies (SPM). Our objectives were to estimate the excess risk of oesophageal and gastric SPMs in patients with malignancies of the pharynx or larynx and, additionally.......004) and hypopharyngeal (OR = 3.9; p cancer compared with 3.4 years (95% CI: 3.1-4.3; range: 0.04-13.7) for patients without...

  3. Drain tube migration into the anastomotic site of an esophagojejunostomy for gastric small cell carcinoma: short report

    OpenAIRE

    Lin Long-Wei; Lo Chiao; Lai Peng-Sheng; Lee Po-Chu

    2010-01-01

    Abstract Background Intraluminal migration of a drain through an anastomotic site is a rare complication of gastric surgery. Case Presentation We herein report the intraluminal migration of a drain placed after a lower esophagectomy and total gastrectomy with Roux-en-Y anastomosis for gastric small cell carcinoma. Persistent drainage was noted 1 month after surgery, and radiographic studies were consistent with drain tube migration. Endoscopy revealed the drain had migrated into the esophagoj...

  4. Inhibition of the Wnt palmitoyltransferase porcupine suppresses cell growth and downregulates the Wnt/β-catenin pathway in gastric cancer

    OpenAIRE

    Mo, Min-Li; LI, MENG-RU; Chen, Zhao; LIU, XING-WEI; Sheng, Qing; Zhou, Hai-Meng

    2013-01-01

    Similarly to the Wnt protein palmitoyltransferase, porcupine (PPN) is essential to the activation of the Wnt/β-catenin signaling pathway. However, little is known about the role of PPN activity in human gastric cancer, one of the most common causes of cancer-related mortality. Real-time quantitative PCR was used to detect the expression levels of PPN in paired gastric cancer tissues. Cell proliferation, migration and invasion assays were performed following treatment using a newly developed s...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Too Many Chiefs

    Institute of Scientific and Technical Information of China (English)

    Joseph Schumpeter

    2010-01-01

    @@ When it comes to job titles, we live in an age of rampant inflation. Everybody you come across seems to be a chief or president of some variety. Title inflation is producing its own vocabulary: "uptitling" and "title-fluffing". It is also producing technological aids. One website provides a simple formula: just take your job title, mix in a few grand words, such as "global", "interface" and "customer", and hey presto.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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

  9. Selective killing of gastric cancer cells by a small molecule targeting ROS-mediated ER stress activation.

    Science.gov (United States)

    Zou, Peng; Xia, Yiqun; Chen, Tongke; Zhang, Junru; Wang, Zhe; Chen, Wenbo; Chen, Minxiao; Kanchana, Karvannan; Yang, Shulin; Liang, Guang

    2016-06-01

    Gastric cancer is one of the leading causes of cancer mortality in the world. Curcumin is a natural product with multiple pharmacological activities, while its clinical application has been limited by the poor chemical stability. We have previously designed a series of curcumin derivatives with high stability and anticancer potentials. The present study aims to identify the anti-cancer effects and mechanisms of WZ26, an analog of curcumin, in gastric cancer cells. In vitro, WZ26 showed higher chemical stability and much stronger anti-proliferative effects than curcumin, accompanied by dose-dependent induction of cell cycle arrest and apoptosis in gastric cancer cells. Mechanistically, the novel compound WZ26 induced ROS production, resulting in the activation of JNK-mitochondrial and ER stress apoptotic pathways. Blockage of ROS production totally reversed WZ26-induced JNK activation, Bcl-2/Bax decrease, ER stress activation, and final cell apoptosis in SGC-7901 cells. WZ26 also exhibited potent anti-tumor effects in human gastric cancer cell xenograft models. WZ26 could be considered as a potential chemotherapeutic agent for the treatment of advanced gastric cancer. In addition, this study also demonstrated that ROS production could be act as a vital candidate pathway for inducing tumor cell apoptosis by targeting mitochondrial and ER stress-related death pathway. © 2015 Wiley Periodicals, Inc. PMID:26086416

  10. Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Natália R Costa; Nuno Mendes; Nuno T Marcos; Celso A Reis; Thomas Caffrey; Michael A Hollingsworth; Filipe Santos-Silva

    2008-01-01

    AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells.METHODS:Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were performed to measure the adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with different VNTR lengths.RESULTS:Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher (P<0.05) adhesion to all the cell lines and clones tested,when compared to the non-pathogenic strain HPTx30a.Bacteria showed a significantly higher (P<0.05)adhesion to the GP202 cell line,when compared to the MKN45 cell line.Furthermore,both strains showed a significantly higher (P<0.05) adhesion to GP202 clones with larger MUC1 VNTR domains.CONCLUSION:This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells.The extent of bacterial adhesion depends on the size of the MUC1 VNTR domain.The adhesion is further dependent on bacterial pathogenicity and the gastric cell line.MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.

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

    International Nuclear Information System (INIS)

    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

  12. Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Tie Chen; Xinzu Chen; Fang Wang; Fan Zeng; Hong Xu; Jiankun Hu; Xianming Mo; Kun Yang; Jianhua Yu; Wentong Meng; Dandan Yuan; Feng Bi; Fang Liu; Jie Liu; Bing Dai

    2012-01-01

    Gastric cancer is the fourth most common cancer worldwide,with a high rate of death and low 5-year survival rate.To date,there is a lack of efficient therapeutic protocols for gastric cancer.Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation,invasion,metastasis,and resistance to anticancer therapies.Thus,therapies that target gastric CSCs are attractive.However,CSCs in human gastric adenocarcinoma (GAC)have not been described.Here,we identify CSCs in tumor tissues and peripheral blood from GAC patients.CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers,generated tumors that highly resemble the original human tumors when injected into immunodeficient mice,differentiated into gastric epithelial cells in vitro,and self-renewed in vivo and in vitro.Our findings suggest that effective therapeutic protocols must target GCSCs.The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis,and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.

  13. Effects of chitosan nanoparticle-mediated BRAF siRNA interference on invasion and metastasis of gastric cancer cells.

    Science.gov (United States)

    Huo, Jian

    2016-08-01

    To observe the changes in invasion capacity of gastric cancer BGC823 cells after being treated with chitosan-encapsulated BRAF siRNA nanoparticles, and to evaluate the effects of the nanoparticle-mediated BRAF siRNA interference on cell invasion and metastasis, BRAF siRNA was encapsulated with chitosan into nanoparticles sized 350 nm to treat gastric cancer cells. Silencing of BRAF was detected by Western blot and PCR, and cell invasion was observed by the Transwell assay. The nanoparticles significantly downregulated BRAF expression in BGC823 cells (P < 0.01) and inhibited their invasion (P < 0.001). Chitosan nanoparticle-mediated BRAF siRNA interference evidently reduced the invasion capacity of gastric cancers. PMID:25794798

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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

  17. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2

    Directory of Open Access Journals (Sweden)

    Zhang P

    2015-04-01

    Full Text Available Ping Zhang, He-Sheng Luo, Ming Li, Shi-yun Tan Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China Abstract: Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, flow cytometric analysis of annexin V–fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    OpenAIRE

    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...

  20. Detection of cancer cells in peripheral blood with nested RT-PCR and itssignificance in patients with gastric carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jia Zeng Xia; Hao Ran Yin; Zheng Gang Zhu; Min yan

    2000-01-01

    AIM To study the detection of micrometastasis in peripheral blood of patients with gastric carcinomas andits clinical significance.METHODS A cytokeratin 19 (CK19)-specific nested reverse transcriptase-polimerase chain reaction (RT-PCR) assay was developed to detect CK19 expressing cancer cells, the sensitivity was determined by serialdilution method using CK19 expressing gastric cancer cells, the specificity was assessed by examining 12negative controls and 12 positive controls. Then pre-operative peripheral blood from 42 patients with gastriccancer was detected and the relationship between positive results and biological behavior was studied.RESULTS CK19mRNA was expressed in all the 12 gastric cancer tissues but not in peripheral blood from12 healthy individuals;sensitivity of nested RT-PCR amplification for CK19mRNA was confirmed to be 1/106 by serial dilution method using human gastric cancer line SGC-7901; micrometastases in pre-operativeperipheral blood were detected in 13 (30,9%) patients with gastric carcinomas, the frequency ofmicrometastasis in peripheral blood was significantly correlated with tumor size,depth of invasion and TNMstage (x2 test, P<0.05).CONCLUSION Nested RT-PCR amplification for CK19mRNA is a sensitive and specific method for thedetection of micrometastases in peripheral blood in gastric cancer patients; pre-operative detection ofmicrometastasis in peripheral blood may be helpful in the prediction of tumor progression.

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

    Science.gov (United States)

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

    2014-11-01

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

  2. CD44 alternative splicing in gastric cancer cells is regulated by culture dimensionality and matrix stiffness.

    Science.gov (United States)

    Branco da Cunha, Cristiana; Klumpers, Darinka D; Koshy, Sandeep T; Weaver, James C; Chaudhuri, Ovijit; Seruca, Raquel; Carneiro, Fátima; Granja, Pedro L; Mooney, David J

    2016-08-01

    Two-dimensional (2D) cultures often fail to mimic key architectural and physical features of the tumor microenvironment. Advances in biomaterial engineering allow the design of three-dimensional (3D) cultures within hydrogels that mimic important tumor-like features, unraveling cancer cell behaviors that would not have been observed in traditional 2D plastic surfaces. This study determined how 3D cultures impact CD44 alternative splicing in gastric cancer (GC) cells. In 3D cultures, GC cells lost expression of the standard CD44 isoform (CD44s), while gaining CD44 variant 6 (CD44v6) expression. This splicing switch was reversible, accelerated by nutrient shortage and delayed at lower initial cell densities, suggesting an environmental stress-induced response. It was further shown to be dependent on the hydrogel matrix mechanical properties and accompanied by the upregulation of genes involved in epithelial-mesenchymal transition (EMT), metabolism and angiogenesis. The 3D cultures reported here revealed the same CD44 alternative splicing pattern previously observed in human premalignant and malignant gastric lesions. These findings indicate that fundamental features of 3D cultures - such as soluble factors diffusion and mechanical cues - influence CD44 expression in GC cells. Moreover, this study provides a new model system to study CD44 dysfunction, whose role in cancer has been in the spotlight for decades.

  3. CD44 alternative splicing in gastric cancer cells is regulated by culture dimensionality and matrix stiffness.

    Science.gov (United States)

    Branco da Cunha, Cristiana; Klumpers, Darinka D; Koshy, Sandeep T; Weaver, James C; Chaudhuri, Ovijit; Seruca, Raquel; Carneiro, Fátima; Granja, Pedro L; Mooney, David J

    2016-08-01

    Two-dimensional (2D) cultures often fail to mimic key architectural and physical features of the tumor microenvironment. Advances in biomaterial engineering allow the design of three-dimensional (3D) cultures within hydrogels that mimic important tumor-like features, unraveling cancer cell behaviors that would not have been observed in traditional 2D plastic surfaces. This study determined how 3D cultures impact CD44 alternative splicing in gastric cancer (GC) cells. In 3D cultures, GC cells lost expression of the standard CD44 isoform (CD44s), while gaining CD44 variant 6 (CD44v6) expression. This splicing switch was reversible, accelerated by nutrient shortage and delayed at lower initial cell densities, suggesting an environmental stress-induced response. It was further shown to be dependent on the hydrogel matrix mechanical properties and accompanied by the upregulation of genes involved in epithelial-mesenchymal transition (EMT), metabolism and angiogenesis. The 3D cultures reported here revealed the same CD44 alternative splicing pattern previously observed in human premalignant and malignant gastric lesions. These findings indicate that fundamental features of 3D cultures - such as soluble factors diffusion and mechanical cues - influence CD44 expression in GC cells. Moreover, this study provides a new model system to study CD44 dysfunction, whose role in cancer has been in the spotlight for decades. PMID:27187279

  4. Trefoil factor 3 peptide regulates migration via a Twist-dependent pathway in gastric cell.

    Science.gov (United States)

    Zheng, Qianqian; Gao, Jian; Li, Honglin; Guo, Wendong; Mao, Qi; Gao, Enhui; Zhu, Ya-qin

    2013-08-16

    Trefoil factor 3 (TFF3) is a member of the TFF-domain peptide family and essential in regulating cell migration and maintaining mucosal integrity in gastrointestinal tract. However, the role of TFF3 and its downstream regulating mechanisms in cancer cell migration remain unclear. We previously reported that TFF3 prolonged the up-regulation of Twist protein to modulate IL-8 secretion in intestinal epithelial cells. In this study, we investigated the role of Twist protein in TFF3-induced migration of SGC7901 cells. While Twist was activated by TFF3, siRNA-mediated knockdown of Twist abolished TFF3-induced cell migration. Furthermore, the migration related marker CK-8 as well as ZO-1 and MMP-9 was also regulated by TFF3 via a Twist-dependent mechanism. Our study suggests that Twist, as an important potential downstream effector, plays a key role in TFF3-modulated metastasis in gastric cancer and can be a promising therapeutic target against intestinal-type gastric cancer.

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Zhao; Wen-Lu Shen

    2005-01-01

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

  7. Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.

    Directory of Open Access Journals (Sweden)

    Sachiko Hirai

    Full Text Available Up-regulated sirtuin 1 (SIRT1, an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53. Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5. In the KatoIII cell line (TP53-null, DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors.

  8. Effects of Helicobacter pylori infection on gastric epithelial cell kinetics in patients with chronic renal failure

    Institute of Scientific and Technical Information of China (English)

    Selim Aydemir; Binnaz Handan Ozdemir; Gurden Gur; Ibrahim Dogan; Ugur Yilmaz; Sedat Boyacioglu

    2005-01-01

    AIM: To evaluate the effects of Helicobacter pylori infection on gastric epithelial cell kinetics in patients with chronic renal failure (CRF).METHODS: Forty-four patients were enrolled in this study and divided into four groups with respect to their Helicobacter pylori (H pylori) and CRF status. Groups were labeled as follows: 1a: normal renal function, H pylori negative (n = 12), 1b: normal renal function,H pylori positive (n = 11), 2a: CRF, H pylori negative (n = 10), 2b: CRF, H pylori positive (n = 11). Upper gastrointestinal endoscopy was done in all the patients involved in the study. During endoscopical investigation,antral biopsy specimens were taken from each patient.In order to evaluate the cell apoptosis and proliferation in gastric epithelial cells, Bax and proliferating cell nuclear antigen (PCNA) labeling indexes (LI) were assessed with immunohistochemical staining method.RESULTS: For groups 1a, 1b, 2a, and 2b, mean Bax LI was identified as 34.4±13.7, 44.1±16.5, 46.3±20.5,60.7±13.8, respectively and mean PCNA LI was identified as 36.2±17.2, 53.6±25.6, 59.5±25.6, 67.2±22,respectively. When the one-way ANOVA test was applied,statistically significant differences were detected between the groups for both Bax LI (P = 0.004 <0.01) and PCNA LI (P = 0.009 <0.01). When groups were compared further in terms of Bax LI and PCNA LI with Tukey's HSD test for multiple pairwise comparisons, statistically significant difference was observed only between groups 1a and 2b (P = 0.006 <0.01).CONCLUSION: In gastric epithelial cells, expression of both the pre-apoptotic protein Bax and the proliferation marker PCNA increase with H pylori infection. This increase is more evident in patients with uremia. These findings suggest that uremia accelerates apoptosis and proliferation in gastric epithelial cells.

  9. Cell nuclei attributed relational graphs for efficient representation and classification of gastric cancer in digital histopathology

    Science.gov (United States)

    Sharma, Harshita; Zerbe, Norman; Heim, Daniel; Wienert, Stephan; Lohmann, Sebastian; Hellwich, Olaf; Hufnagl, Peter

    2016-03-01

    This paper describes a novel graph-based method for efficient representation and subsequent classification in histological whole slide images of gastric cancer. Her2/neu immunohistochemically stained and haematoxylin and eosin stained histological sections of gastric carcinoma are digitized. Immunohistochemical staining is used in practice by pathologists to determine extent of malignancy, however, it is laborious to visually discriminate the corresponding malignancy levels in the more commonly used haematoxylin and eosin stain, and this study attempts to solve this problem using a computer-based method. Cell nuclei are first isolated at high magnification using an automatic cell nuclei segmentation strategy, followed by construction of cell nuclei attributed relational graphs of the tissue regions. These graphs represent tissue architecture comprehensively, as they contain information about cell nuclei morphology as vertex attributes, along with knowledge of neighborhood in the form of edge linking and edge attributes. Global graph characteristics are derived and ensemble learning is used to discriminate between three types of malignancy levels, namely, non-tumor, Her2/neu positive tumor and Her2/neu negative tumor. Performance is compared with state of the art methods including four texture feature groups (Haralick, Gabor, Local Binary Patterns and Varma Zisserman features), color and intensity features, and Voronoi diagram and Delaunay triangulation. Texture, color and intensity information is also combined with graph-based knowledge, followed by correlation analysis. Quantitative assessment is performed using two cross validation strategies. On investigating the experimental results, it can be concluded that the proposed method provides a promising way for computer-based analysis of histopathological images of gastric cancer.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  11. LY294002 induces p53-dependent apoptosis of SGC7901 gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Chun-gen XING; Bao-song ZHU; Hui-hui LIU; Fang LIN; Hui-hua YAO; Zhong-qin LIANG; Zheng-hong QIN

    2008-01-01

    Aim:To study the effects of LY294002, an inhibitor of class Ⅰ phosphatidylinositol 3-kinase (PI3K), on proliferation and apoptosis of SGC7901 gastric cancer cells. Methods:The MTT assay was used to determine the cytotoxic effects of LY294002. Cell cycle distribution was analyzed using flow cytometry and apoptosis was assessed using flow cytometry analysis after staining DNA with propidium iodide. Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Expression of p53 and PUMA was determined using real-time RT-PCR and West-ern blotting analysis. Results:The viability of SGC7901 cells was significantly reduced by LY294002 treatment. Expression of p53 and PUMA was induced, and mitochondrial membrane potential collapsed after treatment with LY294002. LY294002 induced apoptotic cell death. Conclusion:Activation of the p53 path-way is involved in LY294002-induced SGC7901 cell death.

  12. Presence of S100A9-positive inflammatory cells in cancer tissues correlates with an early stage cancer and a better prognosis in patients with gastric cancer

    International Nuclear Information System (INIS)

    S100A9 was originally discovered as a factor secreted by inflammatory cells. Recently, S100A9 was found to be associated with several human malignancies. The purpose of this study is to investigate S100A9 expression in gastric cancer and explore its role in cancer progression. S100A9 expression in gastric tissue samples from 177 gastric cancer patients was assessed by immunohistochemistry. The expression of its dimerization partner S100A8 and the S100A8/A9 heterodimer were also assessed by the same method. The effect of exogenous S100A9 on motility of gastric cancer cells AGS and BGC-823 was then investigated. S100A9 was specifically expressed by inflammatory cells such as macrophages and neutrophils in human gastric cancer and gastritis tissues. Statistical analysis showed that a high S100A9 cell count (> = 200) per 200x magnification microscopic field in cancer tissues was predictive of early stage gastric cancer. High S100A9-positive cell count was negatively correlated with lymph node metastasis (P = 0.009) and tumor invasion (P = 0.011). S100A9 was identified as an independent prognostic predictor of overall survival of patients with gastric cancer (P = 0.04). Patients with high S100A9 cell count were with favorable prognosis (P = 0.021). Further investigation found that S100A8 distribution in human gastric cancer tissues was similar to S100A9. However, the number of S100A8-positive cells did not positively correlate with patient survival. The inflammatory cells infiltrating cancer were S100A8/A9 negative, while those in gastritis were positive. Furthermore, exogenous S100A9 protein inhibited migration and invasion of gastric cancer cells. Our results suggested S100A9-positive inflammatory cells in gastric cancer tissues are associated with early stage of gastric cancer and good prognosis

  13. AMP18 interacts with the anion exchanger SLC26A3 and enhances its expression in gastric cancer cells.

    Science.gov (United States)

    Di Stadio, Chiara Stella; Altieri, Filomena; Miselli, Giuseppina; Elce, Ausilia; Severino, Valeria; Chambery, Angela; Quagliariello, Vincenzo; Villano, Valentina; de Dominicis, Gianfranco; Rippa, Emilia; Arcari, Paolo

    2016-02-01

    AMP18 is a stomach-specific secreted protein expressed in normal gastric mucosa but absent in gastric cancer. AMP18 plays a major role in maintaining gastric mucosa integrity and is characterized by the presence of a BRICHOS domain consisting of about 100 amino acids, present also in several unrelated proteins, and probably endowed with a chaperon-like activity. In this work, we exploited a functional proteomic strategy to identify potential AMP18 interactors with the aim to add knowledge on its functional role within gastric cell lines and tissues. To this purpose, recombinant biotinylated AMP18 was purified and incubated with protein extract from human normal gastric mucosa by applying an affinity chromatography strategy. The interacting proteins were identified by peptide mass fingerprinting using MALDI-TOF mass spectrometry. The pool of interacting proteins contained SLC26A3, a protein expressed in the apical membrane of intestinal epithelial cells, supposed to play a critical role in Cl(-) absorption and fluid homeostasis. The interaction was also confirmed by Western blot with anti-SLC26A3 on transfected AGS cell extract following AMP18 pull-down. Furthermore, the interaction between AMP18 and SLC26A3 was also validated by confocal microscopy that showed a co-localization of both proteins at plasma membrane level. More importantly, for the first time, we showed that SLC26A3 is down-regulated in gastric cancer and that the overexpression of AMP18 in AMP-transfected gastric cancer cells up-regulated the expression of SLC26A3 both at transcriptional and translational level, the latter probably through the activation of the MAP kinases pathway. These findings strongly suggest that AMP18 might play an anti-inflammatory role in maintaining mucosal integrity also by regulating SLC26A3 level. PMID:26700142

  14. Inhibitory effect of schisandrin B on gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the inhibitory effect and possible mechanism of action of schisandrin B in SC-B on gastric cancer cells in vitro.METHODS: SC-B consisted of schisandrin B, aloeemodin, and Astragalus polysaccharides. Exponentially growing human gastric cancer SGC-7901 cells were divided into six treatment groups: (1) control group (RPMI 1640 medium); (2) negative control group (2% DMSO);(3) positive control group (50 mg/L 5-Fluorouracil,5-FU); (4) low-dose group (LSC, final concentration of schisandrin B, 25 mg/L); (5) moderate-dose group (MSC,final concentration of schisandrin B, 50 mg/L); (6) high-dose group (HSC, final concentration of schisandrin B,100 mg/L). Follow-up was done at 12-48 h. An MTT (Methylthiazolyldiphenyl-tetrazolium bromide) assay was used to examine the inhibitory effect of SC-B on gastric cancer cells. The mitosis index was assessed using an inverted microscope. Flow cytometry was used to visualize the cell cycle. An RT-PCR (Reverse transcription-Polymerase chain reaction) -based assay was used to detect mRNA expression for cyclin D1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).RESULTS: The MTT assay showed that the number of living cells in the LSC, MSC and HSC groups was significantly smaller than that in the DMSO-treated group (P < 0.05) at 12-48 h. The inhibitory rate (IR) of the LSC group was 41.15% ± 3.86%, 59.24% ± 5.34% and 69.93% ± 7.81% at 12, 24 and 48 h, respectively. The IR of the MSC group was 42.82% ± 4.94%, 62.68% ± 7.58% and 71.79% ± 8.12% at 12, 24 and 48 h,respectively. The IR of the HSC group was 37.50% ± 3.21%, 40.34% ± 2.98% and 61.99% ± 4.88% at 12,24 and 48 h, respectively. These results suggested that a moderate dosage had the most obvious inhibitory efficacy at 48 h. Compared to the DMSO group, the mitosis index of the LSC, MSC, HSC groups was greatly decreased (P < 0.05) at all time points. Any dose of SC-B suppressed mitosis within 12-48 h. Compared to the DMSO group, the percentage of cells

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

    Directory of Open Access Journals (Sweden)

    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

  16. Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

    Science.gov (United States)

    Tanigawa, T; Ahluwalia, A; Watanabe, T; Arakawa, T; Tarnawski, A S

    2015-08-01

    A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100β protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing

  17. Elevation of HLA-G-expressing DC-10 cells in patients with gastric cancer.

    Science.gov (United States)

    Xu, Dan-Ping; Shi, Wei-Wu; Zhang, Tong-Tong; Lv, Hai-Yan; Li, Jing-Bo; Lin, Aifen; Yan, Wei-Hua

    2016-09-01

    DC-10 is a distinct subset of human tolerogenic dendritic cells (DCs) which express high levels of human leukocyte antigen-G (HLA-G). DC-10 could induce adaptive type 1 regulatory T cells through the IL-10 dependent ILT4/HLA-G signaling pathway. However, the significance of DC-10 in malignancies remains unclear. In this study, the frequency and mean fluorescence intensity (MFI) of HLA-G+ DC-10 in the peripheral blood of 124 patients with gastric cancer (GC) and 130 normal controls was analyzed with flow cytometry. Plasma sHLA-G was analyzed with ELISA. Results showed both the percentages of peripheral HLA-G+ DC-10 (median: 0.13% vs 0.01%; pG on these cells (median: 310.0 vs 91.5; pG+ DC-10 in GC patients was strongly relative to the tumor grade (p=0.021). sHLA-G levels in GC patients were significantly higher than in healthy controls (median: 85.80U/ml vs 61.20U/ml; pG (p>0.05). However, the increased HLA-G+ DC-10, HLA-G MFI and plasma sHLA-G in patients with gastric cancer could be a diagnostic factor with the area under the ROC curve with 0.947 (p<0.01), 0.882 (p<0.01) and 0.700 (p<0.01) respectively. Given the immune tolerant function of DC-10 could play, the increased DC-10 might play an important role in immune suppression for patients with gastric cancer, while more studies are necessary to illustrate the clinical relevance of DC-10 in cancer patients.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  19. Up-regulation of T-lymphoma and metastasis gene 1 in gastric cancer and its involvement in cell invasion and migration

    Institute of Scientific and Technical Information of China (English)

    SHI Yu-long; MIAO Rui-zheng; CHENG Li; GUO Xiao-bo; YANG Bo; JING Chang-qing; ZHANG Li

    2013-01-01

    Background T-lymphoma and metastasis gene 1 (Tiam1) produces a guanine nucleotide exchange factor (GNEF) that regulates guanosine triphosphatase,which transforms guanosine diphosphate to guanosine triphosphate.Recently published data indicate that Tiam1 was associated with gastric cancer.The aim of this study was to investigate biological effects and potential mechanisms of Tiam1 in gastric carcinoma.Methods We analyzed the expression of Tiam1 in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR.We investigated Tiam1 expression and its prognostic value for gastric cancer.Furthermore,the functions of Tiam1 over-expression were analyzed with stable-expression Tiam1 plasmid in human gastric cancer cell lines.Results Tiam1 expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiam1 mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues.Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiam1 expression had significantly shorter overall survival time than those with negative Tiam1 expression.Ectopic expression of Tiam1 promoted cell growth,migration and invasion of gastric cancer cells in vitro.Conclusions In gastric cancer cells,Tiam1 affects multiple properties associated with acquisition of the metastatic phenotype,and may be a marker ofgastric cancer progression and metastasis in a subset of cancer.

  20. Isoproterenol regulates CD44 expression in gastric cancer cells through STAT3/MicroRNA373 cascade.

    Science.gov (United States)

    Wei, Bo; Sun, Xiaoyan; Geng, Zhijun; Shi, Ming; Chen, Zhida; Chen, Lin; Wang, Yongan; Fu, Xiaobing

    2016-10-01

    Gastric cancer is a heterogeneous disease, and stem cells are thought to be the cell of origin contributed to this malignancy. However, studies with breast and intestinal cancer models show non-stem cancer cells can change their surface phenotype and convert into tumor-initiating cells induced by the signals emanating from surrounding tumor microenvironment. Here, we show that CD44 was expressed at different levels in gastric metastases compared with primary tumors, and also negatively correlated with the expression of miR-373. By using a panel of human gastric cancer cell lines and analysis of archived data from The Cancer Genomics Altas (TCGA) database, we verified the inverse correlation between CD44 and miR-373. Furthermore, the stress-associated hormone, isoproterenol, could increase the expression levels of "stem"-related proteins, such as CD44, Nanog, and Rex-1, and induce chemoresistance in gastric cancer cells. Transfection with miR-373, however, reversed not only the effect of isoproterenol on phenotypic conversion but also its effect on drug sensitivity. Isoproterenol triggered downstream target STAT3 mainly through β2-adrenergic receptors (β2-ARs). Activated STAT3 functioned as a miR-373 suppressor by binding to its promoter, which forms a positive feedback circuit to maintain CD44 activity and direct the phenotypic conversion from CD44(low) to CD44(hi) expression. Our data suggest an important role of β2-AR/STAT3/miR-373 signaling on the transformation of gastric cancer cells. This study also suggests a potential therapeutic or preventive treatment for gastric cancer patients who are especially prone to psychosocial stress. PMID:27512943

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

    OpenAIRE

    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...

  2. Protective role of intracellular superoxide dismutase against extracellular oxidants in cultured rat gastric cells.

    OpenAIRE

    Hiraishi, H; Terano, A; Sugimoto, T.; Harada, T; Razandi, M; Ivey, K J

    1994-01-01

    We examined the role of intracellular superoxide dismutase (SOD) as an antioxidant by studying the effect of diethyldithiocarbamate (DDC) on extracellular H2O2-induced damage in cultured rat gastric mucosal cells. 51Cr-labeled monolayers from rat stomachs were exposed to glucose oxidase-generated H2O2 or reagent H2O2, which both caused a dose-dependent increase in 51Cr release. DDC dose-dependently enhanced 51Cr release by hydrogen peroxide, corresponding with inhibition of endogenous SOD act...

  3. Chief Editors’ Introduction

    Directory of Open Access Journals (Sweden)

    Kerry Carrington

    2015-12-01

    Full Text Available It has been a great year for the journal:  our most successful ever. This edition marks three years of publication of the International Journal for Crime, Justice and Social Democracy. In 2015 the journal was selected for inclusion into Scopus and Web of Science data bases. This is a terrific success story and testimony to the high quality of the articles, the editorship, the reviewing and the international readership of the journal. We are grateful as ever to our distinguished International Editorial Board and all our reviewers who are anonymous to readers and authors due to the norms of blind peer reviewing. We also thank the out-going foundational co-editor-in-chief Reece Walters for his efforts in making this journal the success it is. The journal has now surpassed 150,000 abstract views and 100,000 full PDF downloads. This journal is one of only a few in the world of criminology to support fully on-line free-to-download articles, and to promote creative commons copyright: that is, authors’ rights to reproduce their own material. We support the democratisation of knowledge and are delighted to be leaders in high quality international journal publishing.Download the PDF file here for the Chief Editors’ introduction to this issue and be motivated by the eclectic and impressive range of topics offered by our contributors to read further.

  4. Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells

    International Nuclear Information System (INIS)

    Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells. Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The in vitro invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells. Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the in vitro invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the in vitro angiogenesis of cancer cells in a dose-dependent manner. These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells in vitro, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer

  5. Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shibuya, Akiko [Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Onda, Kenji, E-mail: knjond@toyaku.ac.jp [Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Kawahara, Hirofumi; Uchiyama, Yuka; Nakayama, Hiroko; Omi, Takamasa; Nagaoka, Masayoshi [Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Matsui, Hirofumi [Division of Gastroenterology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305-8575 (Japan); Hirano, Toshihiko [Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan)

    2010-07-30

    Research highlights: {yields} Sofalcone increases HO-1 in gastric epithelial cells. {yields} The induction of HO-1 by sofalcone treatment follows the activation of Nrf2. {yields} The production of VEGF by sofalcone treatment is mediated by HO-1 induction. -- Abstract: Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction in gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    韦尉元

    2013-01-01

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

  8. MiR-9 downregulates CDX2 expression in gastric cancer cells.

    Science.gov (United States)

    Rotkrua, Pichayanoot; Akiyama, Yoshimitsu; Hashimoto, Yutaka; Otsubo, Takeshi; Yuasa, Yasuhito

    2011-12-01

    Ectopic expression of CDX2, a caudal-related homeobox protein, is known to be associated with the development of intestinal metaplasia in the stomach and gastric carcinogenesis. Previously, we reported that DNA methylation was partly responsible for CDX2 silencing in gastric cancer (GC). However, the mechanism underlying the aberrant expression of CDX2 during malignant transformation remained unclear. MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators. To elucidate the role of miRNAs in CDX2 downregulation in GC cells, putative miRNAs, such as miR-9, were computationally predicted. After exogenous pre-miR-9 precursor transfection, the luciferase activity of a reporter vector containing a part of the 3'-UTR of CDX2 was downregulated in HEK-293T cells. The inverse correlation between the miR-9 and CDX2 protein levels was demonstrated in GC cell lines. By means of miR-9 overexpression and knockdown techniques, the expression levels of the CDX2 protein and downstream target genes (p21, MUC2 and TFF3) were responsively altered in MKN45 and NUGC-3 cells. Transfection of an anti-miR-9 molecule significantly inhibited cell growth by promoting G(1) cell cycle arrest in MKN45 cells similarly to the effect of CDX2 overexpression. Moreover, examination of the miR-9 levels in primary GC tissues revealed that the amounts of miR-9 in the CDX2-negative group were significantly higher than those in the CDX2-positive group (p = 0.004). Therefore, miR-9 might repress CDX2 expression via the binding site in the 3'-UTR, resulting in the promotion of cell proliferation in GCs.

  9. Nanoliposomal formulation of Agrostemma githago aqueous extract shows enhanced cytotoxic effect on gastric cancer cell line

    Directory of Open Access Journals (Sweden)

    Shahab Bohlooli

    2015-01-01

    Full Text Available Objective(s: The objective of this study was to determine the cytotoxic effects of nanoliposomal form of lyophilized aqueous extract of Agrostemma githago (A. githago seeds on gastric cancer cell line (AGS using cell viability tests. Materials and Methods: Lyophilized aqueous extract of A. githago seeds was prepared. Liposomes were also prepared by thin-film hydration method and their stability and size were characterized by SEM. The size and zeta potential were determined by Malvern Zetasizer. Cytotoxic effects of nanoliposomes on gastric cancer cell line was determined using MTT, Neutral Red and Frame methods. Results: The size of liposomes was around 171.5 nm with proper dispersion (PDI=0.268. The morphology of the liposomes was suitable according to SEM images. The IC50 values indicated that the nanoliposomal form of extract was 3-4 times more active than extract alone. Average IC50 values for extract and liposomal form of extract were 13.02 ± 0.95 and 4.43 ± 1.49 ug/ml, respectively. Conclusion: This study showed that liposomal form of aqueous extract of A. githago seeds exerts cytotoxic effect at significantly lower concentrations than the extract itself.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  11. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    Science.gov (United States)

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Effect of Helicobacter pylori VacA on gene expression of gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Wang; Zhen-Hong Li; Jian-Ping Yuan; Wei Zhao; Xiao-Dong Shi; Shan-Qing Tong; Xiao-Kui Guo

    2005-01-01

    AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells.METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA+ and VacA- Hpylori broth culture supernatants (BCS), was detected by the cDNA microarray technique. Cytoskeleton changes of SGC7901 and HeLa cells were observed through high-resolution laser scanning confocal microscopy.RESULTS: A total of 16 000 cDNA clones were detected.The percentage of genes with heterogeneous expression in SGC7901 cells challenged by VacA+ BCS reached 5%,compared with that challenged by Vac A- BCS. There were 865 genes/EST with 2-fold differential expression levels and 198 genes/EST with 3-fold differential expression levels.Host of these genes were involved in vital cell events including signal transduction, regulation of gene expression, cytoskeleton,apoptosis, stress response and inflammation, cell cycle and tumor development. Cells co-cultured with VacA+ BCS showed collapsed and disrupted microtubular cytoarchitecture.CONCLUSION: VacA+ BCS can disrupt cytoskeletal architecture,likely through affecting the expression of cytoskeleton-associated genes, directly induce the expression of tumor promoter-related genes and inhibit the expression of tumor suppressor genes, thus favoring the development of tumors.VacA+ BCS can also alter the expression of inflammation and stress response genes. This suggests that VacA may play an important role in the pathogenicity of H pylori.

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

    Institute of Scientific and Technical Information of China (English)

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

    2001-01-01

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

  17. CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Shu-Kui Wang; Hui-Fang Zhu; Bang-Shun He; Zhen-Yu Zhang; Zhi-Tan Chen; Zi-Zheng Wang; Guan-Ling Wu

    2007-01-01

    AIM: To characterize the immune responses including local and systemic immunity induced by infection with H pylori, especially with CagA+ H pylori strains and the underlying immunopathogenesis.METHODS: A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA), the presence of T helper (Th) cells and regulatory T (Treg)cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines, and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test, urea [14C]breath test, immunoblotting test, flow cytometry, real time RT-PCR and immunohistochemistry.RESULTS: Of the patients, 629 (88.47%) were infected with H pylori; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains, Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis, while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection,CONCLUSION: Polarization of Th cell immune responses occurs in patients with CagA+ H pylori infection, which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.

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

    Science.gov (United States)

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

    2015-09-29

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

  19. Effects for Sequential Treatment of siAkt and Paclitaxel on Gastric Cancer Cell Lines.

    Science.gov (United States)

    Ku, Minhee; Kang, Myounghwa; Suh, Jin-Suck; Yang, Jaemoon

    2016-01-01

    Real-time screening of cellular response on the drugs could provide valuable insights for the early detection of therapeutic efficiency and the evaluation of disease progression. Cancer cells have the ability to vary widely in response to stress in a manner to adjust the signaling pathway to promote the survival or having a resistance to stimulation. Cell-based label-free technologies using electronic impedance sensor have strategies for constructing the signature profiles of each cells. To achieve exquisite sensitivity to substantially change of live-cell response have an important role that predict the potential of therapeutic effects. In this study, we use an impedance-based real-time cell analysis system to investigate dynamic phenotypes of cells described as a cellular index value. We show that gastric cancer cells generated characteristic kinetic patterns that corresponded to the treatment order of therapeutics. The kinetic feature of the cells offers insightful information that cannot be acquired from a conventional single end-point assay. Furthermore, we employ a 'sequential treatment strategy' to increase cytotoxic effects with minimizing the use of chemotherapeutics. Specifically, treatment of paclitaxel (PTX) after down-regulating Akt gene expression using RNAi reduces the cell proliferation and increases apoptosis. We propose that the sequential treatment may exhibit more effective approach rather than traditional combination therapy. Moreover, the dynamic monitoring of cell-drug interaction enables us to obtain a better understanding of the temporal effects in vitro. PMID:27648001

  20. Effects for Sequential Treatment of siAkt and Paclitaxel on Gastric Cancer Cell Lines

    Science.gov (United States)

    Ku, Minhee; Kang, Myounghwa; Suh, Jin-Suck; Yang, Jaemoon

    2016-01-01

    Real-time screening of cellular response on the drugs could provide valuable insights for the early detection of therapeutic efficiency and the evaluation of disease progression. Cancer cells have the ability to vary widely in response to stress in a manner to adjust the signaling pathway to promote the survival or having a resistance to stimulation. Cell-based label-free technologies using electronic impedance sensor have strategies for constructing the signature profiles of each cells. To achieve exquisite sensitivity to substantially change of live-cell response have an important role that predict the potential of therapeutic effects. In this study, we use an impedance-based real-time cell analysis system to investigate dynamic phenotypes of cells described as a cellular index value. We show that gastric cancer cells generated characteristic kinetic patterns that corresponded to the treatment order of therapeutics. The kinetic feature of the cells offers insightful information that cannot be acquired from a conventional single end-point assay. Furthermore, we employ a 'sequential treatment strategy' to increase cytotoxic effects with minimizing the use of chemotherapeutics. Specifically, treatment of paclitaxel (PTX) after down-regulating Akt gene expression using RNAi reduces the cell proliferation and increases apoptosis. We propose that the sequential treatment may exhibit more effective approach rather than traditional combination therapy. Moreover, the dynamic monitoring of cell-drug interaction enables us to obtain a better understanding of the temporal effects in vitro.

  1. Narrator-in-Chief

    DEFF Research Database (Denmark)

    Herron, Mark A.

    The dissertation Narrator-in-Chief: The Narrative Rhetoric of Barack Obama seeks to show how the concept of “narrative” can be used in rhetorical criticism of presidential speeches, particularly when considering the speeches and the biographical text, Dreams from My Father (1995), of Barack Obama....... The use of narratives of and by presidents in the White House can be seen as an essential part of the ceremonial role of the presidency. This use of narratives in epideictic speech has increased with modern day interests in the domestic life of the president, and the use of visual mass media...... as a communication platform for the president. While this has been described as a negative development (Stuckey, 1991; Salmon, 2010) this dissertation argues that narrative rhetoric should not be seen only as a negative part of political rhetoric, but also as a possibly vital way to educate the audience on issues...

  2. High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis

    Science.gov (United States)

    Shimazu, Kazuhiro; Fukuda, Koji; Yoshida, Taichi; Inoue, Masahiro; Shibata, Hiroyuki

    2016-01-01

    AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis. METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 mL of peripheral venous blood drawn using a CellSearch kit and a CellTracks AutoPrep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells (CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 mL of peripheral blood (median of 1724). These values were much higher than common gastric cancers (2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d (median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance (Y = 234.6 - 0.03X, P = 0.085). CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.

  3. Isolation of melittin from bee venom and evaluation of its effect on proliferation of gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Mahmoodzadeh A

    2013-03-01

    Full Text Available Background: Gastric cancer (GC is one of the most common cancers worldwide and in Iran. Conventional therapies are surgery and chemotherapy. Current studies are evaluating natural compounds in inhibiting growth of cancer cell. In this study isolated peptide melittin with 26 amino acids from bee venom and its impact on the viability and proliferation of gastric cancer cells was investigated. Methods: At first melittin was purified from honeybee venom using a reversed-phase high performance liquid chromatography (RP- HPLC and C18 column. In order to investigate whether melittin, a 26 amino acids peptide which is the main components of honeybee venom, inhibits proliferation of human gastric adenocarcinoma cell line (AGS cells, MTT ((3-(4, 5-dimethylthiazol-2-yl-2, 5- diphenyltetrazolium bromide assay was performed. Hemolytic assay carried out in order to confirm the biologic activity of the isolated melittin. AGS cells were plated in a 96-well plate and treated with serially diluted concentrations of melittin for 6 and 12 hours. The mortality of the cells was measured via MTT assay at 540 nm.Results: The obtained chromatogram from RP-HPLC showed that melittin comprises 50% of the studied bee venom. SDS-PAGE analysis of melittin fraction confirmed purity of isolated melittin. Hemolytic activity assay indicates that isolated melittin shows a strong hemolytic activity (HD50=0.5. MTT assay showed that melittin strongly inhibits proliferation of gastric cancer cells at concentrations more than 2µg/ml. This inhibitory effect is dependent to melittin concentration and incubation time.Conclusion: This study provides evidence that melittin inhibits proliferation of the gastric cancer cells. Results showed that isolated melittin from honey bee venom have cytotoxic effect on AGS cell line with a trend of increasing cytotoxicity with increasing concentration and incubation time.

  4. Lactobacilli Reduce Helicobacter pylori Attachment to Host Gastric Epithelial Cells by Inhibiting Adhesion Gene Expression.

    Science.gov (United States)

    de Klerk, Nele; Maudsdotter, Lisa; Gebreegziabher, Hanna; Saroj, Sunil D; Eriksson, Beatrice; Eriksson, Olaspers Sara; Roos, Stefan; Lindén, Sara; Sjölinder, Hong; Jonsson, Ann-Beth

    2016-05-01

    The human gastrointestinal tract, including the harsh environment of the stomach, harbors a large variety of bacteria, of which Lactobacillus species are prominent members. The molecular mechanisms by which species of lactobacilli interfere with pathogen colonization are not fully characterized. In this study, we aimed to study the effect of lactobacillus strains upon the initial attachment of Helicobacter pylori to host cells. Here we report a novel mechanism by which lactobacilli inhibit adherence of the gastric pathogen H. pylori In a screen with Lactobacillus isolates, we found that only a few could reduce adherence of H. pylori to gastric epithelial cells. Decreased attachment was not due to competition for space or to lactobacillus-mediated killing of the pathogen. Instead, we show that lactobacilli act on H. pylori directly by an effector molecule that is released into the medium. This effector molecule acts on H. pylori by inhibiting expression of the adhesin-encoding gene sabA Finally, we verified that inhibitory lactobacilli reduced H. pylori colonization in an in vivo model. In conclusion, certain Lactobacillus strains affect pathogen adherence by inhibiting sabA expression and thereby reducing H. pylori binding capacity.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Liu Rui-hua

    2012-04-01

    Full Text Available Abstract Background Human olfactomedin 4 (OLFM4 gene is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be frequently up-regulated in many types of human tumors including gastric cancer and it was believed to play significant role in the progression of gastric cancer. Although the function of OLFM4 has been indicated in many studies, recent evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell growth and apoptosis. The aim of this study is to examine the role of gastric cancer-specific expression of OLFM4 in cell growth and apoptosis resistance. Methods OLFM4 expression was eliminated by RNA interference in SGC-7901 and MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2 or tumor necrosis factor-alpha (TNF α were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk. Results The elimination of OLFM4 protein by RNA interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity both in vitro and in vivo by induction of cell G1 arrest (all P 2O2 or TNF α-induced apoptosis and caspase-3 activity (all P 2O2 or TNF α-induced apoptosis in OLFM4 knockdown cells (all P Conclusion Our study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H2O2 or TNF α treatment by increasing caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition and anticancer drugs treatment may provide therapeutic potential in gastric cancer intervention.

  7. Prognostic impact of the number of viable circulating cells with high telomerase activity in gastric cancer patients: a prospective study.

    Science.gov (United States)

    Ito, Hiroaki; Inoue, Haruhiro; Kimura, Satoshi; Ohmori, Tohru; Ishikawa, Fumihiro; Gohda, Keigo; Sato, Jun

    2014-07-01

    The identification of circulating tumor cells (CTCs) in peripheral blood is a useful approach to estimate prognosis, monitor disease progression and measure treatment effects in several types of malignancies. We have previously used OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein (GFP) gene. GFP-positive cells (GFP+ cells) were counted under a fluorescence microscope. Our results showed that the number of at least 7.735 µm in diameter GFP+ cells (L-GFP+ cells) in the peripheral blood was a significant marker of prognosis in gastric cancer patients. However, tumor cells undergoing epithelial-mesenchymal transition (EMT) have been reported to be smaller in size than cells without EMT features; thus, CTCs undergoing EMT may escape detection with this technique. Therefore, in this study, we analyzed the relationship between patient outcome and the number of GFP+ cells of any size. We obtained peripheral blood samples from 65 patients with gastric cancer. After infection of OBP-401, GFP+ cells were counted and measured. The relationship between the number of GFP+ cells and surgical outcome was analyzed. The median follow-up period of the surviving patients was 36 months. A significant difference in overall survival was found between patients with 0-5 and patients with ≥6 L-GFP+ cells. No clear relationship was established between the number of small-sized GFP+ cells and patient prognosis. The number of L-GFP+ cells was significantly related to overall survival in patients with gastric cancer. The detection of L-GFP+ cells using OBP-401 may be a useful prognostic marker in gastric cancer.

  8. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

    LENUS (Irish Health Repository)

    Backert, Steffen

    2011-11-01

    Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA\\/B, SabA, AlpA\\/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA\\/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

  9. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Backert Steffen

    2011-11-01

    Full Text Available Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ and the cag (cytotoxin-associated genes pathogenicity island encoding a type IV secretion system (T4SS. The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

  10. Crosstalk between Helicobacter pylori and gastric epithelial cells is impaired by docosahexaenoic acid.

    Directory of Open Access Journals (Sweden)

    Marta Correia

    Full Text Available H. pylori colonizes half of the world's population leading to gastritis, ulcers and gastric cancer. H. pylori strains resistant to antibiotics are increasing which raises the need for alternative therapeutic approaches. Docosahexaenoic acid (DHA has been shown to decrease H. pylori growth and its associated-inflammation through mechanisms poorly characterized. We aimed to explore DHA action on H. pylori-mediated inflammation and adhesion to gastric epithelial cells (AGS and also to identify bacterial structures affected by DHA. H. pylori growth and metabolism was assessed in liquid cultures. Bacterial adhesion to AGS cells was visualized by transmission electron microscopy and quantified by an Enzyme Linked Immunosorbent Assay. Inflammatory proteins were assessed by immunoblotting in infected AGS cells, previously treated with DHA. Bacterial total and outer membrane protein composition was analyzed by 2-dimensional gel electrophoresis. Concentrations of 100 µM of DHA decreased H. pylori growth, whereas concentrations higher than 250 µM irreversibly inhibited bacteria survival. DHA reduced ATP production and adhesion to AGS cells. AGS cells infected with DHA pre-treated H. pylori showed a 3-fold reduction in Interleukin-8 (IL-8 production and a decrease of COX2 and iNOS. 2D electrophoresis analysis revealed that DHA changed the expression of H. pylori outer membrane proteins associated with stress response and metabolism and modified bacterial lipopolysaccharide phenotype. As conclusions our results show that DHA anti-H. pylori effects are associated with changes of bacteria morphology and metabolism, and with alteration of outer membrane proteins composition, that ultimately reduce the adhesion of bacteria and the burden of H. pylori-related inflammation.

  11. Anti-Warburg effect of rosmarinic acid via miR-155 in gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Han S

    2015-05-01

    Full Text Available Shuai Han,* Shaohua Yang,* Zhai Cai, Dongyue Pan, Zhou Li, Zonghai Huang, Pusheng Zhang, Huijuan Zhu, Lijun Lei, Weiwei Wang Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this study Background: The Warburg effect refers to glycolytic production of adenosine triphosphate under aerobic conditions, and is a universal property of most cancer cells. Chronic inflammation is a key factor promoting the Warburg effect. This study aimed to determine whether rosmarinic acid (RA has an anti-Warburg effect in gastric carcinoma in vitro and in vivo. The mechanism for the anti-Warburg effect was also investigated.Methods: An MTT assay was used to examine MKN45 cell growth in vitro. An enzyme-linked immunosorbent assay was used to detect proinflammatory cytokines. Real-time polymerase chain reaction was used to evaluate levels of microRNA expression in cells. Protein expression was determined by Western blotting assay. Mouse xenograft models were established using MKN45 cells to assess the anti-Warburg effect in gastric carcinoma in vivo.Results: RA suppressed glucose uptake and lactate production. It also inhibited expression of transcription factor hypoxia-inducible factor-1α, which affects the glycolytic pathway. Inflammation promoted the Warburg effect in cancer cells. As expected, RA inhibited proinflammatory cytokines and microRNAs related to inflammation, suggesting that RA may suppress the Warburg effect via an inflammatory pathway, such as that involving interleukin (IL-6/signal transducer and activator of transcription-3 (STAT3. miR-155 was found to be an important mediator in the relationship between inflammation and tumorigenesis. We further showed that miR-155 was the target gene regulating the Warburg effect via inactivation of the IL-6/STAT3 pathway. Moreover, we found that RA suppressed the Warburg effect in vivo.Conclusion: RA might

  12. Gastric LTi cells promote lymphoid follicle formation but are limited by IRAK-M and do not alter microbial growth.

    Science.gov (United States)

    Shiu, J; Piazuelo, M B; Ding, H; Czinn, S J; Drakes, M L; Banerjee, A; Basappa, N; Kobayashi, K S; Fricke, W F; Blanchard, T G

    2015-09-01

    Lymphoid tissue inducer (LTi) cells are activated by accessory cell IL-23, and promote lymphoid tissue genesis and antibacterial peptide production by the mucosal epithelium. We investigated the role of LTi cells in the gastric mucosa in the context of microbial infection. Mice deficient in IRAK-M, a negative regulator of TLR signaling, were investigated for increased LTi cell activity, and antibody mediated LTi cell depletion was used to analyze LTi cell dependent antimicrobial activity. H. pylori infected IRAK-M deficient mice developed increased gastric IL-17 and lymphoid follicles compared to wild type mice. LTi cells were present in naive and infected mice, with increased numbers in IRAK-M deficient mice by two weeks. Helicobacter and Candida infection of LTi cell depleted rag1(-/-) mice demonstrated LTi-dependent increases in calprotectin but not RegIII proteins. However, pathogen and commensal microbiota populations remained unchanged in the presence or absence of LTi cell function. These data demonstrate LTi cells are present in the stomach and promote lymphoid follicle formation in response to infection, but are limited by IRAK-M expression. Additionally, LTi cell mediated antimicrobial peptide production at the gastric epithelium is less efficacious at protecting against microbial pathogens than has been reported for other tissues.

  13. Peptide nucleic acids arrest the growth of gastric cancer cells SGC7901

    Institute of Scientific and Technical Information of China (English)

    王宽; 张岂凡; 王锡山; 薛英威; 庞达; 傅松滨

    2004-01-01

    Background Peptide nucleic acid (PNA) has many characteristics useful in molecular biology. This paper described an effective way to raise the cell ingestion rate of PNA so as to kill gastric cancer cells.Methods Heteroduplexes of PNAs and oligonucleotides, wrapped by Lipofectamine 2000, were used to infect SGC7901 cells. The inhibitive effect of heteroduplexes was evaluated by analyzing cell clone forming and cell growth rate. Telomerase activity of SGC7901 cells was detected by polymerase chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) and silver staining assay.Results PNAs showed a dose-dependent inhibition of cell proliferation. The percentage of proliferation inhibition was 99.4% after 7 days; the rate of cloning inhibition was 98.2% after 8 days;whereas for oligonucleotide groups, at the same concentration, the percentages were 50. 1% and 67. 5% respectively. Antisense PNA-DNA-Lipofectamine 2000 group (AP-D-L group) exhibited significantly different percentages from the control groups (P<0.05). The test result indicated that telomerase activity of the AP-D-L group was inhibited (P<0.05). At the same time, the impact on cell morphology was observed.Conclusions The results showed that PNAs are potent antisense reagents. The telomeraseassociated therapies are very promising for the treatment of malignant tumours.

  14. STUDY ON EFFECTS OF ARSENIC TRIOXIDE ON GASTRIC CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    顾琴龙; 朱正纲; 洪鹤群; 刘炳亚; 尹浩然; 林言箴; 李宁丽

    2002-01-01

    Objective To evaluate the effects of arsenic trioxide (As2O3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As2O3 at different concentrations, then the apoptosis rates and cell cycle were determined by flow cytometry assays, the morphologic changes were observed under fluorescence microscopy and electronic microscopy, and the gene expressions were tested with immunohistologic staining. Results Higher apoptosis rates of GCCL were seen in the As2O3-treated group at concentrations of 5μmol and 10μmol, as compared with those in the 5-Fu-treated group. Cell-nuclear pyknosis and chromosomal condensation were observed. The As2O3 at a concentration of 0.5μmol could induce the cell cycle changes of GCCL, revealing an increase in the proportion of G1/G0 phase cells and a decrease in the proportion of S phase cells. From the fifth day after treatment of SGC7901 with As2O3 at a low concentration, P53 and bcl-XL genes expression rates were reduced, Bax gene expression rate increased, and bcl-2 gene expression showed little change. Conclusion As2O3 could induce GCCL apoptosis at a high concentration and differentiation at a low concentration, but it could not completely reverse the malignant biological behaviours of cancer cells.

  15. MicroRNA-19a mediates gastric carcinoma cell proliferation through the activation of nuclear factor-κB.

    Science.gov (United States)

    Yang, Fan; Wang, Hongjian; Jiang, Zhenyu; Hu, Anxiang; Chu, Lisha; Sun, Yiling; Han, Junqing

    2015-10-01

    In gastric carcinoma, the nuclear factor‑κB (NF‑κB) signaling pathway is highly active, and the constitutive activation of NF‑κB prompts malignant cell proliferation. MicroRNAs are considered to be important mediators in the regulation of the NF‑κB signaling pathway. The present study predominantly focussed on the effects of microRNA (miR)‑19a on NF‑κB activation. Reverse transcription‑quantitative polymerase chain reaction was used to quantify the relative levels of miR‑19a in gastric carcinoma cells. MTT assays were used to determine the effect of miR‑19a on cellular proliferation. To detect the activation of NF‑κB, western blotting was performed to measure the protein levels of NF‑κB and the products of its downstream target genes. To define the target genes, luciferase reporter assays were used. miR‑19a was found to be markedly upregulated in gastric carcinoma cells. The overexpression of miR‑19a resulted in proliferation and enhanced migratory capabilities of the MGC‑803 gastric carcinoma cell line. The results of the western blot analysis demonstrated that the protein levels of p65 increased when the MGC‑803 cells were transfected with miR‑19a mimics. In addition, the downstream target genes of miR‑19a, including intercellular adhesion molecule, vascular cell adhesion molecule and monocyte chemoattractant protein‑1, were upregulated. The results of the luciferase assay indicated that IκB‑α was the target gene of miR‑19a. Therefore, the results of the present study suggested that miR‑19a enhances malignant gastric cell proliferation by constitutively activating the NF‑κB signaling pathway.

  16. [Signal transudation pathways in parietal cells of the gastric mucosa in experimental stomach ulcer].

    Science.gov (United States)

    Ostapchenko, L I; Drobins'ka, O V; Chaĭka, V O; Bohun, L I; Bohdanova, O V; Kot, L I; Haĭda, L M

    2009-01-01

    The goal of the presented work was the research of signal transduction mechanism in the rat gastric parietal cells under stomach ulcer conditions. In these cells activation of adenylate cyclase (increase of cAMP level and proteinkinase A activity) and phosphoinositide (increases [Ca2+]i; cGMP and phoshatidylinocitole levels; proteinkinase C, proteinkinase G, and calmodulin-dependent-proteinkinase activity) of signals pathway was shown. An increase of plasma membrane phospholipids (PC, PS, PE, PI, LPC) level was shown. Under conditions of influence of the stress factor the membran enzymes activity (H+, K+ -ATPase, 5'-AMPase, Na+, K+ -ATPase, Ca2+, Mg2+ -ATPase and H+, K+ -ATPase) was considerably increased. The intensification of lipid peroxidation processes in rats was demonstrated.

  17. [Gastric Acid].

    Science.gov (United States)

    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

  18. The role of microRNA-1274a in the tumorigenesis of gastric cancer: Accelerating cancer cell proliferation and migration via directly targeting FOXO4

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are a series of 18–25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial–mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy. - Highlights: • MiR-1274a expression was augmented in gastric cancer. • MiR-1274a promoted proliferation, migration and induced EMT in cancer cells. • MiR-1274a directly targeted FOXO4 expression. • MiR-1274a triggered PI3K/Akt signaling in cancer cells. • MiR-1274a significantly increased tumor xenografts growth

  19. The role of microRNA-1274a in the tumorigenesis of gastric cancer: Accelerating cancer cell proliferation and migration via directly targeting FOXO4

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Guo-Jun, E-mail: wwangguojun@163.com; Liu, Guang-Hui; Ye, Yan-Wei; Fu, Yang; Zhang, Xie-Fu

    2015-04-17

    MicroRNAs (miRNAs) are a series of 18–25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial–mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy. - Highlights: • MiR-1274a expression was augmented in gastric cancer. • MiR-1274a promoted proliferation, migration and induced EMT in cancer cells. • MiR-1274a directly targeted FOXO4 expression. • MiR-1274a triggered PI3K/Akt signaling in cancer cells. • MiR-1274a significantly increased tumor xenografts growth.

  20. Increased Cell Proliferation in Chronic Helicobacter pylori Positive Gastritis and Gastric Carcinoma – Correlation between Immuno-Histochemistry and Tv Image Cytometry

    Directory of Open Access Journals (Sweden)

    Erika Szaleczky

    2000-01-01

    Full Text Available Backgound: Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium.

  1. Effect of NF-κB, survivin, Bcl-2 and Caspase3 on apoptosis of gastric cancer cells induced by tumor necrosis factor related apoptosis inducing ligand

    Institute of Scientific and Technical Information of China (English)

    Liu-Qin Yang; Dian-Chun Fang; Rong-Quan Wang; Shi-Ming Yang

    2004-01-01

    AIM: To study the effect of NF-κB, survivin, Bcl-2 and Caspase3 on tumor necrosis factors related apoptosis inducing ligand (TRAIL) induced apoptosis of gastric cancer cells.METHODS: Gastric cancer cells of SGC-7901, MKN28,MKN45 and AGS lines were cultured in PRMI-1640 medium and the apoptosis rates of the cells of 4 lines were observed after treatment of tumor necrosis factors related apoptosis inducing ligand (TRAIL) with a flow cytometer. The expression of NF-κB, survivin, Bcl-2 and Caspase3 in gastric cancer cells of 4 lines was analyzed with Western blot.RESULTS: After the gastric cancer cells were exposed to TRAIL 300 ng/ml for 24 hours, the apoptosis rate was 36.05%, 20.27%, 16.50% and 11.80% in MKN28, MKN45,AGS and SGC-7901cells respectively. Western blot revealed that the expressions of NF-κB and survivin were lower in MKN28 cells than in MKN45, AGS and SGC-7901 cells. In contrast, the expression of Caspase3 was higher in MKN28 cells than in MKN45, AGS and SGC-7901 cells.CONCLUSION: There is a selectivity of TRAIL potency to induce apoptosis in gastric cancer cells of different cell lines.The anticancer potency of TRAIL is associated with the decreased expression of NF-κB and survivin and increased expression of Caspase3 of gastric cancer cells.

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

    OpenAIRE

    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 ...

  3. Cyclooxygenase-2 mediated regulation of E-cadherin occurs in conventional but not early-onset gastric cancer cell lines

    NARCIS (Netherlands)

    R. Sitarz; R.J. Leguit; W.W.J. de Leng; F.H.M. Morsink; W.P. Polkowski; R. Maciejewski; G.J.A. Offerhaus; A.N. Milne

    2009-01-01

    Background: COX-2 and E-cadherin, involved in invasion and metastasis, are molecules critical for gastric carcinogenesis. A relationship between them is documented in non-small cell lung and prostate cancer. We present novel evidence of a relationship between COX-2 and E-cadherin expression in gastr

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  6. Histone demethylase JMJD2B is required for tumor cell proliferation and survival and is overexpressed in gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wenjuan; Zhao, Li; Zang, Wen; Liu, Zhifang; Chen, Long; Liu, Tiantian [Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012 (China); Xu, Dawei, E-mail: Dawei.Xu@ki.se [Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012 (China); Department of Medicine, Division of Hematology, Karolinska University Hospital, Solna and Karolinska Institutet, Stockholm (Sweden); Jia, Jihui, E-mail: jiajihui@sdu.edu.cn [Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012 (China)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer JMJD2B is required for cell proliferation and in vivo tumorigenesis. Black-Right-Pointing-Pointer JMJD2B depletion induces apoptosis and/or cell cycle arrest. Black-Right-Pointing-Pointer JMJD2B depletion activates DNA damage response and enhances p53 stabilization. Black-Right-Pointing-Pointer JMJD2B is overexpressed in human primary gastric cancer. -- Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Jumonji domain containing 2B (JMJD2B) is a newly identified histone demethylase that regulates chromatin structure or gene expression by removing methyl residues from trimethylated lysine 9 on histone H3. Recent observations have shown oncogenic activity of JMJD2B. We explored the functional role of JMJD2B in cancer cell proliferation, survival and tumorigenesis, and determined its expression profile in gastric cancer. Knocking down JMJD2B expression by small interfering RNA (siRNA) in gastric and other cancer cells inhibited cell proliferation and/or induced apoptosis and elevated the expression of p53 and p21{sup CIP1} proteins. The enhanced p53 expression resulted from activation of the DNA damage response pathway. JMJD2B knockdown markedly suppressed xenograft tumor growth in vivo in mice. Moreover, JMJD2B expression was increased in primary gastric-cancer tissues of humans. Thus, JMJD2B is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of gastric cancer.

  7. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yanagihara Kazuyoshi

    2009-06-01

    Full Text Available Abstract Background Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS, which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. Methods DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. Results DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20 of gastric cancer cell lines (8–18-fold amplification and 4.7% (4/86 of primary gastric tumors (8–50-fold amplification. KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild

  8. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    International Nuclear Information System (INIS)

    Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild-type KRAS resulted in the inhibition of cell growth and

  9. Long-term palliative treatment of patient with signet ring cell gastric cancer using endoscopic photodynamic therapy

    Directory of Open Access Journals (Sweden)

    V. V. Sokolov

    2014-01-01

    Full Text Available A case of multiple course of photodynamic therapy (PDT in patient with gastric cancer T1N0M0. Morpholological diagnosis in this patient was signet ring cell cancer. For 8 years the patient underwent endoscopic organ-sparing treatment: PDT with Photohem (17 courses, electrocoagulation of tumor (3 sessions. The drug Photohem was introduced intravenously at dose of 3.0 mg/kg body weight for 48 h before PDT. The treatment result was only partial regression of gastric tumor, the maximal follow-up period with no endoscopic and morphological signs of tumor growth accounted for 8 months. However besides incomplete removal of gastric tumor and morphological type, for check-up examination 8 years after the onset of endoscopic treatment there were no features of regional and distant metastases according to chest and abdominal CT and US. 

  10. Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin's lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-me history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

  11. Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Guanglin Cui; Helge L Waldum

    2007-01-01

    Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms.Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like (ECL) cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, longterm hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels,leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

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    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.

  15. Methyl jasmonate abolishes the migration, invasion and angiogenesis of gastric cancer cells through down-regulation of matrix metalloproteinase 14

    International Nuclear Information System (INIS)

    Recent evidence indicates that methyl jasmonate (MJ), a plant stress hormone, exhibits anti-cancer activity on human cancer cells. The aim of this study is to determine whether sub-cytotoxic MJ can abolish the migration, invasion and angiogenesis gastric cancer cells. Human gastric cancer cell lines SGC-7901 and MKN-45 were treated with diverse concentrations of MJ. Cell viability, proliferation, migration, invasion and angiogenesis capabilities of cancer cells were measured by MTT colorimetry, EdU incorporation, scratch assay, matrigel invasion assay, and tube formation assay. Gene expression was detected by western blot and real-time quantitative RT-PCR. Binding of transcription factor on gene promoter was detected by chromatin immunoprecipitation. Sub-cytotoxic (0.05 to 0.2 mM) MJ attenuated the migration, invasion and angiogenesis, but not the cell viability or proliferation, of gastric cancer cells in a time- and dose-dependent manner, with down-regulation of matrix metalloproteinase 14 (MMP-14) and its downstream gene vascular endothelial growth factor. Restoration of MMP-14 expression rescued the SGC-7901 and MKN-45 cells from sub-cytotoxic MJ-inhibited migration, invasion and angiogenesis. In addition, sub-cytotoxic MJ decreased the specificity protein 1 (Sp1) expression and binding on MMP-14 promoter, while restoration of Sp1 expression rescued the cancer cells from sub-cytotoxic MJ-mediated defects in MMP-14 expression, migration, invasion and angiogenesis. Sub-cytotoxic MJ attenuates the MMP-14 expression via decreasing the Sp1 expression and binding on MMP-14 promoter, thus inhibiting the migration, invasion and angiogenesis of gastric cancer cells

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

    Institute of Scientific and Technical Information of China (English)

    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. Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Yuan Zhou

    Full Text Available BACKGROUND: Casticin is one of the main active components obtained from Fructus Viticis and has been reported to exert anti-carcinogenic activity on a variety of cancer cells but the precise mechanism underlying this activity remains unclear. MATERIALS AND METHODS: Apoptotic activities of casticin (1.0 µmol/l and TRAIL (25, 50 ng/ml alone or in combination in the gastric cancer cell lines BGC-823, SGC-7901 and MGC-803 were detected by the use of a cell apoptosis ELISA detection kit, flow cytometry (FCM with propidium iodide (PI staining and activities of caspase-3, -8 and -9 by ELISA and cleavage of polyADP-ribose polymerase (PARP protein using western blot analysis. Death receptors (DR expression levels were evaluated using FCM analysis and western blotting. 2', 7'-dichlorofluorescein diacetate (DCFH-DA was used as a probe to measure the increase in reactive oxygen species (ROS levels in cells. Multiple interventions, such as siRNA transfection and pharmacological inhibitors were used to explore the mechanisms of these actions. RESULTS: Subtoxic concentrations of casticin significantly potentiated TRAIL-induced cytotoxicity and apoptosis in BGC-823, SGC-7901 and MGC-803 cells. Casticin dramatically upregulated DR5 receptor expression but had no effects on DR4 or decoy receptors. Deletion of DR5 by siRNA significantly reduced the apoptosis induced by the co-application of TRAIL and casticin. Gene silencing of the CCAAT/enhancer binding protein homologous protein (CHOP and pretreatment with salubrinal, an endoplasmic reticulum (ER stress inhibitor, attenuated casticin-induced DR5 receptor expression, and apoptosis and ROS production. Casticin downregulated the expression levels of the cell survival proteins cFLIP, Bcl-2, XIAP, and survivin. In addition, casticin also induced the expressions of DR5 protein in other gastric cancer cells (SGC-7901 and MGC-803. CONCLUSION/SIGNIFICANCE: Casticin enhances TRAIL-induced apoptosis through the

  18. Effects of simulated carbon dioxide and helium peumoperitoneum on proliferation and apoptosis of gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ying-Xue Hao; Hua Zhong; Chao Zhang; Dong-Zu Zeng; Yan Shi; Bo Tang; Pei-Wu Yu

    2008-01-01

    AIM: To investigate the effects of carbon dioxide (CO2)and helium insufflation administered at different pressures on the growth and apoptosis of cultured human gastric cancer cells.METHODS: The gastric cancer cells MKN-45 were exposed to a CO2 and helium environment maintained at different pressures (0, 5, 10 and 15 mmHg). The cells were exposed to simulated pneumoperitoneum environment for 4 h, and pH of the culture media was measured after it was moved to normal conditions for 0, 2, 4, 6 and 8 h. Proliferation viability of MKN-45 was examined by 3-[4,5Dimethylthiazol-2-yl],5-diphenyltetrazolium bromide or triazolyl blue (MTT) assay after it was moved to normal conditions. Apoptotic ratio was measured by Annexin V-FITC/PI double labelled staining.RESULTS: The pH of media was acid and recovered to normal after 4 h in the CO2 group while it was basic in the helium group. There was no difference between CO2 groups (under 10 mmHg ) and control group (P > 0.05)in the proliferative viability of the cells. The cultured cells exposed to 15 mmHg CO2 environment grew more slowly than control group from 4 to 7 d (P < 0.01 ) while there was no difference from 1 to 3 d (P > 0.05). The proliferative viability in helium group was not obviously different from the control group (P > 0.05). The apoptotic ratio of the cultured cells was markedly higher than that of the control group (P < 0.01) at 10 and 15 mmHg CO2 insufflation pressure. In helium group, the apoptotic ratio was not obviously different from the control group (P > 0.05).CONCLUSION: There is no obvious effect in the proliferation and apoptosis of MKN-45 cells under 10 mmHg CO2 insufflation pressure and helium in any pressure. Fifteen mmHg CO2 insufflation pressure can inhibit the proliferation of the cells and improve apoptosis.

  19. Enterococcus faecalis infection causes inflammation, intracellular oxphos-independent ROS production, and DNA damage in human gastric cancer cells.

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    Jesper A B Strickertsson

    Full Text Available BACKGROUND: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. METHODS: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA. Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR. Mitochondrial mutations were determined by sequencing. RESULTS: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos. Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. CONCLUSIONS: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-κB inflammatory response as well as impaired DNA damage response and cell cycle control gene

  20. The chief strategy officer.

    Science.gov (United States)

    Breene, R Timothy S; Nunes, Paul F; Shill, Walter E

    2007-10-01

    They're nominally and ultimately responsible for strategy, but today's CEOs have less and less time to devote to it. As a result, CEOs are appointing "chief strategy officers"--executives specifically tasked with creating, communicating, executing, and sustaining a company's strategic initiatives. In this article, three authors from Accenture share the results of their research on this emerging organizational role. The typical CSO or top strategy executive is not a pure strategist, conducting long-range planning in relative isolation. Most CSOs consider themselves doers first, with the mandate, credentials, and desire to act as well as advise. They are seasoned executives with a strong strategy orientation who have usually worn many operations hats before taking on the role. Strategy executives are charged with three critical jobs that together form the very definition of strategy execution. First, they must clarify the company's strategy for themselves and for every business unit and function, ensuring that all employees understand the details of the strategic plan and how their work connects to corporate goals. Second, CSOs must drive immediate change. The focus of the job almost always quickly evolves from creating shared alignment around a vision to riding herd on the ensuing change effort. Finally, a CSO must drive decision making that sustains organizational change. He or she must be that person who, in the CEO's stead, can walk into any office and test whether the decisions being made are aligned with the strategy and are creating the desired results. When decisions below the executive suite aren't being made in accordance with strategy, much of the CSO's job involves learning why and quickly determining whether to stay the course or change tack.

  1. Extensive gastric varices demonstrated by technetium-99m red blood cell scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Shih, W.J.; Domstad, P.A.; Loh, F.G.; Pulmano, C.

    1987-04-01

    An alcohol abuse patient complicated by chronic pancreatitis had splenic vein thrombosis leading to gastric varices and underwent abdominal Tc-99m red blood cell scintigraphy. First pass study, sequential images up to 1 hour, and a 2.5 hour image showed abnormal radioactivity in the left side of the abdomen and midabdomen. In 24 hour images, the high level of activity in the left side persisted; in addition, there was accumulation of radioactivity in the cecum, ascending, transverse colon, the splenic flexure, and descending colon. A splenectomy was performed and during the surgical procedure, a large dilated vein in the greater omentum was noted. It is reemphasized that delayed imaging up to 24 hours is important when the results of earlier images are equivocal or negative.

  2. Induction of Apoptosis by L-NMMA, via FKHRL1/ROCK Pathway in Human Gastric Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    YONG-ZHONG WANG; ZHEN-QING FENG

    2006-01-01

    To investigate the apoptosis-inducing effect of endogenous nitric oxide (NO) suppression in gastric cancer cells and its mechanisms. Methods Apoptosis of gastric cancer cells was detected by flow cytometry. Expression of phosphorylated FKHRL1 (thr-32, ser-253) and FKHRL1 in gastric cancer cells was analyzed using Western blotting.Immunofluorescence assay was performed to localize the intracellular phosphorylated FKHRL1 (thr-32, ser-253) and FKHRL1.Transfection of FKHRL1-HA wild type and mutant FKHRL1-HA T32A constructs was performed by lipofectamine plus reagent. NO generation was determined by Griess reaction. Results Gastric cancer cells were significantly apoptotic after treatment with NG-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor), compared with the control (P<0.01).The apoptosis of gastric cancer cells induced by L-NMMA was dose-dependent and time-independent. However, the Z-DEVD-fmk, a caspase-3, 6, 7, 8, 10 inhibitor, did not prevent the apoptosis. The immunofluorescence assays showed that FKHRL1 protein was strongly expressed in the nucleu and p-FKHRL1 thr-32 protein was strongly expressed in the cytoplasm of SGC-7901 cells when endogenous nitric oxide generation was blocked by L-NMMA, but no change in FKHRL1 ser-253phosphorylation. Nevertheless, ROCK protein was strongly expressed in p-FKHRL1 thr-32-positive SGC-7901 cells. The wortmannin, an inhibitor of phosphoinositol-3-OH kinase (PI3K), did not block the phosphorylated FKHRL1 thr-32 protein induced by L-NMMA. However, Y-27632, a specific inhibitor of the protein kinase ROCK, significantly blocked apoptosis induced by phosphorylated FKHRL1 thr-32 (P<0.01), which was mediated by L-NMMA. A significant decrease in NO generation (P<0.01) and a significant increase in apoptosis (P<0.01) were observed when FKHRL1-HA wild-type cells were transfected, which caused increased FKHRL1 thr-32 phosphorylation. Conclusions L-NMMA triggers gastric carcinoma cell apoptosis, possibly by

  3. Epigenetic mechanisms involved in differential MDR1 mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy

    Directory of Open Access Journals (Sweden)

    Kim Kyung-Jong

    2008-08-01

    Full Text Available Abstract Background The membrane transporters such as P-glycoprotein (Pgp, the MDR1 gene product, are one of causes of treatment failure in cancer patients. In this study, the epigenetic mechanisms involved in differential MDR1 mRNA expression were compared between 10 gastric and 9 colon cancer cell lines. Methods The MDR1 mRNA levels were determined using PCR and real-time PCR assays after reverse transcription. Cytotoxicity was performed using the MTT assay. Methylation status was explored by quantification PCR-based methylation and bisulfite DNA sequencing analyses. Results The MDR1 mRNA levels obtained by 35 cycles of RT-PCR in gastric cancer cells were just comparable to those obtained by 22 cycles of RT-PCR in colon cancer cells. Real-time RT-PCR analysis revealed that MDR1 mRNA was not detected in the 10 gastric cancer cell lines but variable MDR1 mRNA levels in 7 of 9 colon cancer cell lines except the SNU-C5 and HT-29 cells. MTT assay showed that Pgp inhibitors such as cyclosporine A, verapamil and PSC833 sensitized Colo320HSR (colon, highest MDR1 expression but not SNU-668 (gastric, highest and SNU-C5 (gastric, no expression to paclitaxel. Quantification PCR-based methylation analysis revealed that 90% of gastric cancer cells, and 33% of colon cancer cells were methylated, which were completely matched with the results obtained by bisulfite DNA sequencing analysis. 5-aza-2'-deoxcytidine (5AC, a DNA methyltransferase inhibitor increased the MDR1 mRNA levels in 60% of gastric cells, and in 11% of colon cancer cells. Trichostatin A (TSA, histone deacetylase inhibitor increased the MDR1 mRNA levels in 70% of gastric cancer cells and 55% of colon cancer cells. The combined treatment of 5AC with TSA increased the MDR1 mRNA levels additively in 20% of gastric cancer cells, but synergistically in 40% of gastric and 11% of colon cancer cells. Conclusion These results indicate that the MDR1 mRNA levels in gastric cancer cells are significantly

  4. Dynamic expansion of gastric mucosal doublecortin-like kinase 1-expressing cells in response to parietal cell loss is regulated by gastrin.

    Science.gov (United States)

    Choi, Eunyoung; Petersen, Christine P; Lapierre, Lynne A; Williams, Janice A; Weis, Victoria G; Goldenring, James R; Nam, Ki Taek

    2015-08-01

    Doublecortin-like kinase 1 (Dclk1) is considered a reliable marker for tuft cells in the gastrointestinal tract. We investigated the dynamic changes of tuft cells associated with mouse models of oxyntic atrophy and metaplasia in the stomach. Increases in the numbers of Dclk1-positive tuft cells were observed in several models of parietal cell loss. However, the expanded population of Dclk1-expressing cells showed a morphologically distinct structure in apical microvilli and acetylated microtubules, which was not seen in the tuft cells present in the normal gastric mucosa. These microvillar sensory cells (MVSCs) showed no evidence of proliferation. The expansion of the MVSCs induced by oxyntic atrophy was reversible after the return of parietal cells. More important, expansion of MVSCs after induced parietal cell loss was not observed in Gast(-/-) mice. Although the Dclk1-expressing cells in the normal gastric mucosa were in part derived from Lrig1-expressing stem cells, the Lrig1-lineaged cells did not produce the expanded Dclk1-expressing cells associated with oxyntic atrophy. These studies indicate that loss of parietal cells leads to the reversible emergence of a novel Dclk1-expressing sensory cell population in the gastric mucosa. PMID:26073039

  5. Discovery of Drug Synergies in Gastric Cancer Cells Predicted by Logical Modeling.

    Science.gov (United States)

    Flobak, Åsmund; Baudot, Anaïs; Remy, Elisabeth; Thommesen, Liv; Thieffry, Denis; Kuiper, Martin; Lægreid, Astrid

    2015-08-01

    Discovery of efficient anti-cancer drug combinations is a major challenge, since experimental testing of all possible combinations is clearly impossible. Recent efforts to computationally predict drug combination responses retain this experimental search space, as model definitions typically rely on extensive drug perturbation data. We developed a dynamical model representing a cell fate decision network in the AGS gastric cancer cell line, relying on background knowledge extracted from literature and databases. We defined a set of logical equations recapitulating AGS data observed in cells in their baseline proliferative state. Using the modeling software GINsim, model reduction and simulation compression techniques were applied to cope with the vast state space of large logical models and enable simulations of pairwise applications of specific signaling inhibitory chemical substances. Our simulations predicted synergistic growth inhibitory action of five combinations from a total of 21 possible pairs. Four of the predicted synergies were confirmed in AGS cell growth real-time assays, including known effects of combined MEK-AKT or MEK-PI3K inhibitions, along with novel synergistic effects of combined TAK1-AKT or TAK1-PI3K inhibitions. Our strategy reduces the dependence on a priori drug perturbation experimentation for well-characterized signaling networks, by demonstrating that a model predictive of combinatorial drug effects can be inferred from background knowledge on unperturbed and proliferating cancer cells. Our modeling approach can thus contribute to preclinical discovery of efficient anticancer drug combinations, and thereby to development of strategies to tailor treatment to individual cancer patients.

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

    Institute of Scientific and Technical Information of China (English)

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

    1999-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and invasive growth of gastric epithelial cells

    Directory of Open Access Journals (Sweden)

    Rieder Gabriele

    2011-11-01

    Full Text Available Abstract Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of Helicobacter pylori (H. pylori infected gastric epithelial cells leading to cell migration and invasive growth. Considering the cellular mechanisms, the type IV secretion system (T4SS and the effector protein cytotoxin-associated gene A (CagA of H. pylori are well-studied initiators of distinct signal transduction pathways in host cells targeting kinases, adaptor proteins, GTPases, actin binding and other proteins involved in the regulation of the actin lattice. In this review, we summarize recent findings of how H. pylori functionally interacts with the complex signaling network that controls the actin cytoskeleton of motile and invasive gastric epithelial cells.

  9. p42.3 gene expression in gastric cancer cell and its protein regulatory network analysis

    Directory of Open Access Journals (Sweden)

    Zhang Jianhua

    2012-12-01

    Full Text Available Abstract Background To analyze the p42.3 gene expression in gastric cancer (GC cell, find the relationship between protein structure and function, establish the regulatory network of p42.3 protein molecule and then to obtain the optimal regulatory pathway. Methods The expression of p42.3 gene was analyzed by RT-PCR, Western Blot and other biotechnologies. The relationship between the spatial conformation of p42.3 protein molecule and its function was analyzed using bioinformatics, MATLAB and related knowledge about protein structure and function. Furthermore, based on similarity algorithm of spatial layered spherical coordinate, we compared p42.3 molecule with several similar structured proteins which are known for the function, screened the characteristic nodes related to tumorigenesis and development, and established the multi variable relational model between p42.3 protein expression, cell cycle regulation and biological characteristics in the level of molecular regulatory networks. Finally, the optimal regulatory network was found by using Bayesian network. Results (1 The expression amount of p42.3 in G1 and M phase was higher than that in S and G2 phase; (2 The space coordinate systems of different structural domains of p42.3 protein were established in Matlab7.0 software; (3 The optimal pathway of p42.3 gene in protein regulatory network in gastric cancer is Ras protein, Raf-1 protein, MEK, MAPK kinase, MAPK, tubulin, spindle protein, centromere protein and tumor. Conclusion It is of vital significance for mechanism research to find out the action pathway of p42.3 in protein regulatory network, since p42.3 protein plays an important role in the generation and development of GC.

  10. Computer modeling of gastric parietal cell: significance of canalicular space, gland lumen, and variable canalicular [K+].

    Science.gov (United States)

    Crothers, James M; Forte, John G; Machen, Terry E

    2016-05-01

    A computer model, constructed for evaluation of integrated functioning of cellular components involved in acid secretion by the gastric parietal cell, has provided new interpretations of older experimental evidence, showing the functional significance of a canalicular space separated from a mucosal bath by a gland lumen and also shedding light on basolateral Cl(-) transport. The model shows 1) changes in levels of parietal cell secretion (with stimulation or H-K-ATPase inhibitors) result mainly from changes in electrochemical driving forces for apical K(+) and Cl(-) efflux, as canalicular [K(+)] ([K(+)]can) increases or decreases with changes in apical H(+)/K(+) exchange rate; 2) H-K-ATPase inhibition in frog gastric mucosa would increase [K(+)]can similarly with low or high mucosal [K(+)], depolarizing apical membrane voltage similarly, so electrogenic H(+) pumping is not indicated by inhibition causing similar increase in transepithelial potential difference (Vt) with 4 and 80 mM mucosal K(+); 3) decreased H(+) secretion during strongly mucosal-positive voltage clamping is consistent with an electroneutral H-K-ATPase being inhibited by greatly decreased [K(+)]can (Michaelis-Menten mechanism); 4) slow initial change ("long time-constant transient") in current or Vt with clamping of Vt or current involves slow change in [K(+)]can; 5) the Na(+)-K(+)-2Cl(-) symporter (NKCC) is likely to have a significant role in Cl(-) influx, despite evidence that it is not necessary for acid secretion; and 6) relative contributions of Cl(-)/HCO3 (-) exchanger (AE2) and NKCC to Cl(-) influx would differ greatly between resting and stimulated states, possibly explaining reported differences in physiological characteristics of stimulated open-circuit Cl(-) secretion (≈H(+)) and resting short-circuit Cl(-) secretion (>H(+)).

  11. Gastric Adenocarcinoma Presenting with Gastric Outlet Obstruction in a Child

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    Abdulrahman Al-Hussaini

    2014-01-01

    Full Text Available Gastric carcinoma is extremely rare in children representing only 0.05% of all gastrointestinal malignancies. Here, we report the first pediatric case of gastric cancer presenting with gastric outlet obstruction. Upper endoscopy revealed a markedly thickened antral mucosa occluding the pylorus and a clean base ulcer 1.5 cm × 2 cm at the lesser curvature of the stomach. The narrowed antrum and pylorus underwent balloon dilation, and biopsy from the antrum showed evidence of Helicobacter pylori gastritis. The biopsy taken from the edge of the gastric ulcer demonstrated signet-ring-cell type infiltrate consistent with gastric adenocarcinoma. At laparotomy, there were metastases to the liver, head of pancreas, and mesenteric lymph nodes. Therefore, the gastric carcinoma was deemed unresectable. The patient died few months after initiation of chemotherapy due to advanced malignancy. In conclusion, this case report underscores the possibility of gastric adenocarcinoma occurring in children and presenting with gastric outlet obstruction.

  12. hPOT1 antisense-nucieic acids inhibit the proliferation of gastric cancer cell line SGC7901

    Institute of Scientific and Technical Information of China (English)

    帖君

    2006-01-01

    Objective To investigate the effect of hPOT1 (human protection of telomeres,hPOT1) on the growth and proliferation of human gastric cancer cell line SGC7901. Methods The constructed sense and antisense hPOT1 gene eukaryotic expressing vectors were transfected into SGC7901 cells respectively, and positive clones were selected by G418. Changes of hPOT1 protein expression,

  13. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST) mimicking hereditary GIST syndromes

    OpenAIRE

    Mafalda Costa Neves; Gordon Stamp; Satvinder Mudan

    2015-01-01

    Introduction: Gastrointestinal stromal tumours (GISTs) are thought to derive from or differentiate towards the interstitial cells of Cajal (ICC) as most demonstrate a similar immunoprofile: CD117+, CD34+ and DOG1+. ICC hyperplasia refers to KIT-expressing microscopic spindle cell proliferations involving the myenteric plexus. Case report: 74 year-old male presented with a 5-year history of heartburn and dysphagia. Imaging revealed a 4 cm GIST in the gastric fundus. Pathology of the resecte...

  14. Honey and Apoptosis in Human Gastric Mucosa

    OpenAIRE

    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...

  15. Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats.

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    Carl Frederik Hansen

    Full Text Available BACKGROUND AND AIMS: Roux-en-Y gastric bypass (RYGB leads to a rapid remission of type 2 diabetes mellitus (T2DM, but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1 and peptide YY (PYY are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal. METHODS: The full rostrocaudal extension of the gut was analyzed in rats after RYGB and in sham-operated controls ad libitum fed or food restricted to match the body weight of RYGB rats. Total number of L-cells, as well as regional numbers, densities and mucosa volumes were quantified using stereological methods. Preproglucagon and PYY mRNA transcripts were quantified by qPCR to reflect the total and relative hormone production capacity of the L-cells. RESULTS: RYGB surgery induced hypertrophy of the gut mucosa in the food exposed regions of the small intestine coupled with a doubling in the total number of L-cells. No changes in L-cell density were observed in any region regardless of surgery or food restriction. The total gene expression capacity of the entire gut revealed a near 200% increase in both PYY and preproglucagon mRNA levels in RYGB rats associated with both increased L-cell number as well as region-specific increased transcription per cell. CONCLUSIONS: Collectively, these findings indicate that RYGB in rats is associated with gut hypertrophy, an increase in L-cell number, but not density, and increased PYY and preproglucagon gene expression. This could explain the enhanced gut hormone dynamics seen after RYGB.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  18. Heterotopic gastric mucosa involving the gallbladder and biliary tree

    Energy Technology Data Exchange (ETDEWEB)

    Madrid, Carmen; Berrocal, Teresa; Gorospe, Luis; Prieto, Consuelo [Department of Paediatric Radiology, Hospital Infantil ' ' La Paz' ' , Paseo de la Castellana 261, 28046 Madrid (Spain); Gamez, Manuel [Department of Paediatric Surgery, Hospital Infantil ' ' La Paz' ' , Madrid (Spain)

    2003-02-01

    A case of heterotopic gastric mucosa in the common bile duct, cystic duct and gallbladder is reported in a 3-year-old girl with abdominal pain and jaundice. Abdominal US and CT showed dilatation of the biliary tree and a well-defined mass in the common bile duct that narrowed its lumen. The gallbladder was contracted in both examinations. The common bile duct and the gallbladder were resected and a choledochojejunostomy was performed. Although gastric heterotopy has been described throughout the entire length of the gastrointestinal tract, it is a very uncommon finding in the gallbladder and extremely rare in the biliary tree. A firm diagnosis of gastric heterotopia is based on the presence of fundal mucosa replete with parietal and chief cells. To our knowledge, this is the fifth reported case of heterotopic gastric tissue within the common bile duct, and the first to describe the US and CT findings. A relevant literature review and brief outline of the histological and radiological features are included in the discussion. (orig.)

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  20. Primary rectal signet ring cell carcinoma with peritoneal dissemination and gastric secondaries

    Institute of Scientific and Technical Information of China (English)

    Hsien-Lin Sim; Kok-Yang Tan; Pak-Leng Poon; Anton Cheng

    2008-01-01

    Disseminated signet ring cell carcinomas frequently arise from the stomach. However, primaries in the colon and rectum have also been reported. We present a 68 year old lady who presented with a change in her bowel habit. Colonoscopy showed a stenosing rectal tumour at 7 cm to 8 cm from the anal verge. Multiple scattered ulcers were also noted along the entire length of the colon. Biopsy of the lesions revealed signet ring cell adenocarcinoma. Gastroscopy showed multiple nodules with ulceration over several areas of the stomach which were similar in appearance to the colonic lesions. However, no primary tumour of the stomach was seen. Biopsy of the gastric lesions also showed signet ring cell adenocarcinoma. Computed tomography scan of the abdomen and pelvis revealed circumferential tumour at the rectosigmoid junction with possible invasion into the left ischiorectal fossa. The overall picture was that of a primary rectal signet ring cell carcinoma with peritoneal dissemination. The patient was referred for palliative chemotherapy in view of the disseminated disease. In the present report, we discuss this interesting pathological entity and review the role of various histolological techniques in helping to identify the primary tumor.

  1. Cysteamine increases expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets

    Institute of Scientific and Technical Information of China (English)

    Zhi-Min Shi; Gai-Mei Du; Xi-Hui Wei; Lei Zhang; Jie Chen; Ru-Qian Zhao

    2005-01-01

    AIM: To determine the in vivo andin vivo effects of cysteamine (CS) on expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets.METHODS: Eighteen litters of newborn Xinhuai piglets were employed in the in vivo experiment and allocated to control and treatment groups. From 12 d of age (D12), piglets in control group were fed basal diet, while the treatment group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28 (one week before weaning), D35(weaning), D36.5, D38, D42, and D45 (36 h, 72 h,one week and 10 d after weaning), respectively. Semiquantitative RT-PCR was performed todetermine the levels of H+-K+-ATPase mRNA in gastric mucosa. H+-K+-ATPase activity in gastric mucosa homogenate was also determined. Gastric mucosal epithelial cells from piglets through primary cultures were used to further elucidate the effect of CS on expression and activity of H+-K+-ATPase in vivo. Cells were treated for 20 h with 0.001,0.01, and 0.1 mg/mL of CS (n = 4), respectively. The mRNA expression of H+-K+-ATPase and somatostatin (SS)as well as the H+-K+-ATPase activity were determined.RESULTS: in vivo, both mRNA expression and activity of H+-K+-ATPase in gastric mucosa of control group exhibited a trend to increase from D28 to D45, reaching a peak on D45, but did not show significant age differences. Furthermore, neither the mRNA expression nor the activity of H+-K+-ATPase was affected significantly by weaning. CS increased the mRNA expression of H+-K+-ATPase by 73%, 53%, 30% and 39% on D28(P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45(P = 0.046), respectively. In accordance with the mRNA expression, H+-K+-ATPase activities were significantly higher in treatment group than in control group on D35(P = 0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA expression and activity of H+-K+-ATPase. Both H+-K+-ATPase m

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

    Directory of Open Access Journals (Sweden)

    Jiang Guocheng

    2008-12-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

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

    International Nuclear Information System (INIS)

    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. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis.

    Science.gov (United States)

    Miyatani, Kozo; Saito, Hiroaki; Murakami, Yuki; Watanabe, Joji; Kuroda, Hirohiko; Matsunaga, Tomoyuki; Fukumoto, Yoji; Osaki, Tomohiro; Nakayama, Yuji; Umekita, Yoshihisa; Ikeguchi, Masahide

    2016-05-01

    IgG4-related disease is a newly defined disease characterized by elevated serum IgG4 levels and infiltration of affected organs by IgG4-positive plasma cells. Recently, increased IgG4 levels were reported to be closely related with malignancy. To assess the relationship between IgG4 and the progression of gastric cancer, we immunohistochemically stained in this study gastric cancer tissue samples for IgG4-positive cells using an anti-IgG4 antibody. In addition, pre- and postoperative serum concentrations of IgG4 were measured, using an enzyme-linked immunosorbent assay. In gastric cancer samples, the number of CD138-positive plasma cells was significantly lower and the number of IgG4-positive cells significantly higher than in non-cancerous gastric mucosa. The number of IgG4-positive cells was significantly correlated with gross tumor appearance, tumor depth, lymph node metastasis, venous invasion, and lymphatic invasion. Prognosis was significantly poorer in patients with a high number of IgG4-positive cells than in those with a low number. Multivariate analysis indicated that both the number of IgG4-positive cells and the depth of tumor invasion were independently prognostic of survival. In conclusion, in gastric cancer, the number of IgG4-positive cells is increased and this is closely associated with gastric cancer progression.

  5. S100A6 protein negatively regulates CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation and tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Xiaoxuan Ning

    Full Text Available Calcyclin-binding protein (CacyBP/SIP, identified on the basis of its ability to interact with S100 proteins in a calcium-dependent manner, was previously found to inhibit the proliferation and tumorigenesis of gastric cancer cells in our laboratory. Importantly, the effects of S100 proteins on the biological behavior of CacyBP/SIP in gastric cancer remain unclear. Herein, we report the construction of eukaryotic expression vectors for wild-type CacyBP/SIP and a truncated mutant lacking the S100 protein binding domain (CacyBP/SIPΔS100. The expressions of the wild-type and truncated recombinant proteins were demonstrated by transfection of MKN45 gastric cancer cells. Co-immunoprecipitation assays demonstrated interaction between S100A6 and wild-type CacyBP/SIP in MKN45 cells. Removal of the S100 protein binding domain dramatically reduced the affinity of CacyBP/SIP for S100 proteins as indicated by reduced co-immunoprecipitation of S100A6 by CacyBP/SIPΔS100. The MTT assay, FACS assay, clonogenic assay and tumor xenograft experiment were performed to assess the effect of CacyBP/SIP on cell growth and tumorigenesis in vitro and in vivo. Overexpression of CacyBP/SIP inhibited the proliferation and tumorigenesis of MKN45 gastric cancer cells; the proliferation and tumorigenesis rates were even further reduced by the expression of CacyBP/SIPΔS100. We also showed that S100 proteins negatively regulate CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation, through an effect on β-catenin protein expression and transcriptional activation of Tcf/LEF. Although the underlying mechanism of action requires further investigation, this study provides new insight into the interaction between S100 proteins and CacyBP/SIP, which might enrich our knowledge of S100 proteins and be helpful for our understanding of the development of gastric cancer.

  6. Anti-stomach serum induces contraction of isolated smooth muscle cells from gastric antrum.

    Science.gov (United States)

    Bobo, M H; Ammor, S; Magous, R; Mingard, P; Bali, J P

    1993-01-01

    In this work, we investigated the ability of anti-tissue sera to cause contraction of smooth muscle cells (SMC) in vitro. Therefore, we compared the effects of a horse immune serum raised against hog gastric tissue (SER 292), of its globulin fraction (SER 292 globulin), and of its IgG fraction (SER 292 IgG), on concentration of isolated SMC from the gastric antrum of the rabbit. Our results showed that SER 292 IgG induced a dose-dependent contraction of SMC with a higher potency than SER 292 globulin and SER 292. Preincubation of SER 292 globulin with anti-F(ab')2 but not with anti-Fc reduced the contractile activity of this anti-tissue serum. A serum raised against reticulo-endothelial system (SER 108) as well as a non immune serum (SENI) did not show any contractile activity. Our data provide evidence that SER 292 interacts with plasma membrane of SMC through its F(ab')2 fragments. Withdrawal of extracellular Ca2+ caused a significant reduction of the contractile effect induced by SER 292 IgG. When 45 Ca influx was measured, SER 292 IgG induced a specific and significant 45 Ca uptake which was blocked by pinaverium, a 'L-type' calcium channel blocker. These findings tend to show that contraction of SMC induced by SER 292 IgG involves an increase of intracellular Ca2+ concentration due in part to an influx of external Ca2+ via plasma membrane Ca2+ channels sensitive to 'L-type' channel blockers. PMID:8288445

  7. Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhaode Bu; Zhixue Zheng; Ziyu Li; xiaojiang Wu; Lianhai Zhang; Aiwen Wu; Xianglong Zong

    2013-01-01

    To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma (MGC) and signet-ring cell carcinoma (SRCC).Methods:Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery,Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed.The clinicopathological features were analyzed statistically using x2 test.Survival was analyzed using the Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression model (backward,stepwise).Results:A total of 181 patients with gastric cancer (74 MGC,107 SRCC) were included.MGC,when compared with SRCC,was featured by senile patients,stage Ⅲ and Ⅳ,,upper third stomach,large tumor size,positive lymph node metastasis,and positive lymphatic vascular invasion (P<0.05).The overall 5-year survival rate showed no difference between the two groups (48.8% vs.44.8%,P>0.05).However,the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age <60 years,negative distant metastasis,and tumor localized at upper third stomach (P<0.05).Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group,and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group.Conclusions:While compared with SRCC,MGC is associated with a more aggressive tumor biologic behavior.There is no statistically significant difference in distant metastasis,an independent prognostic indicator for both MGC and SRCC,which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.

  8. Synthesis of CdTe quantum dot-conjugated CC49 and their application for in vitro imaging of gastric adenocarcinoma cells

    OpenAIRE

    ZHANG, YUN-PENG; Sun, Peng; Zhang, Xu-Rui; YANG, WU-LI; Si, Cheng-Shuai

    2013-01-01

    The purpose of this experiment was to investigate the visible imaging of gastric adenocarcinoma cells in vitro by targeting tumor-associated glycoprotein 72 (TAG-72) with near-infrared quantum dots (QDs). QDs with an emission wavelength of about 550 to 780 nm were conjugated to CC49 monoclonal antibodies against TAG-72, resulting in a probe named as CC49-QDs. A gastric adenocarcinoma cell line (MGC80-3) expressing high levels of TAG-72 was cultured for fluorescence imaging, and a gastric epit...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  10. 3,3'-Diindolylmethane induces anti-human gastric cancer cells by the miR-30e-ATG5 modulating autophagy.

    Science.gov (United States)

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

    2016-09-01

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

  11. Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901

    OpenAIRE

    Zhang, Jian-Hua; Wan, Ming-Xi; Yuan, Jia-Ying; Pan, Bo-Rong

    2004-01-01

    AIM: To construct and identify the recombinant vectors carrying herpes simplex virus thymidine kinase (HSV-TK) and tumor necrosis factor alpha (TNF-α) or interleukin-2 (IL-2) genes expressed in gastric carcinoma cell line SGC7901.

  12. Overexpression of CDX2 in gastric cancer cells promotes the development of multidrug resistance.

    Science.gov (United States)

    Yan, Lin-Hai; Wei, Wei-Yuan; Cao, Wen-Long; Zhang, Xiao-Shi; Xie, Yu-Bo; Xiao, Qiang

    2015-01-01

    Modulator of multidrug resistance (MDR) gene is a direct transcriptional target of CDX2. However, we still speculate whether CDX2 affects MDR through other ways. In this study, a cisplatin-resistant (SGC7901/DDP) and a 5-fluoro-2, 4(1h,3h)pyrimidinedione-resistant (BGC823/5-FU) gastric cancer cell line with stable overexpression of CDX2 were established. The influence of overexpression of CDX2 on MDR was assessed by measuring IC50 of SGC7901/DDP and BGC823/5-FU cells to cisplatin, doxorubicin, and 5-fluorouracil, rate of doxorubicin efflux, apoptosis, and cell cycle progression detected by flow cytometry. In addition, we determined the in vivo effects of CDX2-overexpression lentiviral vector (LV-CDX2-GFP) on tumor size, and apoptotic cells in tumor tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and hematoxylin and eosin staining. Results showed that LV-CDX2-GFP led to up-regulation of CDX2 mRNA and protein expression. It significantly inhibited the sensitivity of SGC7901/DDP and BGC823/5-FU cells to cisplatin, doxorubicin, and 5-fluorouracil. Flow cytometry confirmed that the percentage of apoptotic cells decreased after CDX2 up-regulation. This notion was further supported by the observation that up-regulation of CDX2 blocked entry into the M-phase of the cell cycle. Furthermore, up-regulation of CDX2 significantly decreased intracellular accumulation of doxorubicin. In molecular studies, quantitative reverse-transcriptase real-time polymerase chain reaction and western blotting revealed that CDX2 up-regulation could suppress expression of Caspase-3, Caspase-9 and PTEN, and increased the expression of MDR1, MRP, mTOR, HIF-1α. PMID:25628941

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Analysis of metastasis suppressing function of E-cadherin in gastric cancer cells by RNAi

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Zheng; Xiu-Ju Sun; Hai-Tao Zhou; Chao Shang; Hong Ji; Kai-Lai Sun

    2005-01-01

    AIM: To study the effect of inhibited E-cadherin expression on invasion of cancer cells.METHODS: We designed the nucleotide sequence of siRNA corresponding to 5' non-coding and coding sequence of E-cadherin. 21-nucleotide dssiRNA was synthesized by in vitro transcription with Ambion Silencer TM siRNA Construction Kit. siRNA was transfected into gastric cancer MKN45 using TransMessenger transfection Kit. RT-PCR and immunofluorescent assay were used to investigate the inhibition of the expression of mutated Ecadherin. Invasive ability of cancer cells was determined by Transwell assay.RESULTS: The synthesis of E-cadherin mRNA rather than protein expression was suppressed dramatically 7 d after interference. Decreased protein expression was observed on d 10 after interference. On d 11, invasion ability was enhanced significantly.CONCLUSION: siRNA targeted at non-coding and coding sequence of E-cadherin showed significant inhibition on mRNA and protein expression. Inhibited E-cadherin expression results in increased invasion ability of cancer cells.

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

    Science.gov (United States)

    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. 29 CFR 457.16 - Chief, DOE.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Chief, DOE. 457.16 Section 457.16 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR STANDARDS OF CONDUCT GENERAL Meaning of Terms as Used in This Chapter § 457.16 Chief, DOE. Chief, DOE means the Chief of the...

  17. miR-449 inhibits cell proliferation and is down-regulated in gastric cancer

    DEFF Research Database (Denmark)

    Bou Kheir, Tony; Futoma-Kazmierczak, Ewa; Jacobsen, Anders;

    2011-01-01

    Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser...

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

    OpenAIRE

    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...

  19. R-CHOP with dose-attenuated radiation therapy could induce good prognosis in gastric diffuse large B cell lymphoma

    Directory of Open Access Journals (Sweden)

    Mishima Yuko

    2012-09-01

    Full Text Available Abstract Background The treatment strategy for gastric diffuse large cell lymphoma (DLBCL has not been standardized in such as to the cycles of chemotherapy, dose of radiation, or necessity for the surgery. Although the results of CHOP or R-CHOP treatments have demonstrated the good prognosis, the treatments have been controversial in many cases. Methods We retrospectively analyzed 40 gastric DLBCL patients receiving chemotherapy with or without radiation in our institute. Those in stages II-IV were treated with six cycles of R-CHOP without radiation; for those in stage I, we administered three cycles of R-CHOP with radiation. Results The three-year overall survival (OS and progression-free survival (PFS rates were 95.2 and 91.8%, respectively. Those in stage I obtained 100% of OS. The radiation dose prescribed was 30.6 Gy for CR cases and 39.6 to 40 Gy for PR after chemotherapy. Although survival rates tended to correlate with staging groups or age-adjusted IPI classifications, multivariate statistical analysis did not show clear differences. All 14 patients with initial bleeding were successfully managed without surgery during treatment. Conclusion R-CHOP therapy was very effective for gastric DLBCL. It may be not necessary to use more than 30.6 Gy of radiotherapy in the highly chemo-sensitive cases. Less toxic treatments should be made available to gastric DLBCL patients.

  20. Degradation of retinoid X receptor α by TPA through proteasome pathway in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Ye; Su Liu; Qiao Wu; Xiao-Feng Lin; Bing Zhang; Jia-Fa Wu; Ming-Qing Zhang; Wen-Jin Su

    2003-01-01

    AIM: To investigate and determine the mechanism and signal pathway of tetradecanoylphorbol-1, 3-acetate (TPA) in degradation of RXRα.METHODS: Gastric cancer cell line, BGC-823 was used in the experiments. The expression level of R XRα protein was detected by Western blot. Nuclear and cytoplasmic protein fractions were prepared through lysis of cell and centrifugation.Localization and translocation of RXRα were observed under laser-scanning confocal microscope through labeling specific anti-RXRα antibody and corresponding immunofiuorescent antibody as secondary antibody. Different inhibitors were used as required.RESULTS: In BGC-823 cells, RXRα was expressed in the nucleus. When cells were treated with TPA, expression of RXRα was repressed in a time-dependent and TPAconcentration-dependent manner. Meanwhile, translocation of RXR from the nucleus to the cytoplasm occurred, also in a time-dependent manner. When cells were pre-incubated with proteasome inhibitor MG132 for 3 hrs, followed by TPA for another 12 hrs, TPA-induced RXRα degradation was inhibited. Further observation of RXRα translocation in the presence of MG132 showed that MG-132 could block TPAinduced RXRα redistribution. Conversely, when RXRαtranslocation was inhibited by LMB, an inhibitor for blocking protein export from the nucleus, TPA could not repress expression of RXRα.CONCLUSION: TPA could induce the degradation of RXRα protein in BGC-823 cells, and this degradation is time-and TPA-concentration-dependent. Furthermore, the degradation of RXRα by TPA is via a proteasome pathway and associated with RXRα translocation from the nucleus to the cytoplasm.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  2. β-Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells

    Directory of Open Access Journals (Sweden)

    Bing Yan

    2013-01-01

    Full Text Available Emerging evidence suggests that cancer stem cells are involved in tumor angiogenesis. The Notch signaling pathway is one of the most important regulators of these processes. β-Elemene, a naturally occurring compound extracted from Curcumae Radix, has been used as an antitumor drug for various cancers in China. However, its underlying mechanism in the treatment of gastric cancer remains largely unknown. Here, we report that CD44+ gastric cancer stem-like cells (GCSCs showed enhanced proliferation capacity compared to their CD44− counterparts, and this proliferation was accompanied by the high expression of Notch-1 (in vitro. These cells were also more superior in spheroid colony formation (in vitro and tumorigenicity (in vivo and positively associated with microvessel density (in vivo. β-Elemene was demonstrated to effectively inhibit the viability of GCSCs in a dose-dependent manner, most likely by suppressing Notch-1 (in vitro. β-Elemene also contributed to growth suppression and attenuated the angiogenesis capacity of these cells (in vivo most likely by interfering with the expression of Notch-1 but not with Dll4. Our findings indicated that GCSCs play an important role in tumor angiogenesis, and Notch-1 is one of the most likely mediators involved in these processes. β-Elemene was effective at attenuating angiogenesis by targeting the GCSCs, which could be regarded as a potential mechanism for its efficacy in gastric cancer management in the future.

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

    Science.gov (United States)

    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

  4. Autoimmune gastritis and parietal cell reactivity in two children with abnormal intestinal permeability

    NARCIS (Netherlands)

    Greenwood, Deanne L. V.; Crock, Patricia; Braye, Stephen; Davidson, Patricia; Sentry, John W.

    2008-01-01

    Autoimmune gastritis is characterised by lymphocytic infiltration of the gastric submucosa, with loss of parietal and chief cells and achlorhydria. Often, gastritis is expressed clinically as cobalamin deficiency with megaloblastic anaemia, which is generally described as a disease of the elderly. H

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

    Science.gov (United States)

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

    2008-05-01

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

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

    OpenAIRE

    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...

  7. Intracellular receptor for somatostatin in gastric mucosal cells: Decomposition and reconstitution of somatostatin-stimulated phosphoprotein phosphatases

    OpenAIRE

    1982-01-01

    Using 32P-labeled histone as exogenous substrate, we showed a potent stimulatory effect of somatostatin on cytosolic phosphoprotein phosphatases (PPPases; phosphoprotein phosphohydrolase, EC 3.1.3.16) in rat gastric mucosal cells. Partial purification of cytosolic fraction in DEAE-Sephadex ion-exchange chromatography and further gel filtration on Sephadex C-75 and Sephadex G-100 separated somatostatin-dependent PPPases into three distinct molecular species. One corresponding to Mr 130,000 was...

  8. Lysophosphatidic acid stimulates gastric cancer cell proliferation via ERK1-dependent upregulation of sphingosine kinase 1 transcription

    OpenAIRE

    Ramachandran, Subramaniam; Shida, Dai; Nagahashi, Masayuki; Fang, Xianjun; Milstien, Sheldon; Takabe, Kazuaki; Spiegel, Sarah

    2010-01-01

    In MKN1 gastric cancer cells, lysophosphatidic acid (LPA) upregulates expression of sphingosine kinase 1 (SphK1) and its downregulation or inhibition suppresses LPA-mediated proliferation. Although LPA activates numerous signaling pathways downstream of its receptors, including ERK1/2, p38, JNK, and Akt, and the transactivation of the EGF receptor, pharmacological and molecular approaches demonstrated that only activation of ERK1, in addition to the CCAAT/enhancer-binding protein β (C/EBPβ) t...

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

    Directory of Open Access Journals (Sweden)

    Yanfei Jia

    Full Text Available 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.

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

    Science.gov (United States)

    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

  11. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

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

    Science.gov (United States)

    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

  13. Effects of Cyclin D1 Antisense Oligodeoxyneucleotides on the Growth and Expression of G1 Phase Regulators in Gastric Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    帅晓明; 韩高雄; 王国斌

    2003-01-01

    To investigate the effects of Cyclin D1 antisense oligodeoxyneucleotides (ASODN) on the growth, cell cycle progression and expression of G1 phase regulators in human gastric carcinoma cell lines SGC7901 and HS746T, phosphorothioate-modified Cyclin D1 ASODN were encapsulated by LipofectAMINE2000 and transfected into gastric carcinoma cells. Dose-dependent inhibitory effects were induced by Cyclin D1 ASODN in two gastric carcinoma cell lines. Treatment of gastric carcinoma cells with 0.2 μmol/L Cyclin D1 ASODN for 24 h could significantly inhibit their growth in vitro and in vivo, reduce expression of Cyclin DlmRNA to 26.3 % (SGC7901) and 17.3 %(HS746T) respectively. The percentage of cells in G0/G1 phase was increased as revealed by flow cytometry. Immunohistochemical staining showed that the expression of p21 was increased and the expression of Cyclin D1 and pRb was decreased in the two cell lines; the expression of p27 was increased in HS746T, but unchanged in SGC7901. Cyclin D1 ASODN could inhibit the growth and the expression of Cyclin D1 mRNA in gastric carcinoma cells, influence the cell cycle and expression of its regulators.

  14. Effect of interleukin-1β and tumor necrosis factor α gene silencing on mouse gastric cancer cell proliferation and migration

    OpenAIRE

    SUN, ZHONGWEI; Meng, Yan; Liu, Guoqin; Jiang, Yongsheng; Meng, Qinghua; Hu, Sanyuan

    2016-01-01

    The aim of the present study was to investigate the effect of interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) gene co-silencing in mouse gastric cancer (GC) cells. Respectively, three pairs of liposome-encapsulated IL-1β and TNFα small interfering RNA (siRNA) were transfected into the mouse GC cell line MFC. The most effective siRNA, as identified by reverse transcription-polymerase chain reaction, was used for co-suppression of IL-1β and TNFα genes. The activities of cell prolifera...

  15. Impact of Fumonisin B1 on the Production of Inflammatory Cytokines by Gastric and Colon Cell Lines

    Directory of Open Access Journals (Sweden)

    Majid Mahmoodi

    2012-06-01

    Full Text Available Fumonisins, a family of mycotoxins, are mainly toxic and carcinogenic. The present study was carried out to evaluate fumonisin B1 (FB1 effects on the production of inflammatory cytokines by gastric and colon cell lines.The study was performed on two cell lines under in vitro condition, including gastric epithelial cell line (AGS and human colon adenocarcinoma cell line (SW742. Lipopolysaccharide  (LPS  was  used  for  inflammatory  cytokine  induction.  The  culture medium was supplemented with 4.5–72 mg/l of FB1 for 72 h before cell induction. The supernatants were harvested 24 h after the induction and measured for cytokines by using enzyme-linked immunosorbent assay.FB1 induced a dose-dependent increase in the production of tumor necrosis factor-α and interleukin-1β in both AGS and SW742 cell lines. This increase was statistically significant with concentration of FB1 between 9 and 72 mg/l (P < 0.05. FB1 also induced a dose- dependent decrease in interleukin-8 production. This decrease was seen in both cell lines and showed a statistical significance with FB1 concentration (P < 0.05.The results show that FB1 increases inflammatory cytokines production by various gastric and intestinal cells. This effect in the long run can possibly be the basis for the occurrence or development of inflammation and subsequent atrophy in the above-mentioned tissues.

  16. 功能性消化不良患儿胃黏膜肥大细胞与胃排空的关系%Relationship between Gastric Mucosa Mast Cell and Gastric Emptying in Children with Functional Dyspepsia

    Institute of Scientific and Technical Information of China (English)

    覃肇源; 叶辉霞; 何真

    2011-01-01

    目的 探讨功能性消化不良(FD)患儿胃黏膜肥大细胞(MC)的密度及其活化状态与胃排空的关系.方法 按罗马Ⅱ标准选择FD患儿40例,每例患儿均取胃窦黏膜1块,应用免疫组织化学法检测其MC数及其脱颗粒数,然后行固体胃排空检测,固体胃排空正常患儿为胃排空正常组,其他患儿为胃排空延迟组;统计所有标本MC的密度及脱颗粒程度,比较二组患儿的MC密度及活化状态的差异,比较MC密度正常患儿与异常患儿的胃排空差异,评估MC的脱颗粒指数与胃排空间的关系,最后进行胃排空与MC密度及脱颗粒指数间的相关性分析.结果 1.FD患儿的胃黏膜MC脱颗粒指数为(65.7±23.9)%,其中>50%者占82.5%;2.与1h胃排空正常组相比,1h胃排空延迟组MC密度显著升高(P=0.010);3.与MC密度正常组相比,MC密度异常组1h胃排空明显延迟(P=0.001);4.MC脱颗粒指数与胃排空无明显关系;5.MC密度与1h胃排空率呈负相关(P=0.030).结论 FD患儿的胃排空延迟与MC密度升高有关,MC可能通过影响胃排空介导儿童FD的发生和发展.%Objective To investigate the correlations of gastric mucosa mast cells (MC) density and activation states with gastric emptying in children with functional dyspepsia( FD). Methods Forty pediatric patients diagnosed as FD according to Rome II criteria were recruited in this study. After an antral biopsy was obtained for calculating the amount and degranulation index of MC, the gastric emptying was detected for each patient. Statistical analysis was used to evaluate the density and the degranulation degrees of MC ,then the MC density and its activation state between normal and abnormal gastric emptying groups were compared,and the gastric emptying between normal and abnormal MC density groups were compared, and the correlation of MC degranulation index was evaluated with gastric emptying. And then, interactions of MC density and activation states

  17. Gastric giardiasis.

    OpenAIRE

    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 ...

  18. Effects of fluoxetine on mast cell morphology and protease-1 expression in gastric antrum in a rat model of depression

    Institute of Scientific and Technical Information of China (English)

    Zhen-Hua Chen; Ling Xiao; Ji-Hong Chen; He-Shen Luo; Gao-Hua Wang; Yong-Lan Huang; Xiao-Ping Wang

    2008-01-01

    AIM: To investigate the effects of fluoxetine on depression-induced changes of mast cell morphology and protease-1 (rMCP-1) expression in rats.METHODS: A Sprague-Dawley rat model of chronic stress-induced depression was established. Fifty experimental rats were randomly divided into the following groups: normal control group, fluoxetine +normal control group, depressed model group, saline + depressed model group, and fluoxetine + depressed model group. Laser scanning confocal microscopy (LSCM) immunofluorecence and RT-PCR techniques were used to investigate rMCP-1 expression in gastric antrum. Mast cell morphology was observed under transmission electron microscopy. ANOVA was used for statistical analysis among groups.RESULTS: Morphologic observation indicated that depression induced mast cell proliferation, activation,and granule hyperplasia. Compared with the normal control group, the average immunofluorescence intensity of gastric antrum rMCP-1 significantly increased in depressed model group (37.4 4- 7.7 vs 24.5+ 5.6, P < 0.01) or saline + depressed model group (39.9 4- 5.0 vs 24.5 ± 5.6, P < 0.01), while there was no significant difference between fluoxetine + normal control group (23.1 4- 3.4) or fluoxetine + depressed model group (26.1 4- 3.6) and normal control group.The average level of rMCP-lmRNA of gastric antrum significantly increased in depressed model group (0.759 ± 0.357 vs 0.476 ± 0.029, P < 0.01) or saline + depressed model group (0.781 4- 0.451 vs 0.476 ±0.029, P < 0.01 ), while no significant difference was found between fluoxetine + normal control group (0.460 ± 0.027) or fluoxetine + depressed model group (0.488 ± 0.030) and normal control group. Fluoxetine showed partial inhibitive effects on mast cell ultrastructural alterations and de-regulated rMCP-1 expression in gastric antrum of the depressed rat model.CONCLUSION: Chronic stress can induce mast cell proliferation, activation, and granule hyperplasia in gastric antrum. Fluoxetine

  19. Effect of silencing Bcl-2 expression by small interfering RNA on radiosensitivity of gastric cancer BGC823 cells

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Liu; Chun-Lei Lu

    2013-01-01

    Objective: To explore the influence of silencing Bcl-2 expression by small interfering RNA (siRNA) on Bcl-2 protein expression, cell apoptosis rate and radiosensitivity of gastric cancer BGC823 cells. Methods: siRNA segment for Bcl-2 gene was designed and synthesized, then was induced into gastric cancer BGC 823 cells by liposome transfection. Bcl-2 protein expression was detected by Western Blotting. After X radiation, flow cytometry and clone forming assay were used to determine the effects of RNA interference on BGC823 cell apoptosis rate and radiosensitivity.Result:After the transfection of Bcl-2 siRNA, the positive expression rate of Bcl-2 protein in BGC823 cells was (35.45±2.35)%. Compared with the control group and negative siRNA transfection group, the rate was significantly decreased (P<0.01). The apoptosis rate of BGC823-RNAi cell was (10.81±0.91)%, which was significantly higher than the control group and negative siRNA transfection group (P<0.01). After 48h X radiation, the apoptosis rate of BGC823-RNAi was (28.91 ±1.40)%, which was significantly higher than the control group and the group without radiation (P<0.01). During clone forming assay D0, Dq and SF2 values in Bcl-2 siRNA1 transfection group were all lower than those in the control group. The radiosensitivity ratio was 1.28 (the ratio of D0) and 1.60 (the ratio of Dq). Conclusions: Specific siRNA of Bcl-2 gene can effectively inhibit the expression of Bcl-2 gene, enhance the radiosensitivity and apoptosis of gastric cancer BGC823 cells, having good clinical application perspective.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  2. FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway

    International Nuclear Information System (INIS)

    Highlights: ► The article revealed FoxP3 gene function in gastric cancer firstly. ► Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. ► Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. ► Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. ► FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.

  3. FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Gui-Fen [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: shiyao_chen@163.com [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Sun, Zhi-Rong [Department of Anesthesiology, Cancer Center, Fudan University, Shanghai (China); Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Li-Li; Lian, Jing-Jing [Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Song, Dong-Li [Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer The article revealed FoxP3 gene function in gastric cancer firstly. Black-Right-Pointing-Pointer Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. Black-Right-Pointing-Pointer Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. Black-Right-Pointing-Pointer Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Black-Right-Pointing-Pointer FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis

  4. Relation Between Fluorodeoxyglucose Uptake and Glucose Transporter 1 Expression in Gastric signet Ring Cell Carcinoma

    International Nuclear Information System (INIS)

    Gastic signet ring cell carcinoma (GSRC) is known to have low fluorodeoxyglucose (FDG) uptake. The aim of the study was to investigate the relation between FDG uptake and glucose transporter (GLUT) 1 expression and clinicopathologic parameters in cases of GSRC. Forty patients (28 men, mean age 54±12 years) with histologically confirmed GSRC who underwent pre operative [18F]FDG PET/CT were enrolled. Maximum standardized uptake values (SUVmax) were compared with clinicopathologic parameters and GLUT 1 expression. Cases were divided based on GLUT 1 expression in tumor tissues into a membranous group (n=17) and a cytoplasmic group (n=23). Mean SUVmax was significantly higher in the membranous group than in the cytoplasmic group (6.06±2.79 vs, 3.67±1.54, P=0.03). Gastric wall invasion, depth of invasion, extent of LN metastasis, overall stage, and tumor size were found to be related to SUVmax. On the other hand, age, sex, and the presence of distant metastasis were not related to SUVmax. Multiveriate analysis revealed that membranous GLCT 1 expression and the extent of LN metastasis independently predicted high FDG uptake. This study demonstrates that high FDG uptake is mediated by membranous GLUT 1 expression in GSRC

  5. [A case of pulmonary low-grade B cell lymphoma (MALT type) presenting seven years after gastric lymphoma resection].

    Science.gov (United States)

    Tojima, Hirokazu; Shimura, Ryuhi; Nishiwaki, Tetsu; Kawabata, Yoshinori

    2003-02-01

    A 71-year-old man was admitted to our hospital because of systemic edema and exertional dyspnea. Chest radiographs revealed infiltrative shadows in both lung fields, pleural effusion, and pericardial effusion. Seven years before, he had undergone gastric surgery for a gastric ulcer with lymphoid hyperplasia. In the pathologic diagnosis based on the percutaneous lung biopsy, hyalinizing granuloma was suspected. For a more thorough diagnosis, the patient was subjected to an open lung biopsy, and the final diagnosis was low-grade B-cell lymphoma of the MALT (mucosa-associated lymphoid tissue) type. Gallium scintigraphy showed accentuated accumulation in the left neck and hypothyroidism was present. Histologic re-examination of the resected stomach revealed infiltration of centrocyte-like cells and lymphoepithelial lesions, compatible with the pathologic features of MALT lymphoma. We considered that the gastric neoplasm and the pulmonary, pleural, and thyroid tumors of MALT lymphoma had occurred seven years apart in this case. Thyroid hormone replacement and CHOP therapy improved the symptoms and decreased the lung tumor size by 73%. MALT lymphomas tend to remain localized for a long period. The multiorgan involvement seen in this case is rather rare. PMID:12722333

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

    Institute of Scientific and Technical Information of China (English)

    Yan Xin; Xiao Ling Li; Yan Ping Wang; Su Min Zhang; Hua Chuan Zheng; Dong Ying Wu; Yin Chang Zhang

    2001-01-01

    AIM To reveal the correlation between thefunctional differentiation phenotypes of gastriccarcinoma cells and the invasion and metastasisby a new way of cell-function classification.METHODS Surgically resected specimens of361 gastric carcinomas (GC) were investigatedwith enzyme-, mucin-, and tumor-related markerimmunohistochemist ry. According to thedirection of cell-function differentiation,stomach carcinomas were divided into fivefunctionally differentiated types.iation type (AFDT): there were 82 (22.7%)patients including 76 (92.7%) aged 45 years.Sixty-nine (84.1%) cases belonged to theintestinal type. Thirty-eight (46.3%) expressedCD44v6 and 9 (13.6%) of 66 male patientsdeveloped liver metastasis. The 5-year survivalrate of patients in this group (58.5%) was higherMucin secreting function differentiation type(MSFDT): 54 (15%) cases. Fifty-three (98.1%)tumors had penetrated the serosa, 12 (22.2%)expressed ER and 22 (40.7%) expressedCD44v6. The postoperative 5-year survival ratefunction differentiation type (AMPFDT): therewere 180 (49.9%) cases, including 31 (17.2%)aged yanger than 45 years. The tumor was morecommon in women (62, 34.4%,) and expressedmore frequently estrogen receptors (ER) ( 129,81.7%) than other types (P<0.01). Ovarymetastasis was found in 12 (19.4%) out of 62female subjects. The patients with this type GChad the lowest 5-year survival rate (24.7%)differentiation type (SFDT): 13 (3.6%) cases.Nine (69.2%) tumors of this type derived fromAPUD system, the other 4 (30.7%) were ofdifferent histological differentiation. Sixty percent of the patients survived at least five years.(8.9%) cases. Nineteen (59.4%) cases hadlymph node metastases but no one with liver orovary metastasis. The 5-year survival rate was28.1%.CONCLUSION This new cell-functionclassification of GC is helpful in indicating thecharacteristics of invasion and metastasis of GCwith different cell-function differentiationphenotypes. Further study is needed to disclosethe correlation

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  9. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M.; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  10. Galectin 3 acts as an enhancer of survival responses in H. pylori-infected gastric cancer cells.

    Science.gov (United States)

    Subhash, Vinod Vijay; Ho, Bow

    2016-02-01

    Galectin 3 (Gal-3) is upregulated in gastric epithelial cells as a host response to Helicobacter pylori infection. However, the significance of Gal-3 expression in H. pylori-infected cells is not well established. We analyzed Gal-3 intracellular expression, localization, and its effects in H. pylori-infected gastric epithelial cells. The predominantly nuclear confined Gal-3 was shown to be upregulated and exported out to the cytoplasm in H. pylori-infected AGS cells. The nuclear export was channeled through CRM-1 (exportin-1) protein. Interestingly, knock down of Gal-3 expression led to reduced NF-κB promoter activity and interleukin-8 (IL-8) secretion, suggesting its pro-inflammatory roles. Furthermore, Gal-3 was found to be pro-proliferative and anti-apoptotic in nature, as its knock down caused a reduction in cell proliferation and an increase in apoptosis, respectively. Taken together, our data suggest the expression and upregulation of Gal-3 as a critical endogenous event in H. pylori infection that interferes with various intracellular events, causing prolonged cell survival, which is characteristic in carcinogenesis. PMID:27044250

  11. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells.

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  12. Insulin Sensitivity and β-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents

    Science.gov (United States)

    Inge, Thomas H.; Prigeon, Ronald L.; Elder, Deborah A.; Jenkins, Todd M.; Cohen, Robert M.; Xanthakos, Stavra A.; Benoit, Stephen C.; Dolan, Lawrence M.; Daniels, Stephen R.; D’Alessio, David A.

    2016-01-01

    Objective To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). Study design A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5–20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. Results In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m2 (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved β-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). Conclusions RYGB reduced body mass index and improved both insulin sensitivity and β-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. Trial registration ClinicalTrials.gov: NCT00360373. PMID:26363548

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  14. Gastric digestion of pea ferritin and modulation of its iron bioavailability by ascorbic and phytic acids in caco-2 cells

    Institute of Scientific and Technical Information of China (English)

    Satyanarayana Bejjani; Raghu Pullakhandam; Ravinder Punjal; K Madhavan Nair

    2007-01-01

    AIM: To understand the digestive stability and mechanism of release and intestinal uptake of pea ferritin iron in caco-2 cell line model.METHODS: Pea seed ferritin was purified using salt fractionation followed by gel filtration chromatography.The bioavailability of ferritin iron was assessed using coupled in vitro digestion/Caco-2 cell model in the presence or absence of ascorbic acid and phytic acid.Caco-2 cell ferritin formation was used as a surrogate marker of iron uptake. Structural changes of pea ferritin under simulated gastric pH were characterized using electrophoresis, gel filtration and circular dichroism spectroscopy.RESULTS: The caco-2 cell ferritin formation was significantly increased (P < 0.001) with FeSO4 (19.3±9.8 ng/mg protein) and pea ferritin (13.9 ± 6.19 ng/mg protein) compared to the blank digest (3.7 ± 1.8 ng/mg protein). Ascorbic acid enhanced while phytic acid decreased the pea ferritin iron bioavailability. However,either in the presence or absence of ascorbic acid, the ferritin content of caco-2 cells was significantly less with pea ferritin than with FeSO4. At gastric pH, no band corresponding to ferritin was observed in the presence of pepsin either on native PAGE or SDS-PAGE. Gel filtration chromatography and circular dichroism spectroscopy revealed a pH dependent loss of quaternary and secondary structure.CONCLUSION: Under gastric conditions, the iron core of pea ferritin is released into the digestive medium due to acid induced structural alterations and dissociation of protein. The released iron interacts with dietary factors leading to modulation of pea ferritin iron bioavailability,resembling the typical characteristics of non-heme iron.

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

    Science.gov (United States)

    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

  16. Gene transcription patterns of pH- and salt-stressed Listeria monocytogenes cells in simulated gastric and pancreatic conditions.

    Science.gov (United States)

    Mataragas, Marios; Greppi, Anna; Rantsiou, Kalliopi; Cocolin, Luca

    2014-02-01

    A Listeria monocytogenes subgenomic array, targeting 54 genes involved in the adhesion, adaptation, intracellular life cycle, invasion, and regulation of the infection cycle was used to investigate the gene expression patterns of acid- and salt-stressed Listeria cells after exposure to conditions similar to those in gastric and pancreatic fluids. Three L. monocytogenes strains, one laboratory reference strain (EGDe) and two food isolates (wild strain 12 isolated from milk and wild strain 3 isolated from fermented sausage), were used during the studies. Differences in the expressed genes were observed between the gastric and pancreatic treatments and also between the serotypes. Increased transcripts were observed of the genes belonging to the adaptation and regulation group for serotype 4b (strain 12) and to the invasion and regulation group for serotype 1/2a (strain EGDe). Interestingly, no significantly differentially expressed genes were found for serotype 3c (strain 3) in most cases. The genes related to adaptation (serotype 1/2a) and to intracellular life cycle and invasion (serotype 4b) were down-regulated in order to cope with the hostile environment of the gastric and pancreatic fluids. These findings may provide experimental evidence for the dominance of serotypes 1/2a and 4b in clinical cases of listeriosis and for the sporadic occurrence of serotype 3c. PMID:24490919

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

    Directory of Open Access Journals (Sweden)

    Chiara Di Lorenzo

    2016-07-01

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

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

    Science.gov (United States)

    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

  19. AGE AND SEX CHARACTERISTICS OF MELATONIN-POSITIVE-LABELED CELLS OF THE GASTRIC MUCOSA IN DESYNCHRONOSIS IN RATS.

    Science.gov (United States)

    Hnatiuk, V; Kononenko, N; Kozub, T; Chikitkina, V; Galiy, L

    2016-06-01

    The aim of the research was to study the state of melatonin-positive-labeled cells (MPLC) of GM in desynchronosis in rats of different age and gender. 780 sections of the pyloric part of the gastric mucosa were studied in rats of both genders at the age of 9, 15 and 20 months. Animals were divided into intact control groups and the groups of the animals kept under the conditions of continuous light for 14 days - desynchronosis. The study was performed by the method of immunohistochemical staining with the primary antibodies to melatonin (Biorbyt, UK) and the secondary Alexa Fluor 488-conjugated antibody (Abcam, UK). In the course of the research it was found that MPLC in all experimental groups were mainly located in the basal and middle segments of the tubular glands of gastric mucosa and were represented by three types of cells. In desynchronosis the number of melatonin-positive-labeled cells significantly reduced in almost every age group, with the exception of females at the age of 20 months. Thus in elderly males and females the number of melatonin-positive-labeled cells of type III increases, whereas in young and mature males it decreases, and cells of type I predominate. PMID:27441544

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  1. Correlations Between the Density of Tryptase Positive Mast Cells (DMCT) and that of New Blood Vessels (CD105+) in Patients with Gastric Cancer.

    Science.gov (United States)

    Micu, Gianina Viorica; Stăniceanu, Florica; Sticlaru, Liana Cătălina; Popp, Cristiana Gabriela; Bastian, Alexandra Eugenia; Gramada, Eliza; Pop, G; Mateescu, R B; Rimbaş, M; Archip, Bianca; Bleotu, Coralia

    2016-06-01

    Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells) and CD 105 (for new vessels). Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement. PMID:27352440

  2. Correlations Between the Density of Tryptase Positive Mast Cells (DMCT and that of New Blood Vessels (CD105+ in Patients with Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Micu Gianina Viorica

    2016-06-01

    Full Text Available Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells and CD 105 (for new vessels. Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  4. Effect of HERG Protein on the Proliferation of Gastric Cancer Cells%HERG蛋白对胃癌细胞增殖能力的影响

    Institute of Scientific and Technical Information of China (English)

    邵晓冬; 张永国; 陈江; 林浩; 郭晓钟

    2013-01-01

    目的 研究人eag相关基因(human ether-a-go-go-related gene,HERG)蛋白对胃癌细胞增殖能力的影响.方法 以基因重组方法构建HERG的siRNA质粒载体;然后将质粒载体转染胃癌细胞系,利用质粒抗性筛选稳定转染的细胞系,分别从蛋白和电流水平进行检测验证.采用四甲基偶氮唑盐(microculture tetrazolium,MTT)法对胃癌细胞进行生长曲线的描绘;采用平板克隆形成实验检测胃癌细胞的克隆形成能力.结果 成功构建了HERG-siRNA载体,载体稳定转染胃癌细胞,转染细胞中HERG蛋白及相应电流均减弱,增殖能力减弱,克隆形成能力明显下降(P<0.05).结论 HERG-siRNA可以抑制胃癌细胞的增殖和克隆形成能力,提示HERG电流在胃癌细胞的增殖中发挥作用,HERG蛋白是一个潜在的胃癌生物治疗的靶分子.%Objective To investigate the effect of human ether-a-go-go-related gene (HERG) protein on the proliferation of gastric cancer cells.Methods SiRNA vector of HERG was produced and transfected into gastric cancer cells.After transfection with HERG-siRNA,the proliferation curve of transfected gastric cancer cells was drawn with microculture tetrazolium (MTT),and the number of clone formation of transfected gastric cancer cells was calculated.Results The expression of HERG protein and HERG current in gastric cancer cells transfected with HERG-siRNA was decreased.The proliferation of gastric cancer cells and clone formation ability of gastric cancer cells were reduced (P<0.05) due to inhibiting HERG protein and current with siRNA.Conclusion HERG-siRNA can inhibit the proliferation and clone formation of gastric cancer cells.HERG protein is a potential target for gastric cancer biological therapy.

  5. Cell death triggered by alpha-emitting {sup 213}Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, Christof; Schroeck, Hedwig; Seidenschwang, Sabine; Beck, Roswitha; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Schmid, Ernst [National Research Center for Environment and Health, Institute of Radiation Biology, GSF, Neuherberg (Germany); Abend, Michael [German Armed Forces, Institute of Radiobiology, Munich (Germany); Becker, Karl-Friedrich [Technische Universitaet Muenchen, Institute of Pathology, Munich (Germany); National Research Center for Environment and Health, Institute of Pathology, GSF, Neuherberg (Germany); National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany); Apostolidis, Christos; Nikula, Tuomo K. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Kremmer, Elisabeth [National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany)

    2005-03-01

    Radioimmunotherapy with {alpha}-particle-emitting nuclides, such as{sup 213}Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by {sup 213}Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of {sup 213}Bi-d9MAb targeting d9-E-cadherin and {sup 213}Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as {sup 213}Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and {sup 213}Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with {sup 213}Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of {alpha}-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific {sup 213}Bi-d9MAb compared with unspecific {sup 213}Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound {sup 213}Bi-immunoconjugates per cell exceeded 2 x 10{sup 4}, most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by {sup 213}Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. {sup 213}Bi-immunoconjugates seem

  6. Cell death triggered by alpha-emitting 213Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death

    International Nuclear Information System (INIS)

    Radioimmunotherapy with α-particle-emitting nuclides, such as213Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by 213Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of 213Bi-d9MAb targeting d9-E-cadherin and 213Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as 213Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and 213Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with 213Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of α-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific 213Bi-d9MAb compared with unspecific 213Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound 213Bi-immunoconjugates per cell exceeded 2 x 104, most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by 213Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. 213Bi-immunoconjugates seem to induce a mode of cell death different from apoptosis in HSC45-M2 cells. (orig.)

  7. Induction of apoptosis by genipin inhibits cell proliferation in AGS human gastric cancer cells via Egr1/p21 signaling pathway.

    Science.gov (United States)

    Ko, Hyeonseok; Kim, Jee Min; Kim, Sun-Joong; Shim, So Hee; Ha, Chang Hoon; Chang, Hyo Ihl

    2015-10-01

    Natural compounds are becoming important candidates in cancer therapy due to their cytotoxic effects on cancer cells by inducing various types of programmed cell deaths. In this study, we investigated whether genipin induces programmed cell deaths and mediates in Egr1/p21 signaling pathways in gastric cancer cells. Effects of genipin in AGS cancer cell lines were observed via evaluation of cell viability, ROS generation, cell cycle arrest, and protein and RNA levels of p21, Egr1, as well as apoptotic marker genes. The cell viability of AGS cells reduced by genipin treatment via induction of the caspase 3-dependent apoptosis. Cell cycle arrest was observed at the G2/M phase along with induction of p21 and p21-dependent cyclins. As an upstream mediator of p21, the transcription factor early growth response-1 (Egr1) upregulated p21 through nuclear translocation and binding to the p21 promoter site. Silencing Egr1 expression inhibited the expression of p21 and downstream molecules involved in apoptosis. We demonstrated that genipin treatment in AGS human gastric cancer cell line induces apoptosis via p53-independent Egr1/p21 signaling pathway in a dose-dependent manner.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods To separate the changes induced by bacteria from those of the inflammatory cells...... we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression...

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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

  13. PKCα translocation from mitochondria to nucleus is closely related to induction of apoptosis in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    WU; Qiao(吴乔); LIU; Su(刘苏); DING; Liang(丁亮); YE; Xiaofeng(叶晓峰); SU; Wenjin(苏文金)

    2002-01-01

    PKCs have been implicated in the regulation of cellular differentiation, proliferation, apoptosis and signal transduction. It was demonstrated in this study that PKC? was located both at mitochondria and in cytosol in gastric cancer cell line BGC-823. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the translocation of PKCα from both mitochondria and cytosol to nucleus as clearly shown by laser-scanning-confocal microscopy, while the protein level of PKCα was not changed by TPA treatment as detected by Western blot. The results also revealed that TPA-induced translocation of PKCα was in close association with apoptosis induction, and such association was further affirmed by other experiments where various apoptotic stimuli and specific inhibitors of PKC were used. Taken together, these findings indicate that translocation of PKCα from both mitochondria and cytosol to nucleus in gastric cancer cell is accompanied by induction of apoptosis, and may imply a new mechanism of the potential linking between cell apoptosis and PKCα translocation.

  14. Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2

    NARCIS (Netherlands)

    Simmini, Salvatore; Bialecka, Monika; Huch, Meritxell; Kester, Lennart; van de Wetering, Marc; Sato, Toshiro; Beck, Felix; van Oudenaarden, Alexander; Clevers, Hans; Deschamps, Jacqueline

    2014-01-01

    The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation programme and in the gene

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

    Science.gov (United States)

    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

  16. Tumor MICA status predicts the efficacy of immunotherapy with cytokine-induced killer cells for patients with gastric cancer.

    Science.gov (United States)

    Chen, Yu; Lin, Wan-Song; Zhu, Wei-Feng; Lin, Jing; Zhou, Zhi-Feng; Huang, Chuan-Zhong; Chen, Gang; Shi, Yi; Guo, Zeng-Qing; Ye, Yun-Bin

    2016-02-01

    In this study, we determine the relationship between the expression of major histocompatibility complex class I chain-related gene A (MICA) in gastric cancer tumors after D2 gastrectomy and the clinical outcome of a CIK-containing adjuvant therapy. Ninety-five consecutive patients with gastric cancer after D2 gastrectomy who received adjuvant chemotherapy combined with CIK cell therapy were enrolled. The MICA expression of their tumors was determined by immunohistochemistry (IHC). High expression of MICA protein was documented by IHC in 38 of 95 tumor samples (40.0 %). The MICA status was significantly associated with the age and stage, p = 0.008 and 0.023, respectively. Analysis of NKG2D on in vitro expanded CIK cells showed that the percentages of NKG2D+ in CD3+/CD56+, CD3-/CD56+, and CD3+/CD8+ cells populations were 97.2 ± 1.4, 97.9 ± 1.8, and 95.6 ± 2.1 %, respectively. For patient with high MICA-expressing tumors, the median DFS and OS were longer than for the patients with tumors with low expression of MICA; 46.0 versus 41.0 months (p = 0.027), and 48.0 versus 42.0 months (p = 0.031), respectively. In a multivariate analysis, stage and MICA expression were independent prognostic factors for DFS and OS. Our findings show that adjuvant chemotherapy plus CIK therapy treatment is a promising modality for treating gastric cancer patients after D2 gastrectomy. Especially, those who have tumors with high expression of MICA were more likely to benefit from such a treatment strategy. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.

  17. miR-194 targets RBX1 gene to modulate proliferation and migration of gastric cancer cells.

    Science.gov (United States)

    Chen, Xiaonan; Wang, Yuanyuan; Zang, Wenqiao; Du, Yuwen; Li, Min; Zhao, Guoqiang

    2015-04-01

    RING box protein1 (RBX1), an essential component of SCF E3 ubiquitin ligases, plays an important role in gastric cancer. In the study, miR-194 and RBX1 expression was evaluated in 76 pairs of gastric tumor and non-tumor tissue samples by qRT-PCR, and clinicopathological characteristics were analyzed. CCK8, transwell assay, wound healing assay, and flow cytometry assay were performed to evaluate the effect of miR-194 on gastric cancer (GC) cellular proliferation, invasion, migration, apoptosis, and cell cycle, respectively. Luciferase reporter assays and Western blotting were used to evaluate whether RBX1 is a direct target of miR-194. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between miR-194 or RBX1 expression and patient survival. Then, we found that miR-194 was significantly downregulated and RBX1 upregulated in GC tissues; both of which showed significant association with tumor size, location, invasion, and tumor node metastasis. Cell proliferation, invasion, and migration were significantly restricted with miR-194 overexpression. miR-194 downregulated RBX1 protein expression, and luciferase assays showed that binding sites in the RBX1 3'UTR were required for miR-194-mediated repression of RBX1, indicating that RBX1 was a direct target of miR-194. Transfection of RBX1 without the 3'UTR restored the miR-194-inhibiting migration function. miR-194 overexpression or RBX1 lowexpression was associated with prolonged survival of GC patients. In conclusion, upregulation of miR-194 can inhibit proliferation, migration, and invasion of GC cells, possibly by targeting RBX1. Aberrant expression of miR-194 and RBX1 is correlated to GC patient survival time. PMID:25412959

  18. Antiproliferative effect of octreotide on gastric cancer cell smediated by inhibition of Akt/PKB and telomerase

    Institute of Scientific and Technical Information of China (English)

    Shan Gao; Bao-Ping Yu; Yan Li; Wei-Guo Dong; He-Sheng Luo

    2003-01-01

    AIM: To investigate the antiproliferative effect of octreotide,a long-acting analogue of somatostatin, on gastric cancer cell line SGC7901 and its possible molecular mechanisms.METHODS: Gastric cancer cell line SGC7901 employed in the study was treated with 0.008, 0.04, 0.2, 1, 5 and 25μg@ml-1 of octreotide respectively for 24 h to evaluate the antiproliferative effect of somatostatin analog on the tumor cells by MTT assay method. To elucidate the underlying mechanism, the cells were exposed to 1 μg@ml-1 of octreotide for 0, 12, 24 and 48 h, when their Akt/PKB and telomerase activities were respectively determined using PCR-ELSIA and nonradioactive protein kinase assay protocols. The same experimental procedures were also performed in the control cells that were treated with corresponding vehicles instead of somatostatin analog.RESULTS: After exposed to octreotide for 24 h at the concentrations of more than 1 μg@ml-1 SGC7901 cells exhibited a dose-dependent inhibition of growth with the inhibiting rate to be as high as 34.66 % when 25 μg@ml-1 of octreotide was applied. The Akt/PKB and telomerase activity of SGC7901 cells was significantly inhibited when the cells were exposed to 1 μg@ml-1 of octreotide for 12, 24 and 48 h compared with that of their control counterparts (P<0.01),both of which exhibited in a time-dependent manner.CONCLUSION: The antiproliferative effect of octreotide on SGC7901 cells might be mediated by the inhibition of Akt/PKB and telomerase.

  19. Local pH elevation mediated by the intrabacterial urease of Helicobacter pylori cocultured with gastric cells

    OpenAIRE

    Athmann, Christoph; Zeng, Ningxin; Kang, Tao; Marcus, Elizabeth A.; Scott, David R.; Rektorschek, Marina; Buhmann, Anita; Melchers, Klaus; Sachs, George

    2000-01-01

    Helicobacter pylori resists gastric acidity by modulating the proton-gated urea channel UreI, allowing for pHout-dependent regulation of urea access to intrabacterial urease. We employed pH- and Ca2+-sensitive fluorescent dyes and confocal microscopy to determine the location, rate, and magnitude of pH changes in an H. pylori-AGS cell coculture model, comparing wild-type bacteria with nonpolar ureI-deletion strains (ureI-ve). Addition of urea at pH 5.5 to the coculture resulted first in eleva...

  20. Opposite effects of flurbiprofen and the nitroxybutyl ester of flurbiprofen on apoptosis in cultured guinea-pig gastric mucous cells

    OpenAIRE

    Johal, Kamaljit; Hanson, Peter J

    2000-01-01

    The nitric oxide (NO)-donating nitroxybutyl ester of flurbiprofen (NO-flurbiprofen), shows reduced gastro-intestinal toxicity relative to flurbiprofen. NO may exert either pro- or anti-apoptotic effects, while non-steroidal anti-inflammatory drugs may induce apoptosis. The aim of the present work was therefore to compare the effects of flurbiprofen and NO-flurbiprofen on apoptosis in guinea-pig gastric mucous cells.Apoptotic activity was assessed by assay of caspase activity and from the frag...

  1. Differential distribution of ghrelin-O-acyltransferase (GOAT) immunoreactive cells in the mouse and rat gastric oxyntic mucosa

    OpenAIRE

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Taché, Yvette; Sachs, George; Lambrecht, Nils W. G.

    2010-01-01

    The enzyme that acylates ghrelin was recently identified in mice as the fourth member of the membrane-bound O-acyltransferases superfamily (MBOAT4) and named ghrelin-O-acyltransferase (GOAT). Only one report showed GOAT mRNA expression in ghrelin-expressing cells of the mouse stomach. We investigated the distribution of GOAT protein in peripheral tissues and co-expression with endocrine markers in the gastric mucosa using a custom-made anti-GOAT antibody. Tissues were collected from male Spra...

  2. Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901

    Institute of Scientific and Technical Information of China (English)

    Chungen Xing; Baosong Zhu; Huihui Liu; Huihua Yao; Lifeng Zhang

    2008-01-01

    We aimed to study the effects of LY294002, an inhibitor of classIphosphatidylinositol 3-kinase (PDK), on proliferation,apoptosis, and autophagy in gastric cancer cell line SGC7901.In this study, we showed that LY294002 inhibited the viability of gastric cancer SGC7901 cells.We also showed that LY294002 increased the expression of microtubule-associated protein 1 light chain 3(LC3),and increased monodansylcadaverine(MDC)-labeled vesicles.LY294002 activated autophagy by activating p53 and caspase-3,and induced apoptosis by up-regulating p53 and p53-up-regulated modulator of apoptosis(PUMA).Therefore,LY294002 might induce cytotoxicity in SGC7901 cells through activation of p53 and the downstream point PUMA.These findings suggest that inhibition of the class I PI3K signaling pathway is a potential strategy for managing gastric cancers.

  3. Effect of apoptosis on gastric adenocarcinoma cell line SGC—7901 induced by cis—9,trans—11—conjugated linoleic acid

    Institute of Scientific and Technical Information of China (English)

    Jia-RenLiu; Bing-QingChen; Yan-MeiYang; Xuan-LingWang; Ying-BenXue

    2002-01-01

    AIM:To determine the effect of apoptosis on gastric cancer cells(SGC-7901)induced by cis-9,trans-11-conjugated linoleic acid(c9,t11-CLA)and its possible mechanism in the inhibition of cancer cells growth.

  4. Splenic irradiation-induced gastric variceal bleeding in a primary splenic diffuse large B-cell lymphoma patient: a rare complication successfully treated by splenectomy with short gastric vein ligation

    Directory of Open Access Journals (Sweden)

    Lin Ying-Chu

    2012-07-01

    Full Text Available Abstract Primary splenic diffuse large B-cell lymphoma (DLBCL is a rare clinical condition, which is generally treated by six to eight cycles of chemotherapy involving a combination of rituximab and the cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP regimen. However, the treatment for chemorefractory primary splenic DLBCL remains controversial. Therapeutic splenic irradiation (SI might be a reasonable and possibly the only treatment option with curative intention for patients with chemorefractory primary splenic DLBCL. However, the efficacy and safety of therapeutic SI are unclear. Herein, we present the case of a primary splenic DLBCL patient who was refractory to multiple chemotherapy regimens but achieved complete remission after administration of therapeutic SI. However, his condition was complicated with severe gastric variceal bleeding due to splenic venous thrombosis, which was successfully treated via splenectomy and short gastric vein ligation. On the basis of our findings, we concluded that the splenic venous thrombosis-induced gastric variceal bleeding was a rare but life-threatening adverse effect of the therapeutic SI administered for primary splenic DLBCL. Surgical intervention involving splenectomy and short gastric vein ligation is mandatory and should be performed as soon as possible for such patients.

  5. Band-like arrangement of taste like sensory cells at the gastric groove: evidence for paracrine communication

    Directory of Open Access Journals (Sweden)

    Julia Anna-Maria Eberle

    2013-04-01

    Full Text Available The discovery of taste-related elements within the gastrointestinal tract has led to a growing interest in the mechanisms and physiological significance of chemosensory monitoring of chymus composition. Previous work suggests that brush cells located in the gastric groove, which parallels the limiting ridge, a structure in rodents that divides the fundus from the corpus, are candidate sensory cells. A novel sectioning technique revealed that these cells are arranged in a palisade-like manner forming a band which borders the whole length of the corpus epithelium. Using transgenic PLCβ2 promoter-GFP mice and specific antibodies, we have demonstrated that most of these cells express gustducin, PLCβ2 and TRPM5; typical signaling proteins of gustatory sensory type II cells. These molecular features strongly suggest that the cells may be capable of sensing nutrient or non-nutrient constituents of the ingested food. Since there is no evidence that brush cells are endocrine cells, attempts were made to explore how such putative chemosensory cells might transmit the information to effector cells. It was found that most of the cells express the neuronal nitric oxide synthase suggesting some paracine interaction with adjacent cells. Moreover, they also express choline acetyltransferase as well as the vesicular protein SNAP25, indicating the potential for cholinergic transmission, possibly with subjacent enteric nerve fibers.

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

    Science.gov (United States)

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

    2016-07-01

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

  7. Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins.

    Science.gov (United States)

    Chiou, Shiun-Kwei; Hoa, Neil; Hodges, Amy; Ge, Lishen; Jadus, Martin R

    2014-09-01

    Regular usage of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with reduced incidence of a variety of cancers. The molecular mechanisms underlying these chemopreventive effects remain poorly understood. This current investigation showed that in gastric cancer cells: (1) Indomethacin treatment enhanced the degradation of chromosomal passenger proteins, Survivin and Aurora B kinase; (2) Indomethacin treatment down-regulated Aurora B kinase activity in a cell cycle-independent fashion; (3) siRNA knockdown of Survivin level promoted Aurora B kinase protein degradation, and vice versa; (4) ectopic overexpression of Survivin blocked reduction of Aurora B kinase level and activity by indomethacin treatment, and vice versa; (5) siRNA knockdown of Aurora B kinase level and AZD1152 inhibition of its activity induced apoptosis, and overexpression of Aurora B kinase inhibited indomethacin-induced apoptosis; (6) indomethacin treatment reduced Aurora B kinase level, coinciding with reduction of Survivin level and induction of apoptosis, in KATO III and HT-29 cells, and in mouse gastric mucosa. A role for Aurora B kinase function in NSAID-induced apoptosis was not previously explored. Thus this report provides better understanding of the molecular mechanisms underlying the anti-cancer effect of NSAIDs by elucidating a significant role for Aurora B kinase in indomethacin-induced apoptosis.

  8. Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a gastric adenocarcinoma cell line (PG100).

    Science.gov (United States)

    Sousa, J M C; Matos, L A; Alcântara, D F A; Ribeiro, H F; Santos, L S; Oliveira, M N; Brito-Junior, L C; Khayat, A S; Guimarães, A C; Cunha, L A; Burbano, R R; Bahia, M O

    2013-01-01

    There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions. PMID:24114206

  9. Treatment and prognosis of primary gastric B-cell lymphoma. Special Reference to therapeutic strategy of MALT lymphoma

    International Nuclear Information System (INIS)

    To evaluate the influence of therapeutic methods on the prognosis of primary gastric B-cell lymphoma, we analyzed the prognostic factors for 322 patients, comprised of 186 with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 54 with diffuse large B-cell lymphoma (DLBL) plus MALT lymphoma, and 82 with DLBL without MALT lymphoma. Among them, the clinical course of 96 patients who were treated by Helicobacter pylori eradication was also evaluated. Patients who underwent stomach-conserving treatment (H. pylori eradication, chemotherapy or radiation; n=100) showed a better overall survival probability than those treated by surgery (n=222), but the progression-free probability did not differ between the two groups. After H. pylori eradication, complete remission was achieved in 55 patients, of whom histologic relapse was observed in 4 patients (7%). Second line treatment for 34 patients, who failed to respond to eradication therapy, including oral monochemotherapy with cyclophosphamide, radiation, CHOP (CHOP; cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy, and gastrectomy resulted in complete remission in 29 patients (85%). These results suggest stomach- conserving treatment to be an optimal therapeutic modality for primary gastric B-cell lymphoma. (author)

  10. Transcriptional and Functional Characterization of the G Protein-Coupled Receptor Repertoire of Gastric Somatostatin Cells

    DEFF Research Database (Denmark)

    Egerod, Kristoffer L; Engelstoft, Maja S; Lund, Mari L;

    2015-01-01

    In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion of gastric acid and pepsinogen and endocrine secretion of gastrin, ghrelin, and histamine. Using reporter mice expressing red fluorescent protein (RFP) under control of the SST promotor, we have...

  11. Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1 and matrix metalloproteinase-1 (MMP-1.

    Directory of Open Access Journals (Sweden)

    Seok-Jun Kim

    Full Text Available BACKGROUND: Galectin-3 is known to regulate cancer metastasis. However, the underlying mechanism has not been defined. Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1 (PAR-1 and matrix metalloproteinase-1 (MMP-1 PAR-1 thereby promoting gastric cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs. We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion. These studies demonstrated that: a galectin-3 silencing decreases the expression of PAR-1. b galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation. c galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription. d galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression. e Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model. f Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients. CONCLUSIONS/SIGNIFICANCE: Galectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis. Galectin-3 has the potential to serve as a useful pharmacological target for prevention of gastric cancer metastasis.

  12. RUNX3-mediated up-regulation of miR-29b suppresses the proliferation and migration of gastric cancer cells by targeting KDM2A.

    Science.gov (United States)

    Kong, Ye; Zou, Shuiyan; Yang, Fenghua; Xu, Xia; Bu, Wenhong; Jia, Jihui; Liu, Zhifang

    2016-10-10

    RUNX3 is a transcriptional factor that has been shown to regulate protein-coding gene expression at the transcriptional level. However, the regulation of RUNX3 on miRNAs is not fully understood. In this study, we used miRNA microarray to identify the miRNAs that are regulated by RUNX3 and found that miR-29b showed the most up-regulation in RUNX3 over-expressed cells compared with the control cells. We used qRT-PCR to confirm the miRNA microarray results in several gastric cancer cells and found that RUNX3 could bind to the miR-29b promoter directly and cooperate with Smad3 to increase the promoter activity of miR-29b. In the clinical setting, both RUNX3 and miR-29b are down-regulated significantly in human gastric cancer tissues. A positive correlation between miR-29b and RUNX3 was found in the gastric cancer tissues. Additionally, we found that miR-29b suppressed the proliferation and metastasis of gastric cancer cells by directly targeting KDM2A. The miR-29b/KDM2A axis was involved in the RUNX3-mediated inhibition of gastric cancer cell proliferation and metastasis. Taken together, our results suggested that RUNX3-mediated up-regulation of miR-29b inhibited the proliferation and migration of gastric cancer cells by targeting KDM2A, representing a novel molecular mechanism for the tumor suppression action of RUNX3.

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

  14. IMAGE OF A CHIEF WOMAN

    Directory of Open Access Journals (Sweden)

    Aleksandra KOLESNIKOVA

    2014-01-01

    Full Text Available The paper considered a trend showing the women who strive to get leading posts increase in numbers every year. However, on the other hand, stereotypes persist on women as a staffer unable to perform the executive du-ties. The study examined the working men and women who told their mind on an image of a chief woman; how the image correlated to a concept of an ideal woman. The authors have carried out a qualitative survey thereto with the sentence completion technique applied.

  15. Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction.

    Science.gov (United States)

    Kosai, Nik Ritza; Gendeh, Hardip Singh; Norfaezan, Abdul Rashid; Razman, Jamin; Sutton, Paul Anthony; Das, Srijit

    2015-06-01

    Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)-associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy.

  16. Leadership certificate program for chief residents

    Directory of Open Access Journals (Sweden)

    Jeffrey E. Pettit

    2014-07-01

    Full Text Available Background. Chief resident leadership development programs need to be more than a one/two day symposium to sustain leadership development. This article describes the structure and outcomes for an eight-month leadership development program for chief residents conducted over the past three years at the University of Iowa Hospitals & Clinics (UIHC, USA. Additionally, it provides keys to success and logistical issues for any institution that is considering a similar program. Innovation. Current chiefs must formally apply in late August. Sessions are held on the second Tuesday of each month for two hours. Facilitators guide each session in such a manner that they allow participants to do most of the discussion. Facilitators also provide opportunities for insight from other chiefs, and provoke deeper understanding of behaviors or thoughts. Eight topics are covered during the year with intersession assignments. Additionally, chiefs are required to attend 75% of the sessions, develop a leadership philosophy, and conduct some type of leadership presentation within their own department. Evaluation. Each year since 2010, the number of participating chiefs has risen (6, 9, 9. Evaluation data indicates a marked increase in before and after leadership knowledge and self-awareness. Additionally, chiefs have reported positive behavioral impacts regarding their leadership. Chiefs are the best advertising source for the program. Conclusions. The leadership program continues to evolve and evaluation results indicate that the content is instructive and the format is supportive for participants. Most chiefs recommend it highly for future chiefs.

  17. Ultrastructure of endocrine cells in the mucosa of the body of stomach and its relations with chief cells and parietal cells in mice%小鼠胃体部黏膜内分泌细胞的超微结构及与主细胞、壁细胞的关系

    Institute of Scientific and Technical Information of China (English)

    宋励; 王彤; 乔从进

    2011-01-01

    Objective To observe the ultrastructure of endocrine cell in the mucosa of stomach and identify its relations with chief cells and parietal cells in mice. Methods The mucosa of the adult mouse stomach was observed with the transmission electron microscope.Results The endocrine cells could be divided into three types,namely type Ⅰ , Ⅱ Ⅲ based on their ultrastructure of the secretory granules. All types of endocrine cells were in contact with the chief cells or parietal cells and the" Ω" -shaped invagination was observed on the endocrine cell membrane. Conclusion Type Ⅰ endocrine cells could be basically confirmed as enterochromaffin like cells ( ECI cells ). It could be assumed that ECL cells not only could functionally exercise influence on the acid secretion from the parietal cells,but also have a close relation with the chief cells. Furthermore,the endocrine cells also have a paracrine effect on the adjacent cells.%目的 观察小鼠胃体部黏膜内分泌细胞的超微结构,及其与胃底腺主细胞、壁细胞的相互关系.方法 取成年小鼠胃体部黏膜在透射电镜下观察内分泌细胞及主细胞、壁细胞的超微结构.结果 根据胞质中颗粒超微结构的不同特点,将内分泌细胞分为Ⅰ、Ⅱ、Ⅲ型.三型细胞均可见与主细胞及壁细胞紧密相邻,内分泌细胞的胞膜局部呈"Ω"型凹陷.结论 基本确认Ⅰ型内分泌细胞即为肠嗜铬样细胞(enterochromaffin like cell,ECL细胞),推测ECL细胞除影响壁细胞泌酸外,在功能上与主细胞也存在密切关系.胃体部内分泌细胞除以经典内分泌方式释放激素外,也可以旁分泌方式对周围细胞产生影响.

  18. Intervention effect of pinelliae decoction for purging stomach-fire on malignant transformation of bone marrow mesenchymal stem cells in the gastric cancer microenvironment

    Science.gov (United States)

    Liu, Xi-Ping; Ming, Hai-Xia; Li, Pei-Qing

    2016-01-01

    Objective: The study aimed to simulate the microenvironment of gastric cancer to promote the malignant transformation of bone marrow mesenchymal stem cells (BMSCs) and further evaluate the effect of Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions on BMSCs. Methods: Transwell co-culture was performed on the human gastric cancer cell strains BGC-823 and BMSCs to simulate the microenvironment of gastric cancer. The drug-containing serum prepared by Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions was used, and its influence on BMSCs with malignant transformation was observed. Results: BMSCs were harvested successfully from the rat bone marrow, and flow cytometer identification indicated that CD44+/CD34- cells accounted for 70.64%. The co-culture of BGC-823 cells can induce malignant transformation of BMSCs. And the drug-containing serum can induce G2 phase arrest, inhibit cell proliferation, simultaneously inhibit TERT and c-myc expression, lower the cellular ability of chemotactic migration, inhibit the tumor-forming ability of BGC-823 in nude rats and promote the tumor apoptosis. Conclusion: The effective components of Pinelliae Decoction for Purging Stomach-Fire in gastric cancer treatment are pinelliae and dried ginger, and the main acting mechanism is to inhibit tumor cell proliferation and chemotactic migration and promote apoptosis. PMID:27508014

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

    AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indomethacin (20 mg/kg), an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethacin (3 mg/kg). In cultured human gastric mucous cells, EP4 agonist effect on indomethacininduced apoptosis was assessed by flow cytometry. RESULTS: The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epitheli