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Sample records for human gastric carcinoma

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

    PubMed

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

    2007-11-01

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

  2. Expression of the Ets-1 proto-oncogene in human gastric carcinoma: correlation with tumor invasion.

    PubMed Central

    Nakayama, T.; Ito, M.; Ohtsuru, A.; Naito, S.; Nakashima, M.; Fagin, J. A.; Yamashita, S.; Sekine, I.

    1996-01-01

    The proto-oncogene Ets-1 is a transcription factor known to control the expression of a number of genes involved in extracellular matrix remodeling and has been postulated to play a role in cell migration and tumor invasion. To elucidate the involvement of Ets-1 in human gastric carcinomas, we examined 11 cases of gastric adenoma and 110 cases of gastric carcinoma by immunohistochemistry and compared the degree of Ets-1 expression with the depth of carcinoma invasion. Ets-1 was not expressed either in the normal gastric epithelium or in gastric adenomas. Among the 110 cases with gastric adenocarcinoma, 70 (63.6%) showed positive staining for the Ets-1 protein. In mucosal carcinomas, only 3 of 26 cases (11.5%) showed positive immunostaining for Ets-1. In contrast, 67 of 84 cases (79.8%) with submucosal or more invasive carcinomas showed immunopositivity and intense staining for Ets-1 in the tumor cells. The pattern of Ets-1 immunostaining in mucosal carcinomas was weak and differed from that of other local invasive carcinomas (P < 0.001). Histologically, signet-ring cell and mucinous carcinomas expressed relatively weak positivity for Ets-1. Ets-1 expression correlated significantly with the presence of lymph node metastasis (P < 0.001). In situ hybridization, using an Ets-1 oligonucleotide probe, also confirmed the presence of Ets-1 mRNA in gastric carcinomas. Expression of Ets-1 mRNA was also detected in four different kinds of cultured human gastric carcinoma cell lines by the reverse transcription polymerase chain reaction method. These findings suggest that Ets-1 is overexpressed in gastric mucosal cells that have undergone malignant conversion and that Ets-1 is one of the factors involved in the penetration of gastric carcinoma beyond the muscularis mucosa. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8952528

  3. GAGE12 mediates human gastric carcinoma growth and metastasis.

    PubMed

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

    2015-05-15

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

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

    PubMed Central

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

    2006-01-01

    AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. METHODS: Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent. PMID:17006982

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

    PubMed Central

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

    2016-01-01

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

  6. Blocking effects of genistein on cell proliferation and possible mechanism in human gastric carcinoma

    PubMed Central

    Cui, Hong-Bin; Na, Xiao-Lin; Song, Dan-Feng; Liu, Ying

    2005-01-01

    AIM: To study the blocking effects of genistein on cell proliferation cycle in human gastric carcinoma cells (SGC-7901) and the possible mechanism. METHODS: MTT assay was applied in the detection of the inhibitory effects of genistein on cell proliferation. Flow cytometry was used to analyze the cell cycle distribution. Immunocytochemical technique and Western blotting were performed to detect the protein expression of cyclin D1, cyclin B1 and p21waf1/cip1. RESULTS: Genistein significantly inhibited the growth and proliferation of human gastric carcinoma cells (SGC-7901). Seven days after treatment with different concentrations of genistein (2.5, 5.0, 10.0, 20.0 μg /mL), the growth inhibitory rates were 11.2%, 28.8%, 55.3%, 84.7% respectively and cell cycles were arrested at the G(2)/ M phase. Genistein decreased cyclin D1 protein expression and enhanced cyclin B1 and p21waf/cip1 protein expression in a concentration-dependent manner. CONCLUSION: The growth and proliferation of SGC-7901 cells can be inhibited by genistein via blocking the cell cycle, with reduced expression of cyclin D1 and enhanced expression of cyclin B1 and p21waf/cip1 protein in the concentration range of 0-20 μg /mL. PMID:15609399

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

    PubMed

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

    1992-04-01

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

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

    PubMed Central

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

    2006-01-01

    AIM: To study the expression levels of E- selectin, integrin β1 and immunoglobulin supperfamily member-intercellular 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 β1 were 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 difference (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. PMID:16773720

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

    PubMed

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

    2007-10-01

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

  10. Epstein-barr virus in gastric carcinoma.

    PubMed

    Nishikawa, Jun; Yoshiyama, Hironori; Iizasa, Hisashi; Kanehiro, Yuichi; Nakamura, Munetaka; Nishimura, Junichi; Saito, Mari; Okamoto, Takeshi; Sakai, Kouhei; Suehiro, Yutaka; Yamasaki, Takahiro; Oga, Atsunori; Yanai, Hideo; Sakaida, Isao

    2014-11-07

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

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

    PubMed

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

    2014-08-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    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. PMID:16440412

  14. Evaluation of the Expression of the Human Epithelial Receptor 2 (HER2) in Gastric Carcinoma

    PubMed Central

    Claro, Laura Carolina Lopez; Fukuhara, Daniel Kenji; Thuler, Fábio Rodrigues; Ilias, Elias Jirjoss

    2016-01-01

    Objective. To evaluate the HER2 expression on gastric adenocarcinoma from a Brazilian population and also to analyze the relations between the receptor and clinical characteristics, as well as the survival status. Materials and Methods. A retrospective analysis was conducted from January of 2008 to July of 2012, considering only gastrectomies with curative intent. Tumors were tested for HER2 status using immunohistochemistry. The relation between HER2 status and clinical aspects, surgical findings, and survival were also analyzed. Results. 222 patients with gastric carcinoma were submitted to surgery during that period, but only 121 (54,5%) were with curative intention. The immunohistochemistry revealed that 4 patients (3,3%) were HER2-positive, 6 patients (4,9%) HER2-undetermined, and 111 patients (91,7%) HER2-negative. There was no statistical concordance between HER2 status and survival or the clinical aspects. Conclusion. The HER2 overexpression rate was very low in this Brazilian population sample and cannot be considered as a prognostic factor. PMID:28105465

  15. Mast Cell Interaction with Neutrophils in Human Gastric Carcinomas: Ultrastructural Observations

    PubMed Central

    Branca, Giovanni; Alberto Caruso, Rosario

    2016-01-01

    Aim. The role of mast cells in cell-cell immune interactions has received increasing attention, although their functional interaction with neutrophils still remains to be clarified in tumors. The aim of the present study was to investigate the association between mast cells and neutrophils in a series of gastric carcinomas (GC). Patients and Methods. 52 surgically resected GC specimens were routinely processed for both light and electron microscopy. Only cases showing both mast cells and neutrophils in the tumor stroma were considered in the analysis. Results. Only 9 GC (M : F = 5 : 4; age range: 50–82 years) showed both mast cells and neutrophils in the tumor stroma. At ultrathin sections, we identified heterotypic aggregation and intermingling of mast cells and neutrophils. Mast cells had mature phenotype and showed full complement of granules with homogeneous, scroll, particle, and mixed pattern. In addition, we found normal-appearing or early apoptosis showing neutrophils. Conclusion. Our histological findings showed the likely interaction between mast cells and neutrophils in GC. We hypothesize that the granular content of mast cells may be released in small quantity through a mechanism called “kiss-and-run fusion,” which is alternative to well-known massive anaphylactic or piecemeal degranulation. PMID:27882290

  16. Trametes robiniophila may induce apoptosis and inhibit MMPs expression in the human gastric carcinoma cell line MKN-45

    PubMed Central

    Ji, Xuening; Pan, Chunxia; Li, Xiaowen; Gao, Yunbin; Xia, Lu; Quan, Xiulian; Lv, Jinyan; Wang, Ruoyu

    2017-01-01

    Gastric carcinoma (GC) is one of the most common malignant tumors and is mainly treated by invasive surgeries. The present study aimed to investigate the treatment potential of Trametes robiniophila on GC using the human GC cell line MKN-45. Cells were incubated with Trametes robiniophila at a concentration of 0, 5 and 10 mg/ml for 24 h. The apoptosis of the cell line was examined with acridine orange/ethidium bromide staining and flow cytometry. The expression of B-cell lymphoma (Bcl)-2, Fas, caspase-3, matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed using reverse transcription-polymerase chain reaction and western blotting. With increasing drug concentrations, the proportion of apoptotic and necrotic cells increased. For a certain concentration, the apoptotic ratio also increased with increasing response times. Compared with the control group, the Bcl-2, MMP-2 and MMP-9 expression levels in the MKN-45 cell line decreased, while the expression levels of Fas and caspase-3 increased (P<0.05), and the expression patterns were strengthened with increasing drug concentrations. The present study revealed that Trametes robiniophila had treatment potential on GC, and it may act on gastric cells through apoptotic induction and MMPs expression inhibition. Based on the present results, Trametes robiniophila may be considered as an alternative approach for noninvasive therapy of GC. However, future studies should be performed to clarify this further. PMID:28356967

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

    NASA Astrophysics Data System (ADS)

    Dong, Wei; Zhou, Siqi; Dong, Yan; Wang, Jingwen; Liu, Shuang; Zhu, Pengxia

    2015-03-01

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

  18. Inhibition of human gastric carcinoma cell growth in vitro by a polysaccharide from Aster tataricus.

    PubMed

    Zhang, Yunxin; Wang, Qiusheng; Wang, Tie; Zhang, Haikui; Tian, Ying; Luo, Hong; Yang, Shen; Wang, Yuan; Huang, Xun

    2012-11-01

    A water-soluble polysaccharide (WATP), with a molecular weight of 6.3 × 10⁴ Da, was isolated from Aster tataricus. According to gas chromatography (GC) analysis, WATP was composed of galactose, glucose, fucose, rhamnose, arabinose and mannose with molar ratios of 2.1:1.3:0.9:0.5:0.3:0.6. The effects of WATP on cell proliferation and apoptosis in human gastric cancer SGC-7901 cells were examined. MTT assay showed that WATP had a perfectly tumor growth inhibitory activity on SGC-7901 cells, but no cytotoxicity on SGC-7901 and primary human polymorphonuclear (PMN) cells analyzed using LDH assay. Flow cytometry analysis indicated that WATP could significantly induce apoptosis of SGC-7901 cells. Furthermore using Rh123 and Fluo-3 as fluorescent probes, respectively, it was found that mitochondrial transmembrane potential (ΔΨ(m)) of treatment groups was significantly lower than that in un-treatment group and the concentration of calcium in cells exposed to WATP for 24 h was increased in a dose dependent manner compared with unexposed group. These results suggest that WATP induces apoptosis of SGC-7901 cells through calcium- and ΔΨ(m)-dependent pathways, indicating that it is potentially useful as a natural anti-cancer agent.

  19. Apoptotic pathway induced by transduction of RUNX3 in the human gastric carcinoma cell line MKN-1.

    PubMed

    Nagahama, Yumi; Ishimaru, Mika; Osaki, Mitsuhiko; Inoue, Toshiaki; Maeda, Akihiro; Nakada, Chisato; Moriyama, Masatsugu; Sato, Kenzo; Oshimura, Mitsuo; Ito, Hisao

    2008-01-01

    The human runt-related transcription factor 3 gene (RUNX3) is considered to be a candidate tumor suppressor gene in gastric carcinoma. However, the role of RUNX3 in the regulation of cell proliferation remains unclear. In the present study, we constructed an adenoviral vector encoding human RUNX3 cDNA under the control of a Tet-responsive promoter (Ad-Tet-FLAG-RUNX3), which regulates the expression of RUNX3 in the presence or absence of doxycycline. A recombinant adenoviral expression vector encoding LacZ (Ad-Tet-LacZ) was used as a negative control. The effect of the transduction of RUNX3 on cell growth was examined using the Tet-On system in a human gastric carcinoma cell line, MKN-1. Exogenous RUNX3 expression was induced successfully by Ad-Tet-FLAG-RUNX3, but not Ad-Tet-LacZ, in the presence of doxycycline in the MKN-1 cells. At 72 h after infection, the proliferative activity in RUNX3-expressing cells was 55% or less of that of the control cells. Flow cytometry revealed that the sub-G(1) peak was increased in cells expressing RUNX3 (34.11%), indicating that the inhibition of cell growth was due to apoptosis, which was confirmed based on Hoechst 33258 staining, the release of cytochrome c from mitochondria into the cytosol, and detection of cleaved caspase-3 by western blotting in MKN-1 cells. Comprehensive analysis using a cDNA microarray showed that RUNX3 upregulated 17 apoptosis-related genes (including FADD, TRAF6, caspase-2, ING1, ING4, Calpain 10, and DNase1) and downregulated 135 apoptosis-related genes (including FLIP, PEA15, TXN2, HSPD1, IKK, and TIAL1) in MKN-1 cells. Pathway analyses to generate functional networks of the genes suggested that promotion of the formation of the death-inducing signaling complex and activation of the mitochondria-mediated pathway were associated with RUNX3-induced apoptosis. In conclusion, our findings suggest that exogenous RUNX3 expression suppressed cell proliferation by inducing apoptosis via the death

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

    PubMed

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

    2016-05-01

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

  1. [Evaluation of combination chemotherapy with 5-FU, CDDP and CPT-11 for human gastric carcinoma transplanted into nude mice - comparative study of in vivo chemosensitivity test].

    PubMed

    Kanamori, Noriaki; Fujii, Masashi; Kochi, Mitsugu; Kaiga, Teruo; Takahashi, Tohru; Takayama, Tadatoshi

    2007-06-01

    We performed in vivo chemosensitivity tests on human gastric carcinoma. To evaluate the efficacy of some combined chemotherapy for human gastric carcinoma maintained in the subcutaneous space in nude mice, we designed the following six experimental groups: 1) 5-FU group, 2) CDDP group, 3) CPT-11 group, 4) combined therapy group of 5-FU and CDDP, 5) combined therapy group of 5-FU and CPT-11, and 6) combined therapy group of CPT-11 and CDDP. An in vivo nude mice assay was performed. Histopathological changes of the tumors in nude mice, treated with anti-cancer agents,were also evaluated and compared to the results of the nude mice assay. Based on histopathological grading,the true positive rate of the nude mice assay was 0%, the true negative rate was 83.3%, and the accuracy rate was 83.3%. CPT-11 appeared to be highly efficacious when given in combination with CDDP in human gastric cancer cell lines. These results suggest that combination chemotherapy with CPT-11 and CDDP is clinically effective for gastric cancer patients.

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

    PubMed

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

    2002-08-01

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

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

    PubMed

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

    2017-01-13

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

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

    PubMed Central

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

    2017-01-01

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

  5. Ethanolic extract of Tulipa edulis Bak induces apoptosis in SGC-7901 human gastric carcinoma cells via the mitochondrial signaling pathway.

    PubMed

    Lin, Ruhui; Li, Zuanfang; Lin, Jiumao; Ye, Jinxia; Cai, Qiaoyan; Chen, Lidian; Peng, Jun

    2015-10-01

    Tulipa edulis Bak (TEB) is an active ingredient in various traditional Chinese medicine compounds and is commonly used to treat swelling and redness, remove toxicity and eliminate stagnation, as well as to prevent and treat certain cancer types. However, the underlying molecular mechanism of the anticancer activity of TEB remains unclear. The aim of the current study was to investigate the effect and underlying mechanism of the ethanolic extract of TEB (EETEB) on SGC-7901 human gastric carcinoma cells. An MTT assay was performed to analyze cell viability. In addition, transmission electron microscopy, an Annexin V/fluorescein isothiocyanate assay, a JC-1 assay and laser scanning confocal microscopy with DAPI staining were used to determine the rate of apoptosis. Furthermore, reverse transcription-polymerase chain reaction and western blot analysis were used to detect the expression levels of the apoptosis gene and protein. EETEB was identified to inhibit the growth of SGC-7901 cells in a dose-dependent manner and induce changes in cell morphology. At the molecular level, EETEB induced SGC-7901 cell DNA fragmentation, loss of plasma membrane and asymmetrical collapse of the mitochondrial membrane potential, while it increased the expression of pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein and reduced expression of anti-apoptotic Bcl-2. Thus, the results of the current study revealed that the application of EETEB may inhibit the growth of the SGC-7901 cells due to mitochondria-mediated apoptosis.

  6. Ethanolic extract of Tulipa edulis Bak induces apoptosis in SGC-7901 human gastric carcinoma cells via the mitochondrial signaling pathway

    PubMed Central

    LIN, RUHUI; LI, ZUANFANG; LIN, JIUMAO; YE, JINXIA; CAI, QIAOYAN; CHEN, LIDIAN; PENG, JUN

    2015-01-01

    Tulipa edulis Bak (TEB) is an active ingredient in various traditional Chinese medicine compounds and is commonly used to treat swelling and redness, remove toxicity and eliminate stagnation, as well as to prevent and treat certain cancer types. However, the underlying molecular mechanism of the anticancer activity of TEB remains unclear. The aim of the current study was to investigate the effect and underlying mechanism of the ethanolic extract of TEB (EETEB) on SGC-7901 human gastric carcinoma cells. An MTT assay was performed to analyze cell viability. In addition, transmission electron microscopy, an Annexin V/fluorescein isothiocyanate assay, a JC-1 assay and laser scanning confocal microscopy with DAPI staining were used to determine the rate of apoptosis. Furthermore, reverse transcription-polymerase chain reaction and western blot analysis were used to detect the expression levels of the apoptosis gene and protein. EETEB was identified to inhibit the growth of SGC-7901 cells in a dose-dependent manner and induce changes in cell morphology. At the molecular level, EETEB induced SGC-7901 cell DNA fragmentation, loss of plasma membrane and asymmetrical collapse of the mitochondrial membrane potential, while it increased the expression of pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein and reduced expression of anti-apoptotic Bcl-2. Thus, the results of the current study revealed that the application of EETEB may inhibit the growth of the SGC-7901 cells due to mitochondria-mediated apoptosis. PMID:26622854

  7. The Transcription Factor MIST1 Is a Novel Human Gastric Chief Cell Marker Whose Expression Is Lost in Metaplasia, Dysplasia, and Carcinoma

    PubMed Central

    Lennerz, Jochen K. M.; Kim, Seok-Hyung; Oates, Edward L.; Huh, Won Jae; Doherty, Jason M.; Tian, Xiaolin; Bredemeyer, Andrew J.; Goldenring, James R.; Lauwers, Gregory Y.; Shin, Young-Kee; Mills, Jason C.

    2010-01-01

    The lack of reliable molecular markers for normal differentiated epithelial cells limits understanding of human gastric carcinogenesis. Recognized precursor lesions for gastric adenocarcinoma are intestinal metaplasia and spasmolytic polypeptide expressing metaplasia (SPEM), defined here by ectopic CDX2 and TFF2 expression, respectively. In mice, expression of the bHLH transcription factor MIST1, normally restricted to mature chief cells, is down-regulated as chief cells undergo experimentally induced metaplasia. Here, we show MIST1 expression is also a specific marker of human chief cells. SPEM, with and without MIST1, is present in human lesions and, akin to murine data, likely represents transitional (TFF2+/MIST1+ = “hybrid”-SPEM) and established (TFF2+/MIST1− = SPEM) stages. Co-visualization of MIST1 and CDX2 shows similar progressive loss of MIST1 with a transitional, CDX2+/MIST1− hybrid-intestinal metaplasia stage. Interinstitutional analysis and comparison of findings in tissue microarrays, resection specimens, and biopsies (n > 400 samples), comprising the entire spectrum of recognized stages of gastric carcinogenesis, confirm MIST1 expression is restricted to the chief cell compartment in normal oxyntic mucosa, rare in established metaplastic lesions, and lost in intraepithelial neoplasia/dysplasia and carcinoma of various types with the exception of rare chief cell carcinoma (∼1%). Our findings implicate MIST1 as a reliable marker of mature, healthy chief cells, and we provide the first evidence that metaplasia in humans arises at least in part from the chief cell lineage. PMID:20709804

  8. Tumour gastrin expression and serum gastrin concentrations in dogs with gastric carcinoma are poor diagnostic indicators.

    PubMed

    Seim-Wikse, T; Kolbjørnsen, O; Jörundsson, E; Benestad, S L; Bjornvad, C R; Grotmol, T; Kristensen, A T; Skancke, E

    2014-01-01

    Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator for gastric carcinoma in man. Gastric carcinoma is rare in dogs and generally carries a grave prognosis. In this study, the expression of gastrin was investigated immunohistochemically in gastric biopsy samples from 64 dogs with gastric carcinoma. Serum gastrin concentrations were measured in 15 of these dogs and compared with those of seven healthy control dogs. Tumour tissue expressed gastrin in 8% (5/64) of the dogs with gastric carcinoma. There was no significant difference in serum gastrin concentrations between dogs with gastric carcinoma and healthy controls (P = 0.08). Expression of gastrin in gastric carcinomas is less common in dogs than in man and may therefore not be relied on as a prognostic marker in this species. Serum gastrin concentration alone is also not a useful biomarker for gastric carcinoma in dogs.

  9. Gastric metastasis by lung small cell carcinoma

    PubMed Central

    Casella, Giovanni; Bella, Camillo Di; Cambareri, Antonino Roberto; Buda, Carmelo Antonio; Corti, Gianluigi; Magri, Filippo; Crippa, Stefano; Baldini, Vittorio

    2006-01-01

    Metastatic tumors of the gastrointestinal tract are rare. We describe a case of gastric metastasis due to primary lung cancer, revealed by an upper gastrointestinal endoscopy (UGIE). Haematogenous metastases to the stomach are a rare event. To our knowledge, only 55 cases have been described in the international literature. In these patients, the prognosis is very poor. We report herein a case of gastric metastasis by lung small cell carcinoma, with a review of the literature about this rare entity. PMID:16810769

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

    PubMed

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

    2014-09-01

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

  11. The full-length DNA sequence of Epstein Barr virus from a human gastric carcinoma cell line, SNU-719.

    PubMed

    Song, Kyung-A; Yang, San-Duk; Hwang, Jinha; Kim, Jong-Il; Kang, Myung-Soo

    2015-12-01

    The consistent presence of Epstein-Barr virus (EBV) in malignant cells of EBV-associated gastric carcinoma (EBVaGC) suggests it plays an important role during the development of EBVaGC. However, the entire genomic sequence of EBV from EBVaGC has yet to be determined. This study first determined, annotated, and analyzed the full genomic sequence of EBV from the naturally infected gastric carcinoma cell line SNU-719 using next-generation sequencing and comparative analyses. In consistent with the notion that EBV sequence isolates better reflect their geographic area than tissue origin, the SNU-719 EBV (named as GC1) was categorized as an East Asian type I EBV. Compared with the prototype B95.8 sequence, SNU-719 EBV contained 1372 variations, with 937 and 435 within coding and non-coding regions, respectively. Of the 937 variations, 465 were non-synonymous changes, while 472 synonymous changes included partial internal deletions in the coding regions of LMP1 and gp350. The RNAseq transcriptome revealed that multiple BART transcripts comprised the majority of EBV RNA reads. The SNU-719 EBV expressed high levels of BART, LF3, BHLF1, and BNLF2. Evidence of RNA editing at multiple sites in the host chromosome was found; however, no evidence of genome integration was seen. The annotated SNU-719 EBV sequence will be a useful reference in future EBVaGC studies.

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

    PubMed Central

    2010-01-01

    Background Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation. Methods Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0. Results From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%). Conclusions Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively. PMID:20163738

  13. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    PubMed Central

    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

  14. Gastric carcinoma: is radical gastrectomy worth while?

    PubMed Central

    Longmire, William P

    1980-01-01

    Total gastrectomy as the treatment of choice for gastric carcinoma was evaluated by a number of centres during the decade 1945-55. The operative mortality was found to be higher, the 5-year survival rate was lower, and the undesirable digestive side effects were greater than those following subtotal resection. The very radical subtotal resections with miniature gastric remnants were also found to result in postgastrectomy symptoms quite similar to those of total gastrectomy. Technical refinements of oesophagojejunal anastomoses and the use of nutritional supplements and antianaemic therapy have reduced but have not eliminated the sequelae of radical gastrectomy. A review of 15 reports of gastric cancer treatment from 8 countries suggests that in recent years total gastrectomy has been utilised in 25.4% of resections, with an average operative mortality of 21.7% and a 5-year survival of 12.3%. Radical resection or total gastrectomy is recommended for certain specific conditions, but for the usual antral gastric cancer subtotal resection distal to the vasa brevia with preservation of the gastric fundus and spleen is recommended PMID:7362184

  15. [Surgical treatment of gastric carcinoma: lymphadenectomy].

    PubMed

    Crucitti, F; Pacelli, F; Doglietto, G B; Crucitti, P; Alfieri, S; Caprino, P

    1997-01-01

    The review of the literature shows the improvement of outcome of patients with gastric cancer after resection and extended lymphadenectomy. Lymphadenectomy D2/D3 was performed in 206 out of 639 patients with gastric cancer: 5-year survival was 66.3% versus 41.5% of the 121 patients that underwent D1 resection (p < 0.0001). Univariate and multivariate analyses show that proximal location of the cancer, advanced stage and lymphadenectomy limited to perigastric stations are negative prognostic factors. Although there are still different opinions regarding D2 or D3 lymphadenectomies for the operative risks, pancreatic resection (preferring pancreas sparing techniques) and splenectomy is subtotal gastrectomy for antral carcinoma, extended lymphadenectomy remains an important point to improve survival.

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

    PubMed Central

    Stokes, Matthew P.; Farnsworth, Charles L.; Gu, Hongbo; Jia, Xiaoying; Worsfold, Camilla R.; Yang, Vicky; Ren, Jian Min; Lee, Kimberly A.; Silva, Jeffrey C.

    2015-01-01

    Gaining insight into normal cellular signaling and disease biology is a critical goal of proteomic analyses. The ability to perform these studies successfully to extract the maximum value and discovery of biologically relevant candidate biomarkers is therefore of primary importance. Many successful studies in the past have focused on total proteome analysis (changes at the protein level) combined with phosphorylation analysis by metal affinity enrichment (changes at the PTM level). Here, we use the gastric carcinoma cell line MKN-45 treated with the c-Met inhibitor SU11274 and PKC inhibitor staurosporine to investigate the most efficient and most comprehensive strategies for both total protein and PTM analysis. Under the conditions used, total protein analysis yielded few changes in response to either compound, while analysis of phosphorylation identified thousands of sites that changed differentially between the two treatments. Both metal affinity and antibody-based enrichments were used to assess phosphopeptide changes, and the data generated by the two methods was largely complementary (non-overlapping). Label-free quantitation of peptide peak abundances was used to accurately determine fold-changes between control and treated samples. Protein interaction network analysis allowed the data to be placed in a biologically relevant context, and follow-up validation of selected findings confirmed the accuracy of the proteomic data. Together, this study provides a framework for start-to-finish proteomic analysis of any experimental system under investigation to maximize the value of the proteomic study and yield the best chance for uncovering actionable target candidates. PMID:28248267

  17. Nicotinamide N-methyltransferase: a potential biomarker for worse prognosis in gastric carcinoma.

    PubMed

    Chen, Chen; Wang, Xin; Huang, Xing; Yong, Hongmei; Shen, Jiajia; Tang, Qi; Zhu, Jin; Ni, Jian; Feng, Zhenqing

    2016-01-01

    In clinical practice, cancer stage (or grade) and some biomarkers, such as carcinoembryonic antigen (CEA) and CA199, are widely used to predict the prognosis of gastric carcinoma patients. Due to the limited role of prognostic indicators for gastric carcinoma, this condition remains one of the most fatal human malignancies with a dismal prognosis. Nicotinamide N-methyltransferase (NNMT, EC.2.1.1.1), a metabolizing enzyme, is involved in the development and progression of various carcinomas. However, the prognostic and biological functions of NNMT in gastric carcinoma are not yet clear. In the present study, NNMT was found to be overexpressed at the mRNA and protein levels in gastric carcinoma tissues compared with adjacent tissues. Importantly, the survival analysis verified that NNMT expression is an independent prognostic factor for overall survival of gastric cancer patients. Moreover, NNMT expression was related to primary tumor size, lymph node metastasis, distant metastasis, and TNM (tumor, node, and metastasis) stage. We also demonstrated that knockdown of NNMT inhibits cellular proliferation, invasion and migration in vitro and in vivo. Overall, the results of this study suggest that NNMT is a promising prognostic predictor for gastric cancer patients and could be used as a new target for gastric cancer therapy.

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

    PubMed Central

    Mao, Qian; Zhang, Pin-Hu; Yang, Jie; Xu, Jin-Di; Kong, Ming; Shen, Hong; Zhu, He; Bai, Min; Zhou, Li; Li, Guang-Fu

    2016-01-01

    Ginsenoside F2 (F2), a protopanaxdiol type of saponin, was reported to inhibit human gastric cancer cells SGC7901. To better understand the molecular mechanisms of F2, an iTRAQ-based proteomics approach was applied to define protein expression profiles in SGC7901 cells in response to lower dose (20 μM) and shorter duration (12 hour) of F2 treatment, compared with previous study. 205 proteins were screened in terms of the change in their expression level which met our predefined criteria. Further bioinformatics and experiments demonstrated that F2 treatment downregulated PRR5 and RPS15 and upregulated RPL26, which are implicated in ribosomal protein-p53 signaling pathway. F2 also inhibited CISD2, Bcl-xl, and NLRX1, which are associated with autophagic pathway. Furthermore, it was demonstrated that F2 treatment increased Atg5, Atg7, Atg10, and PUMA, the critical downstream effectors of ribosomal protein-p53 signaling pathway, and Beclin-1, UVRAG, and AMBRA-1, the important molecules in Bcl-xl/Beclin-1 pathway. The 6 differentially abundant proteins, PRR5, CISD2, Bcl-xl, NLRX1, RPS15, and RPL26, were confirmed by western blot. Taken together, ribosomal protein-p53 signaling pathway and Bcl-xl/Beclin-1 pathway might be the most significantly regulated biological process by F2 treatment in SGC7901 cells, which provided valuable insights into the deep understanding of the molecular mechanisms of F2 for gastric cancer treatment. PMID:27829861

  19. Ndrg2 promoter hypermethylation triggered by helicobacter pylori infection correlates with poor patients survival in human gastric carcinoma

    PubMed Central

    Ling, Zhi-Qiang; Ge, Ming-Hua; Lu, Xiao-Xiao; Han, Jin; Wu, Yi-Chen; Liu, Xiang; Zhu, Xin; Hong, Lian-Lian

    2015-01-01

    N-myc downstream regulated gene 2 (Ndrg2) is a candidate suppressor of cancer metastasis. We found that Ndrg2 promoter was frequently hypermethylated in gastric cancer cell lines and in 292 gastric tumor tissues. This resulted in down-regulation of Ndrg2 mRNA and protein. Ndrg2 promoter methylation was associated with H. pylori infection and worse prognosis of gastric cancer patients, which is an independent prognostic factor for the disease-free survival (DFS). We found that H. pylori silenced Ndrg2 by activating the NF-κB pathway and up-regulating DNMT3b, promoting gastric cancer progression. These findings uncover a previously unrecognized role for H. pylori infection in gastric cancer. PMID:25823664

  20. MicroRNA‑145 inhibits the malignant phenotypes of gastric carcinoma cells via downregulation of fascin 1 expression.

    PubMed

    Xue, Minghui; Zhao, Lunde; Yang, Fang; Li, Zhenjuan; Li, Guangyan

    2016-01-01

    MicroRNA (miR)‑145 has been demonstrated to act as a tumor suppressor, and deregulation of fascin 1 (FSCN1) has been observed in several types of human malignancy, including gastric carcinoma. However, the molecular mechanism underlying the function of miR‑145, specifically its targets in gastric carcinoma have yet to be fully elucidated. In the present study, downregulation of miR‑145 and upregulation of FSCN1 was identified in gastric carcinoma cell lines, compared with normal gastric mucosal epithelial cells. A luciferase reporter assay demonstrated that miR‑145 was able to bind to the 3'‑untranslated region of FSCN1 mRNA. Overexpression of miR‑145 led to a significant decrease in FSCN1 expression levels, whereas knockdown of miR‑145 resulted in increased FSCN1 expression levels in gastric carcinoma cells. Furthermore, overexpression of miR‑145 inhibited proliferation, migration and invasion in gastric carcinoma cells. Similar effects were also observed in gastric carcinoma cells transfected with FSCN1 small interfering RNA. In addition, overexpression of FSCN1 reversed the suppressive effects of miR‑145 upregulation on proliferation, migration and invasion in gastric carcinoma cells, suggesting that FSCN1 is indeed involved in the miR‑145‑mediated malignant phenotype of gastric carcinoma cells. The present study revealed an anti‑oncogenic role of miR‑145 in gastric carcinoma via inhibition of FSCN1, and suggested that miR‑145 may be used for the treatment of gastric carcinoma.

  1. Inhibition of matrix metalloproteinase activities and tightening of tight junctions by diallyl disulfide in AGS human gastric carcinoma cells.

    PubMed

    Park, Hyun Soo; Kim, Gi-Young; Choi, Il-Whan; Kim, Nam Deuk; Hwang, Hye Jin; Choi, Young-Whan; Choi, Yung Hyun

    2011-05-01

    The effect of diallyl disulfide (DADS), a major component of an oil-soluble allyl sulfide garlic (Allium sativum) derivative, on the correlation between anti-invasive activity and tightening of tight junctions (TJs) was investigated in human gastric adenocarcinoma AGS cells. Our data indicated that the inhibitory effects of DADS on cell motility and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with DADS, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels and proteins were increased. Additionally, immunoblotting results indicated that DADS repressed the levels of claudin proteins (claudin-2, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Although further studies are needed, these results suggest that DADS treatment may inhibit tumor cell motility and invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

  2. Fentanyl inhibits the progression of human gastric carcinoma MGC-803 cells by modulating NF-κB-dependent gene expression in vivo

    PubMed Central

    HE, GUODONG; LI, LI; GUAN, ENJIAN; CHEN, JING; QIN, YI; XIE, YUBO

    2016-01-01

    Fentanyl is widely used to treat acute and chronic pain. Previous in vitro studies by the present authors demonstrated that fentanyl inhibits the progression of the MGC-803 human gastric carcinoma cell line by affecting apoptosis-related genes, including nuclear factor-kappa B (NF-κB) and phosphatase and tensin homolog. In the present study, the effects of fentanyl on NF-κB-dependent gene expression were investigated in vivo. Nude mice were inoculated with an MGC-803 cell suspension, and mice that developed subcutaneous tumors measuring >1.0×1.0 cm were selected for study. Mice were administered intraperitoneal injections of fentanyl (0.05 mg/kg, group F1; 0.1 mg/kg, group F2; 0.2 mg/kg, group F3; and 0.4 mg/kg, group F4) for 14 consecutive days. Non-fentanyl-treated mice (group C) and normal saline-treated mice (group N) served as the control groups. Tumor growth was monitored by calculating the time-shift of the growth curve. Morphological changes were also observed using microscopy. The expression of NF-κB, B-cell lymphoma-2 (Bcl-2), B-cell associated X protein (Bax), vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) in the subcutaneous tumor tissue was also analyzed by reverse transcription-polymerase chain reaction and western blot analysis, and confirmed using immunohistochemistry. The relative tumor volumes of groups F1, F2, F3 and F4 were significantly reduced compared with groups C and N. Furthermore, subcutaneous tumor cells exhibited nuclear swelling, chromatin condensation, reduced chromatin and nuclear fragmentation in the F1, F2, F3 and F4 groups. The number of NF-κB+, Bcl-2+, VEGF-A+ and MMP-9+ subcutaneous tumor cells was reduced, whereas the number of Bax+ cells was increased in the F1, F2, F3 and F4 groups. Additionally, in these groups, tumor expression of NF-κB, Bcl-2, VEGF-A and MMP-9 transcripts and proteins was downregulated, while Bax messenger RNA and protein expression levels were upregulated. The

  3. Pb2+ induces gastrin gene expression by extracellular signal-regulated kinases 1/2 and transcription factor activator protein 1 in human gastric carcinoma cells.

    PubMed

    Chan, Chien-Pin; Tsai, Yao-Ting; Chen, Yao-Li; Hsu, Yu-Wen; Tseng, Joseph T; Chuang, Hung-Yi; Shiurba, Robert; Lee, Mei-Hsien; Wang, Jaw-Yuan; Chang, Wei-Chiao

    2015-02-01

    Divalent lead ions (Pb(2+) ) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb(2+) from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb(2+) affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 μM lead nitrate. We found that Pb(2+) induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb(2+) . MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb(2+) -induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb(2+) also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb(2+) on gastrin gene activity in cell culture.

  4. Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas.

    PubMed

    Zhou, Yong; Wu, Xu-Dong; Shi, Quan; Jia, Jing

    2013-03-28

    Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.

  5. Effect of prostaglandin reductase 1 (PTGR1) on gastric carcinoma using lentivirus-mediated system.

    PubMed

    Yang, Shuo; Luo, Fen; Wang, Jun; Mao, Xiang; Chen, Zongyou; Wang, Zhiming; Guo, Fenghua

    2015-01-01

    Gastric carcinoma is a digestive related malignant tumor with poor diagnosis and prognosis for advanced patients. PTGR1 (prostaglandin reductase 1), as a potential cancer biomarker, has not been reported in gastric carcinoma occurrence. To investigate the role of PTGR1 on gastric carcinoma cells, human PTGR1 was efficiently silenced by lentivirus-mediated system in MGC-803 cells confirmed by quantitative real-time PCR (qRT-PCR) and western blot. Then cell proliferation, colony formation and cell cycle were determined after knockdown of PTGR1 by MTT assay, colony assay and flow cytometry, respectively and data suggested that PTGR1 down regulated MGC-803 cells significantly suppressed the proliferation and colony formation ability and induced cell cycle arrest in the G0/G1 phase compared to controls (P < 0.001). Further investigation demonstrated knockdown of PTGR1 influenced cell proliferation and cell cycle via activating p21 and p53 signaling pathway described by Western blot assay. Our findings indicate that PTGR1 may be an oncogene in human gastric carcinoma and identified as a diagnosis and prognosis target for gastric carcinoma.

  6. Gastric neuroendocrine carcinomas in bearded dragons (Pogona vitticeps).

    PubMed

    Ritter, J M; Garner, M M; Chilton, J A; Jacobson, E R; Kiupel, M

    2009-11-01

    This article describes a newly recognized highly malignant neoplastic entity in young bearded dragons (Pogona vitticeps), gastric neuroendocrine carcinomas, which readily metastasize. Ten bearded dragons with histories of anorexia (8), vomiting (3), hyperglycemia (2), and anemia (3) were included in this study. All animals had neoplastic masses in their stomach, with metastasis to the liver. Microscopically, 6 of these neuroendocrine carcinomas were well-differentiated and 4 were poorly differentiated. For further characterization, immunohistochemistry for protein gene product 9.5, neuron-specific enolase, endorphin, chromogranins A and B, synaptophysin, somatostatin, insulin, glucagon, gastrin, pancreatic polypeptide, and vasoactive intestinal peptide was performed on 5 animals. Because only immunolabeling for somatostatin was consistently observed in all neoplasms, a diagnosis of somatostatinoma was made for these 5 bearded dragons. Some neoplasms also exhibited multihormonal expression. Electron microscopy performed on 1 tumor confirmed the presence of neuroendocrine granules within neoplastic cells. Gastric neuroendocrine carcinomas, and specifically somatostatinomas, have not been previously reported in bearded dragons, or other reptiles, and may be underdiagnosed due to inconsistent, ambiguous clinical signs. In humans, pancreatic somatostatinomas are associated with a syndrome of hypersomatostatinemia, which includes hyperglycemia, weight loss, and anemia, as observed in some of these bearded dragons. Somatostatinomas in humans are commonly associated with neurofibromatosis type 1 (Von Recklinghausen's disease), caused by a mutation in the tumor suppressor gene NF1, which results in decreased expression of neurofibromin. In all 5 animals examined, neoplasms exhibited decreased neurofibromin expression compared with control tissues, suggesting that decreased functional neurofibromin may play a role in the pathogenesis of somatostatinomas in bearded dragons.

  7. HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas.

    PubMed Central

    López-Nevot, M. A.; Esteban, F.; Ferrón, A.; Gutiérrez, J.; Oliva, M. R.; Romero, C.; Huelin, C.; Ruiz-Cabello, F.; Garrido, F.

    1989-01-01

    The expression of HLA class I antigens was studied in 99 primary tumour (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: +/-, +/+, -/+, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples. Images Figure 1 Figure 2 PMID:2649129

  8. DBGC: A Database of Human Gastric Cancer

    PubMed Central

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

    2015-01-01

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

  9. DBGC: A Database of Human Gastric Cancer.

    PubMed

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

    2015-01-01

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

  10. ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion.

    PubMed

    Yagi, R; Tanaka, M; Sasaki, K; Kamata, R; Nakanishi, Y; Kanai, Y; Sakai, R

    2011-03-24

    During the analysis of phosphotyrosine-containing proteins in scirrhous gastric carcinoma cell lines, we observed an unusual expression of Arf-GAP with Rho-GAP domain, ankyrin repeat and PH domain 3 (ARAP3), a multimodular signaling protein that is a substrate of Src family kinases. Unlike other phosphotyrosine proteins, such as CUB domain-containing protein 1 (CDCP1) and Homo sapiens chromosome 9 open reading frame 10/oxidative stress-associated Src activator (C9orf10/Ossa), which are overexpressed and hyperphosphorylated in scirrhous gastric carcinoma cell lines, ARAP3 was underexpressed in cancerous human gastric tissues. In this study, we found that overexpression of ARAP3 in the scirrhous gastric carcinoma cell lines significantly reduced peritoneal dissemination. In vitro studies also showed that ARAP3 regulated cell attachment to the extracellular matrix, as well as invasive activities. These effects were suppressed by mutations in the Rho-GTPase-activating protein (GAP) domain or in the C-terminal two tyrosine residues that are phosphorylated by Src. Thus, the expression and phosphorylation state of ARAP3 may affect the invasiveness of cancer by modulating cell adhesion and motility. Our results suggest that ARAP3 is a unique Src substrate that suppresses peritoneal dissemination of scirrhous gastric carcinoma cells.

  11. Gastric carcinoma in a South American sea lion (Otaria flavescens).

    PubMed

    Yamazaki, Mutsumi; Koutaka, Mitsuru; Une, Yumi

    2016-08-01

    A 22-year-old captive male South American sea lion (Otaria flavescens) developed an undifferentiated carcinoma originating in the cardiac region of the stomach. Clinical symptoms included vomiting, anorexia and weight loss. Ultrasonography and endoscopy showed gastric wall thickness. At necropsy, the gastric wall had significant thickening around the cardiac region, and metastases were found in some organs. Histologically, samples from the stomach wall and metastases showed the same tumor tissue. Immunohistochemistry was positive for epithelium markers. Ductal growth, keratinocytes or signet ring cells were absent. The tumor was classified as an undifferentiated carcinoma using the World Health Organization's (WHO) guide to international classification of tumors in domestic animals. This is the first report of a primary gastric carcinoma in a pinniped.

  12. Gastric carcinoma in a South American sea lion (Otaria flavescens)

    PubMed Central

    YAMAZAKI, Mutsumi; KOUTAKA, Mitsuru; UNE, Yumi

    2016-01-01

    A 22-year-old captive male South American sea lion (Otaria flavescens) developed an undifferentiated carcinoma originating in the cardiac region of the stomach. Clinical symptoms included vomiting, anorexia and weight loss. Ultrasonography and endoscopy showed gastric wall thickness. At necropsy, the gastric wall had significant thickening around the cardiac region, and metastases were found in some organs. Histologically, samples from the stomach wall and metastases showed the same tumor tissue. Immunohistochemistry was positive for epithelium markers. Ductal growth, keratinocytes or signet ring cells were absent. The tumor was classified as an undifferentiated carcinoma using the World Health Organization’s (WHO) guide to international classification of tumors in domestic animals. This is the first report of a primary gastric carcinoma in a pinniped. PMID:27052463

  13. High expression of Wls is associated with lymph node metastasis and advanced TNM stage in gastric carcinomas.

    PubMed

    Zhang, Wei; Tao, Hong; Chen, Xiao; Sugimura, Haruhiko; Wang, Jiandong; Zhou, Ping

    2017-03-01

    The roles of Wnt protein in carcinogenesis have been well documented in human cancers. Wls is a key modulator for the secretion of Wnt protein. We previously found that Wls was aberrantly expressed in colorectal carcinomas. Studies have revealed that dysregulation of Wnt signal transduction plays an important role in gastric carcinoma. We hypothesized that Wls may play a role in the development and progression of gastric carcinoma. In this study, three gastric cancer cell lines MGC-803, SGC-7901, and AGS, and a set of gastric carcinoma tissue specimens were subjected to immunohistochemistry. The relationship between the expression of Wls and clinicopathological parameters was analyzed. Wls was negatively detected in MGC-803, positively detected in SGC-7901 and AGS cell lines. Wls was weakly expressed in 9.7% (15/154), moderately in 33.1% (51/154), and strongly in 57.1% (88/154) of tested gastric carcinoma specimens. High expression of Wls was positively associated with well and moderately differentiated tumors (P = 0.035, rs  = 0.170), lymph node metastasis (P = 0.001, rs  = 0.276), and advanced TNM stage (P = 0.006, rs  = 0.219). Our data suggest that Wls protein is related to tumor metastasis and advanced TNM stage, and may be used as a new marker for prognosis of gastric carcinoma.

  14. The electrophoresis of human gastric juice

    PubMed Central

    Piper, D. W.; Stiel, Mirjam C.; Builder, Janet E.

    1962-01-01

    The electrophoretic pattern of normal human gastric juice is described. The effect of autodigestion of gastric juice and of the peptic digestion of albumin is described. The fallacies involved in the study of gastric juice proteins where peptic digestion of the protein constituent has not been prevented are emphasized. In this study the gastric juice was neutralized within the stomach to prevent changes due to autodigestion. PMID:13943717

  15. The RNA-binding protein PCBP2 facilitates gastric carcinoma growth by targeting miR-34a

    SciTech Connect

    Hu, Cheng-En; Liu, Yong-Chao; Zhang, Hui-Dong; Huang, Guang-Jian

    2014-06-13

    Highlights: • PCBP2 is overexpressed in human gastric cancer. • PCBP2 high expression predicts poor survival. • PCBP2 regulates gastric cancer growth in vitro and in vivo. • PCBP2 regulates gastric cancer apoptosis by targeting miR-34a. - Abstract: Gastric carcinoma is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. However, the mechanism underling gastric cancer is still not fully understood. Here in the present study, we identify the RNA-binding protein PCBP2 as an oncogenic protein in human gastric carcinoma. Our results show that PCBP2 is up-regulated in human gastric cancer tissues compared to adjacent normal tissues, and that high level of PCBP2 predicts poor overall and disease-free survival. Knockdown of PCBP2 in gastric cancer cells inhibits cell proliferation and colony formation in vitro, whereas opposing results are obtained when PCBP2 is overexpressed. Our in vivo subcutaneous xenograft results also show that PCBP2 can critically regulate gastric cancer cell growth. In addition, we find that PCBP2-depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. Mechanically, we identify that miR-34a as a target of PCBP2, and that miR-34a is critically essential for the function of PCBP2. In summary, PCBP2 promotes gastric carcinoma development by regulating the level of miR-34a.

  16. Fatal submucosal invasive gastric adenosquamous carcinoma detected at surveillance after gastric endoscopic submucosal dissection

    PubMed Central

    Shirahige, Akinori; Suzuki, Haruhisa; Oda, Ichiro; Sekiguchi, Masau; Mori, Genki; Abe, Seiichiro; Nonaka, Satoru; Yoshinaga, Shigetaka; Sekine, Shigeki; Kushima, Ryoji; Saito, Yutaka; Fukagawa, Takeo; Katai, Hitoshi

    2015-01-01

    An 80-year-old man was under annual surveillance esophagogastroduodenoscopy after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Two years after the initial ESD, a 0-IIc type metachronous EGC lesion, 8 mm in size, without an ulcer scar, was found in the gastric antrum. The estimated tumor depth was up to the mucosa, and biopsy revealed well and poorly differentiated adenocarcinoma. ESD was performed for this lesion and en bloc resection with negative margins was achieved. Histopathological examination revealed an adenosquamous carcinoma 8 mm in size invading the deep submucosal layer (1600 μm), with lymphovascular invasion, consistent with the diagnosis of non-curative resection. Additional gastrectomy was recommended for this patient; however, two months after the ESD, preoperative computed tomography revealed multiple liver metastases, and the patient was considered as an unsuitable candidate for surgical resection. Systemic chemotherapy was therefore started; however, the patient died of gastric cancer 27 mo after the second ESD. Early gastric adenosquamous carcinoma localized to the mucosa and submucosa is extremely rare and its clinical behavior is not well known. The present report is very significant in that it underscores the distinct possibility of gastric adenosquamous carcinoma being very aggressive and fatal even when detected at an early cancer. PMID:25892891

  17. The expression and location of midkine in gastric carcinomas of Chinese patients.

    PubMed

    Huang, Yaling; Cao, Guochun; Wang, Hui; Wang, Qingling; Hou, Yayi

    2007-04-01

    Midkine (MK), a heparin-binding growth factor, can regulate cell growth, survival and differentiation. MK is expressed at high levels in a variety of human carcinomas. Recently, the urine and serum MK concentration was analyzed in gastric cancer patient. However, the association of the cytokine mRNA expression with the categorical clinicopathological variables of the tumors and the location of its protein expression in the tumor tissues are still elusive. MK mRNA expression from the surgically resected specimens of healthy gastric tissues (9 cases), gastric cancer tissues and the matched non-cancerous tissues adjacent to the cancer (37 cases) were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR. Immunohistochemical analysis was performed to locate MK in gastric cancer. The expression of MK mRNA in gastric cancer was much higher in tumor tissues than that in the non-cancerous tissues and control tissue samples. And its expression was significantly associated with the pTNM stage and distant metastasis, but not with the differentiation grade, tumor size and nodal involvement. MK protein was ubiquitous in the tumor, especially in the adenoid part of tumors. In addition, it was found in the cytoplasm of tumor cells and highly concentrated in nucleus and nucleolus. The expression level and location of MK in gastric tumor tissues of Chinese patients may be related to the tumor genesis and progression. Further study is necessary on the mechanism of MK in gastric tumorigenesis and tumor growth.

  18. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  19. Chalcone flavokawain B induces autophagic-cell death via reactive oxygen species-mediated signaling pathways in human gastric carcinoma and suppresses tumor growth in nude mice.

    PubMed

    Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Lin, Kai-Yuan; Way, Tzong-Der; Korivi, Mallikarjuna; Liao, Jiuun-Wang; Yang, Hsin-Ling

    2017-04-03

    Flavokawain B (FKB), a naturally occurring chalcone in kava extracts, has been reported to possess anticancer activity. However, the effect of FKB on gastric cancer remains unclear. We examined the in vitro and in vivo anticancer activity and autophagy involvement of FKB and determined the underlying molecular mechanisms. FKB is potently cytotoxic to human gastric cancer cells (AGS/NCI-N87/KATO-III/TSGH9201) and mildly toxic towards normal (Hs738) cells and primary mouse hepatocytes. FKB-induced AGS cell death was characterized by autophagy, not apoptosis, as evidenced by increased LC3-II accumulation, GFP-LC3 puncta and acidic vesicular organelles (AVOs) formation, without resulting procaspase-3/PARP cleavage. FKB further caused p62/SQSTM1 activation, mTOR downregulation, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Silencing autophagy inhibitors CQ/3-MA and LC3 (shRNA) significantly reversed the FKB-induced cell death of AGS cells. FKB-triggered ROS generation and ROS inhibition by NAC pre-treatment diminished FKB-induced cell death, LC3 conversion, AVO formation, p62/SQSTM1 activation, ATG4B inhibition and Beclin-1/Bcl-2 dysregulation, which indicated ROS-mediated autophagy in AGS cells. Furthermore, FKB induces G2/M arrest and alters cell-cycle proteins through ROS-JNK signaling. Interestingly, FKB-induced autophagy is associated with the suppression of HER-2 and PI3K/AKT/mTOR signaling cascades. FKB inhibits apoptotic Bax expression, and Bax-transfected AGS cells exhibit both apoptosis and autophagy; thus, FKB-inactivated Bax results in apoptosis inhibition. In vivo data demonstrated that FKB effectively inhibited tumor growth, prolonged the survival rate, and induced autophagy in AGS-xenografted mice. Notably, silencing of LC3 attenuated FKB-induced autophagy in AGS-xenografted tumors. FKB may be a potential chemopreventive agent in the activation of ROS-mediated autophagy of gastric cancer cells.

  20. Allelic loss of chromosome 6q in gastric carcinoma.

    PubMed

    Li, Brenda C Y; Chan, Wing Y; Li, Christine Y S; Chow, Chit; Ng, Enders K W; Chung, S C Sydney

    2003-12-01

    Loss of the long arm of chromosome 6 (6q) has frequently been reported in gastric carcinoma, and most gastric cancer patients have evidence of intestinal metaplasia in the stomach. However, the relationship between loss of chromosome 6q and intestinal metaplasia has not been studied. In the first part of the study, we define the critical deletion region of chromosome 6q using loss of heterozygosity technique (LOH). Seventeen microsatellite markers were used to detect loss of heterozygosity (LOH) in 37 microdissected gastric tumors. We also examined intestinal metaplasia (IM) foci of the stomach in the same cancer patient (17 cases). Losses on chromosome 6q were detected in high frequency (51%) by LOH. Two distinct regions of common allelic loss were identified: one centered on the marker D6S300 (at 6q16.1) and the second on D6S446 (at 6q27), with LOH frequency of 36% and 31.3%, respectively. The deletions fall into 2 discrete regions, suggesting the existence of at least 2 tumor suppressor genes in 6q. The losses at 6q27 were confirmed by fluorescence in situ hybridization study (FISH). In the cases with LOH in the tumor, no LOH were detected in the autologous IM areas, but losses were detected by FISH. In some cases, these genetic changes may be acquired in the transition from normal gastric mucosa to intestinal metaplasia.

  1. Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma.

    PubMed

    Park, Hyung Kyu; Lee, Kyung-Yung; Yoo, Moon-Won; Hwang, Tae Sook; Han, Hye Seung

    2016-06-01

    Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005-2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.

  2. Critical evaluation of the tetracycline fluorescence test in the diagnosis of gastric carcinoma.

    PubMed

    WORSLEY, G H; McKENNA, R D; BECKIT

    1963-06-29

    Exfoliative cytology is a useful tool in the differential diagnosis of gastric lesions. The simplified method developed by Klinger and Katz(4) using tetracycline fluorescence was subjected to a critical evaluation. Five cases of gastric carcinoma, two of esophageal carcinoma, 21 of benign peptic ulcer, one case of carcinoma eroding into the bile duct, one case of carcinoma of the pancreas penetrating into the stomach, five normal controls on no medication and two normal controls taking vitamin B(2) were studied. The most apparent drawback of this technique is the number of false negatives encountered in cases of gastric carcinoma (three negative results in five cases of carcinoma). One false-positive test was recorded among 21 patients with benign ulcer. Vitamin B(2) if taken a half hour prior to the test will also produce a false-positive test. It is concluded, therefore, that the tetracycline fluorescence test is inferior to accurate studies of exfoliative cytology.

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

    PubMed

    Walker, Latoya R; Erler, Brian

    2011-01-01

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

  4. Renal cell carcinoma: complete pathological response in a patient with gastric metastasis of renal cell carcinoma.

    PubMed

    García-Campelo, Rosario; Quindós, Maria; Vázquez, Diana Dopico; López, Margarita Reboredo; Carral, Alberto; Calvo, Ovidio Fernández; Soto, José Manuel Rois; Grande, Enrique; Durana, Jesús; Antón-Aparicio, Luis Miguel

    2010-01-01

    A 75-year-old-man, with a 2-month history of abdominal pain, underwent a standard diagnostic workup that included a CT scan that showed a large right renal mass and subcentimeter nodes in the right and left lung lobes. In December 2003, the patient underwent right nephrectomy with adrenalectomy and a diagnosis of renal cell carcinoma (pT3N0M0 stage) was made. No further treatment was proposed and patient was followed up regularly. In October 2006, the annual gastrointestinal endoscopy showed asymptomatic multilobulated and polypoid masses in the gastric fundus and gastric body that corresponded to metastasis of the renal carcinoma that had been resected three years ago. Surgical treatment was refused and oral treatment with sunitinib (50 mg/day consecutively for 4 weeks followed by 2 weeks off) was initiated. Patient completed one cycle and development of acute toxicity (grade 3 asthenia, anorexia and mucositis) led to treatment interruption. After recovering from acute toxicity, the patient was proposed to reinitiate treatment with dose reduction, but he refused any medical treatment. At the follow-up visit, three months later, the gastrointestinal endoscopy showed four unspecific 2 mm nodules without malignant evidence. The whole-body CT did not reveal any other abnormality except for the known lung nodes. PET scan six months after treatment confirmed complete gastric response.

  5. Candida glabrata infection in gastric carcinoma patient mimicking cutaneous histoplasmosis.

    PubMed

    Gugic, Dijana; Cleary, Timothy; Vincek, Vladimir

    2008-02-28

    Candida glabrata is the second most common Candida species detected among hospitalized patients in USA. In tissue C. glabrata present as yeasts, 3-5 microns in size, which are difficult to visualize on H&E stained slides but can be detected on Grocott methenamine silver (GMS) stained slides. The presence of yeasts only, without any hyphal elements, makes C. glabrata difficult to distinguish from Histoplasma capsulatum yeasts that are of similar size. Mycology culture is the method of choice for definitive identification of C. glabrata. Rapid identification is necessary, as mortality rate due to C. glabrata infection in immunocompromised patients is particularly high. We herein report a patient with inoperable gastric carcinoma, who developed cutaneous and septic form of C. glabrata infection.

  6. Hepatocellular Carcinoma Supplied From the Short Gastric Artery: Treatment With Chemoembolization

    SciTech Connect

    Jeon, Ung Bae Lee, Jun Woo Baik, Seung Kug Kim, Tae Un Choo, Ki Seok Kim, Kun Il Kim, Yong-Woo Moon, Tae-Yong

    2012-12-15

    We report a case of transcatheter arterial chemoembolization (TACE) to treat hepatocellular carcinoma (HCC) that was supplied by the short gastric artery. A 67-year-old woman with two nodular HCCs underwent repeated TACE. One of the nodules was supplied by the short gastric artery.

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

    PubMed

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

    2015-08-01

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

  8. Clinicopathological, treatment, and prognosis study of 43 gastric neuroendocrine carcinomas

    PubMed Central

    Liu, De-Jun; Fu, Xue-Liang; Liu, Wei; Zheng, Lu-Ying; Zhang, Jun-Feng; Huo, Yan-Miao; Li, Jiao; Hua, Rong; Liu, Qiang; Sun, Yong-Wei

    2017-01-01

    AIM To provide more information and therapeutic methods about gastric neuroendocrine carcinomas (G-NECs) which occur rarely but are highly malignant and clinically challenging. METHODS We retrospectively analyzed the clinicopathological characteristics, treatments, and prognosis of 43 G-NEC patients at our hospital between January 2007 and December 2014. The diagnosis was based on the 2010 World Health Organization criteria. RESULTS Forty-three G-NECs containing 39 small cell carcinomas and 4 large cell NECs with Ki67 > 60% were included in this study, accounting for only 0.95% of all gastric carcinomas. The median patient age was 62 years (range, 33-82) and the male-to-female ratio was 4.4:1. All patients underwent surgery, including 38 curative resections and 5 palliative resections. Among these 43 patients, nearly half (48.84%) of these tumors were located in the cardiac region of the stomach, regional lymph node metastasis was found in 31 cases (72.09%), and liver metastasis was found in 6 cases (13.95%). Follow-up information was got for 40 patients. Twenty-three die of this disease with a median survival of 31 mo (range 1-90). The 1-year, 2-year, 3-year, and 5-year survival rate was 77.50%, 57.04%, 44.51%, and 35.05%, respectively. Survival was better in patients with tumor located in the cardiac region of the stomach, less than 7 lymph nodes metastasis and no liver metastasis. Five patients did not undergo postoperative chemotherapy, and the median survival time for these patients was 15 mo. For the remaining 34 patients who received postoperative chemotherapy, the median survival time was 44 mo and those received etoposide, cisplatin, and Paclitaxel survived the best. One patient with resected liver metastasis who received postoperative Capecitabine plus Oxaliplatin and Paclitaxel systemic chemotherapy plus octreotide LAR (30 mg intramuscularly, every 4 wk, for 2 years) has survived for 74 mo with no recurrence. CONCLUSION G-NECs are mostly nonfunctioning

  9. Clinical significance of TIPE expression in gastric carcinoma

    PubMed Central

    Hu, Ruyi; Qiu, Xingfeng; Hong, Shifu; Meng, Luxi; Hong, Xinya; Qiu, Jinhua; Yang, Jingjing; Zhuang, Guohong; Liu, Zhongchen

    2016-01-01

    Background TNFAIP8, also known as TIPE, is a suppressor of apoptosis. High expression of both TIPE mRNA and protein has been detected in various cancer cell lines and clinical specimens compared to healthy tissues. Many reports have shown that there is a strong correlation between TIPE overexpression and cancer progression and poor prognosis in human solid cancers. Methods To illustrate the functional and clinical significance of TIPE in gastric cancer, we used reverse transcription polymerase chain reaction, quantitative real-time polymerase chain reaction, and immunohistochemistry to measure TIPE expression in clinical gastric specimens. Then, TIPE expression was knocked down by using shRNA and anti-DR5ScFv, to examine different expressions of TIPE in BGC823 cell lines, while cell proliferation and apoptosis were induced. Results We found that there was a strong correlation between TIPE expression and TNM stage (P=0.044), tumor depth (P=0.016), lymph node metastasis (P=0.026), and distant metastasis (P=0.045). No significant correlation was found between TIPE expression with the patients’ age (P=0.062) or sex (P=0.459). Anti-DR5ScFv induced TIPE depletion both in vitro and in vivo and resulted in apoptosis and suppression of proliferation. Conclusion Our results suggested that TIPE expression was associated with gastric cancer progression, and most importantly, suppressing TIPE expression might be an effective therapeutic strategy. PMID:27524904

  10. Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells.

    PubMed

    Bimczok, D; Kao, J Y; Zhang, M; Cochrun, S; Mannon, P; Peter, S; Wilcox, C M; Mönkemüller, K E; Harris, P R; Grams, J M; Stahl, R D; Smith, P D; Smythies, L E

    2015-05-01

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

  11. PLK1 promotes epithelial-mesenchymal transition and metastasis of gastric carcinoma cells

    PubMed Central

    Cai, Xiao Peng; Chen, Liang Dong; Song, Hai Bin; Zhang, Chun Xiao; Yuan, Ze Wei; Xiang, Zhen Xian

    2016-01-01

    Cancer cell epithelial-mesenchymal transition (EMT) is the crucial event for cancer progression and plays a vital role in the metastasis of cancer cells. Activation of Polo-like kinase 1 (PLK1) signaling has been implicated as the critical event in several tumor metastasis and EMT, however, whether PLK1 participates in gastric carcinoma metastasis and EMT still remains unclear. For this study, we elucidated the potential physiological function of PLK1 in the metastasis of gastric tumors, as well its distinct role in cells EMT and subsequently determined the mechanism involved in PLK1 regulated. Immunoblotting assay and Oncomine data mining analysis indicated that PLK1 expression was highly up-regulated in gastric carcinoma. Kaplan-Meier survival analysis for the relationship between survival outcomes and PLK1 expression in gastric carcinoma was performed with an online Kaplan-Meier plotter (http://kmplot.com/analysis/). Over-expression of PLK1 in gastric cancer cells SGC-7901 and MKN-28 significantly promoted cells profound morphological changes and enhanced metastatic ability of tumor cells. On the contrary, silencing of PLK1 induced mesenchymal epithelial transition (MET)-like morphological and inhibited the metastatic process. Furthermore, we found that the metastatic characters promoting effects of PLK1 in gastric carcinoma was related to the activation of protein kinase B (AKT). Our mechanistic investigations revealed that AKT inhibition reversed PLK1-induced EMT, blocked gastric carcinoma cells invasiveness and metastasis. Additionally, over-expression of AKT promoted the migratory and invasion ability of the two cell lines, which was disrupted by PLK1 down-regulation. To conclude, our findings demonstrate that PLK1 accelerates the metastasis and epithelial-mesenchyme transition of gastric cancer cells through regulating the AKT pathway. PMID:27830001

  12. Gastric carcinoma: imaging diagnosis, staging and assessment of treatment response

    PubMed Central

    Hallinan, James Thomas Patrick Decourcy

    2013-01-01

    Abstract Gastric carcinoma (GC) is one of the most common causes of cancer-related death worldwide. Surgical resection is the only cure available and is dependent on the GC stage at presentation, which incorporates depth of tumor invasion, extent of lymph node and distant metastases. Accurate preoperative staging is therefore essential for optimal surgical management with consideration of preoperative and/or postoperative chemotherapy. Multidetector computed tomography (MDCT) with its ability to assess tumor depth, nodal disease and metastases is the preferred technique for staging GC. Endoscopic ultrasonography is more accurate for assessing the depth of wall invasion in early cancer, but is limited in the assessment of advanced local or stenotic cancer and detection of distant metastases. Magnetic resonance imaging (MRI), although useful for staging, is not proven to be effective. Positron emission tomography (PET) is most useful for detecting and characterizing distant metastases. Both MDCT and PET are useful for assessment of treatment response following preoperative chemotherapy and for detection of recurrence after surgical resection. This review article discusses the usefulness of imaging modalities for detecting, staging and assessing treatment response for GC and the potential role of newer applications including CT volumetry, virtual gastroscopy and perfusion CT in the management of GC. PMID:23722535

  13. Current State of Gastric Stump Carcinoma in Japan: Based on the Results of a Nationwide Survey

    PubMed Central

    Nomura, Eiji; Lee, Sang-Woong; Kaminishi, Michio; Sugiyama, Mitsugu; Aikou, Takashi; Kitajima, Masaki

    2010-01-01

    Background Carcinoma of the gastric remnant after partial gastrectomy for benign disease or cancer is unusual but an important cancer model. The Japanese Society for the Study of Postoperative Morbidity after Gastrectomy (JSSPMG) performed a nationwide questionnaire survey to understand the current state of gastric stump carcinoma in Japan. Methods In the questionnaire survey of November 2008, gastric stump carcinoma was defined as an adenocarcinoma of the stomach occurring 10 years or more after Billroth I or Billroth II gastrectomy for benign condition or cancer disease. The survey was conducted at the request of reports on five or more patients with gastric stump carcinoma for each institution. Items for the survey included gender, age, methods of reconstruction in an original gastrectomy, original diseases, time interval between original gastrectomy and first detection of stump carcinomas, locations of stump carcinomas, tumor histology, tumor depth, and extent of lymph node metastasis. The questionnaire was sent to 163 surgical institutions in the JSSPMG. Results Ninety-five institutions (58.3%) responded to the survey, and the data of 887 patients satisfied the required conditions for the survey. A total of 887 patients were composed of 368 patients who received Billroth I distal gastrectomy and 519 who received Billroth II. The Billroth II group has a significantly higher number of original benign lesions than the Billroth I group (P < 0.001). This study confirmed the following issues: (1) The remnant stomach after gastrectomy for cancer disease had a higher prevalence to develop stump carcinomas occurring in a shorter time interval since original gastrectomy; (2) Patients with Billroth II gastrectomy had stump carcinomas most frequently in the anastomotic area, but not in the non-stump area as in Billroth I gastrectomy; (3) Tumor histology of 72.4% of 304 stump carcinomas at an early stage was intestinal type adenocarcinoma, i.e., well or moderately

  14. Clinical relevance of Helicobacter pylori vacA and cagA genotypes in gastric carcinoma.

    PubMed

    Ferreira, Rui M; Machado, José C; Figueiredo, Ceu

    2014-12-01

    Helicobacter pylori infection is the major etiological factor of gastric carcinoma. This disease is the result of a long, multistep, and multifactorial process, which occurs only in a small proportion of patients infected with H. pylori. Gastric carcinoma development is influenced by host genetic susceptibility factors, environmental factors, and H. pylori virulence. H. pylori is genetically highly variable, and variability that affects H. pylori virulence factors may be useful to identify strains with different degrees of pathogenicity. This review will focus on VacA and CagA that have polymorphic regions that impact their functional properties. The characterization of H. pylori vacA and cagA-associated could be useful for identifying patients at highest risk of disease, who could be offered H. pylori eradication therapy and who could be included in programs of more intensive surveillance in an attempt to reduce gastric carcinoma incidence.

  15. Lymphoepithelioma-like gastric carcinoma in a patient with rectal laterally spreading tumor: A case report

    PubMed Central

    CHEN, MIN; YIN, LINGDI; YAO, YULING; WANG, LEI; XU, GUIFANG; ZHANG, XIAOQI; LV, YING; SUN, QI; FAN, XIANGSHAN; ZOU, XIAOPING

    2016-01-01

    Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the stomach that accounts for 1–4% of all gastric cancer cases. It is characterized by the presence of a lymphoid stroma with cells arranged primarily in micro alveolar, thin trabecular and primitive tubular patterns or isolated cells. In the present study, the case of a 50-year-old male patient with LELGC and rectal laterally spreading tumor is presented. Following endoscopic submucosal dissection, a diagnosis of carcinoma was reached and the patient underwent total radical gastrectomy. The postoperative pathological stage was IA T1bN0cM0 according to the Tumor-Node-Metastasis classification of gastric carcinoma, and the patient recovered well. The present case is reported to summarize the endoscopic and pathological characteristics of LELGC. PMID:27073504

  16. Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray

    PubMed Central

    Zhang, Zhi-Qiang; Li, Xiu-Juan; Liu, Gui-Tao; Xia, Yu; Zhang, Xiang-Yang; Wen, Hao

    2013-01-01

    AIM: To study the differential expression of Annexin A1 (ANXA1) protein in human gastric adenocarcinoma. This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma. METHODS: Purified gastric adenocarcinoma cells (GAC) and normal gastric epithelial cells (NGEC) were obtained from 15 patients with gastric cancer by laser capture microdissection. All of the peptide specimens were labeled as 18O/16O after trypsin digestion. Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry (nano-RPLC-MS/MS). The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis. The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry (IHC). The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed. RESULTS: A total of 78 differential proteins were identified. Western blotting revealed that ANXA1 expression was significantly upregulated in GAC (2.17/1, P < 0.01). IHC results showed the correlations between ANXA1 protein expression and the clinicopathological parameters, including invasive depth (T stage), lymph node metastasis (N stage), distant metastasis (M stage) and tumour-lymph node metastasis stage (P < 0.01). However, the correlations between ANXA1 protein expression and the remaining clinicopathological parameters, including sex, age, histological differentiation and the size of tumour were not found (P > 0.05). CONCLUSION: The upregulated ANXA1 expression may be associated with carcinogenesis, progression, invasion and metastasis of GAC. This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC. PMID:24282368

  17. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein.

    PubMed Central

    Imai, S; Koizumi, S; Sugiura, M; Tokunaga, M; Uemura, Y; Yamamoto, N; Tanaka, S; Sato, E; Osato, T

    1994-01-01

    In 1000 primary gastric carcinomas, 70 (7.0%) contained Epstein-Barr virus (EBV) genomic sequences detected by PCR and Southern blots. The positive tumors comprised 8 of 9 (89%) undifferentiated lymphoepithelioma-like carcinomas, 27 of 476 (5.7%) poorly differentiated adenocarcinomas, and 35 of 515 (6.8%) moderately to well-differentiated adenocarcinomas. In situ EBV-encoded small RNA 1 hybridization and hematoxylin/eosin staining in adjacent sections showed that the EBV was present in every carcinoma cell but was not significantly present in lymphoid stroma and in normal mucosa. Two-color immunofluorescence and hematoxylin/eosin staining in parallel sections revealed that every keratin-positive epithelial malignant cell expressed EBV-determined nuclear antigen 1 (EBNA1) but did not significantly express CD45+ infiltrating leukocytes. A single fused terminal fragment was detected in each of the EBNA1-expressing tumors, thereby suggesting that the EBV-carrying gastric carcinomas represent clonal proliferation of cells infected with EBV. The carcinoma cells had exclusively EBNA1 but not EBNA2, -3A, -3B, and -3C; leader protein; and latent membrane protein 1 because of methylation. The patients with EBV-carrying gastric carcinoma had elevated serum EBV-specific antibodies. The EBV-specific cellular immunity was not significantly reduced; however, the cytotoxic T-cell target antigens were not expressed. These findings strongly suggest a causal relation between a significant proportion of gastric carcinoma and EBV, and the virus-carrying carcinoma cells may evade immune surveillance. Images PMID:8090780

  18. Intracranial hypertension as the primary symptom of gastric signet-ring cell carcinoma

    PubMed Central

    Pu, Jiali; Xu, Lingjia; Yin, Xinzhen; Zhang, Baorong

    2016-01-01

    Abstract Background: Intracranial hypertension (IH) is a neurological disorder characterized by increased intracranial pressure. It is a poorly understood syndrome that most commonly manifests nonspecific symptoms such as stroke-like headache, vision changes, nausea, vomiting, and papilledema. IH has been reported in young cancer patients but never in association with gastric signet-ring cell carcinoma. Methods: Here, we discuss the case of an 18-year-old girl with gastric signet-ring cell carcinoma in which IH was the primary symptom accompanied by the even rarer symptom of cutaneous metastases. We also present a review of the relevant literature. The patient experienced frequent headaches, vomiting, and blurred vision but showed no abnormal findings on cranial imaging studies. Further examination showed multiple skin nodules on the abdomen. Then pathological and immunohistochemical examination of gastroscopic specimens and the biopsied subcutaneous nodules were done. Results: Pathological and immunohistochemical examination of gastroscopic specimens and the biopsied subcutaneous nodules confirmed gastric signet-ring cell carcinoma with skin metastases. Conclusion: To our knowledge, this is the first reported case of gastric signet-ring cell carcinoma primarily presenting IH and accompanied by subcutaneous metastases. This case emphasizes the importance of excluding malignancy from the differential diagnosis of IH. PMID:27583897

  19. Histological characterisation and prognostic evaluation of 62 gastric neuroendocrine carcinomas

    PubMed Central

    Chen, Xiaohui; Ye, Yuhong; Shi, Xi; Zhu, Kunshou; Huang, Liming; Zhang, Sheng; Ying, Mingang; Lin, Xuede

    2016-01-01

    Aim of the study To determine the significance of expression of synaptophysin, chromogranin A, and Ki-67 and their association with clinicopathological parameters, and to find out the possible prognostic factors in gastric neuroendocrine carcinoma (G-NEC). Material and methods We investigated the immunohistochemical features and prognosis of 62 G-NECs, and evaluated the association among expressions of synaptophysin, chromogranin A, and Ki-67, clinicopathological variables, and outcome. Results Chromogranin A expression was found more commonly in small-cell NECs (9/9, 100%) than in large-cell NECs (27/53, 51%) (p = 0.008). No statistical significance was found in Ki-67 (p = 0.494) or synaptophysin (p > 0.1) expression between NEC cell types. Correlation analyses revealed that Ki-67 expression was significantly associated with mid-third disease of stomach (p = 0.005) and vascular involvement (p = 0.006), and had a trend of significant correlation with tumour relapse (p = 0.078). High expression of chromogranin A was significantly associated with histology of small-cell NECs (p = 0.008) and lesser tumour greatest dimension (p = 0.038). The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests, and as a result, early TNM staging and postoperative chemotherapy were found to be correlated with longer overall survival (p < 0.05). Univariate analysis revealed associations between poor prognosis in NECs and several factors, including high TNM staging (p = 0.048), vascular involvement (p = 0.023), relapse (p = 0.004), and microscopic/macroscopic residual tumour (R1/2, p < 0.001). In a multivariate analysis, relapse was identified as the sole independent prognostic factor. Conclusions No significant correlation between survival and expression of synaptophysin, chromogranin A, or Ki-67 has been determined in G-NECs. Our study indicated that early diagnosis, no-residual-tumour resection, and postoperative chemotherapy were

  20. A gastric neuroendocrine carcinoma expressing somatostatin in a bearded dragon (Pogona vitticeps).

    PubMed

    Lyons, Jeremiah A; Newman, Shelley J; Greenacre, Cheryl B; Dunlap, John

    2010-03-01

    A metastatic gastric neuroendocrine carcinoma in a 2.5-year-old inland bearded dragon (Pogona vitticeps) with a chronic history of anorexia, weight loss, depression, and acute melena is described. Histologic examination of the gastric mass revealed a densely cellular tumor arranged in nests and occasional rosettes of hyperchromatic cells with oval to spindle-shaped nuclei and minimal cytoplasm; the tumor was supported by a moderate fibrovascular stroma. Similar cells invaded through the gastric mucosa, and there were multiple hepatic metastases. The neoplastic cells were weakly immunopositive for neuron-specific enolase and moderately positive for somatostatin but were negative for chromogranin AB and gastrin. Ultrastructural studies revealed scattered neurosecretory granules in the neoplastic cells, confirming the diagnosis of a neuroendocrine carcinoma.

  1. Effect of sulglycotide on gastric bicarbonate secretion in humans.

    PubMed

    Guslandi, M; Nannini, D; Tittobello, A

    1985-01-01

    The effect of sulglycotide, a cytoprotective agent with a healing effect on ulcers, on gastric bicarbonate secretion in humans was evaluated. Fifteen healthy volunteers were treated with sulglycotide 400 mg t.i.d. for 10 days. Before and after treatment the bicarbonate content of basal gastric juice was determined by Feldman and Barnett's method. Sulglycotide was found to increase significantly (p less than 0.0001) basal HCO3- production from the human stomach, thus strengthening the gastric mucosal defences. It was concluded that the cytoprotective and therapeutic properties of the drug are partially related to stimulation of gastric alkaline secretion.

  2. Immunohistochemical analysis of thymidylate synthase expression in gastric carcinoma: correlation with clinicopathological parameters and survival.

    PubMed

    Rogoza-Mateja, Wiesława; Domagala, Pawel; Kaczmarczyk, Mariusz; Mieżyńska-Kurtycz, Joanna; Ławniczak, Małgorzata; Sulżyc-Bielicka, Violetta; Bielicki, Dariusz; Karpińska-Kaczmarczyk, Katarzyna; Domagala, Wenancjusz

    2017-02-01

    The correlation of thymidylate synthase (TS) expression in gastric cancers with tumor histology and prognostic or predictive information remains unclear. Most studies have involved Asian populations, with few conducted in European cohorts. Moreover, all published studies analyze TS expression using semi-quantitative methods. This retrospective study evaluated the association of TS expression in tumor cells with gastric carcinoma histological type, with selected clinicopathological parameters, and with the prognosis of patients who underwent surgical treatment. TS expression was detected using immunochemistry and objectively assessed by computerized image analysis of tumor cells in 100 gastric cancers. We found that high TS expression was significantly more common in intestinal than in diffuse type of gastric cancer according to Lauren classification (P=0.0003); in type I carcinomas compared to type IV according to Goseki classification (P=0.002); and in gastric cancers in men than women (P=0.04). Low TS expression was found more often in carcinomas in the middle and lower third of the stomach than in cancers in the upper third of the stomach (P=0.009 and P=0.001, respectively). In the subgroup of 25 patients without lymph node metastases (stage I+II), high TS expression was associated with better DFS (83% for high TS expression versus 38,5% for low TS expression, P=0.03). The results (1) indicate significant correlation between the Lauren and Goseki histopathological classifications of gastric cancer and TS expression in tumor cells, (2) suggest that high TS expression may be a positive prognostic marker with regard to DFS in patients with gastric cancer without involvement of regional lymph nodes who underwent radical surgical treatment and were not treated with preoperative chemotherapy. Prognostic results need confirmation in larger cohorts.

  3. Gastric Carcinoma at the Era of Targeted Therapies.

    PubMed

    Dreanic, Johann; Dhooge, Marion; Sion, Elena; Brezault, Catherine; Chaussade, Stanislas; Coriat, Romain

    2016-01-01

    Gastric and gastro-esophageal cancers (GC/GEJ) appear as the second cancer-related death worldwide. Diagnosis is made at an advanced stage offering a curative attempt in less than 50% of cases. Despite the improvements of the systemic cytotoxic chemotherapy regimens, the prognosis of patients with metastatic GC/GEJ cancer remains poor. Recent insights in biochemical pathways have permitted to identify potential targets. The extracellular domain of HER2 receptors is implicated in cells' proliferation and in the anti-apoptotic process occurring in GC/GEJ cancers. Trastuzumab, a monoclonal antibody targeting HER2, in addition to chemotherapy permitted to obtain more than one year of survival in HER2-positive advanced GC/GEJ cancers. Recently, ramucirumab, a humanized monoclonal antibody targeting VEGFR-2 receptor demonstrated its efficacy as a second line treatment for patients with advanced GC/GEJ cancer. These encouraging results have justified evaluating targeted therapies in GC/GEJ cancers. In this review, we summarize targeted therapies that might present clinical efficacy in the treatment of advanced GC/GEJ cancers.

  4. 18F-FLT PET/CT in Patients with Gastric Carcinoma

    PubMed Central

    Małkowski, Bogdan; Staniuk, Tomasz; Śrutek, Ewa; Zegarski, Wojciech; Studniarek, Michał

    2013-01-01

    The aim of the study was to evaluate the usefulness of 18F-FLT PET/CT in the detection and differentiation of gastric cancers (GC). 104 consecutive patients (57 cases of adenocarcinoma tubulare (G2 and G3), 17 cases of mucinous adenocarcinoma, 6 cases of undifferentiated carcinoma, 14 cases of adenocarcinoma partim mucocellulare, and 10 cases of end stage gastric cancer) with newly diagnosed advanced gastric cancer were examined with FLT PET/CT. For quantitative and comparative analyses, the maximal standardized uptake value (SUVmax) was calculated for both the tumors and noninvaded gastric wall. Results. There were found, in the group of adenocarcinoma tubulare, SUVmax 1.5–23.1 (7.46 ± 4.57), in mucinous adenocarcinoma, SUVmax 2.3–10.3 (5.5 ± 2.4), in undifferentiated carcinoma, SUVmax 3.1–13.6 (7.28 ± 3.25), in adenocarcinoma partim mucocellulare, SUVmax 2–25.3 (7.7 ± 6.99), and, in normal gastric wall, SUVmax 1.01–2.55 (1.84 ± 0.35). For the level of 2.6 cut-off value between the normal wall and neoplasm FLT uptake from ROC analysis, all but five gastric cancers showed higher accumulation of FLT than noninfiltrated mucosa. Conclusion. Gastric cancer presents higher accumulation of 18F-FLT than normal, distended gastric mucosa. Significantly higher accumulation was shown in cancers better differentiated and with higher cellular density. PMID:24454342

  5. The cytologic diagnosis of gastric carcinoma related to the histologic type.

    PubMed

    Pilotti, S; Rilke, F; Clemente, C; Alasio, L; Grigioni, M

    1977-01-01

    In gastric smears obtained by direct vision fiberoptic brush technique from 78 patients with carcinoma of the stomach, an attempt was made to recognize cytologically the histologic type of the tumor with reference to Lauren's classification. The cytologic diagnosis of intestinal type carcinoma was made in 36/45 positive cases on the basis of an abundant cellularity and the presence of rather large pleomorphic cohesive cells often arranged in sheets with a moderately increased N/C ratio. One case of intramucous and two of "early" invasive carcinoma revealed malignant cells which did not differ from those of the advanced cases. In these cases as well as in some of the advanced ones, atypical epithelial cells were found in addition to the malignant ones; these cells could have derived from the histologic areas of atypical hyperplasia of the gastric mucosa surrounding the carcinoma. 14/15 cases of advanced diffuse carcinoma of the stomach could be cytologically identified on the basis of a scanty cellularity and the presence of rather small, monomorphic poorly differentiated cells with a high N/C ratio. The cytologic diagnosis of the mixed-type carcinoma was made in 2/5 positive cases on the basis of the presence of an admixture of both cell types described above. In two cases of the mixed-type carcinoma, only intestinal type cells were found. In the smears of nine cases of intestinal type carcinoma, one of which was intramucous, and of one case of mixed-type carcinoma, the tumor cells could not be specified. 13/78 cases (16.7%) showed negative cytology. The overall accuracy rate was 83.3 per cent. The statistical analysis of a number of cytologic parameters indicated that morphologic differences between Type I and Type D carcinomas of the stomach do exist and that they can be evaluated for differential diagnostic purposes.

  6. Effect of Splenectomy Combined with Resection for Gastric Carcinoma on Patient Prognosis

    PubMed Central

    Pan, Dun; Chen, Hui; Li, Liang-qing; Li, Zong-fang

    2016-01-01

    Background For patients with stage IV gastric cancer, it is unclear whether splenectomy combined with palliative surgery is needed to reduce tumor load and relieve symptoms. The objective of the present study was to investigate the effect of splenectomy combined with palliative resection for stage IV gastric carcinoma on immunological dysfunction and patient prognosis. Material/Methods We retrospectively analyzed medical records of 106 stage IV gastric cancer patients who underwent palliative surgery; of these, 49 patients were treated with palliative resection for gastric carcinoma combined with splenectomy, while the other 57 patients retained their spleens. The immunologic function and prognosis in these 2 groups were examined and compared. Results The immune function of patients in the group that retained their spleens was better later in the postoperative course than in the resection group. The groups did not show statistically significant differences in postoperative infectious complications, median survival time, and survival rate; however, the average postoperative hospitalization time of patients in the retained group was significantly shorter. Conclusions Splenectomy combined with gastric cancer resection did not improve the prognosis of the patients; patients who retained their spleens had faster recovery and improved immune function. However, whether retaining the spleen is an independent factor improving the prognosis needs further investigation. PMID:27816984

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

    PubMed

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

    2017-02-01

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

  8. Evidence of cell fusion in carcinogen-induced mice gastric carcinoma.

    PubMed

    Yan, Yongjia; Hsu, Yiling; He, Xianghui; Lu, Ning; Wei, Wei; Zhang, Zhixiang; Zhu, Liwei

    2015-07-01

    The role of bone marrow-derived cells in gastric cancer formation was not fully understood. In this study, bone marrow from female green fluorescent protein transgenic mice was transplanted into male wild-type mice to generate sex-mismatched chimeric mice. The chimeric mice were treated with carcinogen to induce gastric cancer. At time of sacrifice, 18.2 % (2/11) of mice showed severe dysplasia and 25 % (3/12) of mice successfully induced with cancer. Fluorescence in situ hybridization results showed that bone marrow-derived cells participated in renewal of gastric mucosa and cell fusion was observed in both precancerous lesions and adenocarcinoma, but no sign of fusion was observed in squamous cell carcinoma. Our findings suggest that bone marrow-derived cells participate in renewal of gastric mucosa during chronic damage and might have acquired the phenotype of gastric epithelial cells through cell fusion. Fusion between gastric epithelial cells and bone marrow-derived cells was involved in increased carcinogenesis.

  9. MiR-101-3p Suppresses HOX Transcript Antisense RNA (HOTAIR)-induced Proliferation and Invasion Through Directly Targeting SRF in Gastric Carcinoma Cells.

    PubMed

    Wu, Xiaoyu; Zhou, Jin; Wu, Zhenfeng; Chen, Che; Liu, Jiayun; Wu, Guannan; Zhai, Jing; Liu, Fukun; Li, Gang

    2017-03-02

    MiR-101-3p was identified as a tumor suppressor in several cancers, but its exact role in gastric adenocarcinoma is still largely unknown. In this study, we found that, compared with the RGM-1 human normal gastric epithelial cells, miR-101-3p was significantly downregulated in all the 6 human gastric adenocarcinoma cell lines, including BGC-823, MNK-45, MGC-803, SGC-7901, AGS and HGC-27. Overexpression miR-101-3p suppressed both the proliferation and invasion of AGS gastric adenocarcinoma cells and knockdown of miR-101-3p displayed an opposite effect. In addition, miR-101-3p could directly target and suppress the expression SRF gene, which is a transcription factor of HOTAIR, a well-characterized tumor promoter lncRNA. MiR-101-3p negatively regulated SRF-mediated transcription of HOTAIR. Moreover, either silence of SRF or silence of HOTAIR could counteract the promotion of gastric adenocarcinoma cell proliferation and invasion by miR-101-3p inhibition. Our findings indicate that miR-101-3p suppresses HOTAIR-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells.

  10. [Production of human monoclonal antibody reactive with gastrointestinal carcinoma].

    PubMed

    Soyama, N; Ohyanagi, H; Saitoh, Y

    1990-12-01

    Lymphocytes obtained from regional lymph nodes and spleen in the patients with gastrointestinal carcinoma were fused with the human B lymphoblastoid cell line GC01 and human hybridomas producing human monoclonal antibody (MoAb) were derived. Human MoAb No. 235 (IgM) derived from spleen cell of a gastric cancer patient reacted with adenocarcinoma of stomach, colon, and pancreas in the new immunohistochemical assay, modified direct immunoperoxidase method, and reacted with KATO III cells in cultured cell lines. The antigenic determinant of this antibody was suspected to be protein moiety after enzyme treatment. The competitive binding inhibition assay indicated that its epitope was different from anti-CEA monoclonal antibodies (KM10, A10, B9, AH3, JA4) and KM01. These findings suggested the possible use of human MoAb No. 235 for clinical application of targeting cancer chemotherapy in the future.

  11. [Concomitant gastric and pancreatic metastases from renal cell carcinoma: case study].

    PubMed

    Portanova, Michel; Yabar, Alejandro; Lombardi, Emilio; Vargas, Fernando; Mena, Víctor; Carbajal, Ramiro; Palacios, Néstor; Orrego, Jorge

    2006-01-01

    This report describes the case of a patient who underwent total gastrectomy, splenectomy and pancreatomy corporo-postero as a consequence of gastric and pancreatic metastasis from carcinoma to clear cells, five years after having undergone radical nephrectomy. Upper digestive bleeding was the first symptom, and pancreatic lesion was detected in previous CT scans. There are many documented cases of pancreatic metastasis, but only eight gastric metastasis in the last 15 years, although we did not find reports about surgical treatment for concomitant gastric and pancreatic injury. Surgical treatment which in some reports include highly complex surgeries such as gastrectomies with combined resections of invaded organs and pancreatoduodenectomy, are good options for select cases, because good survival rates have been reported.

  12. Deoxycholic acid inhibits the growth of BGC-823 gastric carcinoma cells via a p53‑mediated pathway.

    PubMed

    Yang, Hai-Bo; Song, Wei; Cheng, Mei-Die; Fan, Hai-Fang; Gu, Xu; Qiao, Ying; Lu, Xin; Yu, Rui-He; Chen, Lan-Ying

    2015-04-01

    The aim of the present study was to investigate the effects of deoxycholic acid (DCA) on BGC‑823 human gastric carcinoma cells and to explore the possible mechanisms underlying any such effects. Cell proliferation was detected using a 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyl tetrazolium bromide assay, cell morphology was observed by inverted microscopy, and cell cycle progression and the mitochondrial membrane potential were analyzed using flow cytometry. The expression of Bcl‑2, Bax, p53, Cyclin D1 and cyclin‑dependent kinase (CDK)2 proteins in BGC‑823 cells was analyzed with western blotting. The results demonstrated that DCA significantly inhibited cell growth, and that the cell cycle was arrested at the G1 phase. DCA was also shown to induce BGC‑823 cell apoptosis, which was associated with the collapse of the mitochondrial membrane potential. The mitochondria‑dependent pathway was activated via an increase in the ratio of Bax:Bcl‑2 in BGC‑823 cells. In addition, the expression of p53, cyclin D1 and CDK2 was altered following DCA treatment. These results suggest that DCA induces apoptosis in gastric carcinoma cells through activation of an intrinsic mitochondrial‑dependent pathway, in which p53 is involved.

  13. Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/β-Catenin Signaling Pathway

    PubMed Central

    Zheng, Ruzhen; Deng, Qinghua; Liu, Yuehua; Zhao, Pengjun

    2017-01-01

    Background Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/β-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. Material/Methods We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay. Results Curcumin markedly impaired tumor cell viability and induced apoptosis in vitro. Curcumin significantly suppressed the levels of Wnt3a, LRP6, phospho-LRP6, β-catenin, phospho-β-catenin, C-myc, and survivin. Xenograft growth in vivo was inhibited and the target genes of Wnt/β-catenin signaling were also reduced by curcumin treatment. Conclusions Curcumin exerts anti-proliferative and pro-apoptotic effect in gastric cancer cells and in a xenograft model. Inhibition of the Wnt/β-catenin signaling pathway and the subsequently reduced expression of Wnt target genes show potential as a newly-identified molecular mechanism of curcumin treatment. PMID:28077837

  14. Microsatellite instability and loss of heterozygosity in gastric carcinoma in comparison to family history.

    PubMed Central

    Keller, G.; Rudelius, M.; Vogelsang, H.; Grimm, V.; Wilhelm, M. G.; Mueller, J.; Siewert, J. R.; Höfler, H.

    1998-01-01

    We compared 29 gastric carcinomas from patients with a variably strong family history for gastric cancer (group 1) with 36 gastric carcinomas from patients without a family history of this disease (group 2) for microsatellite instability (MSI) and loss of heterozygosity (LOH) with 12 microsatellite markers. Both study groups had similar proportions of histological types and tumor locations. Widespread MSI (alterations at > or = 6 loci) was seen in 5 of 29 (17%) of the tumors belonging to group 1 and in 4 of 36 (11%) group 2 tumors. MSI at a low level (alterations at 1 to 3 loci) was observed in 12 of 29 (41%) of tumors in group 1 and in 10 of 36 (28%) of tumors in group 2, differences that were not statistically significant. A significant difference with respect to low level MSI was observed between the two groups when considering the overall mutation rate of microsatellites. Seventeen of 281 (6%) analyzed microsatellite loci showed alterations in group 1 and 11 of 381 (2.9%) in group 2 (P = 0.046). Comparison of both types of MSI to the clinicopathological parameters in both groups revealed a significant association of low level MSI with advanced tumor stages (P = 0.046) in the group 2, whereas no such association was observed in group 1. In respect to LOH, a significant difference between the two groups was observed at chromosome 17p12, as 13 of 22 (59%) informative cases of group 1 showed LOH in comparison with 7 of 26 (27%) (P = 0.024) in group 2. No correlation of LOH at chromosome 17p12 to the pathological or clinical data was observed either in the two groups or in the study as a whole. Our data show that gastric carcinomas of patients with a positive family history of gastric cancer in group 1 are characterized by a higher mutation rate in respect to low level MSI, particularly at dinucleotide repeats, and by a higher frequency of LOH at chromosome 17p12, indicating that different genetic pathways are involved in the pathogenesis of gastric carcinomas

  15. Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis.

    PubMed

    Hu, Ting-Zi; Huang, Li-Hua; Xu, Can-Xia; Liu, Xiao-Ming; Wang, Yu; Xiao, Jing; Zhou, Li; Luo, Ling; Jiang, Xiao-Xia

    2015-12-01

    Transcription factors (TFs) are crucial modulators of gene expression during the development and progression of gastric carcinoma. Helicobacter pylori (H. pylori) is one of the most significant risk factors of gastric carcinoma, and it is widely known that chronic inflammation with H. pylori infection triggers gastric carcinogenesis through inflammation-carcinoma chain [gastric carcinogenesis stages: non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)], but its mechanism regarding changed TFs remains unknown. In this study, we investigated the expressional profiles of 345 transcription factors in gastric mucosa of healthy volunteers and patients at different gastric carcinogenesis stages using protein/DNA array-based approach. The data demonstrated the up-regulated TFs such as GATA-3, AP4, c-Myc and Pbx1 in the gastric mucosa of GC patients compared with the healthy volunteers, while other TFs, particularly CCAAT and CACC, showed the consistently decreasing trend along the gastric carcinogenesis. The increased expressions of AP4, Pbx1 and C/EBPα were further validated by quantitative real-time PCR and Western blot in various H. pylori-infected models such as clinical gastric tissues, gastric epithelial cell lines and Mongolian gerbils. This study provides insights into and potential laws for gene transcriptional regulation by identifying potential TFs targets against the development of H. pylori-associated gastric carcinoma.

  16. Chemotherapy as a component of multimodal therapy for gastric carcinoma.

    PubMed

    Kodera, Yasuhiro; Fujiwara, Michitaka; Koike, Masahiko; Nakao, Akimasa

    2006-04-07

    Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase III trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United States exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced (T2-stage) cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase II trials using active drug combinations. In 2005, a large phase III trial testing pre- and postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. Since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase III studies testing this strategy may be warranted in the near future.

  17. Primary gastric adenosquamous carcinoma in an Indian male.

    PubMed

    Bansal, Rinkesh Kumar; Sharma, Praveen; Kaur, Ramneet; Arora, Anil

    2013-01-01

    Adenosquamous carcinoma (ASC) of the stomach is a very rare tumor comprising less than 0.5% of all stomach malignancies. Here, we report a case of a 37-year-old male, who presented with upper gastrointestinal bleeding in the form of hematemesis and malena. A subtotal gastrectomy was done in view of massive uncontrolled bleed. Histology showed evidence of ASC of the body and antrum with metastasis to the liver, perigastric lymph nodes and peritoneal and pleural cavity.

  18. MicroRNA-199a-3p is downregulated in gastric carcinomas and modulates cell proliferation.

    PubMed

    Peng, W; Chen, Z-Y; Wang, L; Wang, Z; Li, J

    2013-08-20

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate the translation of targeted mRNAs. An increasing amount of evidence indicates that miRNAs play important role in cancer pathogenesis, apoptosis, proliferation, and differentiation as oncogenes or tumor suppressors. Recently, miRNA-199a has been shown to be involved in many human cancers, although the role of miRNA-199a-3p in gastric cancer has not yet been evaluated. In the present study, the expression of miRNA-199a-3p was found to be significantly downregulated in human gastric cancer tissues and cells. miRNA-199a-3p induced anti-proliferation effects on human gastric cancer cells. Furthermore, using quantitative RT-PCR (real-time polymerase chain reaction) and luciferase reporter assays, mTOR was identified as a direct target gene of miRNA-199a-3p that is downregulated by it. In conclusion, our findings suggest that miRNA-199a-3p is associated with human gastric cancer through its ability to decrease cancer cell proliferation and target the mTOR signaling pathway, and, therefore, may provide a novel therapeutic target for the treatment of human gastric cancer.

  19. [Minimal Residual Disease (MRD) in gastric carcinoma--an overview].

    PubMed

    Garlipp, B; Steinert, R; Lippert, H; Meyer, F

    2011-02-01

    Despite recent developments in therapy for gastric cancer, the prognosis of this disease remains poor in advanced stages. In many cases even curatively treated patients without any residual tumour develop metachronous metastases. As in other solid tumours, adjuvant therapies can reduce the metastatic risk, which implies that some of these patients harbour isolated tumour cells or micrometastases (minimal residual disease, MRD) that are undetectable by radiological imaging and conventional histopathology but can still be the cause of tumour recurrence. Therefore, reliable methods for diagnosing MRD would be desirable for individually tailoring therapy for these patients. Unfortunately, testing methods for MRD and interpretation of their results are not standardised and studies published on this topic are difficult to interpret due to methodological differences and small sample sizes. As of now, testing for MRD has not become relevant in clinical routine for any of the anatomic compartments lymph nodes, peritoneal lavage fluid, peripheral blood, and bone marrow in the Western hemisphere. Most reliable data on MRD in gastric cancer patients have been reported for peritoneal lavage fluid. In some centres in Japan, this test is routinely being used for making therapeutic decisions, e. g., on the use of intraperitoneal chemotherapy. MRD in resected lymph nodes will be further evaluated in the context of the sentinel lymph node concept and possibly be employed for designing individualised therapy for patients in early disease stages who are not routinely candidates for multimodal treatment. As for tumour cells in peripheral blood and in bone marrow, studies suggest that these cells are only able to form metastases in the presence of certain molecular factors. Therefore, rather than simply confirming the existence of isolated tumour cells in blood or bone marrow, future studies should concentrate on defining their molecular characteristics and the conditions required for

  20. Phase II Study of Oxaliplatin, Irinotecan, and Capecitabine in Advanced Gastric/Gastroesophageal Junction Carcinoma

    ClinicalTrials.gov

    2015-04-15

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  1. Comprehensive characterization of the genomic alterations in human gastric cancer

    PubMed Central

    Cui, Juan; Yin, Yanbin; Ma, Qin; Wang, Guoqing; Olman, Victor; Zhang, Yu; Chou, Wen-Chi; Hong, Celine S.; Zhang, Chi; Cao, Sha; Mao, Xizeng; Li, Ying; Qin, Steve; Zhao, Shaying; Jiang, Jing; Hastings, Phil; Li, Fan; Xu, Ying

    2016-01-01

    Gastric cancer is one of the most prevalent and aggressive cancers worldwide, and its molecular mechanism remains largely elusive. Here we report the genomic landscape in primary gastric adenocarcinoma of human, based on the complete genome sequences of five pairs of cancer and matching normal samples. In total, 103,464 somatic point mutations, including 407 nonsynonymous ones, were identified and the most recurrent mutations were harbored by Mucins (MUC3A and MUC12) and transcription factors (ZNF717, ZNF595 and TP53). 679 genomic rearrangements were detected, which affect 355 protein-coding genes; and 76 genes show copy number changes. Through mapping the boundaries of the rearranged regions to the folded three-dimensional structure of human chromosomes, we determined that 79.6% of the chromosomal rearrangements happen among DNA fragments in close spatial proximity, especially when two endpoints stay in a similar replication phase. We demonstrated evidences that microhomology-mediated break-induced replication was utilized as a mechanism in inducing ~40.9% of the identified genomic changes in gastric tumor. Our data analyses revealed potential integrations of Helicobacter pylori DNA into the gastric cancer genomes. Overall a large set of novel genomic variations were detected in these gastric cancer genomes, which may be essential to the study of the genetic basis and molecular mechanism of the gastric tumorigenesis. PMID:25422082

  2. Scintigraphic detection of gastric and pancreatic carcinomas with In-111 ZCE 025 monoclonal antibody

    SciTech Connect

    Abdel-Nabi, H.H.; Schwartz, A.N.; Wechter, D.G.; Higano, C.S.; Ortman-Nabi, J.A.; Unger, M.W. )

    1991-01-01

    We have evaluated the role of In-111 anti-CEA (carcinoembryonic antigen) monoclonal antibody ZCE 025 in 8 patients. Three patients had a confirmed diagnosis of gastric carcinoma. Three had a confirmed diagnosis of pancreatic carcinoma. Two patients had elevated serum levels of CEA with no known primary. Each patient received 5.5 mCi In-111 ZCE 025 infused at doses of 10-80 mg. Planar and single photon emission computed tomography (SPECT) imaging at 3 and 7 days after infusion detected 9 of 12 known tumor sites and all 5 of the previously identified sites of metastasis. In-111 ZCE 025 MoAb imaging also found 6 previously unsuspected tumor sites and changed the preoperative evaluation in 50% of the patients studied. It changed the clinical management in 2 patients and established the site of primary involvement in 2 others. There were no clinical or biochemical reactions. In-111 ZCE 025 monoclonal antibody scintigraphy is a useful adjunct in the evaluation of patients with either gastric or pancreatic carcinoma. It may have a beneficial impact on the surgical decision making in these patients.

  3. Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens.

    PubMed

    Ahn, Sangjeong; Ahn, Soomin; Van Vrancken, Michael; Lee, Minju; Ha, Sang Yun; Lee, Hyuk; Min, Byung-Hoon; Lee, Jun Haeng; Kim, Jae J; Choi, Sunkyu; Jung, Sin-Ho; Choi, Min Gew; Lee, Jun-Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Kyoung-Mee

    2015-11-10

    Intratumoral heterogeneity of HER2 expression is common in gastric cancers and pose a challenge for identifying patients who would benefit from anti-HER2 therapy. The aim of this study is to compare HER2 expression in biopsy and resection specimens of gastric carcinoma by immunohistochemistry (IHC) and to find the ideal number of biopsy tumor fragments that can accurately predict HER2 overexpression in the corresponding surgically resected specimen. The HER2 IHC results of 702 paired biopsy and resection specimens of gastric cancer were compared.The mean number of biopsy fragments among all cases was 4.3 (range 1-11). HER2 was positive in 130 (18.5%) endoscopic biopsies and in 102 (14.5%) gastrectomy specimens. Intratumoral heterogeneity of HER2 was found in 80 (61.5%) biopsies and 70 (68.6%) resection specimens. Out of the 70 surgical specimens with intratumoral heterogeneity, 24 (34.3%) of the corresponding biopsies were categorized as negative (positive conversion). In the 86 (12.3%) discrepant cases, negative conversion was observed in 57 (66.3%) cases and positive conversion in 29 (33.7%). The fragment numbers were significantly correlated with the discrepancy of results and positive predictability (P = 0.0315 and P = 0.0052). ROC curve analysis and positive predictability showed that 4 fragments should be obtained to minimize the differences in HER2 scores between biopsy and resection specimen.In gastric carcinomas with discrepant HER2 results between biopsy and surgical resection specimens, intratumoral heterogeneity is common with most of them showing positive conversion. To predict HER2 status precisely, at least 4 biopsy fragments containing tumor cells are required.

  4. Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens

    PubMed Central

    Lee, Minju; Ha, Sang Yun; Lee, Hyuk; Min, Byung-Hoon; Lee, Jun Haeng; Kim, Jae J.; Choi, Sunkyu; Jung, Sin-Ho; Choi, Min Gew; Lee, Jun-Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Kyoung-Mee

    2015-01-01

    Intratumoral heterogeneity of HER2 expression is common in gastric cancers and pose a challenge for identifying patients who would benefit from anti-HER2 therapy. The aim of this study is to compare HER2 expression in biopsy and resection specimens of gastric carcinoma by immunohistochemistry (IHC) and to find the ideal number of biopsy tumor fragments that can accurately predict HER2 overexpression in the corresponding surgically resected specimen. The HER2 IHC results of 702 paired biopsy and resection specimens of gastric cancer were compared. The mean number of biopsy fragments among all cases was 4.3 (range 1–11). HER2 was positive in 130 (18.5%) endoscopic biopsies and in 102 (14.5%) gastrectomy specimens. Intratumoral heterogeneity of HER2 was found in 80 (61.5%) biopsies and 70 (68.6%) resection specimens. Out of the 70 surgical specimens with intratumoral heterogeneity, 24 (34.3%) of the corresponding biopsies were categorized as negative (positive conversion). In the 86 (12.3%) discrepant cases, negative conversion was observed in 57 (66.3%) cases and positive conversion in 29 (33.7%). The fragment numbers were significantly correlated with the discrepancy of results and positive predictability (P = 0.0315 and P = 0.0052). ROC curve analysis and positive predictability showed that 4 fragments should be obtained to minimize the differences in HER2 scores between biopsy and resection specimen. In gastric carcinomas with discrepant HER2 results between biopsy and surgical resection specimens, intratumoral heterogeneity is common with most of them showing positive conversion. To predict HER2 status precisely, at least 4 biopsy fragments containing tumor cells are required. PMID:26460823

  5. Efficacy of Gastric Blood Supply Redistribution by Transarterial Embolization: Preoperative Procedure to Prevent Postoperative Anastomotic Leaks Following Esophagoplasty for Esophageal Carcinoma

    SciTech Connect

    Isomura, Takayuki; Itoh, Shigeki; Endo, Tokiko; Akiyama, Seiji; Maruyama, Kunihiro; Ishiguchi, Tsuneo; Ishigaki, Takeo; Takagi, Hiroshi

    1999-03-15

    Purpose: The aim of this study was to evaluate the effect of preoperative redistribution of gastric blood supply on the prevention of anastomotic leakage following surgical reconstruction of the esophagus. Methods: In 37 patients with esophageal carcinoma, transarterial embolization (TAE) of the left gastric, right gastric, and splenic arteries was preoperatively performed with coils so that gastric blood supply was dependent only on the right gastroepiploic artery.Results: In 34 of 37 patients, preoperative redistribution was successfully performed. The gastric tissue blood flow (TBF) of a gastric tube was higher than in 12 nonredistributed patients. Reduction in the gastric TBF during preparation of a gastric tube was 27.5% in successful patients, in contrast to 68.9% in 12 nonredistributed patients (p < 0.005). Conclusion: Preoperative redistribution by TAE reduced the drop in gastric TBF during preparation of a gastric tube and helped prevent postoperative anastomotic leakage in esophageal reconstruction.

  6. Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab

    PubMed Central

    Fuchs, Charles S; Tabernero, Josep; Tomášek, Jiří; Chau, Ian; Melichar, Bohuslav; Safran, Howard; Tehfe, Mustapha A; Filip, Dumitru; Topuzov, Eldar; Schlittler, Luis; Udrea, Anghel Adrian; Campbell, William; Brincat, Stephen; Emig, Michael; Melemed, Symantha A; Hozak, Rebecca R; Ferry, David; Caldwell, C William; Ajani, Jaffer A

    2016-01-01

    Background: Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma. Methods: A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had ⩾1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3. Results: None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI=0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI=0.38, 1.22) and low (HR=0.73, 95% CI=0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression. Conclusions: REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited. PMID:27623234

  7. PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-α expression levels

    PubMed Central

    Xu, Bing; Liu, Chunyan; Li, Chang; Zhang, Xiaoqian; Chang, Xiaotian

    2016-01-01

    PADI4 (peptidyl deiminase isoform 4) is overexpressed in many tumor tissues and converts arginine residues to citrulline residues. This study used an Illumina SNP microarray and a TaqMan assay to determine the possible association of the PADI4 gene with various tumor risks. Both genotyping methods demonstrated significant associations between the tag SNPs rs1635566 and rs882537 in the PADI4 locus with gastric carcinoma in two independent cohorts. Based on this genotyping result, we used the Cancer Pathway Finder, p53 Signaling, Signal Transduction and Tumor Metastasis PCR arrays to investigate the tumorigenic pathway of PADI4 in MNK-45 cells derived from gastric carcinoma. We detected significantly decreased expression levels of CXCR2, KRT14 and TNF-α in MNK-45 cells that were treated with anti-PADI4 siRNA. We also detected increased expression of these three genes in MNK-45 cells transfected with a pcDNA3.1 plasmid overexpressing PADI4. A highly similar result was also obtained for SGC 7901 cells, which also originate from gastric carcinoma. Our result indicates that the PADI4 gene has genetic susceptibility in gastric carcinoma. PADI4 contributes to gastric tumorigenesis by upregulating CXCR2, KRT14 and TNF-α expression, which are well known to activate angiogenesis, cell proliferation, cell migration and the immune microenvironment in tumors. PMID:27556695

  8. Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland.

    PubMed

    Morita, Koji; Sakamoto, Takahiko; Ota, Shuji; Masugi, Hideo; Chikuta, Ikumi; Mashimo, Yamato; Edo, Naoki; Tokairin, Takuo; Seki, Nobuhiko; Ishikawa, Toshio

    2017-01-01

    It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

  9. PD-L1/PD-1 check-point in gastric carcinoma with lymphoid stroma case report with immunochemical study

    PubMed Central

    Crescenzi, Anna; Taffon, Chiara; Donati, Michele; Guarino, Michele Pier Luca; Valeri, Sergio; Coppola, Roberto

    2017-01-01

    Abstract Introduction: Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1–programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. Patient's concerns case study and outcome: We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes. Conclusion: The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery. PMID:28207501

  10. Positive feedback loop of IL-1β/Akt/RARα/Akt signaling mediates oncogenic property of RARα in gastric carcinoma

    PubMed Central

    Huang, Gui-Li; Liu, Yu; Shen, Jin-Xing; Zhou, Pan; Liu, Wen-Ming; Shen, Dong-Yan

    2017-01-01

    Abnormal expression and function of retinoic acid receptor α (RARα) have been reported to be associated with various cancers including acute promyelocytic leukemia and hepatocellular carcinoma. However, the role and the mechanism of RARα in gastric carcinoma (GC) were unknown. Here, the expression of RARα was frequently elevated in human GC tissues and cell lines, and its overexpression was closely correlated with tumor size, lymph node metastasis and clinical stages in GC patients. Moreover, RARα overexpression was related with pathological differentiation. Functionally, RARα knockdown inhibited the proliferation and metastasis of GC cells, as well as enhanced drug susceptibility both in vitro and in vivo. Additionally, RARα knockdown suppressed GC progression through regulating the expression of cell proliferation, cell cycle, invasion and drug resistance associated proteins, such as PCNA, CyclinB1, CyclinD2, CyclinE, p21, MMP9 and MDR1. Mechanistically, the above oncogenic properties of RARα in GC were closely associated with Akt signaling activation. Moreover, overexpression of RARα was induced by IL-1β/Akt signaling activation, which suggested a positive feedback loop of IL-1β/Akt/RARα/Akt signaling in GC. Taken together, we demonstrated that RARα was frequently elevated in GC and exerted oncogenic properties. It might be a potential molecular target for GC treatment. PMID:28035062

  11. Weekly administration of paclitaxel attenuated rectal stenosis caused by multiple peritoneal recurrence 8 years after the resection of gastric carcinoma.

    PubMed

    Sakurai, Yoichi; Yoshida, Ikuo; Tonomura, Shuhei; Sakai, Wakana; Nakamura, Yasuko; Imazu, Hiroki; Matsubara, Toshiki; Ochiai, Masahiro

    2003-01-01

    We report a patient with rectal stenosis caused by peritoneal recurrence 8 years after a curative resection of advanced stage gastric carcinoma; the recurrence was effectively treated with the weekly administration of paclitaxel. The patient was a 66-year-old Japanese woman who was admitted to our hospital complaining of abdominal pain and frequent bowel movements. She had undergone total gastrectomy, due to advanced-stage gastric carcinoma with extensive lymph node metastasis, 8 years before, and had taken an oral anticancer agent, fluoropyrimidine, for 4 years after the operation. Colonofiberscopy performed on admission revealed circumferential rectal stenosis located 10 cm from the anal verge. Barium enema study demonstrated extensive poor expansion of the upper and lower rectum and irregularity of the descending colon. Abdominal computed tomography (CT) scanning revealed wall thickening in the rectum and descending colon. These findings were compatible with rectal stenosis caused by the peritoneal recurrence of gastric carcinoma. Weekly administration of paclitaxel was started. The abdominal symptoms soon disappeared when the second cycle of paclitaxel was completed, and they have not appeared since then. The rectal stenosis was attenuated, as confirmed by imaging analyses. Weekly paclitaxel has been effective for more than 13 months, suggesting that the patient is in a state of tumor dormancy of recurrent gastric carcinoma.

  12. Downregulation of Runx3 is closely related to the decreased Th1-associated factors in patients with gastric carcinoma.

    PubMed

    Li, Yazhen; Ji, Xiaoyun; Su, Zhaoliang; Tong, Jia; Xia, Sheng; Chen, Xiaobo; Lu, Ping; Barnie, Prince Amoah; Wang, Shengjun; Huang, Xinxiang; Xu, Huaxi

    2014-12-01

    Runt-related transcription factor 3 (Runx3) is a tumor-suppressor gene and plays an important role in immune regulation, whose reduced expression may play an important role in the development and progression of gastric carcinoma. The aim of this study was to investigate the role of Runx3 on the levels of transcription factors in patients with gastric carcinoma and analyze the relationship between the expression of Runx3 and Th1-type cytokines in peripheral blood mononuclear cells (PBMCs). Our results showed that the expression levels of Runx3, T-bet, and IFN-γ in patients with gastric carcinoma were obviously lower than those in control groups, and there was a positive correlation between the expression of Runx3 and T-bet or IFN-γ in patients (p < 0.01). In order to further confirm this result, the Runx3 gene was constructed into pIRES2-eGFP and the recombined plasmid was transfected into SGC-7901 cells with liposome in vitro, the results obtained from the reverse transcription PCR indicated that the mRNA of Runx3, T-bet, or IFN-γ was significantly upregulated individually in Runx3 gene-transfected SGC-7901 cells. It suggested that the Runx3 and Th1-associated factors including T-bet and IFN-γ synchronization declines in gastric carcinoma may contribute to the development of cancer.

  13. MiR-29c is downregulated in gastric carcinomas and regulates cell proliferation by targeting RCC2

    PubMed Central

    2013-01-01

    Background Previously, using miRNA microarray, we have found that miR-29c is significantly downregulated in advanced gastric carcinoma. In the present study, we investigated whether miR-29c functions as a tumor-suppressor miRNA in gastric carcinoma cells. For this purpose, we verified the downregulation of miR-29c in gastric carcinoma tissues, and assessed the biological effect of miR-29c on gastric carcinoma cells. Results In miR-29c-transfected cells, both proliferation and colony formation ability on soft agar were significantly decreased. Although apoptosis was not induced, BrdU incorporation and the proportion of cells positive for phospho-histone H3 (S10) were significantly decreased in miR-29c-transfected cells, indicating that miR-29c may be involved in the regulation of cell proliferation. To explain the mechanism of growth suppression by miR-29c, we explored differentially expressed genes (>2-fold) in miR-29c-transfected cells in comparison with negative control transfected cells using microarray. RCC2, PPIC and CDK6 were commonly downregulated in miR-29c-transfected MKN45, MKN7 and MKN74 cells, and all of the genes harbored miR-29c target sequences in the 3’-UTR of their mRNA. RCC2 and PPIC were actually upregulated in gastric carcinoma tissues, and therefore both were identified as possible targets of miR-29c in gastric carcinoma. To ascertain whether downregulation of RCC2 and/or PPIC is involved in the growth suppression by miR-29c, we transfected siRNAs against RCC2 and PPIC into MKN45 and determined cell viability, the rate of BrdU incorporation, and caspase activity. We found that RCC2-knockdown decreased both cell viability and BrdU incorporation without any increase of caspase activity, while PPIC-knockdown did not, indicating that downregulation of RCC2 may be at least partly responsible for the growth suppression by miR-29c. Conclusions Our findings indicate that miR-29c may have tumor-suppressive functions in gastric carcinoma cells, and

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

    PubMed

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

    2011-06-01

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

  15. Gastric neuroendocrine carcinoma after long-term use of proton pump inhibitor.

    PubMed

    Jianu, Constantin S; Lange, Ove J; Viset, Trond; Qvigstad, Gunnar; Martinsen, Tom C; Fougner, Reidun; Kleveland, Per M; Fossmark, Reidar; Hauso, Øyvind; Waldum, Helge L

    2012-01-01

    We present a case of a gastric neuroendocrine carcinoma in a patient with a history of long-term proton pump inhibitor (PPI) use. A 49-year-old man using PPI for the last 15 years due to gastroesophageal reflux disease developed progressive dysphagia, dyspepsia and weight loss. Upper gastrointestinal endoscopy, endoscopic ultrasonography and abdominal CT diagnosed a malignant tumor localized to a hiatal hernia. Fasting serum chromogranin A and gastrin concentrations were elevated (32 nmol/l and 159 pmol/l, respectively). Helicobacter pylori PCR analysis of antral biopsies was negative. Biopsies from endoscopically normal oxyntic mucosa showed enterochromaffin-like (ECL) cell hyperplasia. Tumor biopsies revealed a poorly differentiated neuroendocrine carcinoma. Sevier-Munger staining, immunohistochemistry and electron microscopy indicated ECL cell as origin of the tumor cells. Concerns have previously been raised about the safety of long-term PPI use due to a possible increased risk of cancer. This case illustrates a patient with a poorly differentiated neuroendocrine carcinoma with ECL cell characteristics probably induced by hypergastrinemia secondary to long-term PPI use.

  16. Serum TAG 72 levels in different human carcinomas.

    PubMed

    Correale, M; Abbate, I; Gargano, G; Garrubba, M; Muncipinto, A; Addabbo, L; Colangelo, D

    1991-01-01

    Since December 1988, we have measured the TAG 72 serum levels in 326 patients with different carcinomas, especially breast, gastrointestinal and ovarian, using a RIA kit. With a cut-off value of 5 U/mL, a specificity of 100% in the controls and an overall sensitivity of 22% in the neoplastic patients was obtained, with the highest positivities in ovarian (63%) and gastric (58%) carcinomas. Therefore, TAG 72 can be associated with other tumor markers for these latter neoplasms.

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

    PubMed

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

    2007-01-01

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

  18. Substantial reduction of the gastric carcinoma critical region at 6q16.3-q23.1.

    PubMed

    Carvalho, B; Seruca, R; Carneiro, F; Buys, C H; Kok, K

    1999-09-01

    Deletions of the long arm of chromosome 6 are a common event in gastric carcinomas. In a previous study, deletion mapping of 6q identified two smallest regions of overlap (SROs) of heterozygous deletions: one interstitial, spanning 12-16 cM, bordered by D6S268 (6q16.3-q21) and ARG1 (6q22.3-q23.1), and one distal to IFNGR1 (6q23-q24), spanning more than 30 cM. Loss of heterozygosity (LOH) of the interstitial SRO was detected in 50% of informative tumors. We analyzed 60 primary gastric tumors with 19 highly polymorphic markers from 6q16.3-q23.3 to delimit the interstitial SRO further. Of the 50 tumors that were informative for at least one locus, 18 (36%) showed allelic imbalance (AI). The overlap of these cases allowed us to define an SRO of approximately 3 Mb flanked by D6S278 and D6S404. AI or LOH of this region occurs in all histologic types of gastric carcinoma and in early stages of development, indicating that loss of a gene from this region of 6q is a crucial step in a main route of gastric carcinogenesis. For cases with retention of 6q, alternative routes of gastric carcinogenesis may exist. Genes Chromosomes Cancer 26:29-34, 1999.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    Hou, Dibo; Li, Xian; Cai, Jinhui; Ma, Yehao; Kang, Xusheng; Huang, Pingjie; Zhang, Guangxin

    2014-09-01

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

  1. Molecular Genetic Study of Human Esophageal Carcinoma

    DTIC Science & Technology

    1991-07-16

    activating transmembrane mutations in the c- erbB2 proto-oncogene in human breast cancer. Oncogene, 5:237-239, 1990. Levine, A.J., & Monard, J. Tumor...have demonstrated susceptibility to mutations in different types of neoplasia. In the present investigation, two approaches were undertaken in the...search for such genes which might be mutated during the development of esophageal carcinoma. In the first, the human HER2 oncogene, encoding a

  2. The Prognostic Significance of Her2-Neu Over expression in Gastric Carcinomas

    PubMed Central

    Ansari, J; Chehrei, A; Amini, M; Alizade, SH; Sanei, MH

    2011-01-01

    Background Her2/neu is one of the epidermal growth factor receptors families and seems to have prognostic significance of some solid tumors. The objective of this study is to evaluate the possibility of Her2 expression in gastric cancers and the possible relationship of Her2 with tumor’s clinicopathologic parameters and also its prognostic role. Methods This study was performed on 100 cases of gastric carcinoma with stage I b to III (according to TNM staging). Survival, recurrence date of patients, grade and lymph nodes involvement were assessed. Her2/neu expression was determined by immunohistochemical method on received sample blocks. Survival of patients with or without Her2-neu expression were evaluated by Kaplan- Meier method and compared with the log-rank test followed by multivariate analysis using Cox regression. Results Seven cases were 3+ membranous Her2 reactivity, 5 cases were 2+ and13 cases were 1+; also 75% of cases demonstrated no reactivity. Regardingrelationship between tumor grade and membranous Her2 , all patients with poorly differentiated tumors were Her2 negative but patients with moderate and well differentiated tumor had 18.1% and 19.6% Her2 reactivity respectively; there were no significant difference between groups statistically(P>0.05). Median overall survival was 27.25 and 46 months in Her2 negative and her2 positive cases respectively; there were no significant difference between groups statistically as well (P>0.05). Conclusion Her2 reactivity has not relationship with tumor grade and lymph node involvement as well as tumor stage. From the other point of view no significant correlation is found between Her2 expression and disease free survival or overall survival of gastric cancer patients. PMID:26322194

  3. Accumulation of hypericin in human gastric tumors

    NASA Astrophysics Data System (ADS)

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

    1996-04-01

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

  4. L-Type amino acid transporter 1 (LAT1) expression in lymph node metastasis of gastric carcinoma: Its correlation with size of metastatic lesion and Ki-67 labeling.

    PubMed

    Ichinoe, Masaaki; Yanagisawa, Nobuyuki; Mikami, Tetuo; Hana, Kiyomi; Nakada, Norihiro; Endou, Hitoshi; Okayasu, Isao; Murakumo, Yoshiki

    2015-07-01

    L-Type amino acid transporter 1 (LAT1) is one of the major amino acid transporters. High levels of LAT1 expression have been reported in various tumors, which can act as a novel prognostic marker. Previously, we demonstrated that LAT1 is highly expressed in advanced gastric carcinoma with lymph node metastasis, and proposed that LAT1 is an independent prognostic factor in non-scirrhous gastric carcinoma. The aim of the present study was to investigate the relationship between LAT1 expression and the size of lymph node metastatic lesions in gastric carcinoma. LAT1 and Ki-67 expression was immunohistochemically analyzed in 64 cases of advanced gastric carcinoma with lymph node metastasis. LAT1 expression in the metastatic lymph nodes was correlated with that in the primary lesions. The high LAT1 expression group showed a larger size of metastatic lesion and a higher Ki-67 labeling index than the low LAT1 expression group. LAT1 expression had a weak association with Ki-67 labeling index and tumor diameter of lymph nodes. These results suggest that LAT1 expression is associated with disease progression in gastric carcinoma. We proposed that LAT1 could be a potential therapeutic target for gastric carcinoma cases with large lymph node metastasis.

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

    PubMed

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

    2009-02-17

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

  6. Human gut microbiota in obesity and after gastric bypass

    PubMed Central

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

    2009-01-01

    Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H2-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H2-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H2-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H2-producing bacteria with relatively high numbers of H2-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H2 transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion. PMID:19164560

  7. The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes.

    PubMed

    Ksiaa, Feryel; Ziadi, Sonia; Mokni, Moncef; Korbi, Sadok; Trimeche, Mounir

    2010-04-01

    JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

  8. First Case Report of a Sporadic Adrenocortical Carcinoma With Gastric Metastasis and a Synchronous Gastrointestinal Stromal Tumor of the Stomach.

    PubMed

    Kovecsi, Attila; Jung, Ioan; Bara, Tivadar; Bara, Tivadar; Azamfirei, Leonard; Kovacs, Zsolt; Gurzu, Simona

    2015-09-01

    Adrenocortical carcinoma is a rare tumor with high aggresivity that can associate systemic metastases. A 71-year-old man was hospitalized for gastric cancer. The abdominal computed tomography also revealed a tumor above the right kidney. Total gastrectomy and right adrenalectomy were performed. The encapsulated tumor of the adrenal gland weighed 560 grams and presented diffuse tumor architecture under microscope, with capsular, sinusoidal, and vascular invasion. The large tumor cells had a polygonal shape, with slight basophilic, eosinophilic, or vacuolated cytoplasm, pleomorphic nuclei, and a high mitotic rate. In the stomach, the protruded tumor was covered by normal mucosa; under microscope, the tumor cells were observed only in the submucosal layer. In primary adrenal tumor and gastric metastasis the tumor cells were marked by vimentin, inhibin, synaptophysin, neuron-specific enolase, and calretinin. Based on these criteria, the diagnosis of adrenocortical carcinoma (ACC) with gastric metastasis and no lymph node metastases was established. A synchronous 10 × 10-mm-sized gastrointestinal stromal tumor (GIST) of the stomach, without mitoses, was also identified. So far, as we know, this is the 15th case of ever reported synchronous/metachronous sporadic ACCs; the ACC-related gastric metastases either synchronous ACC and GIST, has not been reported in the literature previously.

  9. Regulation of mRNA expression in drug-sensitive and drug-resistant gastric carcinoma cells is independent of YB-1 expression.

    PubMed

    Kurucz, Reka; Belian, Elisa; Treue, Denise; Lage, Hermann

    2010-02-01

    Y-Box protein 1 (YB-1) is a multifunctional cellular protein expressed in a range of mammalian cells, including human cancer cells. It is involved in the regulation of various genes including cancer-associated genes, but the full range of target genes and regulatory mechanisms have not been fully elucidated. To identify global mRNA expression patterns that are potentially regulated by YB-1, a previously established and well-characterized cell model derived from drug-sensitive (EPG85-257P/tetR/YB-1) and multidrug-resistant (EPG85-257RDB/tetR/YB-1) gastric carcinoma cells in which the expression of YB-1 can be inhibited by tetracycline-dependent activation of the RNA interference (RNAi) pathway, was analyzed by microarray technology. By this approach, various potentially regulated genes encoding members of important cellular pathways such as the Jak/STAT, VEGF and the MAP-kinase signaling pathways were identified. Independent validation of these findings by quantitative real-time reverse transcriptase polymerase chain reaction and Western blot did not confirm these regulatory effects. In conclusion, the findings suggest that YB-1 is not directly involved in the regulation of mRNA expression in drug-sensitive or drug-resistant gastric carcinoma cells.

  10. Sequence variation of Epstein-Barr virus (EBV) BZLF1 gene in EBV-associated gastric carcinomas and nasopharyngeal carcinomas in Northern China.

    PubMed

    Luo, Bing; Tang, Xiuming; Jia, Yuping; Wang, Yun; Chao, Yan; Zhao, Chengquan

    2011-08-01

    Epstein-Barr virus (EBV) BZLF1 gene can trigger EBV from latent infection to lytic replicative phase. The functions of BZLF1 are well known, while little is known about its gene polymorphism. In order to elucidate the sequence variations of BZLF1 and its association with malignancies, we analyzed BZLF1 gene in 24 EBV-associated gastric carcinomas, 41 nasopharyngeal carcinomas and 24 throat washing samples from healthy donors in Northern China using PCR-direct sequencing method. Three types and 8 subtypes of BZLF1 were identified. A dominant type BZLF1-A was found in 67 of 89 (75.3%) isolates. Type BZLF1-B was characterized by a common Ala deletion at residue 127, which was detected in 21 of 89 isolates (23.6%). Type BZLF1-C contained only one isolate (GC103), which had the same sequence with the prototype B95-8. Among 3 functional domains of BZLF1 protein, the transactivation domain had most mutations, followed by the bZIP domains (the DNA binding domain and dimerization domain). No prevalence of any subtypes or mutations in the functional domains among three specimen groups was found (P > 0.05). Our study indicates that BZLF1 subtypes and amino acid changes in functional domains are not preferentially associated with EBV-associated gastric carcinomas or nasopharyngeal carcinomas in Northern China. BZLF1 gene variations are geographically restricted rather than tumor-specific polymorphisms.

  11. Nuclear and cytoplasmic Id-1 expression patterns play different roles in angiogenesis and lymphangiogenesis in gastric carcinoma.

    PubMed

    Si, Chun-Feng; Guo, Jian-Qiang; Yang, Yong-Mei; Zhang, Nan; Pan, Cheng-Ran; Zhang, Qing-Hui; Zhang, Ting-Guo; Zhou, Cheng-Jun

    2011-02-01

    The purpose of the study was to investigate the expression and impact of Id-1 (inhibitor of differentiation) on tumor progression, angiogenesis, and lymphangiogenesis in gastric adenocarcinoma. The study included 97 cases of gastric adenocarcinoma, which were surgically excised at the Second Hospital of Shandong University. Immunohistochemistry was used to detect the Id-1 expression, and dual-labeling immunohistochemistry was used to evaluate the microvessel density (MVD) and lymphatic vessel density (LVD). The Id-1 protein was mainly expressed with nuclear staining in well-differentiated carcinoma, but with cytoplasmic staining in moderately and poorly differentiated carcinoma, which showed a significant difference (P < .0001). Moreover, the expression patterns had different and crucial effects on angiogenesis and lymphangiogenesis. Nuclear staining of Id-1 inhibited angiogenesis, but cytoplasmic staining promoted angiogenesis (MVD, 110.57 ± 32.32 vs 141.45 ± 55.60) (P < .05). Consistent with their roles in angiogenesis, the nuclear and cytoplasmic expressions of Id-1 had similar effects on lymphangiogenesis: nuclear expression inhibited and cytoplasmic expression promoted lymphangiogenesis (LVD, 2.62 ± 1.03 vs 4.05 ± 2.04) (P < .05). Microvessel density and LVD showed no significant difference in low-and high-Id-1 expression groups (P > .05). Aberrant expression of Id-1 from nuclear to cytoplasm is accompanied with tumor malignant progression, which promotes angiogenesis and lymphangiogenesis; and Id-1 should be developed as a target for gastric carcinoma therapy.

  12. Constitutive activation of glycogen synthase kinase-3β correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer

    PubMed Central

    2010-01-01

    Background Aberrant regulation of glycogen synthase kinase-3β (GSK-3β) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3β phosphorylated at Tyr216 (pGSK-3β) and its relationship with other tumor-associated proteins in human gastric cancers. Methods Immunohistochemistry was performed on tissue array slides containing 281 human gastric carcinoma specimens. In addition, gastric cancer cells were cultured and treated with a GSK-3β inhibitor lithium chloride (LiCl) for immunoblot analysis. Results We found that pGSK-3β was expressed in 129 (46%) of 281 cases examined, and was higher in the early-stages of pathologic tumor-node-metastasis (P < 0.001). The expression of pGSK-3β inversely correlated with lymphatic invasion (P < 0.001) and lymph node metastasis (P < 0.001) and correlated with a longer patient survival (P < 0.001). In addition, pGSK-3β expression positively correlated with that of p16, p21, p27, p53, APC, PTEN, MGMT, SMAD4, or KAI1 (P < 0.05), but not with that of cyclin D1. This was confirmed by immunoblot analysis using SNU-668 gastric cancer cells treated with LiCl. Conclusions GSK-3β activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis. Thus, these findings suggest that GSK-3β activation is a useful prognostic marker for the early-stage gastric cancer. PMID:20704706

  13. [A case of chronic pancreatitis occurring in gastric aberrant pancreas poorly distinguishable from gastric aberrant pancreas ductal carcinoma].

    PubMed

    Ogawa, Sayaka; Miyaoka, Youichi; Fujiwara, Aya; Tsukano, Kousuke; Kotani, Satoshi; Yamanouchi, Satoshi; Kusunoki, Ryusaku; Ito, Satoko; Fujishiro, Hirofumi; Kohge, Nariaki; Onuma, Hideyuki

    2015-11-01

    A man in his 40s was referred to our hospital with abdominal pain. A gastric submucosal tumor (SMT) was diagnosed nine years previously, but the patient was lost to follow-up. Upon our evaluation, the SMT had enlarged, as demonstrated by esophagogastroduodenoscopy and abdominal computed tomography. Endoscopic ultrasonography revealed a hypoechoic and isoechoic mosaic mass, which primarily occupied the third and fourth layers of the gastric wall. Aspiration cytodiagnosis was performed, the results of which led to a suspicion of adenocarcinoma arising from gastric ectopic pancreas. Next, we conducted segmental gastrectomy. Pathological examination showed adiponecrosis, a pancreatic stone, chronic inflammatory cell infiltration, and fibrosis. Thus, the patient was diagnosed with chronic pancreatitis occurring in a gastric aberrant pancreas.

  14. The correlation and clinical implication of VEGF-C expression in microvascular density and lymph node metastasis of gastric carcinoma

    PubMed Central

    Dai, Yong; Jiang, Jinbo; Wang, Yanlei; Jin, Zutao; Hu, Sanyuan

    2016-01-01

    As the most common malignant tumor, gastric cancer had persistently high occurrence and mortality rate worldwide. Unfavorable treating outcome occur due to distal metastasis, making the inhibition of angiogenesis and managing tumor metastasis being crucial factors for affecting prognosis. Vascular endothelial growth factor-C (VEGF-C) is one important angiogenesis factor and mainly facilitates proliferation and differentiation of vascular endothelial cells in angiogenesis. It has been indicated in development and occurrence in gastric cancer, while its expression and correlation with microvascular density (MVD)/lymph node metastasis are still unclear. A total of 52 gastric tumor and 25 normal tissue samples were recruited for quantifying mRNA and protein expression of VEGF-C by real-time PCR and Western blotting. MVD and lymph tube density were quantified for further analysis of the correlation between VEGF-C and pathological parameters including clinical stage and lymph node metastasis. Both mRNA and protein levels of VEGF-C were significantly elevated in gastric tissues (p<0.05). In lymph node metastasis cases, VEGF-C was further potentiated compared to non-metastatic group (p<0.05). VEGF-C expression was positively correlated with MVD, lymph tube density and clinical stage (p<0.05) but not with age, sex or differentiation grade. VEGF-C expression is closely correlated with lymph node metastasis of gastric cancer. It may participate in the progression of gastric cancer via facilitating angiogenesis and lymph node metastasis, thus can be used in predicting prognosis of patients with gastric carcinoma. PMID:28078045

  15. Use of lectin microarray to differentiate gastric cancer from gastric ulcer

    PubMed Central

    Huang, Wei-Li; Li, Yang-Guang; Lv, Yong-Chen; Guan, Xiao-Hui; Ji, Hui-Fan; Chi, Bao-Rong

    2014-01-01

    AIM: To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer. METHODS: Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed. Protein was extracted from the frozen tissues and stored. The lectins were dissolved in buffer, and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized. The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block. Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval. Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody. The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray, and then validated by lectin histochemistry. Data are presented as mean ± SD for the indicated number of independent experiments. RESULTS: The glycosylation level of gastric cancer was significantly higher than that in ulcer. In gastric cancer, most of the lectin binders showed positive signals and the intensity of the signals was stronger, whereas the opposite was the case for ulcers. Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin. For MPL and VVA, all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer, especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma. GalNAc bound to MPL showed a significant increase. A statistically significant association between MPL and gastric cancer was observed. As with MPL, there were significant differences in VVA staining between gastric cancer and ulcer. CONCLUSION: Lectin microarray can differentiate the different

  16. miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma

    PubMed Central

    Liang, Hongwei; Wang, Feng; Chu, Danping; Zhang, Weijie; Liao, Zhicong; Fu, Zheng; Yan, Xin; Zhu, Hao; Guo, Wen; Zhang, Yujing; Guan, Wenxian; Chen, Xi

    2016-01-01

    Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been fully elucidated, and no studies have shown the upstream regulation of this gene in gastric cancer. In this study, we used bioinformatics analysis to search for miRNAs that could potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we observed the inverse correlation between miR-93 and PDCD4 protein levels, but not mRNA levels, in human gastric cancer tissues. We further experimentally validated PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric cancer cells after the overexpression or knockdown of miR-93. Additionally, the biological consequences of targeting PDCD4 through miR-93 were examined using cell apoptosis assays in vitro. We demonstrated that the repression of PDCD4 through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we revealed that miR-93 promoted the development of gastric tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, the findings of the present study indicated the oncogenic role of miR-93 in gastric cancer tumorigenesis through targeting PDCD4, particularly in apoptosis. PMID:27021515

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

    PubMed Central

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

    1994-01-01

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

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

    PubMed

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

    2016-02-02

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

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

    PubMed Central

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

    2016-01-01

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

  20. Role of the tumor microenvironment in the pathogenesis of gastric carcinoma

    PubMed Central

    Chung, Hye Won; Lim, Jong-Baeck

    2014-01-01

    Gastric carcinoma (GC) is the 4th most prevalent cancer and has the 2nd highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the past few decades, it is still a serious health problem. Chronic inflammatory status of the stomach, caused by the infection of Helicobacter pylori (H. pylori) and through the production of inflammatory mediators within the parenchyma is suspected to play an important role in the initiation and progression of GC. In this review, the correlation between chronic inflammation and H. pylori infection as an important factor for the development of GC will be discussed. Major components, including tumor-associated macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors, cytokines, and chemokines of GC microenvironment and their mechanism of action on signaling pathways will also be discussed. Increasing our understanding of how the components of the tumor microenviroment interact with GC cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets. PMID:24587646

  1. [Gastric metastasis from ovarian carcinoma revealed by a gastro-splenic perforation].

    PubMed

    Dupuychaffray, Jean-Pierre; Auger, Christine; Funes De La Vega, Mathilde; Riche, Agnès; Boulanger, Vincent; Blanchot, Philippe

    2004-05-01

    Metastatic disease involving the stomach is unusual. We report the case of a gastric metastasis from ovarian cancer revealed by gastro-splenic perforation. The gastric metastasis was diagnosed 17 years after the diagnosis of primary cancer.

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

    PubMed

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

    2016-07-01

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

  3. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

    PubMed Central

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei

    2017-01-01

    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

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

    PubMed Central

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

    2008-01-01

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

  5. E platinum, a newly synthesized platinum compound, induces apoptosis through ROS-triggered ER stress in gastric carcinoma cells.

    PubMed

    Wang, Xiaoping; Guo, Qinglong; Tao, Lei; Zhao, Li; Chen, Yan; An, Teng; Chen, Zhen; Fu, Rong

    2017-01-01

    Gastric cancer (GC) is still one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the antitumor effect of E Platinum, a newly platinum-based chemotherapeutic agent bearing the basic structure of Oxaliplatin, in a variety of gastric carcinoma cells and the underlying mechanisms. We demonstrated that E Platinum significantly induced apoptosis in gastric cancer cells via mitochondrial apoptotic pathway as a result of increased reactive oxygen species (ROS). We also found that E Platinum enhanced Ca(2+) flux out from the endoplasmic reticulum by increasing the protein expression of IP3R type 1 (IP3R1) and decreasing the expression of ERp44. Dysfunction of Ca(2+) homeostasis in endoplasmic reticulum (ER) leads to accumulation of unfolded proteins and ER stress. Mechanically, E Platinum increased ER stress associated protein expression such as GRP78, p-PERK, p-eIF2α, ATF4, and CHOP. However, knocking down CHOP reversed E Platinum-induced apoptosis by blocking mitochondrial apoptotic pathway. Furthermore, 10 mg/kg of E Platinum significantly suppressed BGC-823 tumor growth in vivo without toxicity, which correlated with induction of apoptosis and expression of ER stress related proteins in tumor tissues. Taken together, E Platinum inhibited tumor growth and induced apoptosis by ROS-mediated ER stress activation both in vitro and in vivo. Our study indicated that E Platinum may be a potential and effective treatment for gastric cancer in clinical. © 2016 Wiley Periodicals, Inc.

  6. Gastric cancer in a pregnant woman presenting with low back pain and bilateral erythematous breast hypertrophy mimicking primary inflammatory breast carcinoma.

    PubMed

    Mandato, Vincenzo Dario; Pirillo, Debora; Gelli, Maria Carolina; Cavina, Maurizio; La Sala, Giovanni Battista

    2011-02-01

    This report describes the first case of a pregnant woman presenting low-back pain and breast pain associated with bilateral erythematous breast hypertrophy, proving to be the result of metastatic disease from a gastric carcinoma. A 30-year-old pregnant woman was admitted complaining of persistent severe low back pain, breast pain and concomitant bilateral erythematous breast hypertrophy, mimicking primary inflammatory breast carcinoma. During the caesarean section, widespread disease was found and finally metastatic gastric cancer was detected. Pregnant women with gastric cancer may present symptoms that are considered common during pregnancy. Common symptoms that present warning characteristics, such as the persistent severe pain observed in the presented case, should be carefully investigated as they may be the only warning signs and symptoms of rare ominous conditions such as gastric cancer.

  7. Consensus of the Spanish Society of Medical Oncology (SEOM) and Spanish Society of Pathology (SEAP) for HER2 testing in gastric carcinoma.

    PubMed

    Gómez-Martín, Carlos; Concha, Angel; Corominas, José María; García-Caballero, Tomás; García-García, Elena; Iglesias, Mar; López, José Antonio; Ramón y Cajal, Santiago; Rojo, Federico; Palacios, José; Vera-Sempere, Francisco; Aranda, Enrique; Colomer, Ramon; García-Alfonso, Pilar; Garrido, Pilar; Rivera, Fernando; López-Ríos, Fernando

    2011-09-01

    The identification of HER2 alterations in advanced gastric carcinomas is of critical importance in daily clinical practice as such neoplasms require specific treatment with trastuzumab. For these reasons, pathologists and oncologists with expertise in gastric carcinomas and HER2 testing from both organisations (SEAP and SEOM) have endeavoured to discuss and agree on national guidelines for HER2 testing in gastric carcinomas. These guidelines are based on the experience of those who participated in the discussions and also on experience published internationally. These agreed guidelines give the minimum requirements that a pathological anatomy laboratory must fulfil in order to guarantee adequate HER2 testing in daily practice. Any laboratories which do not meet the minimum standards set out in the guidelines must make every effort to achieve compliance.

  8. Calcium accentuates injury induced by ethanol in human gastric cells.

    PubMed

    Kokoska, E R; Smith, G S; Deshpande, Y; Wolff, A B; Rieckenberg, C; Miller, T A

    1999-01-01

    The mechanism(s) whereby ethanol induces cellular injury remains poorly understood. Furthermore, the role of calcium in gastric mucosal injury under in vitro conditions is poorly defined. The major objectives of this study were to (1) define the temporal relationship between intracellular calcium accumulation induced by ethanol and cellular injury, (2) characterize the mechanism(s) whereby ethanol increases cellular calcium content, and (3) determine whether calcium removal would attenuate ethanol-induced cellular injury. Human gastric cells (AGS) were used for all experiments. Sustained intracellular calcium accumulation induced by ethanol, but not transient changes, preceded and directly correlated with cellular injury. Cells exposed to damaging concentrations of ethanol demonstrated an initial calcium surge that appeared to be a consequence of inositol 1,4,5-triphosphate (IP3) generation and subsequent internal store release followed by a sustained plateau resulting from extracellular calcium influx through store-operated calcium channels. Finally, both morphologic (cellular injury) and functional (clearance of bovine serum albumin) changes induced by ethanol were significantly attenuated when extracellular Ca(+&plus) influx was prevented, and further decreased when intracellular Ca(++) stores were depleted. These data indicate that calcium plays a significant role in cellular injury induced by ethanol.

  9. KISS-1 inhibits the proliferation and invasion of gastric carcinoma cells

    PubMed Central

    Li, Na; Wang, Hong-Xing; Zhang, Jie; Ye, Ya-Ping; He, Guo-Yang

    2012-01-01

    AIM: To investigate the function of the KISS-1 gene in gastric carcinoma cells and to explore its potential mechanism. METHODS: A KISS-1 eukaryotic expression vector was constructed and transfected into BGC-823 cells. Resistant clones were obtained through G418 selection. reverse transcription-polymerase chain reaction and western blotting were used to detect KISS-1 and matrix metalloproteinase-9 (MMP-9) expression in transfected cells. The growth of transfected cells was investigated by 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) proliferation assays, and the cells’ invasive potential was analyzed by basement membrane (Matrigel) invasion assays. The anti-tumor effects of KISS-1 were tested in vivo using allografts in nude mice. RESULTS: The expression level of KISS-1 mRNA and protein in BGC-823/KISS-1 transfected cells were significantly higher than in BGC-823/pcDNA3.1 transfected cells (P < 0.05) or the parental BGC-823 cell line (P < 0.05). The expression level of MMP-9 mRNA and protein in BGC-823/KISS-1 were significantly less than in BGC-823/pcDNA3.1 (P < 0.05) or BGC-823 cells (P < 0.05). MTT growth assays show the proliferation of BGC-823/KISS-1 cells at 48 h (0.642 ± 0.130) and 72 h (0.530 ± 0.164) were significantly reduced compared to BGC-823/pcDNA3.1 (0.750 ± 0.163, 0.645 ± 0.140) (P < 0.05) and BGC-823 cells (0.782 ± 0.137, 0.685 ± 0.111) (P < 0.05). Invasion assays indicate the invasive potential of BGC-823/KISS-1 cells (16.50 ± 14.88) is significantly reduced compared to BGC-823/pcDNA3.1 (20.22 ± 14.87) (P < 0.05) and BGC-823 cells after 24 h (22.12 ± 16.12) (P < 0.05). In vivo studies demonstrate the rate of pcDNA3.1-KISS-1 tumor growth is significantly slower than pcDNA3.1 and control cell tumor growth in nude mice. Furthermore, tumor volume of pcDNA3.1-KISS-1 tumors (939.38 ± 82.08 mm3) was significantly less than pcDNA3.1 (1250.46 ± 44.36 mm3) and control tumors (1284.36 ± 55.26 mm3) (P < 0.05). Moreover, the

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

    PubMed Central

    Compare, Debora

    2015-01-01

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

  11. A human gastric simulator (HGS) to study food digestion in human stomach.

    PubMed

    Kong, Fanbin; Singh, R Paul

    2010-01-01

    The objective of this study was to develop an in vitro stomach model, the Human Gastric Simulator (HGS), for studying gastric digestion of foods. The HGS is designed in such a way as to simulate the continuous peristaltic movement of stomach walls, with similar amplitude and frequency of contraction forces as reported in vivo. The HGS mainly consists of a latex vessel, simulating the stomach chamber, and a series of rollers secured on belts that are driven by motor and pulleys to create a continuous contraction of the latex wall. It also incorporates gastric secretion, emptying systems, and temperature control that enable accurate simulation of dynamic digestion process for detailed investigation of the changes in the physical chemical properties of ingested foods. The simulated gastric contraction force demonstrates a similar pattern as in vivo stomach forces. The precise control of gastric secretion and emptying and the adjustable mechanical forces in the HGS provide a useful tool to study transformation of food constituents under simulated physiological conditions.

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

    PubMed

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

    2015-05-01

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

  13. [Macroscopic and histological studies on the gastric carcinoma having arisen from the cardiac gland mucosa--concerning to the esophageal invasion and the reliable surgical cut-line].

    PubMed

    Misono, T; Nishimata, H; Nishimata, Y; Yamasuji, T; Toujinbara, H; Aosaki, S; Arima, T; Nakamura, K; Kimotsuki, K; Suenaga, T

    1993-04-01

    Cardiac carcinoma is defined as the carcinoma whose center of the mucosal lesion is located at the area of the stomach within 2.0cm from the esophago-gastric junction. Histological and macroscopical examination was performed concerning to the frequency of macroscopic type, the direction of the mucosal invasion, the tendency of the submucosal invasion and the esophageal invasion by using these cardiac carcinomas. The objects of this study are a hundred and thirty-nine cases of cardiac carcinomas. The conclusions are as follows: 1) Depressed type (Type II c) in early carcinoma, Type Borrmann 2 and Borrmann 3 in advanced carcinoma are the most frequent form of macroscopic types. 2) The majority (87.7%) of the early carcinomas was situated at the lesser curvature and the posterior wall of the cardiac mucosa (Figure 1). 3) The early cardiac carcinoma had a tendency to invade in the mucosal layer along the esophago-gastric junction (Table 2). 4) The cardiac carcinoma was thought to invade into the submucosa in its early phase, comparing to the carcinoma on the other area of the stomach (Table 3). Twenty-four out of thirty-five (68.6%) cases of cardiac carcinoma ranged from 11 to 20mm in diameter invaded into the submucosa (Table 3). 5) Twelve out of seventy-three (16.4%) of early cases and fifty-seven out of sixty-six (86.4%) of advanced cases showed the infiltration into the esophagus (Table 4, Figure 6). The reliable and surgical cut-line of the oral site can be established at the area over 11 mm in the distance from the oral margin of the mucosal invasion in the cases of early cardiac carcinoma, over 25mm in the cases of advanced differentiated type, and over 30mm in the cases of advanced undifferentiated type (Figure 6).

  14. Cure of Xenografted Human Carcinomas by BR96-Doxorubicin Immunoconjugates

    NASA Astrophysics Data System (ADS)

    Trail, P. A.; Willner, D.; Lasch, S. J.; Henderson, A. J.; Hofstead, S.; Casazza, A. M.; Firestone, R. A.; Hellstrom, I.; Hellstrom, K. E.

    1993-07-01

    Immunoconjugates (BR96-DOX) were prepared between chimeric monoclonal antibody BR96 and the anticancer drug doxorubicin. The monoclonal antibody binds an antigen related to Lewis Y that is abundantly expressed at the surface of cells from many human carcinomas; it has a high degree of tumor selectivity and is internalized after binding. BR96-DOX induced complete regressions and cures of xenografted human lung, breast, and colon carcinomas growing subcutaneously in athymic mice and cured 70 percent of mice bearing extensive metastases of a human lung carcinoma. Also, BR96-DOX cured 94 percent of athymic rats with subcutaneous human lung carcinoma, even though the rats, like humans and in contrast to mice, expressed the BR96 target antigen in normal tissues.

  15. Her2/neu Protein Expression and Oncogene Amplification in Gastric Carcinoma with Clinico-Pathological Correlation in Egyptian Patients

    PubMed Central

    Hadi, Ahmed Abdel; Hindawi, Ali El; Hareedy, Amal; Khalil, Heba; Ashiry, Ranya Al; Elia, Shady; Sadek, Ahmed; Magdy, Mona; Atta, Rafatt; Anas, Amgad; Bakr, Hisham; Hammam, Olfat

    2016-01-01

    AIM: Amplification of the Her2/neu gene and overexpression of the Her2/neu protein in gastric carcinoma (GC) is a golden criterion for target therapy with trastuzumab (Herceptin). We aim to evaluate the immunohistochemical protein expression and amplification of the oncogene Her2/neu by FISH technique in the epithelial gastric carcinoma and to compare their association with different clinicopathologic parameters aiming at identifying positive cases that may benefit from targeted therapy. MATERIALS AND METHODS: This study was done on eighty-five tumour tissue samples from patients with GC as well as thirty non-malignant lesions (Gastritis, intestinal metaplasia, adenoma with low-grade dysplasia, adenoma with high-grade dysplasia). All were immunohistochemically stained with Her2/neu antibody. RESULTS: All equivocal and some selected GC cases were submitted for FISH technique to detect Her2/neu gene amplification. By immunohistochemistry twenty-three cases (27%) were defined as positive for Her2/neu gene amplification and/or protein overexpression. The levels of Her2/neu positive (3+), Her2/neu equivocal (2+) and Her2/neu negative (1+/0) were measurable in 14.2%, 32.9% and 52.9% of the samples, respectively. FISH showed that Her2/neu gene was amplified in 22 cases, 10 Her2/neu positive (3+), 11 (39.3%) Her2/neu equivocal (2+) and 1 Her2/neu negative (1+) cases with IHC staining those who can benefit from anti Her2/neu target therapy. Her2/neu was overexpressed positivity (3+) more in intestinal type and mixed carcinoma, and moderately differentiated tumours. None of gastritis, intestinal metaplasia or adenoma with low-grade dysplasia cases showed positivity for Her2/neu (3+). The Her2/neu positivity (3+) was associated with both adenocarcinoma cases and high-grade dysplasia (P = 0.002). CONCLUSIONS: The results highlight the necessity of FISH test for further categorization when gastric cancer cases are equivocal (2+) by IHC to determine eligibility for the targeted

  16. babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil.

    PubMed

    Oliveira, Adriana Gonçalves; Santos, Adriana; Guerra, Juliana Becattini; Rocha, Gifone Aguiar; Rocha, Andreia Maria Camargos; Oliveira, Celso Affonso; Cabral, Mônica Maria Demas Alvares; Nogueira, Ana Margarida Miguel Ferreira; Queiroz, Dulciene Maria Magalhães

    2003-08-01

    The babA2 and cagA genes were investigated in 208 Brazilian Helicobacter pylori strains. A strong association between babA2 and duodenal ulcer or gastric carcinoma was observed, even after adjusting for confounding factors, such as age, gender, and cagA status. cagA-positive strains were also independently associated with H. pylori-related diseases.

  17. Thirty-Five-Year-Old Woman with Signet Ring Cell Gastric Carcinoma Secondary to the Chernobyl Nuclear Accident: A Case Report

    PubMed Central

    Mayhall, Kim; Ghayouri, Masoumeh; Henry, Katherine; Margin, Veronica; Copolla, Domeinico; Shackelford, Rodney

    2013-01-01

    The 1986 Chernobyl nuclear accident resulted in radiation exposures throughout much of Europe, with the highest exposures within the city of Pripyat, Ukraine, where the accident occurred. We report a woman who was exposed to the Chernobyl accident at age 13. Beginning in her early thirties, she experienced several years of upper abdominal pain that became progressively more severe. At age 35, she underwent upper endoscopy and gastric biopsy. Histological examination revealed a signet ring cell (SRC) gastric carcinoma. The tumor was discovered at an advanced stage and proved unresectable. She died 3 months following her diagnosis. The mean age for SRC gastric carcinoma diagnosis is about 62 years; the median survival following diagnosis is 13 months. The early appearance and aggressive clinical course of this malignancy in relation to the Chernobyl nuclear accident is discussed. PMID:23626554

  18. Thirty-five-year-old woman with signet ring cell gastric carcinoma secondary to the chernobyl nuclear accident: a case report.

    PubMed

    Mayhall, Kim; Ghayouri, Masoumeh; Henry, Katherine; Margin, Veronica; Copolla, Domeinico; Shackelford, Rodney

    2013-01-01

    The 1986 Chernobyl nuclear accident resulted in radiation exposures throughout much of Europe, with the highest exposures within the city of Pripyat, Ukraine, where the accident occurred. We report a woman who was exposed to the Chernobyl accident at age 13. Beginning in her early thirties, she experienced several years of upper abdominal pain that became progressively more severe. At age 35, she underwent upper endoscopy and gastric biopsy. Histological examination revealed a signet ring cell (SRC) gastric carcinoma. The tumor was discovered at an advanced stage and proved unresectable. She died 3 months following her diagnosis. The mean age for SRC gastric carcinoma diagnosis is about 62 years; the median survival following diagnosis is 13 months. The early appearance and aggressive clinical course of this malignancy in relation to the Chernobyl nuclear accident is discussed.

  19. Intraductal papillary neoplasm of the bile duct, gastric type, arising in the intrapancreatic common bile duct could progress to colloid carcinoma: report of a case.

    PubMed

    Tajima, Shogo; Ohata, Akihiko; Koda, Kenji; Maruyama, Yasuhiko

    2015-01-01

    Intraductal papillary neoplasm of the bile duct (IPNB) exists in a pathway of multistep-carcinogenesis toward cholangiocarcinoma. Four subtypes are observed in IPNB, pancreatobiliary type, intestinal type, gastric type, and oncocytic type, similarly to the corresponding disease in the pancreas, intraductal papillary mucinous neoplasm (IPMN). IPNB can present with or without macroscopically visible mucin secretion. IPNB usually progresses to tubular adenocarcinoma. However, there are a limited number of well-described cases of gastric-type IPNB progressing not to tubular adenocarcinoma but to colloid carcinoma. Herein, we present a case of an 82-year-old female patient with gastric-type IPNB in the intrapancreatic common bile duct without macroscopically visible mucin secretion, which progressed to colloid carcinoma. As IPNB, especially without visible mucin secretion, is considered to be a heterogeneous group of diseases, such an unexpected association could occur.

  20. Gastric Helicobacters in Domestic Animals and Nonhuman Primates and Their Significance for Human Health

    PubMed Central

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

    2009-01-01

    Summary: Helicobacters other than Helicobacter pylori have been associated with gastritis, gastric ulcers, and gastric mucosa-associated lymphoid tissue lymphoma in humans. These very fastidious microorganisms with a typical large spiral-shaped morphology were provisionally designated “H. heilmannii,” but in fact they comprise at least five different Helicobacter species, all of which are known to colonize the gastric mucosa of animals. H. suis, which has been isolated from the stomachs of pigs, is the most prevalent gastric non-H. pylori Helicobacter species in humans. Other gastric non-H. pylori helicobacters colonizing the human stomach are H. felis, H. salomonis, H. bizzozeronii, and the still-uncultivable “Candidatus Helicobacter heilmannii.” These microorganisms are often detected in the stomachs of dogs and cats. “Candidatus Helicobacter bovis” is highly prevalent in the abomasums of cattle but has only occasionally been detected in the stomachs of humans. There are clear indications that gastric non-H. pylori Helicobacter infections in humans originate from animals, and it is likely that transmission to humans occurs through direct contact. Little is known about the virulence factors of these microorganisms. The recent successes with in vitro isolation of non-H. pylori helicobacters from domestic animals open new perspectives for studying these microorganisms and their interactions with the host. PMID:19366912

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2012-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

  4. Germ-line p53-targeted disruption inhibits helicobacter-induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses.

    PubMed

    Fox, James G; Sheppard, Barbara J; Dangler, Charles A; Whary, Mark T; Ihrig, Melanie; Wang, Timothy C

    2002-02-01

    p53 is a tumor suppressor gene that is mutated in many human malignancies, including gastric cancer. It remains unclear why patients with germ-line p53 mutations (i.e., Li-Fraumeni syndrome) are not at increased risk for gastric adenocarcinoma, despite the fact that they show a high rate of many other tumors. Furthermore, the precise relationship between germ-line p53 mutations and the response to chronic bacterial infections (such as Helicobacter spp.) has not been investigated. To assess the role of germ-line p53 deletions in modulating the progression to gastric cancer, p53(+/-) and wild-type (WT) C57BL/6 mice were infected with H. felis. The gastric pathology and immune response in these two groups of mice were analyzed for up to 15 months postinfection. The gastric fundus and antrum were evaluated independently using a 0-4 scale to score inflammation, parietal and chief cell loss, mucus metaplasia, and helicobacter colonization. Nonparametric statistical analysis was performed to determine the effects of p53(+/-), infection status, and postinoculation (p.i.) time on inflammation, preneoplastic changes, invasive lesions, and helicobacter colonization. mRNA expression for gammaIFN, interleukin (IL)-1, IL-10, and IL-4 was quantified by PCR. Sera were also evaluated for H. felis antibody by ELISA. Antral inflammation increased significantly with time in infected mice. There was a significant, protective effect on the development of preneoplastic fundic lesions and invasive carcinoma attributable to the deletion of one p53 allele (P < 0.05). Submucosal invasive foci were observed in 9 of 11 WT-infected mice ranging from 13 to 15 months p.i.; invasion of adjacent submucosal blood vessels by glandular epithelia also was present in 5 of these mice. None of these lesions were observed in 33 p53(+/-) mice, infected or not, at any time p.i. p53(+/-) mice had significantly higher helicobacter colonization consistent with a Th2 host response. In sera from WT mice, IgG2a

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ(2) test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (< 5 cm) compared with large tumors (≥ 5 cm), with a statistically significant difference respectively (P = 0.016, P = 0.009). A decline linear trend appeared when analyzing the statistical difference of VDR expression among normal, premalignant, and malignant gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer.

  7. Substrate and inhibitor studies with human gastric aspartic proteinases.

    PubMed Central

    Baxter, A; Campbell, C J; Grinham, C J; Keane, R M; Lawton, B C; Pendlebury, J E

    1990-01-01

    The separation of pepsin isoenzymes 1, 2, 3 and 5 (gastricsin) in human gastric juice was effected by chromatography on Mono Q ion-exchanger, and slow-moving proteinase was purified to homogeneity by using a modified procedure incorporating a novel affinity-chromatography step. The pH-activity profiles of these enzymes with mucus glycoprotein and basement-membrane substrates were determined; the profiles for pepsin 2 were noticeably different, and, in general, the pH optima for the hydrolysis of basement membrane were more acidic. Pepsin 1 expressed larger specificity constants (kcat./Km) than pepsin 3 with a series of synthetic peptide substrates, reflecting greater binding (smaller Km) by pepsin 1. Inhibitor studies at pH 1.7 and 4.5 with a series of P2-substituted lactoyl-pepstatins implied that valine at position P2 was optimal for inhibiting pepsins 1, 2 and 3 but detrimental for pepsin 5, whereas lysine at position P2 was tolerated well by pepsin 5 but not by pepsins 1, 2 and 3. The potency of lactoyl-pepstatin with lysine at position P2 did not increase as a function of pH. P2-substituted lactoyl-pepstatins failed to show any inhibitory selectivity among pepsins 1, 2 and 3. PMID:2111133

  8. Aberrant EphB/ephrin-B expression in experimental gastric lesions and tumor cells

    PubMed Central

    Uchiyama, Shintaro; Saeki, Noritaka; Ogawa, Kazushige

    2015-01-01

    AIM: To determine whether the expression profiles of EphB receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric mucosa. METHODS: The protein expression and localization of EphB and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and mRNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain reaction. RESULTS: Ephrin-B- and EphB-expressing regions were divided along the pit-gland axis in normal gastric units. EphB2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. EphB2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell lines. CONCLUSION: Robust and stable coexpression of EphB and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, EphB/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer. PMID:25593460

  9. Computer-assisted stereological analysis of gastric volume during the human embryonic period.

    PubMed Central

    Macarulla-Sanz, E; Nebot-Cegarra, J; Reina-de la Torre, F

    1996-01-01

    Morphometric data concerning human embryos and fetuses have become more clinically informative since ultrasound was employed to make prenatal measurements and software preprocessing techniques improved the previous fuzzy ultrasound signals (Mahoney, 1992). The aim of this study was to determine the volume of the human stomach during the embryonic period and to compare its rate of growth with that during the early fetal period. To calculate gastric volume, computer imaging techniques were applied on cross sections of a graded series of human embryos (from Carnegie stage 11) and fetuses. Gastric volume increased progressively, except for a decrease between stages 12 and 13 due principally to the reduction of the right gastric wall. The growth of the left wall of the stomach was predominant over that of the right. Until stage 20 the stomach volume increased due to the predominant growth of the walls, after this stage the gastric cavity volume increased rapidly, and the rate of growth of the gastric volume reached similar values to that of the early fetal period. We concluded that in the beginning the human stomach grows due to the predominant growth of its walls, chiefly of the left, and from stage 20 because of the predominant expansion of its cavity, which may be related to the capacity to swallow amniotic fluid at the end of the embryonic period. The diminution of the right gastric wall volume (stages 12-13) is consistent with an extension of the omental bursa into the mesodermal anlage of the stomach. PMID:8621339

  10. Inhibition of Helicobacter pylori glycosulfatase activity towards human gastric sulfomucin by a gastroprotective agent, sulglycotide.

    PubMed

    Murty, V L; Piotrowski, J; Czajkowski, A; Slomiany, A; Slomiany, B L

    1993-11-01

    1. A glycosulfatase activity towards human gastric sulfomucin was identified in the extracellular material elaborated by Helicobacter pylori, a pathogen implicated in the etiology of gastric disease. 2. The purified enzyme displayed an apparent molecular weight of 30 kDa, and exhibited maximum activity at pH 5.7 in the presence of 0.3% Triton X-100 and 100 mM CaCl2. 3. The H. pylori glycosulfatase activity towards human gastric sulfomucin was inhibited by a gastroprotective agent, sulglycotide. The inhibitory effect was proportional to the concentration of sulglycotide up to 20 micrograms/ml, at which a 98% decrease in mucin desulfation occurred. However, the drug lost the inhibitory effect following its chemical desulfation. 4. The results demonstrate that sulglycotide is a potent inhibitor of H. pylori glycosulfatase and, hence, may be of value in the treatment of gastric disease associated with this bacterial infection.

  11. Gastric Microbiome and Gastric Cancer

    PubMed Central

    Brawner, Kyle M.; Morrow, Casey D.; Smith, Phillip D.

    2014-01-01

    Cancer of the stomach is the fourth most common cancer worldwide. The single strongest risk factor for gastric cancer is Helicobacter pylori-associated chronic gastric inflammation. Among persons with H. pylori infection, strain-specific components, host immune responses, and environmental factors influence the risk for gastric disease, including adenocarcinoma of the stomach, although only a small proportion of infected persons develop the malignancy. Recent advances in DNA sequencing technology have uncovered a complex community of non-cultivatable inhabitants of the human stomach. The interaction between these inhabitants, collectively referred to as the gastric microbiota, and H. pylori likely impacts gastric immunobiology and possibly the sequelae of H. pylori infection. Thus, characterization of the gastric microbiota in subjects with and without H. pylori infection could provide new insight into gastric homeostasis and the pathogenesis of H. pylori-associated disease, including gastric cancer. PMID:24855010

  12. Feasibility of terahertz reflectometry for discrimination of human early gastric cancers

    PubMed Central

    Ji, Young Bin; Park, Chan Hyuk; Kim, Hyunki; Kim, Sang-Hoon; Lee, Gyu Min; Noh, Sam Kyu; Jeon, Tae-In; Son, Joo-Hiuk; Huh, Yong-Min; Haam, Seungjoo; Oh, Seung Jae; Lee, Sang Kil; Suh, Jin-Suck

    2015-01-01

    We have investigated the feasibility of THz time-domain reflectometry for the discrimination of human early gastric cancer (EGC) from the normal gastric region. Eight fresh EGC tissues, which were resected by endoscopic submucosal dissection, were studied. Of them, six lesions were well discriminated on THz images and the regions well correlated with tumor regions on pathologically mapped images. Four THz parameters could be suggested for quantitative discrimination of EGCs. PMID:25909023

  13. Basal cell carcinoma of the nipple in male patients with gastric cancer recurrence: report of a case.

    PubMed

    Takeno, Shinsuke; Kikuchi, Nobuyuki; Miura, Takashi; Anami, Kentaro; Takahashi, Yoshiaki; Hashimoto, Takafumi; Moroga, Toshihiko; Akizuki, Shin-ichiro; Kamei, Mirei; Suehiro, Shuji; Yamashita, Shin-ichi; Kawahara, Katsunobu

    2014-01-01

    Although basal cell carcinoma (BCC) is the most common dermatological malignancy arising from sun exposed skin, BCC of the nipple is extremely rare. To our knowledge only 34 cases have been reported. We report a 78-year-old man who was undergoing chemotherapy for liver metastasis of gastric cancer 1 year after surgery. The chief complaint was exudation and oozing from the nipple. A mass lesion was palpable and detected on mammography and enhanced computed tomography, and atypical cells were detected on cytological examination. Simple resection was performed because histopathological diagnosis of an intraoperative frozen section revealed BCC. Final pathological diagnosis was also BCC. The authors report this case and review the previous reports, and discuss the clinicopathologic characteristics and adequate treatment for this disease.

  14. Adaptive cytoprotection against deoxycholate-induced injury in human gastric cells in vitro: is there a role for endogenous prostaglandins?

    PubMed

    Kokoska, E R; Smith, G S; Rieckenberg, C L; Deshpande, Y; Banan, A; Miller, T A

    1998-04-01

    The majority of previous work investigating adaptive cytoprotection has involved in vivo studies, which have suggested that this protective response is in large part mediated by endogenous prostaglandins (PGs). The aim of this study was to investigate adaptive cytoprotection under in vitro conditions in human gastric cells and to better delineate the role of endogenous PGs in this protective response. AGS cells (a human gastric carcinoma cell line) were characterized morphologically and subsequently used for all experiments. Sodium deoxycholate was used as both the mild irritant and the damaging agent, and cell injury was quantified using both a commercial viability/cytotoxicity kit as well as transepithelial permeability studies. Finally, endogenous PG synthesis in response to varying concentrations of deoxycholate was determined. AGS cells were determined to be morphologically similar to gastric mucous cells. Pretreatment of cells with low-dose deoxycholate significantly attenuated injury upon subsequent exposure to damaging concentrations of deoxycholate, and this protection was determined to be dependent upon both concentration and duration of mild irritant exposure. Preincubation of AGS cells with indomethacin reversed protection induced by mild irritant pretreatment and also significantly increased cellular susceptibility to injury. Results of the permeability studies closely paralleled those assessing cell mortality. While deoxycholate exposure increased PG synthesis, the concentrations required were much higher than those needed to initiate protection. Adaptive cytoprotection exists in AGS cells under in vitro conditions independent of intact blood flow, neural innervation, or circulating humoral mediators. While this protection is reversed by indomethacin, it appears that this reversal results from increased cellular injury secondary to diminished basal PGs, rather than inhibition of endogenous PG synthesis.

  15. Functional association between proximal and distal gastric motility during fasting and duodenal nutrient stimulation in humans.

    PubMed

    Nguyen, N Q; Fraser, R J; Bryant, L K; Holloway, R H

    2007-08-01

    A functional integration exists between proximal and distal gastric motor activity in dogs but has not been demonstrated in humans. To determine the relationship between proximal and distal gastric motor activity in humans. Concurrent proximal (barostat) and distal (antro-pyloro-duodenal (APD) manometry) gastric motility were recorded in 10 healthy volunteers (28 +/- 3 years) during (i) fasting and (ii) two 60-min duodenal infusions of Ensure((R)) (1 and 2 kcal min(-1)) in random order. Proximal and APD motor activity and the association between fundic and propagated antral waves (PAWs) were determined. During fasting, 32% of fundic waves (FWs) were followed by a PAW. In a dose-dependent fashion, duodenal nutrients (i) increased proximal gastric volume, (ii) reduced fundic and antral wave (total and propagated) activity, and (iii) increased pyloric contractions. The proportion of FWs followed by a distal PAW was similar between both infusions and did not differ from fasting. During nutrient infusion, nearly all PAWs were antegrade, propagated over a shorter distance and less likely to traverse the pylorus, compared with fasting. In humans, a functional association exists between proximal and distal gastric motility during fasting and duodenal nutrient stimulation. This may have a role in optimizing intra-gastric meal distribution.

  16. Anti-metastatic activity of fangchinoline in human gastric cancer AGS cells

    PubMed Central

    Chen, Zhengrong; He, Tengfei; Zhao, Kui; Xing, Chungen

    2017-01-01

    Fangchinoline (FCL) is an active component isolated from the traditional medicinal plant Stephania tetrandra S. Moore, and has been reported to possess anti-cancer functions in several types of cancers; however, the effect of FCL on gastric cancer metastasis and its underlying molecular mechanisms remain unknown. The current study aimed to investigate the effect of FCL on the cell migration and invasion of human metastatic gastric cancer AGS cells and its mechanisms. Our study demonstrates that FCL dosage dependently suppressed the adhesion, migration and invasion capacities of human gastric cancer AGS cells without obvious cytotoxic effects. Reverse transcription-polymerase chain reaction and western blot assays demonstrated that FCL greatly inhibited the expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the mRNA and protein levels, while it significantly increased the expression of tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP2 messenger RNAs. Our results also indicated that FCL repressed the phosphorylation of AKT in gastric cancer AGS cells. In summary, FCL may exert its anti-metastatic property in human gastric cancer cells in vitro by suppression of MMP-2 and MMP-9, increase of TIMP1 and TIMP2 genes, and inhibition of AKT phosphorylation. FCL may be a drug candidate for the treatment of gastric cancer metastasis.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

  19. Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor-node-metastasis staging system.

    PubMed

    Jiang, Nan; Deng, Jing-Yu; Liu, Yong; Ke, Bin; Liu, Hong-Gen; Liang, Han

    2014-09-01

    The aim of this study was to determine the prognostic value of perineural invasion (PNI) in patients with gastric cancer who underwent curative resection. We retrospectively analyzed 518 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. Patients with PNI had a significantly larger tumors (≥5.0 cm), lymphatic venous invasion (positive), deeper tumor invasion (T4), more number of lymph node metastases (N3), and higher tumor stage (III). Regarding survival, multivariate analysis showed that PNI emerged as an independent prognostic factor for survival (hazard ratio (HR) = 1.901, P < 0.001). We incorporated the PNI into the 7th edition tumor-node-metastasis (TNM) staging system. Comparing with the 7th edition staging system, the redefinition of TPNI stage had higher -2loglikelihood value (-2loglikelihood = 3,492.259) and lower HR and 95 % confidence interval (CI) (HR = 1.955, 95 % CI = 1.630-2.343); redefinition of NPNI and TNMIIIPNI stage both had lower -2loglikelihood value (-2loglikelihood = 3,306.608; -2loglikelihood = 2,535.151) and higher HR and 95 % CI (HR = 1.879, 95 % CI = 1.720-2.053; HR = 2.268, 95 % CI = 1.900-2.707), which represented the optimum prognostic stratification, together with better homogeneity, discriminatory ability. Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer and it should be incorporated into TNM staging.

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  1. [A case of double cancer of gastric and hepatocellular carcinoma associated with cirrhosis treated by hepatic resection after intra-hepatic arterial infusion chemotherapy].

    PubMed

    Une, Y; Nagabuchi, E; Ogasawara, K; Kamiyama, T; Sato, Y; Kawamukai, Y; Sato, N; Nakajima, Y; Uchino, J

    1990-08-01

    A case of double cancer, early gastric cancer and hepatocellular carcinoma, was reported. The patient was diabetic and had liver cirrhosis. After gastrectomy for gastric cancer which was hemorrhagic, he was treated by intra-hepatic arterial infusion chemotherapy followed by hepatic resection. Histopathologically, about half of the main tumor showed necrosis, but very viable new cancer cell nests were seen around the main nodule. The patient is in good condition without recurrence of hepatic lesion 1 year after resection. The usefulness of arterial infusion chemotherapy was demonstrated in the case of double cancer, in which it is difficult to resect both cancers simultaneously.

  2. Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma.

    PubMed

    Su, Xianwei; Lv, Chengyu; Qiao, Fengchang; Qiu, Xuemei; Huang, Wenbin; Wu, Qingxiang; Zhao, Zhujiang; Fan, Hong

    2010-03-01

    The aim of this study was to detect the expression pattern of DNA methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.

  3. Differential expression of laminin receptors in human hepatocellular carcinoma

    PubMed Central

    Ozaki, I; Yamamoto, K; Mizuta, T; Kajihara, S; Fukushima, N; Setoguchi, Y; Morito, F; Sakai, T

    1998-01-01

    Background—Laminin receptors are involved in cell-extracellular matrix interactions in malignant cells that show invasion and metastasis. Hepatocellular carcinoma frequently shows early invasion into blood vessels, and intrahepatic and extrahepatic metastases. However, the role of laminin receptors in hepatocellular carcinoma is unknown. 
Aims—To examine the expression of mRNA for laminin receptors and their isoforms in hepatocellular carcinoma. 
Methods—The expression of several laminin receptors, including α1 integrin, α6 integrin and its isoforms α6A and α6B, β1 integrin and its isoforms β1A and β1B, and 32kD/67kDa laminin binding protein was examined in human hepatocellular carcinomas and non-cancerous liver tissues using the reverse transcription polymerase chain reaction. 
Results—α6 Integrin, β1 integrin, and laminin binding protein showed notably increased expression in hepatocellular carcinoma, compared with non-cancerous liver tissue, although the α1 integrin did not show a significant change. Furthermore, β1B integrin, a splicing variant of β1 integrin, was overexpressed in hepatocellular carcinoma while the β1A integrin isoform did not show significant changes between hepatocellular carcinoma and surrounding non-cancerous liver tissue. 
Conclusions—The differential upregulation of laminin receptors and their splicing isoforms was shown in hepatocellular carcinoma, suggesting that certain laminin receptors and their isoforms may be involved in the development and progression of hepatocellular carcinoma. 

 Keywords: laminin receptor; integrin α6β1; hepatocellular carcinoma PMID:9824613

  4. The Association between GSTM1, GSTT1 Genetic Variants and Gastric Carcinoma Susceptibility in Chinese: A Systematic Review Article

    PubMed Central

    YOU, Dingyun; LU, Nanjia; DUAN, Donghui; LI, Hui; XING, Wenhua

    2016-01-01

    Background: Glutathione S-transferases (GSTs) have been investigated as potential carcinoma susceptible genes. However, the relationship between GSTs (GSTM1, GSTT1) variants and gastric carcinoma (GC) risk has been controversial in Chinese population. Methods: A comprehensive literature search strategy (PubMed, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wan fang Database, etc.) was launched. Crude odds ratios (ORs) and confidence intervals (95% CI) were applied to estimate the strength of the association. Results: Significant associations between GSTs genetic polymorphisms and GC were evidenced under random-effects model (ORGSTM1=1.56, 95% CI: 1.39 to 1.76, I2=50.7%, P<0.0001; ORGSTT1=1.24, 95% CI: 1.10 to 1.39, I2=43.6%, P=0.014; ORGSTM1-GSTT1=1.51, 95% CI: 1.26 to 1.81, I2=59.7%, P=0.004). The pooled ORs were not qualitatively changed when any single study was omitted by sensitivity analysis. Conclusion: Our results indicated an increased GC risk in Chinese population with GSTM1 and GSTT1 null genotype and GSTM1-GSTT1 dual null genotype. Further multi-center studies are needed to investigate the gene-gene and gene-environment interactions on the susceptibility of GC. PMID:27957455

  5. Involvement of Aquaporin 3 in Helicobacter pylori-Related Gastric Diseases

    PubMed Central

    Chen, Jia; Wang, Tao; Zhang, Guoxin; Shen, Lizong

    2012-01-01

    Background Gastric cancer is one of the most common and lethal malignant cancers worldwide, and numerous epidemiological studies have demonstrated that Helicobacter pylori (H. pylori) infection plays a key role in the development of gastric carcinomas. Our previous studies showed that aquaporin 3 (AQP3) is overexpressed in gastric carcinoma and promotes the migration and proliferation of human gastric carcinoma cells, suggesting that AQP3 may be a potentially important determinant of gastric carcinoma. However, the role of AQP3 in H. pylori carcinogenesis is unknown. Methods The AQP3 protein and H. pylori were detected in human gastric tissues by immunohistochemistry and modified Giemsa staining respectively. AQP3 knockdown was obtained by small interfering (si) RNA. Western blot assays and RT-PCR were used to evaluate the change of AQP3 in the human gastric cancer AGS and SGC7901 cell lines after co-culture with H. pylori. Sprague Dawley rats were orally inoculated with H. pylori to establish a rat model colonized by H. pylori. Results The present study found that AQP3 expression correlated with H. pylori infection status in gastric cancer tissues and corresponding normal mucosa, and H. pylori co-culture upregulated AQP3 expression in human gastric adenocarcinoma cells in vitro via the extracellular signal-regulated kinase signaling pathway. H. pylori infection also increased AQP3 expression in gastric mucosa colonized by H. pylori in a Sprague Dawley rat model. Conclusions These findings provide further information to understand the mechanism of H. pylori carcinogenesis and a potential strategy for the treatment of H. pylori-associated gastric carcinoma. PMID:23152856

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

    PubMed

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

    2016-01-11

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

  7. Effects of titanium dioxide nanoparticles in human gastric epithelial cells in vitro.

    PubMed

    Botelho, Monica Catarina; Costa, Carla; Silva, Susana; Costa, Solange; Dhawan, Alok; Oliveira, Paula A; Teixeira, João P

    2014-02-01

    Manufacturing or using nanomaterials may result in exposure of workers to nanoparticles. Potential routes of exposure include skin, lung and gastrointestinal tract. The lack of health-based standards for nanomaterials combined with their increasing use in many different workplaces and products emphasize the need for a reliable temporary risk assessment tool. Therefore, the aim of this work was to explore the effects of different doses of titanium dioxide nanoparticles on human gastric epithelial cells in vitro. We analyzed proliferation by MTT assay, apoptosis by Tunel, migration by injury assay, oxidative stress by determining GSH/GSSG ratio and DNA damage by Comet assay on nanoparticle-treated AGS human gastric epithelial cell line in comparison to controls. We show and discuss the tumor-like phenotypes of nanoparticles-exposed AGS cells in vitro, as increased proliferation and decreased apoptosis. Our results demonstrate for the first time that nanoparticles induce tumor-like phenotypes in human gastric epithelial cells.

  8. Composition and Gene Expression of the cag Pathogenicity Island in Helicobacter pylori Strains Isolated from Gastric Carcinoma and Gastritis Patients in Costa Rica

    PubMed Central

    Occhialini, Alessandra; Marais, Armelle; Urdaci, Maria; Sierra, Rafaela; Muñoz, Nubia; Covacci, Antonello; Mégraud, Francis

    2001-01-01

    The composition and in vitro expression of the cag pathogenicity island genes in a group of Helicobacter pylori strains obtained from patients suffering from chronic gastritis-associated dyspepsia (n = 26) or gastric carcinoma (n = 17) were analyzed. No significant difference in the distribution of the 10 studied regions was found between the cases and the controls. Nine strains did not harbor any of the selected regions: eight (30.8%) isolated from patients with gastritis only and one (5.9%) from a patient with gastric carcinoma. No association was found between the number of repeated sequences at the 3′ end of the cagA gene or the presence of tyrosine phosphorylation motifs and the clinical origin of the strains. The virB10 homolog gene was the sole gene studied to be significantly expressed more often in cancer strains than in gastritis strains (P = 0.03). PMID:11179371

  9. Composition and gene expression of the cag pathogenicity island in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica.

    PubMed

    Occhialini, A; Marais, A; Urdaci, M; Sierra, R; Muñoz, N; Covacci, A; Mégraud, F

    2001-03-01

    The composition and in vitro expression of the cag pathogenicity island genes in a group of Helicobacter pylori strains obtained from patients suffering from chronic gastritis-associated dyspepsia (n = 26) or gastric carcinoma (n = 17) were analyzed. No significant difference in the distribution of the 10 studied regions was found between the cases and the controls. Nine strains did not harbor any of the selected regions: eight (30.8%) isolated from patients with gastritis only and one (5.9%) from a patient with gastric carcinoma. No association was found between the number of repeated sequences at the 3' end of the cagA gene or the presence of tyrosine phosphorylation motifs and the clinical origin of the strains. The virB10 homolog gene was the sole gene studied to be significantly expressed more often in cancer strains than in gastritis strains (P = 0.03).

  10. Epstein-Barr Virus Associated Lymphoepithelioma-like Carcinoma at the Lesser Curvature of the Upper Gastric Body: A Case Report

    PubMed Central

    Zhang, Q; Shou, C; Liu, X; Yu, H; Yu, J

    2014-01-01

    Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the stomach with dense lymphocytic infiltration. More than 80% of LELGCs are positive for the Epstein-Barr virus (EBV). Here, we report a 64-year old Chinese man with swallowing discomfort while eating food. Endoscopy and computed tomography both showed a submucosal lesion at the lesser curvature of the upper gastric body. The first diagnostic impression was a gastrointestinal stromal tumour. Subsequently, the patient received a wedge resection of the stomach. On histopathological examination, the tumour was found to consist of small nests of neoplastic cells within dense lymphocytic infiltration. Additionally, most of the neoplastic cells were positive for cytokeratin and Epstein-Barr virus-encoded RNA (EBER). Subsequently, the diagnosis of LELGC was made. We believe that physicians should be aware of the diagnosis of submucosal gastric lesions, particularly in older male patients. PMID:25303204

  11. In vitro assessment of the mucoadhesion of cholestyramine to porcine and human gastric mucosa.

    PubMed

    Jackson, S J; Perkins, A C

    2001-09-01

    Previous in vivo studies have suggested that the extended gastric residence and uniform intragastric distribution of cholestyramine may be due to mucoadherent properties. This series of in vitro investigations explored the possibility of the anion exchange resin exhibiting bioadhesive behaviour, and investigated the characteristics, such as particle size and surface charge, that may affect it. Tensile strength measurements were carried out to determine the mucoadhesion of cholestyramine and other test materials (resin particulates, polymers and hydrogels) with varying adhesive properties, to isolated porcine and human gastric mucosa. Optimal instrumental parameters for the system were determined initially and used; all procedures were carried out at room temperature (22 degrees C). The particle size of cholestyramine did not affect mucoadhesion to either porcine or human gastric mucosa (P=0.673, porcine; P=0.969, human), whilst anionic exchangers were found to provide better mucoadhesion than cationic exchangers (P=0.0002, porcine; P=0.0009, human). In some instances, it was found that the detachment forces recorded were lower with human gastric mucosa than with porcine gastric mucosa, although this was not consistently statistically significant. A rank order of mucoadhesion was constructed from a comparison of cholestyramine with eight other test materials. Cholestyramine produced the second highest degree of mucoadhesion, with Carbopol producing the greatest adhesion. Dextran and polyethylene glycol did not display good mucoadhesion under these conditions. From the findings presented here, we have found that cholestyramine demonstrates good mucoadhesion to both porcine and human gastric mucosa when compared to other known bioadhesives. It is suggested that particle size does not contribute to this mucoadherent behaviour but the surface charge of the resin has a significant part to play.

  12. Characterization of human normal and cancerous gastric submucosa based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhong, Jiazhao; Chen, G.; Liu, Y. C.; Zhuo, S. M.; Chen, J. X.; Yan, J.

    2012-03-01

    Gastric cancer is one of the most frequent cancers in the world; almost two-thirds of gastric cancer cases and deaths occur in less developed regions. The initial diagnosis of gastric cancer often is delayed because up to 80 percent of patients are asymptomatic during the early stages of stomach cancer. So the ability to perform real-time in vivo histological diagnosis for early gastric cancer at the cellular level during ongoing endoscopy is a long-standing goal of endoscopists. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), MPM images of human normal and cancerous gastric submucosa were obtained at excitation wavelength of 800 nm. The features such as the appearance of abnormal cells and the large loss of collagen in cancerous gastric submucosa were extracted to be as significant indicators to distinguish cancerous submucosa from normal submucosa. With the implementation of multiphoton microscopy concept in endoscopy applications, multiphoton endoscopy might realize in vivo histological diagnosis goal of endoscopists.

  13. Characterization of human normal and cancerous gastric submucosa based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhong, Jiazhao; Chen, G.; Liu, Y. C.; Zhuo, S. M.; Chen, J. X.; Yan, J.

    2011-11-01

    Gastric cancer is one of the most frequent cancers in the world; almost two-thirds of gastric cancer cases and deaths occur in less developed regions. The initial diagnosis of gastric cancer often is delayed because up to 80 percent of patients are asymptomatic during the early stages of stomach cancer. So the ability to perform real-time in vivo histological diagnosis for early gastric cancer at the cellular level during ongoing endoscopy is a long-standing goal of endoscopists. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), MPM images of human normal and cancerous gastric submucosa were obtained at excitation wavelength of 800 nm. The features such as the appearance of abnormal cells and the large loss of collagen in cancerous gastric submucosa were extracted to be as significant indicators to distinguish cancerous submucosa from normal submucosa. With the implementation of multiphoton microscopy concept in endoscopy applications, multiphoton endoscopy might realize in vivo histological diagnosis goal of endoscopists.

  14. MicroRNA-1225-5p inhibits proliferation and metastasis of gastric carcinoma through repressing insulin receptor substrate-1 and activation of β-catenin signaling

    PubMed Central

    Lin, Xinjian; Huang, Changming; Zhang, Yiqin; Li, Yun; Lin, Jianyin; Chen, Wannan; Lin, Xu

    2016-01-01

    Emerging evidence has linked aberrantly expressed microRNAs (miRNAs) with oncogenesis and malignant development in various human cancers. However, their specific roles and functions in gastric carcinoma (GC) remain largely undefined. In this study we identify and report a novel miRNA, miR-1225-5p, as tumor suppressor in GC development and progression. Microarray analysis revealed that there were fifty-six differentially expressed miRNAs (thirty-two upregulated and twenty-four downregulated) in GC tumor samples compared to their corresponding nontumorous tissues. Downregulation of miR-1225-5p was frequently detected in GC and strongly correlated with more aggressive phenotypes and poor prognosis. Functional assays demonstrated that ectopic overexpression of miR-1225-5p could inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth and metastasis in nude mice. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a downstream effector of miR-1225-5p which acted through β-catenin signaling pathway. These results demonstrate that miR-1225-5p serves to constrain GC growth and metastatic potential via inhibition of IRS1 and β-catenin signaling. Therefore, downregulation of miR-1225-5p is likely to be one of major molecular mechanisms accounting for the development and progression of GC. PMID:26684358

  15. Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients

    PubMed Central

    Ito, S; Nakanishi, H; Kodera, Y; Mochizuki, Y; Tatematsu, M; Yamamura, Y

    2005-01-01

    Prediction of peritoneal relapse is extremely important for gastric cancer patients after curative surgery. The present study prospectively validates the prognostic ability of quantifying carcinoembryonic antigen (CEA) mRNA in peritoneal washes by real-time reverse transcriptase–polymerase chain reaction. Based on a retrospective study of 197 curatively resected gastric cancer patients (training set), we determined a cutoff value of CEA mRNA using receiver-operating characteristic curve. We used this cutoff value to validate the risk of peritoneal recurrence in a new cohort of 86 gastric cancer patients (validation set) between July 2000 and December 2002 in a prospective study. During the median 30 months of postoperative surveillance, 20 of the 86 patients died, and 13 of the 20 developed peritoneal metastases. Peritoneal recurrence-free survival as well as overall survival was significantly worse in patients with positive CEA mRNA (P<0.0001). Multivariate analysis with the Cox proportional hazards model showed that positive CEA mRNA was a significant independent risk factor with both survival (P=0.0130) and peritoneal recurrence-free survival (P=0.0006) as end points. These results indicate that quantitation of CEA mRNA in peritoneal washes is a reliable prognostic indicator of peritoneal recurrence in the clinical setting. PMID:16205696

  16. Synergistic antitumor effect of puerarin combined with 5-fluorouracil on gastric carcinoma.

    PubMed

    Guo, Xu-Feng; Yang, Zi-Rong; Wang, Jun; Lei, Xiao-Fei; Lv, Xiao-Guang; Dong, Wei-Guo

    2015-04-01

    Combination chemotherapy is a crucial method in the treatment of gastric cancer. The aim of the present study was to investigate the inhibitory effects of puerarin and 5‑fluorouracil (5‑FU) on BGC‑823 gastric cancer cells in vitro and in vivo. The in vitro growth inhibition of puerarin or 5‑FU alone or combined on BGC‑823 cells was determined using a cell counting kit 8 (CCK‑8) on living cells. Apoptotic morphological features and proteins expression levels were detected by Hoechst 33258 staining, an Annexin V/propidium iodide apoptosis kit and western blot analysis, respectively. Tumor xenografts were established in nude mice and the inhibitory effects and side effects were detected. Results of the CCK‑8, Hoechst 33258 staining and flow cytometry revealed that the combined treatment was more effective than the separate treatments. The tumor volume was 90.65% of that of the controls and the mean tumor weight was only 0.125 g at the end of the experiment in the combination group compared with the control group (0.822 g). In addition, it was determined that liver and renal toxicity did not increase in combined treatment. These findings showed that puerarin and 5‑FU produced a significant synergic effect on gastric cancer cells, while there was no increase in side effects.

  17. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression.

    PubMed

    Jackson, C B; Judd, L M; Menheniott, T R; Kronborg, I; Dow, C; Yeomans, N D; Boussioutas, A; Robb, L; Giraud, A S

    2007-10-01

    H. pylori infection accounts for most cases of gastric cancer, but the initiating events remain unclear. The principal H. pylori pathogenicity-associated CagA protein disrupts intracellular SHP-2 signalling pathways including those used by the IL-6 family cytokines, IL-6 and IL-11. Imbalanced IL-6 family cytokine signalling in the gp130(757FF) mouse model of gastric cancer arising from hyperactivation of oncogenic STAT3 after altered SHP-2 : ERK1/2 signalling produces dysplastic antral tumours preceded by gastritis and metaplasia. In a cohort of patient gastric biopsies with known H. pylori and CagA status, we investigated whether (i) STAT3 and ERK1/2 activation is altered in H. pylori-dependent gastritis; (ii) these profiles are more pronounced in CagA+ H. pylori infection; and (iii) the expression of pro-inflammatory cytokines that activate STAT3 and ERK 1/2 pathways is associated with progression to gastric cancer. IL-6, IL-11, and activated STAT3 and ERK1/2 were quantified in antral biopsies from gastritic stomach, metaplastic tissue, and resected gastric cancer tissues. We observed significantly increased STAT3 and ERK1/2 activation (p = 0.001) in H. pylori-dependent gastritis, which was further enhanced in the presence of CagA+ H. pylori strains. Of known gastric ligands that drive STAT3 activation, IL-6 expression was increased after H. pylori infection and both IL-6 and IL-11 were strongly up-regulated in the gastric cancer biopsies. This suggests a mechanism by which IL-11 drives STAT3 activation and proliferation during gastric cancer progression. We addressed this using an in vitro approach, demonstrating that recombinant human IL-11 activates STAT3 and concomitantly increases proliferation of MKN28 gastric epithelial cells. In summary, we show increased STAT3 and ERK1/2 activation in H. pylori-dependent gastritis that is likely driven in an IL-6-dependent fashion. IL-11 expression is associated with adenocarcinoma development, but not gastritic lesions

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

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

  19. Recombinant Newcastle disease virus (rL-RVG) triggers autophagy and apoptosis in gastric carcinoma cells by inducing ER stress

    PubMed Central

    Bu, Xuefeng; Zhao, Yinghai; Zhang, Zhijian; Wang, Mubin; Li, Mi; Yan, Yulan

    2016-01-01

    We have reported that the recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing the rabies virus glycoprotein (rL-RVG) could induce autophagy and apoptosis in gastric carcinoma cells. In the present study, we explored the upstream regulators, endoplasmic reticulum (ER) stress that induce autophagy and apoptosis and the relationships among them. For this purpose, SGC-7901 and HGC cells were infected with rL-RVG. NDV LaSota strain and phosphate-buffered saline (PBS) were treated as the control groups. Western blotting and immunofluorescence microscopy were used to detect the expression of the ER stress-related proteins glucose-regulated protein 78 (GRP78) and the transcription factor GADD153 (CHOP), among others. The expression of beclin-1 and the conversion of light chain (LC) 3-I were used to determine the occurrence of autophagy, and flow cytometry (FCM) and western blotting were used to examine apoptosis-related protein expression. Transmission electron microscopy was also performed to monitor the ultrastructure of the cells. Moreover, small interfering (si) RNA was used to knock down CHOP expression. rL-RVG treatment increased the expression of ER stress-related proteins, such as GRP78, CHOP, activating transcriptional factor 6 (ATF6), X-box-binding protein 1 (XBP-1), and phosphorylated eukaryotic initiation factor 2 (p-eIF2α), in a time- and concentration-dependent manner, and knockdown of CHOP reduced LC3-II conversion and beclin-1 expression. When ER stress was inhibited with 4-PBA, the expression of both autophagy-related proteins and apoptosis-related proteins markedly decreased. Interestingly, inhibition of autophagy with 3-methyladenine (3MA) decreased not only apoptosis-related protein expression but also ER stress-related protein expression. Moreover, we found that downregulation of the c-Jun N-terminal kinase (JNK) pathway by SP600125 reduced LC3-II conversion, beclin-1 expression and caspase-3 activation. Collectively, the

  20. Integration of DNA Copy Number Alterations and Transcriptional Expression Analysis in Human Gastric Cancer

    PubMed Central

    Coral, Ho; Yuen, Siu Tsan; Chu, Kent Man; Law, Simon; Zhang, Lianhai; Ji, Jiafu; Leung, Suet Yi; Chen, Xin

    2012-01-01

    Background Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level. Principal Findings We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridization (aCGH). Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72), 20q12–20q13.1 (12/72), 20q13.1–20q13.2 (11/72) and 20q13.2–20q13.3 (6/72). The most frequent deleted region was 9p21 (8/72). Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis. Conclusions This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new therapeutic

  1. Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer.

    PubMed

    Shan, Yan-Shen; Hsu, Hui-Ping; Lai, Ming-Derg; Yen, Meng-Chi; Luo, Yi-Pey; Chen, Yi-Ling

    2015-01-01

    Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin‑embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer.

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

    PubMed Central

    2016-01-01

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

  3. Human Gastric Cancer Kinase Profile and Prognostic Significance of MKK4 Kinase

    PubMed Central

    Wu, Chew-Wun; Li, Anna F.-Y.; Chi, Chin-Wen; Huang, Chen Lung; Shen, King-Han; Liu, Wing-Yiu; Lin, Wen-chang

    2000-01-01

    Alterations of protein tyrosine kinase are often associated with uncontrolled cell growth and tumor progression. Knowledge of the overall expression pattern of tyrosine kinases should prove beneficial in understanding the signaling pathways involved in gastric cancer oncogenesis and in providing possible biomarkers for gastric cancer progression. To establish a general tyrosine-kinase expression profile, degenerated polymerase chain reaction primers designed from the consensus catalytic kinase motifs were used to amplify protein tyrosine kinase molecules from gastric cancer tissues. We observed more than 50 tyrosine and serine/threonine kinases from matching pairs of gastric cancer tissue and normal mucosa. Based on this new kinase profile information, we selected the MKK4 gene for further immunohistochemical studies. Statistical analysis of MKK4 protein expression and clinicopathological features indicated that MKK4 kinase expression could serve as a significant prognostic factor for relapse-free survival and for overall survival. We demonstrated a simple and sensitive method for establishing protein tyrosine-kinase expression profiles of human gastric cancer tissues as well as for discovering novel and useful clinical biomarkers from such kinase expression profiles. PMID:10854223

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

    PubMed

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

    2017-04-01

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

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

    PubMed

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

    2004-02-01

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

  6. Epidermal growth factor and its receptors in human pancreatic carcinoma

    SciTech Connect

    Chen, Y.F.; Pan, G.Z.; Hou, X.; Liu, T.H.; Chen, J.; Yanaihara, C.; Yanaihara, N. )

    1990-05-01

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells.

  7. Immunohistochemical expression of nuclear and cytoplasmic survivin in gastrointestinal carcinoma.

    PubMed

    Shintani, Michiko; Sangawa, Akiko; Yamao, Naoki; Kamoshida, Shingo

    2013-01-01

    Survivin is a protein that is highly expressed in many embryonic tissues, as well as most human tumors. Prior studies have reported both positive and negative correlations between survivin expression and cancer prognosis, but these associations remain controversial. In the present study, we assessed the expression of nuclear and cytoplasmic survivin in gastrointestinal carcinomas. Using these data, we determined the correlation between nuclear and cytoplasmic survivin and, further, investigated correlations between survivin expression and clinicopathological parameters. Seventy-two advanced gastric adenocarcinomas and 78 colorectal adenocarcinomas were analyzed for survivin expression by immunohistochemistry. Expression of both nuclear and cytoplasmic survivin was significantly higher in colorectal carcinomas than in gastric carcinomas (P < 0.01). There was a positive correlation between nuclear and cytoplasmic expression of survivin (r = 0.42, P < 0.001). In gastric carcinomas, the level of survivin protein expression was associated with tumor differentiation, patient age, and lymphatic invasion (P < 0.05, 0.01, and 0.01, respectively). In colorectal carcinomas, the level of nuclear survivin expression was significantly higher in females than in males (P < 0.05). There were no significant associations between survivin expression and most of the clinicopathological parameters. Nevertheless, there was a trend towards an inverse correlation between nuclear survivin expression and tumor aggressiveness in gastric carcinoma; there was a similar trend for cytoplasmic survivin expression. In summary, our results suggest that levels of nuclear and cytoplasmic survivin expression differ between gastric carcinoma and colorectal carcinoma.

  8. Immunohistochemical expression of nuclear and cytoplasmic survivin in gastrointestinal carcinoma

    PubMed Central

    Shintani, Michiko; Sangawa, Akiko; Yamao, Naoki; Kamoshida, Shingo

    2013-01-01

    Survivin is a protein that is highly expressed in many embryonic tissues, as well as most human tumors. Prior studies have reported both positive and negative correlations between survivin expression and cancer prognosis, but these associations remain controversial. In the present study, we assessed the expression of nuclear and cytoplasmic survivin in gastrointestinal carcinomas. Using these data, we determined the correlation between nuclear and cytoplasmic survivin and, further, investigated correlations between survivin expression and clinicopathological parameters. Seventy-two advanced gastric adenocarcinomas and 78 colorectal adenocarcinomas were analyzed for survivin expression by immunohistochemistry. Expression of both nuclear and cytoplasmic survivin was significantly higher in colorectal carcinomas than in gastric carcinomas (P < 0.01). There was a positive correlation between nuclear and cytoplasmic expression of survivin (r = 0.42, P < 0.001). In gastric carcinomas, the level of survivin protein expression was associated with tumor differentiation, patient age, and lymphatic invasion (P < 0.05, 0.01, and 0.01, respectively). In colorectal carcinomas, the level of nuclear survivin expression was significantly higher in females than in males (P < 0.05). There were no significant associations between survivin expression and most of the clinicopathological parameters. Nevertheless, there was a trend towards an inverse correlation between nuclear survivin expression and tumor aggressiveness in gastric carcinoma; there was a similar trend for cytoplasmic survivin expression. In summary, our results suggest that levels of nuclear and cytoplasmic survivin expression differ between gastric carcinoma and colorectal carcinoma. PMID:24294379

  9. Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer.

    PubMed

    Tauchi, Yukie; Tanaka, Hiroaki; Kumamoto, Kanako; Tokumoto, Mao; Sakimura, Chie; Sakurai, Katsunobu; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Kubo, Naoshi; Muguruma, Kazuya; Yashiro, Masakazu; Maeda, Kiyoshi; Ohira, Masaichi; Hirakawa, Kosei

    2016-08-01

    Tumor lymphangiogenesis is a major prognostic indicator of gastric cancer. Tumor-induced inflammation has been shown to attract tumor-associated macrophages that affect lymphangiogenesis. However, detailed mechanisms of macrophage-induced lymphangiogenesis have not been elucidated. Here, we evaluated the interaction between tumor-associated macrophages and lymphatic endothelial cells (LECs) derived from lymph nodes (LNs) of human gastric cancer. Lymphatic endothelial cells were directly or indirectly cocultured with macrophages from healthy human blood, with or without the supernatant of the gastric cancer cell line, OCUM-12. We analyzed the effect of cancer pretreated macrophages and of macrophages from metastatic LNs of gastric cancer on LECs. We observed morphological changes of LECs in coculture and assessed the gene expression of possible lymphangiogenic molecules of macrophages and LECs after contact coculture, and of cancer pretreated macrophages, by quantitative RT-PCR. Specimens of metastatic LN of gastric cancer were immunofluorescently stained. We found that tubulogenesis of LECs was observed only in the contact coculture model. OCUM-12 cells promoted macrophage-induced tubulogenesis of LECs. Relative gene expression of MMP and adhesion molecules was significantly upregulated in both capillary-forming LECs and cocultured macrophages. Cancer pretreated macrophages upregulated lymphangiogenic factors including inflammatory cytokines, MMPs, adhesion molecules, and vascular endothelial growth factor-C. Blocking of intercellular adhesion molecule-1 and macrophage activation suppressed tubulogenesis of LECs. Immunohistochemistry showed macrophages localized around lymphatic vessels. Our results suggested that interaction between LECs and macrophages may be an important initial step of tumor lymphangiogenesis developing LN metastasis. Understanding of its mechanisms could be useful for future therapeutics of gastric cancer.

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

    SciTech Connect

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

    2005-05-15

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

  11. Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells.

    PubMed

    Forte, Maurizio; Iachetta, Giuseppina; Tussellino, Margherita; Carotenuto, Rosa; Prisco, Marina; De Falco, Maria; Laforgia, Vincenza; Valiante, Salvatore

    2016-03-01

    The increase in the use of nanoparticles, as a promising tool for drug delivery or as a food additive, raises questions about their interaction with biological systems, especially in terms of evoked responses. In this work, we evaluated the kinetics of uptake of 44 nm (NP44) and 100 nm (NP100) unmodified polystyrene nanoparticles (PS-NPs) in gastric adenocarcinoma (AGS) cells, as well as the endocytic mechanism involved, and the effect on cell viability and gene expression of genes involved in cell cycle regulation and inflammation processes. We showed that NP44 accumulate rapidly and more efficiently in the cytoplasm of AGS compared to NP100; both PS-NPs showed an energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway. Dose response treatments revealed a non-linear curve. PS-NPs also affected cell viability, inflammatory gene expression and cell morphology. NP44 strongly induced an up-regulation of IL-6 and IL-8 genes, two of the most important cytokines involved in gastric pathologies. Our study suggests that parameters such as time, size and concentration of NPs must be taken carefully into consideration during the development of drug delivery systems based on NPs and for the management of nanoparticles associated risk factors.

  12. Association between Increased Gastric Juice Acidity and Sliding Hiatal Hernia Development in Humans

    PubMed Central

    Kishikawa, Hiroshi; Kimura, Kayoko; Ito, Asako; Arahata, Kyoko; Takarabe, Sakiko; Kaida, Shogo; Kanai, Takanori; Miura, Soichiro; Nishida, Jiro

    2017-01-01

    Objectives Several clinical factors; overweight, male gender and increasing age, have been implicated as the etiology of hiatal hernia. Esophageal shortening due to acid perfusion in the lower esophagus has been suggested as the etiological mechanism. However, little is known about the correlation between gastric acidity and sliding hiatus hernia formation. This study examined whether increased gastric acid secretion is associated with an endoscopic diagnosis of hiatal hernia. Methods A total of 286 consecutive asymptomatic patients (64 were diagnosed as having a hiatal hernia) who underwent upper gastrointestinal endoscopy were studied. Clinical findings including fasting gastric juice pH as an indicator of acid secretion, age, sex, body mass index, and Helicobacter pylori infection status determined by both Helicobacter pylori serology and pepsinogen status, were evaluated to identify predictors in subjects with hiatal hernia. Results Male gender, obesity with a body mass index >25, and fasting gastric juice pH were significantly different between subjects with and without hiatal hernia. The cut-off point of fasting gastric juice pH determined by receiver operating curve analysis was 2.1. Multivariate regression analyses using these variables, and age, which is known to be associated with hiatal hernia, revealed that increased gastric acid secretion with fasting gastric juice pH <2.1 (OR = 2.60, 95% CI: 1.38–4.90) was independently associated with hiatal hernia. Moreover, previously reported risk factors including male gender (OR = 2.32, 95% CI: 1.23–4.35), body mass index >25 (OR = 3.49, 95% CI: 1.77–6.91) and age >65 years (OR = 1.86, 95% CI: 1.00–3.45), were also significantly associated with hiatal hernia. Conclusions This study suggests that increased gastric acid secretion independently induces the development of hiatal hernia in humans. These results are in accordance with the previously reported hypothesis that high gastric acid itself induces

  13. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    PubMed Central

    Martinez, Victor D.; Becker-Santos, Daiana D.; Vucic, Emily A.; Lam, Stephen; Lam, Wan L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epigenomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans. PMID:22175027

  14. Mycobacterium conceptionense Bloodstream Infection in a Patient with Advanced Gastric Carcinoma.

    PubMed

    Yaita, Kenichiro; Matsunaga, Mototsugu; Tashiro, Naotaka; Sakai, Yoshiro; Masunaga, Kenji; Miyoshi, Hiroaki; Oshima, Koichi; Chikamatsu, Kinuyo; Takaki, Akiko; Mitarai, Satoshi; Watanabe, Hiroshi

    2017-01-24

    A 65-year-old Japanese male farmer with advanced gastric adenocarcinoma and multiple hepatic metastases was admitted to our hospital. Blood culture results were positive on day 5, and Gram-positive rods were detected. According to the results of Ziehl-Neelsen staining and a cultured colony of this bacterium, we suspected a mycobacterial infection. Suspecting a rapidly growing mycobacterium (RGM), we started multidrug therapy with levofloxacin, clarithromycin, and ethambutol, and the patient recovered from the bloodstream infection. Further gene examination (16S rRNA, hsp65, and sodA) revealed an isolate of Mycobacterium conceptionense. M. conceptionense was first identified as an RGM in 2006. Among previous case reports of M. conceptionense infections, bone and soft tissue infections in hosts with a disorder of the normal structure (e.g., surgical sites) were dominant. We report the characteristics of M. conceptionense infection in this first Japanese case report and a review of the literature.

  15. [Human papillomavirus: a vaccine against cervical carcinoma uterine].

    PubMed

    Franceschi, Silvia

    2002-01-01

    Human papillomavirus (HPV) has been identified in fewer than 20 years as the central cause of cervical carcinoma and one of the most powerful known human carcinogens. At least 20 different types of HPV have been associated with relative risks of approximately 100 for both squamous-cell carcinoma and the rarer adenocarcinoma of the cervix uteri. Cytologic screening programs have contributed to the decline of cervical cancer mortality in Europe and the United States. Long-term screening programs remain, however, outside the reach of the poorest countries, where 80% of deaths for cervical carcinoma occurs. More than 20 different types of prophylactic and/or therapeutic vaccines against HPV are being evaluated in clinical or preclinical studies. One such type, a prophylactic vaccine based on the marked immunogenicity and safety of the empty viral capsid, will start being evaluated in 2002 in 3 phase-III randomized studies, mostly in the United States and Latin America. The International Agency for Research on Cancer and World Health Organization are planning, in parallel with the studies above, a double blind randomized phase IV study of approximately 40,000 adolescent and young women in Asia. Such study, which should include a cluster randomization (by village of birth); a comparison with another vaccine (rather than with placebo); and, possibly, the inclusion of adolescents and young adults of male sex. Such trial may accelerate by many years the availability of an anti-HPV vaccine among populations at highest risk for cervical carcinoma.

  16. β-casein nanovehicles for oral delivery of chemotherapeutic drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells

    PubMed Central

    Bar-Zeev, Maya; Assaraf, Yehuda G.; Livney, Yoav D.

    2016-01-01

    Multidrug resistance (MDR) is a primary obstacle to curative cancer therapy. We have previously demonstrated that β-casein (β-CN) micelles (β-CM) can serve as nanovehicles for oral delivery and target-activated release of hydrophobic drugs in the stomach. Herein we introduce a novel nanosystem based on β-CM, to orally deliver a synergistic combination of a chemotherapeutic drug (Paclitaxel) and a P-glycoprotein-specific transport inhibitor (Tariquidar) individually encapsulated within β-CM, for overcoming MDR in gastric cancer. Light microscopy, dynamic light scattering and zeta potential analyses revealed solubilization of these drugs by β-CN, suppressing drug crystallization. Spectrophotometry demonstrated high loading capacity and good encapsulation efficiency, whereas spectrofluorometry revealed high affinity of these drugs to β-CN. In vitro cytotoxicity assays exhibited remarkable synergistic efficacy against human MDR gastric carcinoma cells with P-glycoprotein overexpression. Oral delivery of β-CN - based nanovehicles carrying synergistic drug combinations to the stomach constitutes a novel efficacious therapeutic system that may overcome MDR in gastric cancer. PMID:26989076

  17. Cultured High-Fidelity Three-Dimensional Human Urogenital Tract Carcinomas and Process

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor); Prewett, Tacey L. (Inventor); Spaulding, Glenn F. (Inventor); Wolf, David A. (Inventor)

    1998-01-01

    Artificial high-fidelity three-dimensional human urogenital tract carcinomas are propagated under in vitro-microgravity conditions from carcinoma cells. Artificial high-fidelity three-dimensional human urogenital tract carcinomas are also propagated from a coculture of normal urogenital tract cells inoculated with carcinoma cells. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

  18. Telomerase Activity in Human Ovarian Carcinoma

    NASA Astrophysics Data System (ADS)

    Counter, Christopher M.; Hirte, Hal W.; Bacchetti, Silvia; Harley, Calvin B.

    1994-04-01

    Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.

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

    PubMed Central

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

    1997-01-01

    BACKGROUND: The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown. AIM AND METHODS: In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini, and sherry) on gastric acid output and release of gastrin was studied. Gastric acid output was determined by the method of intragastric titration. Plasma gastrin was measured using a specific radioimmunoassay. RESULTS: None of the alcoholic beverages produced by fermentation plus distillation had any significant effect on gastric acid output and release of gastrin compared with control (isotonic glucose and distilled water). Alcoholic beverages produced only by fermentation significantly (p < 0.05) increased the gastric acid output by 57% to 95% of maximal acid output (MAO) and release of gastrin up to 5.1-fold compared with control. If beer, wine, and sherry were distilled, only their remaining parts increased gastric acid output by 53% to 76% of MAO and increased release of gastrin up to 4.3-fold compared with control. CONCLUSIONS: (1) Alcoholic beverages produced by fermentation but not by distillation are powerful stimulants of gastric acid output and release of gastrin; (2) the alcoholic beverage constituents that stimulate gastric acid output and release of gastrin are most probably produced during the process of fermentation and removed during the following process of distillation. PMID:9155575

  20. Enhanced legumain-recognition and NIR controlled released of cisplatin-indocyanine nanosphere against gastric carcinoma.

    PubMed

    Shi, Tianyi; Gu, Lianshuai; Sun, Yu; Wang, Senlin; You, Chaoqun; Zhang, Xiangyang; Zhu, Jin; Sun, Baiwang

    2017-01-05

    Cisplatin-therapy has faced limitations in the gastric cancer therapy. To settle the bottleneck, enhanced specificity and controlled-release property are choosen. We synthesize cisplatin and indocyanine green (ICG) loaded PLGA-(DSPE-PEG2000) nanoparticles, which is abbreviated as CINPs. And we conjugate the Gly-Cys-Gly-Ala-Ala-Asn-Leu (GCGAANL) heptapeptide upon the surface of CINPs, the product is abbreviated as ACINPs. ACINPs with nearly 110nm exhibit good monodispersity and size stability. The EE (efficiency of encapsulation) and LE (loading of encapsulation) of cisplatin loaded into ACINPs are optimized as 29.81% and 3.88%. MGC803 cells overexpressing the legumain and MKN28 cells, which negatively express the legumain as well as the normal stomach cells, are selected. In vitro studies have suggested ACINPs, compared with CINPs, could be recognized by MGC803 cells and efficiently killed the cancer cells, while be harmless to MKN28 cells, which indicates the specificity and safety of ACINPs. Under irradiation of 808nm NIR irradiation, ICG loaded in ACINPs could rapidly transform the light to heat up to 60℃. Nanoparticles compared with non-irraditaion group could be quickly disrupted and release the cisplatin which could enhance the controlled-release ability. Hence, the ACINPs exhibit great potential in avoiding the side effects and enhancing the therapy ability of cisplatin.

  1. Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome

    PubMed Central

    Yamanoi, Kazuhiro; Arai, Eri; Tian, Ying; Takahashi, Yoriko; Miyata, Sayaka; Sasaki, Hiroki; Chiwaki, Fumiko; Ichikawa, Hitoshi; Sakamoto, Hiromi; Kushima, Ryoji; Katai, Hitoshi; Yoshida, Teruhiko; Sakamoto, Michiie; Kanai, Yae

    2015-01-01

    The aim of this study was to clarify the significance of DNA methylation alterations during gastric carcinogenesis. Single-CpG resolution genome-wide DNA methylation analysis using the Infinium assay was performed on 109 samples of non-cancerous gastric mucosa (N) and 105 samples of tumorous tissue (T). DNA methylation alterations in T samples relative to N samples were evident for 3861 probes. Since N can be at the precancerous stage according to the field cancerization concept, unsupervised hierarchical clustering based on DNA methylation levels was performed on N samples (βN) using the 3861 probes. This divided the 109 patients into three clusters: A (n = 20), B1 (n = 20), and B2 (n = 69). Gastric carcinomas belonging to Cluster B1 showed tumor aggressiveness more frequently than those belonging to Clusters A and B2. The recurrence-free and overall survival rates of patients in Cluster B1 were lower than those of patients in Clusters A and B2. Sixty hallmark genes for which βN characterized the epigenetic clustering were identified. We then focused on DNA methylation levels in T samples (βT) of the 60 hallmark genes. In 48 of them, including the ADAM23, OLFM4, AMER2, GPSM1, CCL28, DTX1 and COL23A1 genes, βT was again significantly correlated with tumor aggressiveness, and the recurrence-free and/or overall survival rates. Multivariate analyses revealed that βT was a significant prognostic factor, being independent of clinicopathological parameters. These data indicate that DNA methylation profiles at the precancerous stage may be inherited by gastric carcinomas themselves, thus determining tumor aggressiveness and patient outcome. PMID:25740824

  2. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas

    SciTech Connect

    Moy, R.L.; Eliezri, Y.D.; Bennett, R.G. ); Nuovo, G.J.; Siverstein, S. Columbia Univ., New York, NY ); Zitelli, J.A. )

    1989-05-12

    Ten squamous cell carcinomas (in situ or invasive) of the fingernail region were analyzed for the presence of DNA sequences homologous to human papilloma-virus (HPV) by dot blot hybridization. In most patients, the lesions were verrucae of long-term duration that were refractory to conventional treatment methods. Eight of the lesions contained HPV DNA sequences, and in six of these the sequences were related to HPV 16 as deduced from low-stringency nucleic acid hybridization followed by low- and high-stringency washes. Furthermore, the restriction endonuclease digestion pattern of DNA isolated from four of these lesions was diagnostic of episomal HPV 16. The high-frequency association of HPV 16 with periungual squamous cell carcinoma is similar to that reported for HPV 16 with squamous cell carcinomas on mucous membranes at other sites, notably the genital tract. The findings suggest that HPV 16 may play an important role in the development of squamous cell carcinomas of the finger, most notably those lesions that are chronic and located in the periungual area.

  3. Small molecule R1498 as a well-tolerated and orally active kinase inhibitor for hepatocellular carcinoma and gastric cancer treatment via targeting angiogenesis and mitosis pathways.

    PubMed

    Zhang, Chao; Wu, Xihan; Zhang, Meifang; Zhu, Liangcheng; Zhao, Rong; Xu, Danqing; Lin, Zhaohu; Liang, Chungen; Chen, Taiping; Chen, Li; Ren, Yi; Zhang, Joe; Qin, Ning; Zhang, Xiongwen

    2013-01-01

    Protein kinases play important roles in tumor development and progression. Lots of kinase inhibitors have entered into market and show promising clinical benefits. Here we report the discovery of a novel small molecule, well-tolerated, orally active kinase inhibitor, R1498, majorly targeting both angiogenic and mitotic pathways for the treatment of hepatocellular carcinoma (HCC) and gastric cancer (GC). A series of biochemical and cell-based assays indicated that the target kinase cluster of R1498 included Aurora kinases and VEGFR2 et al. R1498 showed moderate in vitro growth inhibition on a panel of tumor cells with IC50 of micromole range. The in vivo anti-tumor efficacy of R1498 was evaluated on a panel of GC and HCC xenografts in a parallel comparison with another multikinase inhibitor sorafenib. R1498 demonstrated superior efficacy and toxicity profile over sorafenib in all test models with >80% tumor growth inhibition and tumor regression in some xenogratfts. The therapeutic potential of R1498 was also highlighted by its efficacy on three human GC primary tumor derived xenograft models with 10-30% tumor regression rate. R1498 was shown to actively inhibit the Aurora A activity in vivo, and decrease the vascularization in tumors. Furthermore, R1498 presented good in vivo exposure and therapeutic window in the pharmacokinetic and dose range finding studies. Theses evidences indicate that R1498 is a potent, well-tolerated, orally active multitarget kinase inhibitor with a unique antiangiogenic and antiproliferative profile, and provide strong confidence for further development for HCC and GC therapy.

  4. Human lung small-cell carcinoma contains bombesin.

    PubMed Central

    Erisman, M D; Linnoila, R I; Hernandez, O; DiAugustine, R P; Lazarus, L H

    1982-01-01

    The presence of immunoreactive bombesin in a human lung small-cell carcinoma grown in nude mice was established by several criteria: (i) Radioimmunoassay of tissue extracts for bombesin revealed approximately 6.5 pmol/g of tissue; (ii) bombesin was found in 12-14% of the tumor cells by immunohistochemical localization; (iii) gel filtration of small-cell carcinoma extract on Sephadex G-75 and Bio-Gel P-4 gave only a single peak of immunoreactivity, which occurred at the elution volume of bombesin; and (iv) reverse-phase HPLC of acid-solubilized extracts separated the immunoreactive material into three discrete peaks, one of which eluted with a retention time identical to that of synthetic bombesin. The presence of bombesin may represent the ectopic expression of this peptide in small-cell carcinoma, because immunoreactive bombesin was found in human fetal and neonatal lung but apparently not in adult lung tissue [Wharton, J., Polak, J. M., Bloom, S. R., Ghatei, M. A., Solcia, E., Brown, M. R. & Pearse, A. G. E. (1978) Nature (London) 273, 769-770]. The immunoreactive bombesin previously found in mammalian tissues is considerably larger than amphibian bombesin; these data substantiate the presence of a mammalian form of bombesin in a human tumor that may have a structure similar to that of the amphibian peptide. Images PMID:6285381

  5. Autophagy is involved in anticancer effects of matrine on SGC-7901 human gastric cancer cells.

    PubMed

    Zhang, Junqiang; Li, Yumin; Chen, Xiaohui; Liu, Tao; Chen, Yingtai; He, Wenting; Zhang, Quanbao; Liu, Shiyuan

    2011-07-01

    Matrine has a wide range of pharmacological effects including antitumor activity in vitro and in vivo. Autophagy is closely associated with tumors and plays an important role in human tumor suppression, so inducing autophagy is a potential therapeutic strategy in adjuvant chemotherapy. The aim of this study was to investigate whether or not autophagy is involved in antitumor effects of matrine on human gastric cancer SGC-7901 cells, and to further elucidate the underlying molecular mechanisms. Sulphorhodamine B (SRB) assay was used to examine matrine's cytotoxicity against SGC-7901 gastric cancer cells. The effects of matrine on the cell cycle and apoptosis were measured by flow cytometry, and cellular morphology was observed under an inverted phase contrast microscope and transmission electron microscope. Monodansylcadaverine (MDC) staining was used to detect autophagy. The expression levels of Bax and Beclin 1 in SGC-7901 cells were monitored by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed that matrine significantly inhibited the proliferation of SGC-7901 gastric cancer cells and induced G1-phase cell cycle arrest. Furthermore, both autophagy and apoptosis were activated during the matrine-induced death of SGC-7901 cells. Beclin 1 is involved in matrine-induced autophagy and the pro-apoptotic mechanisms of matrine may be associated with its up-regulation of Bax expression. These findings indicate that matrine is a potent antitumor agent for treating gastric cancer. The ability of matrine to induce autophagy underlines its potential utility as a new gastric cancer treatment modality.

  6. Antigen shared by HeLa-like human cell line and gastric mucosa.

    PubMed

    Bobrova, T S; Kryukova, I N; Chuev, Y V; Rottenberg, V I

    1991-01-01

    An antigen of human gastric mucosa immunologically related to the antigen of established HeLa-like cell lines (CL-GMA) is described. In gel-immunodiffusion test the antigen was revealed in 10/10 samples of normal gastric mucosa (including all parts of stomach), in 15/16 samples of cancer patients' gastric mucosa 5-10 cm distant from tumor and in 2/2 samples of ulcer patients' mucosa 5-10 cm distant from the ulcer. However, the antigen was undetectable at a distance 1-2 cm from ulcer. Homogenates of 39 embryonic organs and tissues were screened for the presence of CL-GMA. CL-GMA was detected in 7/7 samples of gastric mucosa. The antigen was revealed in trace amounts in 1/4 samples of small intestine mucosa and in 1/4 samples of spleen. Screening of 66 human tumors revealed CL-GMA in 13/16 samples of gastric cancer and in trace amounts in 2 tumors of non-stomach localization (larynx and rectum). Analysis of aceton-fixed paraffin sections by means of immunofluorescence revealed be CL-GMA in all parts of stomach. CL-GMA localized in the basal area of high columnar epithelial cells. The antigen was almost or totally undetectable in poorly differentiated adenocarcinomas of stomach and in tumors of other localization. We could not detect CL-GMA in the sera of various cancer patients by means of immunodiffusion and/or dot-blotting.

  7. Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori-infected p27-deficient mice

    PubMed Central

    Zhang, Songhua; Kim, Woojin; Pham, Tu T.; Rogers, Arlin B.; Houghton, Jean Marie; Moss, Steven F.

    2016-01-01

    Objective Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells. Design Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients were infected with H. pylori SS1 for one year. Results Mice lacking p27 in either the BM pool or gastric epithelium developed significantly more advanced gastric pathology, including high-grade dysplasia. Co-staining of donor BMDC in dysplastic gastric glands was confirmed by immunofluorescence. Gastric expression of IL-1 beta protein was reduced in groups 2 and 3 (p < 0.05 vs control) whereas expression of IFN-γ and chemokines MIP-1 beta, MIG, IP-10 and RANTES in group 2 were significantly higher than group 3. Conclusions Both bone marrow-derived and gastric epithelial cells contribute to the increased gastric cancer susceptibility of p27-deficient H. pylori-infected mice. PMID:27655701

  8. Genetic lineages of undifferentiated-type gastric carcinomas analysed by unsupervised clustering of genomic DNA microarray data

    PubMed Central

    2013-01-01

    Background It is suspected that early gastric carcinoma (GC) is a dormant variant that rarely progresses to advanced GC. We demonstrated that the dormant and aggressive variants of tubular adenocarcinomas (TUBs) of the stomach are characterized by loss of MYC and gain of TP53 and gain of MYC and/or loss of TP53, respectively. The aim of this study is to determine whether this is also the case in undifferentiated-type GCs (UGCs) of different genetic lineages: one with a layered structure (LS+), derived from early signet ring cell carcinomas (SIGs), and the other, mostly poorly differentiated adenocarcinomas, without LS but with a minor tubular component (TC), dedifferentiated from TUBs (LS−/TC+). Methods Using 29 surgically resected stomachs with 9 intramucosal and 20 invasive UGCs (11 LS+ and 9 LS−/TC+), 63 genomic DNA samples of mucosal and invasive parts and corresponding reference DNAs were prepared from formalin-fixed, paraffin-embedded tissues with laser microdissection, and were subjected to array-based comparative genomic hybridization (aCGH), using 60K microarrays, and subsequent unsupervised, hierarchical clustering. Of 979 cancer-related genes assessed, we selected genes with mean copy numbers significantly different between the two major clusters. Results Based on similarity in genomic copy-number profile, the 63 samples were classified into two major clusters. Clusters A and B, which were rich in LS+ UGC and LS−/TC+ UGC, respectively, were discriminated on the basis of 40 genes. The aggressive pattern was more frequently detected in LS−/TC+ UGCs, (20/26; 77%), than in LS+UGCs (17/37; 46%; P = 0.0195), whereas no dormant pattern was detected in any of the UGC samples. Conclusions In contrast to TUBs, copy number alterations of MYC and TP53 exhibited an aggressive pattern in LS+ SIG at early and advanced stages, indicating that early LS+ UGCs inevitably progress to an advanced GC. Cluster B (enriched in LS−/TC+) exhibited more

  9. Genome-wide analysis of Epstein-Barr virus (EBV) isolated from EBV-associated gastric carcinoma (EBVaGC).

    PubMed

    Liu, Ying; Yang, Wenjun; Pan, Yaqi; Ji, Jiafu; Lu, Zheming; Ke, Yang

    2016-01-26

    Epstein-Barr virus (EBV) is linked to the development of a variety of malignancies, including EBV-associated gastric carcinoma (EBVaGC). In this study, EBVaGC was detected in 15 (7.3%) of 206 GC cases. To identify the EBV genomic variation, EBV genomic sequences isolated from 9 EBVaGC biopsy specimens were successfully retrieved, designated EBVaGC1 to EBVaGC9. By comparative analysis of these strains with another 6 completely sequenced EBV strains, EBV-wild type, B95-8, AG876, GD1, GD2, and HKNPC1, it was demonstrated that EBVaGC1 to 9 were most closely related to the GD1 strain. Phylogenetic analysis of the GC biopsy specimen-derived EBV (GC-EBV) genomes was subsequently performed to assess their genomic diversity and it exhibited the greatest divergence from the type 2 strain, AG876. Compared with the reference EBV strain GD1, they harbored 961 variations in total, including 919 substitutions, 23 insertions, and 19 deletions. Single nucleotide polymorphism (SNP) density varied substantially across all known open reading frames and was highest in latency-associated genes. Moreover, we identified 2 interstrain recombinants at the EBNA1 locus, which provided a further mechanism for the generation of diversity. Some T-cell epitope sequences in EBNA1 and LMP2A genes showed extensive variation across strains, which implied their importance in the development of vaccines and T-cell therapy. In conclusion, we reported the first genome-wide view of sequence variation of EBV isolated from primary EBVaGC biopsy specimens, which might serve as an effective method for further understanding the genomic variations contribute to EBVaGC carcinogenesis and treatment.

  10. Prognostic significance and the role in TNM stage of extranodal metastasis within regional lymph nodes station in gastric carcinoma

    PubMed Central

    Chen, Xiao-Long; Zhao, Lin-Yong; Xue, Lian; Xu, Yu-Hui; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    The role of extranodal metastasis (ENM) in TNM stage in gastric carcinoma (GC) is controversial. This study was aimed to make a detailed investigation of the prognostic significance and the role in TNM stage of ENM in GC. The patients with primary GC, who underwent gastrectomy with curative intention in West China Hospital from January 2005 to December 2011, were retrospectively enrolled. The prognosis and clinicopathological traits were compared between ENM positive (ENMP) and negative (ENMN) groups in all patients, TNM I-II, III and IV stages, respectively. The significance of the number and the role in TNM stage of ENM were also assessed. In our study, 1457 patients were enrolled, with 1324 (90.9%) in ENMN group and 133 (9.1%) in ENMP group. ENMP group had significantly more advanced GC and worse prognosis (all p<0.05) than ENMN group in all patients, TNM I-II stages and TNM III stage. ENM>2 subgroup had remarkably larger tumor size (p=0.002) and more advanced N stage (p=0.016) than ENM=1-2 subgroup. The number of ENM was an independent prognostic factor in ENMP group (p=0.029). The prognosis of ENM>2 in TNM I-III stages was significantly worse than ENMN patients in TNM III stage. The C-index of TNM stage plus the number of ENM was significantly higher than that of current TNM stage alone (p=0.005). In conclusion, the patients in ENMP subgroup had more advanced GC and worse prognosis than those in ENMN subgroup. It might be more reasonable to categorize ENM>2 into TNM IV stage. PMID:27563811

  11. Genome-wide analysis of Epstein-Barr virus (EBV) isolated from EBV-associated gastric carcinoma (EBVaGC)

    PubMed Central

    Yang, Wenjun; Pan, Yaqi; Ji, Jiafu; Ke, Yang

    2016-01-01

    Epstein-Barr virus (EBV) is linked to the development of a variety of malignancies, including EBV-associated gastric carcinoma (EBVaGC). In this study, EBVaGC was detected in 15 (7.3%) of 206 GC cases. To identify the EBV genomic variation, EBV genomic sequences isolated from 9 EBVaGC biopsy specimens were successfully retrieved, designated EBVaGC1 to EBVaGC9. By comparative analysis of these strains with another 6 completely sequenced EBV strains, EBV-wild type, B95–8, AG876, GD1, GD2, and HKNPC1, it was demonstrated that EBVaGC1 to 9 were most closely related to the GD1 strain. Phylogenetic analysis of the GC biopsy specimen-derived EBV (GC-EBV) genomes was subsequently performed to assess their genomic diversity and it exhibited the greatest divergence from the type 2 strain, AG876. Compared with the reference EBV strain GD1, they harbored 961 variations in total, including 919 substitutions, 23 insertions, and 19 deletions. Single nucleotide polymorphism (SNP) density varied substantially across all known open reading frames and was highest in latency-associated genes. Moreover, we identified 2 interstrain recombinants at the EBNA1 locus, which provided a further mechanism for the generation of diversity. Some T-cell epitope sequences in EBNA1 and LMP2A genes showed extensive variation across strains, which implied their importance in the development of vaccines and T-cell therapy. In conclusion, we reported the first genome-wide view of sequence variation of EBV isolated from primary EBVaGC biopsy specimens, which might serve as an effective method for further understanding the genomic variations contribute to EBVaGC carcinogenesis and treatment. PMID:26716899

  12. Crocodile choline from Crocodylus siamensis induces apoptosis of human gastric cancer.

    PubMed

    Mao, Xiao-Mei; Fu, Qi-Rui; Li, Hua-Liang; Zheng, Ya-Hui; Chen, Shu-Ming; Hu, Xin-Yi; Chen, Qing-Xi; Chen, Qiong-Hua

    2017-03-01

    Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.

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

    PubMed

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

    2016-04-11

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

  14. The potential difference response of the human gastric mucosa to cimetidine.

    PubMed

    Sparsø, B H; Luke, M

    1990-07-01

    The effect of cimetidine on the dynamic transmucosal potential difference (PD) of the normal human gastric fundus was studied, to quantitate the influence of the hydrogen ion on measurements. PD was measured between an intravenous flowing bridge of isotonic NaCl and a perfused intragastric probe by means of two calomel half-cells. The probe was used for luminal infusion of different electrolyte solutions, which at the same time functioned as the mucosal measuring electrode. Cimetidine increased PD -12 mV during NaCl infusion. When gastric acidity was neutralized with isotonic NaHCO3, this change of PD decreased to -5 mV. We conclude that 60% of the PD increase seen after H2 blockade may be explained by the mere disappearance of H+ from the gastric juice, and the other 40% by changes in the gastric mucous membrane. PD decreased progressively as luminal NaCl content was lowered, but this reaction was reversed after cimetidine. These findings may be explained by a twofold decrease of transmucosal permeability to Na+ during H2 blockade.

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

    PubMed Central

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

    2015-01-01

    CopA3 is a homodimeric α-helical peptide derived from coprisin which is a defensin-like antimicrobial peptide that was identified from the dung beetle, Copris tripartitus. CopA3 has been reported to have anticancer activity against leukemia cancer cells. In the present study, we investigated the anticancer activity of CopA3 in human gastric cancer cells. CopA3 reduced cell viability and it was cytotoxic to gastric cancer cells in the MTS and LDH release assay, respectively. CopA3 was shown to induce necrotic cell death of the gastric cancer cells by flow cytometric analysis and acridine orange/ethidium bromide staining. CopA3-induced cell death was mediated by specific interactions with phosphatidylserine, a membrane component of cancer cells. Taken together, these data indicated that CopA3 mainly caused necrosis of gastric cancer cells, probably through interactions with phosphatidylserine, which suggests the potential utility of CopA3 as a cancer therapeutic. [BMB Reports 2015; 48(6): 324-329] PMID:25047444

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

    PubMed

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

    2015-06-01

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

  17. Influence of human gastric juice on oxidation of marine lipids--in vitro study.

    PubMed

    Kristinova, Vera; Storrø, Ivar; Rustad, Turid

    2013-12-15

    This study evaluates whether marine lipids can oxidise in acidic stomach environment and whether authentic gastric juice has the potential to act as a pro- or anti-oxidative medium. Oxidation of herring lipids in emulsions and liposomes was followed in in vitro digestion models containing authentic human gastric juice, and compared to models containing hydrochloric acid solution. Peroxide value, concentration of thiobarbituric acid reactive substances and oxygen uptake rate increased in all the models during 2.5 h incubation at pH 4 and 37 °C in darkness. The markers showed no difference between oxidation in gastric juice and hydrochloric acid solution. Gastric juice reduced the prooxidant activity of iron ions measured as oxygen uptake rate, but did not reduce the activity of methemoglobin. Berry juice, green tea, red wine, and caffeic acid reduced oxygen uptake in the acidic environments while coffee, ascorbic acid and orange juice increased oxidation. Beverages accompanying foods containing marine lipids will therefore affect the course of post-prandial lipid oxidation.

  18. Clinicopathologic Characteristics of Microsatellite Instable Gastric Carcinomas Revisited: Urgent Need for Standardization

    PubMed Central

    Mathiak, Micaela; Warneke, Viktoria S.; Behrens, Hans-Michael; Haag, Jochen; Böger, Christine; Krüger, Sandra

    2017-01-01

    Microsatellite instable gastric cancer (MSI-GC) is a specific molecular subtype of GC. We studied the phenotypes, genotypes, and clinicopathologic characteristics of MSI-GC in a white GC cohort and compared our findings with an extended literature review. The study cohort consisted of 482 patients. Specimens were available from 452 cases and were used for immunostaining (MLH1, PMS2, MSH2, MSH6) and molecular biological analyses (BAT-25, BAT-26, NR-21, NR-24, NR-27; Epstein-Barr virus in situ hybridization). Thirty-four (7.5%) GCs were MSI. Loss of MLH1 and/or PMS2 was found in 30 (88%) MSI-GC, 3 (9%) showed loss of MSH2 and/or MSH6. One (3%) MSI-GC was identified only by molecular biological testing. A single case was heterogeneous and contained microsatellite-stable and instable tumor areas. Twenty-one (62%) MSI-GCs showed unusual histologic features. MSI-GC was not found in diffuse-type or Epstein-Barr virus-positive GC. MSI-GC was significantly more prevalent in elderly patients, distal stomach, and was associated with a significantly lower number of lymph node metastases and a significantly better overall and tumor-specific survival. MSI-GC constitutes a small but relevant subgroup of GC with distinct clinicopathologic characteristics. Our literature review illustrates the shortcomings of missing standardized testing algorithms with prevalences of MSI-GC ranging from 0% to 44.5%. Future studies should test the hypothesis that patients with MSI-GCs may not need adjuvant/perioperative chemotherapy. However, this will require a standardized, quality-controlled diagnostic algorithm of MSI for GC. PMID:26371427

  19. Clinicopathological significance of claudin 4 expression in gastric carcinoma: a systematic review and meta-analysis

    PubMed Central

    Chen, Xiaowan; Zhao, Junhua; Li, Ailin; Gao, Peng; Sun, Jingxu; Song, Yongxi; Liu, Jingjing; Chen, Ping; Wang, Zhenning

    2016-01-01

    Background The prognostic significance of claudin 4 (CLDN4) in patients with gastric cancer (GC) is controversial. This meta-analysis aims to assess the correlation between CLDN4 expression and clinicopathological characteristics and assess the prognostic significance of CLDN4 in GC. Methods We searched the PubMed and Embase databases. We performed the meta-analysis with odds ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) as effect values. Results Fourteen studies containing 2,106 patients with GC were analyzed. The overall analysis showed that CLDN4 expression was associated with increasing pT category, tumor size, and lymph node metastasis in patients with GC (pT3–T4 vs pT1–T2: OR =1.56, 95% CI =1.13–2.16; P<0.01; large tumor size vs small tumor size: OR =1.64, 95% CI =1.15–2.34; P<0.01; positive lymph node metastasis vs negative lymph node metastasis: OR =1.49, 95% CI =1.12–1.97; P<0.01). CLDN4 expression was associated with histological differentiation (differentiated type vs undifferentiated type: OR =2.90, 95% CI =1.32–6.37; P=0.01; Lauren intestinal type vs diffuse type: OR =3.51, 95% CI =1.48–8.28; P<0.01). CLDN4 expression was also strongly associated with sex and age. This meta-analysis found no significant association between CLDN4 expression and prognosis for overall survival in patients with GC (HR =0.74, 95% CI =0.43–1.27; P=0.28). Conclusion Present study indicates that aberrant CLDN4 expression plays an important role in the clinicopathological characteristics of GC. PMID:27313466

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

    PubMed

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

    2013-09-01

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

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

    PubMed

    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.

  2. Tumor-suppressing effects of microRNA-429 in human renal cell carcinoma via the downregulation of Sp1

    PubMed Central

    Wu, Deyao; Niu, Xiaobing; Pan, Huixing; Zhou, Yunfeng; Zhang, Zichun; Qu, Ping; Zhou, Jian

    2016-01-01

    MicroRNA (miR)-429 has been frequently reported to be downregulated in various tumors, including renal cell carcinoma (RCC), nasopharyngeal carcinoma, Ehrlich ascites tumor cells, gastric cancer, non-small cell lung cancer and endometrial endometrioid carcinoma. The present study investigated the effects of miR-429 on human RCC A498 and 786-O cells. Following transfection of cells with miR-429 mimics and scrambled control, MTT, cell migration, cell invasion and luciferase assays were performed. In addition, western blotting was performed in order to assess the expression of specificity protein 1 (Sp1), which was predicted to be a target of miR-429 by TargetScan. The present results revealed that miR-429 inhibited cell proliferation, migration and invasion of 786-O and A498 cells. In addition, the present results demonstrated that miR-429 overexpression downregulated Sp1 protein expression, which provides evidence that miR-429 may directly target Sp1 in RCC. These results suggest that miR-429 may be investigated for use as a predictive marker for early detection of tumor metastasis and blocking RCC cells from becoming invasive. PMID:27698878

  3. Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human hepatocellular carcinoma cell lines.

    PubMed

    Ho, Yi-Chien; Liu, Chi-Hsien; Chen, Chien-Nan; Duan, Kow-Jen; Lin, Ming-Tse

    2008-11-01

    Xanthohumol is one of the main flavonoids in hop extracts and in beer. Very few investigations of xanthohumol have studied hepatocellular carcinoma. In this study, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were investigated. The IC(50) values of xanthohumol for two hepatocellular carcinoma cell lines and one normal hepatocyte cell line were 108, 166 and 211 microm, respectively. Normal murine hepatocyte cell line had more resistance to xanthohumol than hepatocellular carcinoma cell lines. Besides, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were attributed to apoptosis as indicated in the results of flow cytometry, fluorescent nuclear staining and electrophoresis of oligonucleosomal DNA fragments. Hop xanthohumol was more efficient in the growth inhibition of hepatocellular carcinoma cell lines than the flavonoids silibinin and naringin from thistle and citrus. It was shown for the first time that xanthohumol from hops effectively inhibits proliferation of human hepatocellular carcinoma cells in vitro.

  4. The effect of macronutrients on gastric volume responses and gastric emptying in humans: A magnetic resonance imaging study.

    PubMed

    Goetze, Oliver; Steingoetter, Andreas; Menne, Dieter; van der Voort, Ivo R; Kwiatek, Monika A; Boesiger, Peter; Weishaupt, Dominik; Thumshirn, Miriam; Fried, Michael; Schwizer, Werner

    2007-01-01

    The effects of macronutrients on gastric volume changes, emptying, and gastrointestinal symptoms are incompletely understood. Three liquid meals of 500 ml (fat emulsion, 375 kcal; protein solution, 375 kcal; glucose solution, 400 kcal) were infused into the stomach of 12 healthy volunteers on three occasions. Studies were performed in seated body position using an open-configuration magnetic resonance imaging (MRI) system. MRI imaging sequences, assessing stomach and meal volumes, were performed prior to and at times t = 0, 3, 6, 9, 12, 15, 25, 35, 45, 60, 75, and 90 min after meal administration. Areas under the curve for the early emptying phase (0-15 and 0-45 min) were calculated, and characteristics of the volume curves were analyzed by a gastric emptying model. Gastrointestinal symptoms were assessed by a self-report scale. Initial (t = 0 min) and early postprandial gastric volumes were highest for glucose because of lower initial emptying. However, in the early emptying phase the characteristics of the volume curves for stomach and meal were uniform for all macronutrients. Perceptions of fullness and satiety were linearly associated with postprandial gastric volumes, but not with macronutrient composition. Isovolumic macronutrient meals modulate gastric volume response by initial meal emptying patterns. Macronutrient specific accommodation responses, as shown in barostat studies, are not reflected as gastric volume responses under noninvasive conditions.

  5. A Phase I Trial of Oblimersen Sodium in Combination With Cisplatin and 5-Fluorouracil in Patients with Advanced Esophageal, Gastroesophageal Junction and Gastric Carcinoma

    PubMed Central

    Raab, Rachel; Sparano, Joseph A.; Ocean, Allyson J.; Christos, Paul; Ramirez, Mark; Vinciguerra, Vincent; Kaubisch, Andreas

    2012-01-01

    Purpose To determine the maximum tolerated dose of oblimersen, an antisense oligonucleotide directed to the Bcl-2 mRNA, in combination with cisplatin and 5-flourouracil in patients with advanced gastric and esophageal carcinoma. Methods Patients were treated with escalating doses of oblimersen administered by continuous intravenous infusion (CIVI) days 1 to7, CIVI 5-fluorouracil (5-FU) days 4 to 7, and cisplatin on day 4 every three weeks. Results Fifteen patients received a total of 49 courses of oblimersen at doses of 3, 5, or 7 mg/kg/d given as a seven day CIVI in combination with 4 or 5 day CIVI of 5-FU (1000 or 750 mg/m2/d) plus intravenous cisplatin (100 or 75 mg/m2 over 2 hours). The recommended phase II dose of oblimersen was 5 mg/kg/day in combination with 5-FU (750 mg/m2/day for 4 days) and cisplatin (75 mg/m2). The most common grade 3 to 4 adverse events that occurred in at least 10% of patients at all dose levels included neutropenia (33%), hypokalemia (27%), infection (20%), and mucositis, fatigue, dizziness, thrombosis, and dehydration (in 13% for each category). Conclusion The combination of oblimersen with 5-FU and cisplatin chemotherapy is feasible in patients with advanced upper gastrointestinal cancer, with antitumor activity observed in gastric carcinoma. PMID:19738454

  6. Lentivirus-mediated RNAi knockdown of LMP2A inhibits the growth of the Epstein-Barr-associated gastric carcinoma cell line GT38 in vitro

    PubMed Central

    Wang, Fangjun; Chen, Weichang; Liu, Pengfei; Zhou, Jundong; Liu, Bingtuan; Ye, Wu; Wang, Wenping; Shen, Xiuyun

    2017-01-01

    In this study, lentivirus-mediated RNA interference (RNAi) was applied to inhibit latent membrane protein 2A (LMP2A) gene expression, in order to explore the effects of LMP2A silencing on the growth of an Epstein-Barr virus-associated gastric carcinoma (EBVaGC) cell line in vitro. Lentivirus-mediated RNAi technology was employed to specifically knock down the LMP2A gene in the EBV-positive gastric carcinoma cell line GT38. After infection, reverse transcription-quantitative polymerase chain reaction, western blotting, flow cytometry and colony formation assays were conducted to evaluate the expression of LMP2A and the biological behavior of the GT38 cell line in vitro. The results showed that the expression of the LMP2A gene was clearly downregulated in the infected cells, which indicated that a highly efficient and stable lentivirus vector was successfully constructed. In the GT38 cells in which the expression of LMP2A was downregulated, the proliferation and colony formation of the cells was significantly inhibited. In addition, it was found that the cell cycle of the GT38 cells was arrested in the G0/G1 phase and the apoptosis rate was increased. These results indicate that lentivirus-mediated RNAi knockdown of LMP2A inhibits the growth of the EBVaGC cell line GT38 in vitro, and suggests that LMP2A is a potential target for gene therapy in the treatment of EBVaGC. PMID:28123488

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

    PubMed Central

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

    2014-01-01

    BACKGROUND & AIMS Trefoil factors (TFFs) regulate mucosal repair and suppress tumor formation in the stomach. Tff1 deficiency results in gastric cancer, whereas Tff2 deficiency increases gastric inflammation. TFF2 expression is frequently lost in gastric neoplasms, but the nature of the silencing mechanism and associated impact on tumorigenesis have not been determined. METHODS We investigated the epigenetic silencing of TFF2 in gastric biopsy specimens from individuals with Helicobacter pylori-positive gastritis, intestinal metaplasia, gastric cancer, and disease-free controls. TFF2 function and methylation were manipulated in gastric cancer cell lines. The effects of Tff2 deficiency on tumor growth were investigated in the gp130F/F mouse model of gastric cancer. RESULTS In human tissue samples, DNA methylation at the TFF2 promoter began at the time of H pylori infection and increased throughout gastric tumor progression. TFF2 methylation levels were inversely correlated with TFF2 messenger RNA levels and could be used to discriminate between disease-free controls, H pylori-infected, and tumor tissues. Genome demethylation restored TFF2 expression in gastric cancer cell lines, so TFF2 silencing requires methylation. In Tff2-deficient gp130F/F/Tff2−/− mice, proliferation of mucosal cells and release of T helper cell type-1 (Th-1) 1 cytokines increased, whereas expression of gastric tumor suppressor genes and Th-2 cytokines were reduced, compared with gp130F/Fcontrols. The fundus of gp130F/F/Tff2−/− mice displayed glandular atrophy and metaplasia, indicating accelerated preneoplasia. Experimental H pylori infection in wild-type mice reduced antral expression of Tff2 by increased promoter methylation. CONCLUSIONS TFF2 negatively regulates preneoplastic progression and subsequent tumor development in the stomach, a role that is subverted by promoter methylation during H pylori infection. PMID:20801119

  8. Human Beta-papillomavirus infection and keratinocyte carcinomas.

    PubMed

    Quint, Koen D; Genders, Roel E; de Koning, Maurits N C; Borgogna, Cinzia; Gariglio, Marisa; Bouwes Bavinck, Jan Nico; Doorbar, John; Feltkamp, Mariet C

    2015-01-01

    Although the role of oncogenic human Alpha-papillomaviruses (HPVs) in the development of mucosal carcinomas at different body sites (eg cervix, anus, oropharynx) is fully recognized, a role for HPV in keratinocyte carcinomas (KCs; basal and squamous cell carcinomas) of the skin is not yet clear. KCs are the most common cancers in Caucasians, with the major risk factor being ultraviolet (UV) light exposure. A possible role for Beta-HPV types (BetaPV) in the development of KC was suggested several decades ago, supported by a number of epidemiological studies. Our current review summarizes the recent molecular and histopathological evidence in support of a causal association between BetaPV and the development of KC, and outlines the suspected synergistic effect of viral gene expression with UV radiation and immune suppression. Further insights into the molecular pathways and protein interactions used by BetaPV and the host cell is likely to extend our understanding of the role of BetaPV in KC.

  9. Classification of human carcinoma cells using multispectral imagery

    NASA Astrophysics Data System (ADS)

    Ćinar, Umut; Y. Ćetin, Yasemin; Ćetin-Atalay, Rengul; Ćetin, Enis

    2016-03-01

    In this paper, we present a technique for automatically classifying human carcinoma cell images using textural features. An image dataset containing microscopy biopsy images from different patients for 14 distinct cancer cell line type is studied. The images are captured using a RGB camera attached to an inverted microscopy device. Texture based Gabor features are extracted from multispectral input images. SVM classifier is used to generate a descriptive model for the purpose of cell line classification. The experimental results depict satisfactory performance, and the proposed method is versatile for various microscopy magnification options.

  10. Merkel Cell Carcinoma: A Virus-Induced Human Cancer

    PubMed Central

    Chang, Yuan; Moore, Patrick S.

    2013-01-01

    Merkel cell polyomavirus (MCV) is the first polyomavirus directly linked to human cancer, and its recent discovery helps to explain many of the enigmatic features of Merkel cell carcinoma (MCC). MCV is clonally integrated into MCC tumor cells, which then require continued MCV oncoprotein expression to survive. The integrated viral genomes have a tumor-specific pattern of tumor antigen gene mutation that incapacitates viral DNA replication. This human cancer virus provides a new model in which a common, mostly harmless member of the human viral flora can initiate cancer if it acquires a precise set of mutations in a host with specific susceptibility factors, such as age and immune suppression. Identification of this tumor virus has led to new opportunities for early diagnosis and targeted treatment of MCC. PMID:21942528

  11. Investigations of the DNA-damaging activity of human gastric juice.

    PubMed

    Kyrtopoulos, S A

    1987-01-01

    Human gastric juice previously treated with nitrite was examined for its ability to cause O6-alkylguanine-type modifications to 2'-deoxyguanosine or DNA in vitro. Analysis by radioimmunoassay indicated that, in five out of ten cases, incubation with 5 mM 2'-deoxyguanosine resulted in the formation of 375-1350 fmol/ml O6-ethyl-2'-deoxyguanosine (O6-etdGuo) or, in one case, 110 pmol/ml O6-methyl-2'-deoxyguanosine O6-medGuo). When gastric juice-treated calf-thymus DNA was examined for its ability to consume (through suicide repair of O6-alkylguanine-type damage) O6-alkylguanine-DNA alkyltransferase (AAT) from rat liver, eight out of eight samples could not. However, in four out of eight cases, a reduction in the rate of removal of O6-[3H]methylguanine from a 3H-methylated DNA substrate was observed. This finding is compatible with the presence, in gastric juice-treated DNA, of damage capable of binding to, but not undergoing repair by, the AAT.

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

    PubMed

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

    1996-01-01

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

  13. Structure of the human gastric bacterial community in relation to Helicobacter pylori status

    PubMed Central

    Maldonado-Contreras, Ana; Goldfarb, Kate C; Godoy-Vitorino, Filipa; Karaoz, Ulas; Contreras, Mónica; Blaser, Martin J; Brodie, Eoin L; Dominguez-Bello, Maria G

    2011-01-01

    The human stomach is naturally colonized by Helicobacter pylori, which, when present, dominates the gastric bacterial community. In this study, we aimed to characterize the structure of the bacterial community in the stomach of patients of differing H. pylori status. We used a high-density 16S rRNA gene microarray (PhyloChip, Affymetrix, Inc.) to hybridize 16S rRNA gene amplicons from gastric biopsy DNA of 10 rural Amerindian patients from Amazonas, Venezuela, and of two immigrants to the United States (from South Asia and Africa, respectively). H. pylori status was determined by PCR amplification of H. pylori glmM from gastric biopsy samples. Of the 12 patients, 8 (6 of the 10 Amerindians and the 2 non-Amerindians) were H. pylori glmM positive. Regardless of H. pylori status, the PhyloChip detected Helicobacteriaceae DNA in all patients, although with lower relative abundance in patients who were glmM negative. The G2-chip taxonomy analysis of PhyloChip data indicated the presence of 44 bacterial phyla (of which 16 are unclassified by the Taxonomic Outline of the Bacteria and Archaea taxonomy) in a highly uneven community dominated by only four phyla: Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. Positive H. pylori status was associated with increased relative abundance of non-Helicobacter bacteria from the Proteobacteria, Spirochetes and Acidobacteria, and with decreased abundance of Actinobacteria, Bacteroidetes and Firmicutes. The PhyloChip detected richness of low abundance phyla, and showed marked differences in the structure of the gastric bacterial community according to H. pylori status. PMID:20927139

  14. Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

    PubMed Central

    Anders, M; Vieth, M; Röcken, C; Ebert, M; Pross, M; Gretschel, S; Schlag, P M; Wiedenmann, B; Kemmner, W; Höcker, M

    2009-01-01

    Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R0-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor. PMID:19142187

  15. Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

    PubMed

    Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

    1985-08-01

    Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

  16. The role of human papillomavirus infection in prostate carcinoma.

    PubMed

    Aghakhani, Arezoo; Hamkar, Rasool; Parvin, Mahmoud; Ghavami, Nastaran; Nadri, Mahsa; Pakfetrat, Attesa; Banifazl, Mohammad; Eslamifar, Ali; Izadi, Nabiollah; Jam, Sara; Ramezani, Amitis

    2011-01-01

    Human papillomavirus (HPV) infections are associated with benign and malignant lesions of the female and male anogenital tract. Currently the possible role of HPV infections in prostate carcinogenesis is a subject of great controversy. In this study we aimed to investigate the role of HPV infection in prostate carcinoma (PCa). The study included formalin-fixed paraffin-embedded tissue samples of 104 primary prostate adenocarcinoma cases and 104 control tissues of benign prostatic hyperplasia (BPH). HPV-DNA was purified and amplified through MY09/MY11 and GP5(+)/GP6(+) primers and subsequently subjected to sequencing. HPV-DNA was found in 13 of 104 (12.5%) PCa and 8 of 104 (7.7%) BPH samples. High-risk HPVs were detected in 10 of 13 (76.9%) PCa and 5 of 8 (62.5%) BPH samples with positive HPV-DNA. Low-risk HPVs were detected in 3 of 13 (23.1%) PCa and 3 of 8 (37.5%) BPH specimens with positive HPV-DNA. There was no significant difference between PCa and BPH specimens regarding HPV-DNA presence or the detection of high-risk and low-risk types of HPV. Our data do not support the role of HPV infection in prostate carcinoma. Further studies are required to elucidate the role of HPV infection in human prostate carcinogenesis.

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

    PubMed

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

    2016-05-01

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

  18. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    PubMed

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  19. Methylation-silencing RCC1 expression is associated with tumorigenesis and depth of invasion in gastric cancer

    PubMed Central

    Lin, Yi-Ling; Chen, Hsiao-Ling; Cheng, Shao-Bin; Yeh, Dah-Cherng; Huang, Chu-Chun; P’eng, Fang-Ku; Tsai, Tung-Chou; Wu, Cheng-Chung; Chen, Chuan-Mu

    2015-01-01

    Introduction: Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator. We firstly identified RCC1 gene hypermethylation in gastric tumor tissues using the differential methylation hybridization (DMH) microarray, but the role of RCC1 in the pathogenesis of gastric carcinoma is largely unknown. Methods: Three gastric cancer cell lines (AGS, MKN45, and TSGH9201) were used to analyze RCC1 gene methylation, mRNA and protein expressions. Furthermore, 85 pairs of matched human gastric carcinoma samples in a tissue microarray were used to analyze RCC1 expression by immunohistochemistry staining. Results: A differential methylation pattern was found in TSGH9201 (100%), MKN45 (87%), and AGS (62%) cell lines at the 9th CpG site of RCC1 exon 1. RCC1 mRNA and protein expressions in AGS cells were significantly higher than in TSGH9201 and MKN45 cell lines (P < 0.05). Tissue array data showed that RCC1 expression was detected in 21% (18/85) of gastric carcinoma tissues and in 80% (76/95) of adjacent non-tumor tissues. The expression of RCC1 in gastric carcinoma tissues was significantly lower than in adjacent non-tumor tissues (P < 0.001). Furthermore, an association between RCC1 expression and clinicopathological features showed that RCC1 expression was closely correlated with tumor differentiation and depth of invasion (P < 0.05). Conclusions: Our data indicate that RCC1 expression is frequently lost in poorly differentiated gastric cell lines and gastric carcinoma tissues. Loss of RCC1 expression is correlated with tumor differentiation and depth of invasion. These findings suggest that RCC1 may play a tumor suppressor role in gastric carcinoma. PMID:26823742

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-05

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

  2. Indomethacin increases susceptibility to injury in human gastric cells independent of PG synthesis inhibition.

    PubMed

    Kokoska, E R; Smith, G S; Deshpande, Y; Wolff, A B; Miller, T A

    1998-10-01

    Indomethacin and other nonsteroidal anti-inflammatory drugs are commonly used to indirectly deduce the possible role of PGs in a process being studied. The objective of this study was to determine if indomethacin, at concentrations comparable to plasma and tissue levels obtained in humans taking therapeutic doses, predisposes human gastric cells to injury through inhibition of PGs or acts through an alternate mechanism. The role of intracellular Ca2+ in this damaging process was also assessed. Indomethacin pretreatment, although by itself nondamaging, was associated with elevated intracellular Ca2+ concentrations and an increased cellular permeability, an effect that was dependent on extracellular Ca2+. Furthermore, indomethacin pretreatment significantly predisposed AGS cells to injury induced by two dissimilar agents (deoxycholate and A-23187), both of which are associated with intracellular Ca2+ accumulation. The addition of exogenous PGs did not reverse the predisposition to injury induced by indomethacin. The observed effects of indomethacin were dependent on concentration and not on ability to inhibit PG synthesis. Similar effects were not observed with equipotent concentrations of ibuprofen or aspirin. Finally, the exacerbation of deoxycholate-induced injury induced by indomethacin was not observed when extracellular Ca2+ was removed. Indomethacin, by disturbing intracellular Ca2+ homeostasis, predisposes human gastric cells to injury through mechanisms independent of PG synthesis. The current study suggests that data resulting from studies employing only indomethacin as a PG synthesis inhibitor should be interpreted with caution.

  3. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    SciTech Connect

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-11-01

    A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with (17 alpha-methyl-TH)promegestone ((TH)R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of (3H)R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of (TH)R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V.

  4. New NCI-N87-derived human gastric epithelial line after human telomerase catalytic subunit over-expression

    PubMed Central

    Saraiva-Pava, Kathy; Navabi, Nazanin; Skoog, Emma C; Lindén, Sara K; Oleastro, Mónica; Roxo-Rosa, Mónica

    2015-01-01

    AIM: To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori (H. pylori) infection. METHODS: Aiming to overcome this limitation, clones of the heterogenic cancer-derived NCI-N87 cell line were isolated, by stably-transducing it with the human telomerase reverse-transcriptase (hTERT) catalytic subunit gene. The clones were first characterized regarding their cell growth pattern and phenotype. For that we measured the clones’ adherence properties, expression of cell-cell junctions’ markers (ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance. The gastric properties of the clones, concerning expression of mucins, zymogens and glycan contents, were then evaluated by haematoxylin and eosin staining, Periodic acid Schiff (PAS) and PAS/Alcian Blue-staining, immunocytochemistry and Western blot. In addition, we assessed the usefulness of the hTERT-expressing gastric cell line for H. pylori research, by performing co-culture assays and measuring the IL-8 secretion, by ELISA, upon infection with two H. pylori strains differing in virulence. RESULTS: Compared with the parental cell line, the most promising NCI-hTERT-derived clones (CL5 and CL6) were composed of cells with homogenous phenotype, presented higher relative telomerase activities, better adhesion properties, ability to be maintained in culture for longer periods after confluency, and were more efficient in PAS-reactive mucins secretion. Both clones were shown to produce high amounts of MUC1, MUC2 and MUC13. NCI-hTERT-CL5 mucins were shown to be decorated with blood group H type 2 (BG-H), Lewis-x (Lex), Ley and Lea and, in a less extent, with BG-A antigens, but the former two antigens were not detected in the NCI-hTERT-CL6. None of the clones exhibited detectable levels of MUC6 nor sialylated Lex and Lea glycans. Entailing good gastric properties, both NCI-hTERT-clones were found to produce

  5. Perforated Carcinoma in the Gastric Remnant: A Case of Conservative Treatment Prior to Successful Curative R0 Resection

    PubMed Central

    Kawashima, Hiroshi; Toyoda, Sho; Okumura, Satoshi; Yamamoto, Kansuke; Mizumura, Naoto; Ito, Aya; Maehira, Hiromitsu; Imagawa, Atsuo; Ogawa, Masao; Kawasaki, Masayasu; Kameyama, Masao

    2016-01-01

    An 80-year-old man who had undergone distal gastrectomy and Billroth-II gastrojejunostomy 38 years previously, for a benign gastric ulcer, was diagnosed with remnant gastric cancer based on upper gastrointestinal endoscopy findings. He presented at our emergency department with acute-onset epigastric pain due to perforated remnant gastric cancer. Conservative medical management was selected, including nasogastric tube insertion, antibiotics, and proton pump inhibitors, because his peritonitis was limited to his epigastrium and his general condition was stable. Twenty-one days after the perforation occurred, curative total remnant gastrectomy and D2 lymphadenectomy were performed. Adhesion between the lateral segment of the liver and the dissected lesser curvature of the gastric remnant may have contributed to the peritonitis in this case, which was limited to the epigastrium. This is the first report of perforated remnant gastric cancer in which conservative treatment was effective prior to curative resection. The protocol reported here may be of use to other clinicians who may encounter this clinical entity in their practices. PMID:27651972

  6. Effect of YB-1 on the regulation of micro RNA expression in drug-sensitive and drug-resistant gastric carcinoma cells.

    PubMed

    Belian, Elisa; Kurucz, Reka; Treue, Denise; Lage, Hermann

    2010-02-01

    The multifunctional Y-Box protein 1 (YB-1) exerts positive and negative regulatory effects on gene expression by different mechanisms. Since transcription can be controlled by micro RNAs (miRNAs), YB-1 could also cause effects on gene expression by regulation of cellular miRNAs. To test this hypothesis, a previously established and well-characterized cell model derived from drug-sensitive (EPG85-257P/tetR/YB-1) and multidrug-resistant (EPG85-257RDB/tetR/YB-1) gastric carcinoma cells, in which the expression of YB-1 can be inhibited by tetracycline-dependent triggering of the RNA interference (RNAi) pathway, was investigated concerning their miRNA expression profiles in the presence and absence of YB-1. Microarray hybridizations demonstrated that six miRNAs (miR-96*, miR-210, miR-503, miR-623, miR-1275, miR-1290) were up-regulated more than 1.5-fold in drug-sensitive cells following YB-1 inhibition, but no differences in miRNA expression could be detected in multidrug-resistant cells. Independent validation of these findings by quantitative real-time reverse transcriptase polymerase chain reaction did not confirm these effects. Likewise, an in silico analysis of potential regulatory effects of the miRNAs on their target genes did not support the potential miRNA regulatory effects of YB-1. In conclusion, the data provide evidence that YB-1 has no direct influence on global miRNA expression pattern in different variants of gastric carcinoma cells and, therewith, does not control gene expression by regulation of miRNAs.

  7. Microbiological survey of the human gastric ecosystem using culturing and pyrosequencing methods.

    PubMed

    Delgado, Susana; Cabrera-Rubio, Raúl; Mira, Alex; Suárez, Adolfo; Mayo, Baltasar

    2013-04-01

    Stomach mucosa biopsies and gastric juices samples of 12 healthy persons were analysed by culturing in selective- and non-selective-rich media. Microbial DNA from four mucosal samples was also amplified by nested PCR using universal bacterial primers, and the 16S rDNA amplicons pyrosequenced. The total number of cultivable microorganisms recovered from the samples ranged from 10(2) to 10(4) cfu/g or ml. The isolates were identified at the species level by PCR amplification and sequencing of the 16S rDNA. Isolates belonged mainly to four genera; Propionibacterium, Lactobacillus, Streptococcus and Staphylococcus. A total of 15,622 high-quality 16S rDNA sequence reads were obtained by pyrosequencing from the four mucosal samples. Sequence analysis grouped the reads into 59 families and 69 genera, revealing wide bacterial diversity. Considerable differences in the composition of the gastric microbiota were observed among the subjects, although in all samples the most abundant operational taxonomic units belonged to Streptococcus, Propionibacterium and Lactobacillus. Comparison of the stomach microbiota with that present in other parts of the human gastrointestinal tract revealed distinctive microbial communities. This is the first study in which a combination of culture and culture-independent techniques has been used to explore the bacterial diversity of the human stomach.

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

    PubMed Central

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

    2016-01-01

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

  9. Cytotoxic effects of β-carboline alkaloids on human gastric cancer SGC-7901 cells

    PubMed Central

    Fan, Yuxiang; Patima, Abulimiti; Chen, Yu; Zeng, Fanye; He, Wenting; Luo, Lingjuan; Jie, Yanghua; Zhu, Yanhua; Zhang, Liping; Lei, Jun; Xie, Xinmei; Zhang, Hongliang

    2015-01-01

    To investigate the cytotoxic effects of β-carboline alkaloids on human gastric cancer SGC-7901 cells. Human gastric cancer SGC-790s1 cells were treated with β-carboline alkaloids at the concentration of 0, 10, 20, 30 and 40 μg/ml for 48 hr. Cell viability was measured by Cell Counting Kit-8 assay. Cell apoptosis was detected by Hoechst 33258 staining and DNA fragmentation analysis. The expression of phosphatase and tensin homolog (PTEN) and extracellular signal-regulated kinase (ERK) was examined by quantitative real-time PCR (qRT-PCR) assay and western blot analysis. β-carboline alkaloids inhibited the growth of SGC-7901 cells concentration dependently. β-carboline alkaloids treated SGC-7901 cells displayed apoptotic nuclei as detected using Hoechst 33258 staining. β-carboline alkaloids also induced DNA ladder, indicative of apoptosis in SGC-7901 cells concentration-dependently. Furthermore, β-carboline alkaloids increased PTEN and decreased ERK mRNA expression in SGC-7901 cells in a concentration dependent manner. They also increased PTEN and decreased ERK protein expression. β-carboline alkaloids inhibit the growth and induce apoptosis of SGC-7901 cells. The cytotoxic effects of β-carboline alkaloids might correlate with increased PTEN expression and decreased ERK expression in SGC-7901 cells. PMID:26550217

  10. Analysis of chromosome 17p13 (p53 locus) alterations in gastric carcinoma cells by dual-color fluorescence in situ hybridization.

    PubMed

    Kobayashi, M; Kawashima, A; Mai, M; Ooi, A

    1996-11-01

    Chromosome 17 and p53 gene locus alterations were determined on 67 gastric carcinomas by dual-color fluorescence in situ hybridization, using probes for centromere 17 and the 17p13.1 (p53 locus). The results were compared with loss of heterozygosity (LOH) at 17p13.3, direct sequencing of exons 5 to 9 of p53, and nuclear overexpression of p53 protein. Deletion of p53 was found in 26 of 67 tumors (39%). All 26 also showed LOH at 17p13.3, frequently overexpressed p53 protein, and had polysomy 17. The functional loss of p53 gene in these tumors, 85% of which were of intestinal type, appears to be caused by both deletion of 17p13.1 and missense mutation of the remaining allele. There were 9 tumors that had neither deletion nor LOH but had a large proportion of cancer cells that overexpressed p53 election. Despite evidence of LOH, there was no p53 deletion in 11 tumors. Finally, 21 tumors, mostly of diffuse type, showed neither deletions, LOH, nor p53 overexpression. Our data suggest that in gastric cancer, deletion of 17p is principally responsible for the allelic loss at the p53 gene and that analysis of deletions by the dual-color fluorescence in situ hybridization is a sensitive and useful approach to clarify chromosomal aberrations.

  11. [Gastric cancer detection using kubelka-Munk spectral function of DNA and protein absorption bands].

    PubMed

    Li, Lan-quan; Wei, Hua-jiang; Guo, Zhou-yi; Yang, Hong-qin; Xie, Shu-sen; Chen, Xue-mei; Li, Li-bo; He, Bol-hua; Wu, Guo-yong; Lu, Jian-jun

    2009-09-01

    Differential diagnosis for epithelial tissues of normal human gastric, undifferentiation gastric adenocarcinoma, gastric squamous cell carcinomas, and poorly differentiated gastric adenocarcinoma were studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 250 to 650 nm, pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the DNA absorption bands at 260 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 68.5% (p < 0.05), 146.5% (p < 0.05), 282.4% (p < 0.05), 32.4% (p < 0.05), 56.00 (p < 0.05) and 83.0% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the protein absorption bands at 280 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 86.8% (p < 0.05), 262.9% (p < 0.05), 660.1% (p < 0.05) and 34% (p < 0.05), 72. 2% (p < 0.05), 113.5% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were

  12. The bile acid receptor GPBAR1 (TGR5) is expressed in human gastric cancers and promotes epithelial-mesenchymal transition in gastric cancer cell lines

    PubMed Central

    Cipriani, Sabrina; Marchianò, Silvia; Marino, Elisabetta; Zampella, Angela; Rende, Mario; Mosci, Paolo; Distrutti, Eleonora; Donini, Annibale; Fiorucci, Stefano

    2016-01-01

    GPBAR1 (also known as TGR5) is a bile acid activated receptor expressed in several adenocarcinomas and its activation by secondary bile acids increases intestinal cell proliferation. Here, we have examined the expression of GPBAR1 in human gastric adenocarcinomas and investigated whether its activation promotes the acquisition of a pro-metastatic phenotype. By immunohistochemistry and RT-PCR analysis we found that expression of GPBAR1 associates with advanced gastric cancers (Stage III-IV). GPBAR1 expression in tumors correlates with the expression of N-cadherin, a markers of epithelial-mesenchymal transition (EMT) (r=0.52; P<0.01). Expression of GPBAR1, mRNA and protein, was detected in cancer cell lines, with MKN 45 having the higher expression. Exposure of MKN45 cells to GPBAR1 ligands, TLCA, oleanolic acid or 6-ECDCA (a dual FXR and GPBAR1 ligand) increased the expression of genes associated with EMT including KDKN2A, HRAS, IGB3, MMP10 and MMP13 and downregulated the expression of CD44 and FAT1 (P<0.01 versus control cells). GPBAR1 activation in MKN45 cells associated with EGF-R and ERK1 phosphorylation. These effects were inhibited by DFN406, a GPBAR1 antagonist, and cetuximab. GPBAR1 ligands increase MKN45 migration, adhesion to peritoneum and wound healing. Pretreating MKN45 cells with TLCA increased propensity toward peritoneal dissemination in vivo. These effects were abrogated by cetuximab. In summary, we report that GPBAR1 is expressed in advanced gastric cancers and its expression correlates with markers of EMT. GPBAR1 activation in MKN45 cells promotes EMT. These data suggest that GPBAR1 antagonist might have utility in the treatment of gastric cancers. PMID:27409173

  13. Crosstalk between mismatch repair and base excision repair in human gastric cancer.

    PubMed

    Simonelli, Valeria; Leuzzi, Giuseppe; Basile, Giorgia; D'Errico, Mariarosaria; Fortini, Paola; Franchitto, Annapaola; Viti, Valentina; Brown, Ashley R; Parlanti, Eleonora; Pascucci, Barbara; Palli, Domenico; Giuliani, Alessandro; Palombo, Fabio; Sobol, Robert W; Dogliotti, Eugenia

    2016-06-20

    DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR. AGS cells over-expressing Polβ were resistant to 6-TG to a similar extent as when MLH1 was inactivated while inhibition of O6-methylguanine-DNA methyltransferase (MGMT) was required to detect resistance to MMS. Upon either treatment, the association with MLH1 down-regulation further amplified the resistant phenotype. Moreover, AGS cells mutated in Polβ were hypersensitive to both 6-TG and MMS killing and their sensitivity was partially rescued by MLH1 silencing. We provide evidence that the critical lethal lesions in this new pathway are double strand breaks that are exacerbated when Polβ is defective and relieved when MLH1 is silenced. In conclusion, we provide evidence of crosstalk between MLH1 and Polβ that modulates the response to alkylation damage. These studies suggest that the Polβ/MLH1 status should be taken into consideration when designing chemotherapeutic approaches for gastric cancer.

  14. Nitrergic Pathway Is the Main Contributing Mechanism in the Human Gastric Fundus Relaxation: An In Vitro Study

    PubMed Central

    Ko, Eun-Ju; Lee, Ji-Yeon; Ahn, Ki Duck; Bae, Je Moon; Rhee, Poong-Lyul

    2016-01-01

    Background Human gastric fundus relaxation is mediated by intrinsic inhibitory pathway. We investigated the roles of nitrergic and purinergic pathways, two known inhibitory factors in gastric motility, on spontaneous and nerve-evoked contractions in human gastric fundus muscles. Methods Gastric fundus muscle strips (12 circular and 13 longitudinal) were obtained from patients without previous gastrointestinal motility disorder who underwent gastrectomy for stomach cancer. Using these specimens, we examined basal tone, peak, amplitude, and frequency of spontaneous contractions, and peak and nadir values under electrical field stimulation (EFS, 150 V, 0.3 ms, 10 Hz, 20 s). To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine (muscarinic antagonist, 1 μM), MRS2500 (a purinergic P2Y1 receptor antagonist, 1 μM), and N-nitro-L-arginine (L-NNA, a nitric oxide synthase inhibitor, 100 μM) were added sequentially for spontaneous and electrically-stimulated contractions. Tetrodotoxin was used to confirm any neuronal involvement. Results In spontaneous contraction, L-NNA increased basal tone and peak in both muscle layers, while amplitude and frequency were unaffected. EFS (up to 10 Hz) uniformly induced initial contraction and subsequent relaxation in a frequency-dependent manner. Atropine abolished initial on-contraction and induced only relaxation during EFS. While MRS2500 showed no additional influence, L-NNA reversed relaxation (p = 0.012 in circular muscle, and p = 0.006 in longitudinal muscle). Tetrodotoxin abolished any EFS-induced motor response. Conclusions The relaxation of human gastric fundus muscle is reduced by nitrergic inhibition. Hence, nitrergic pathway appears to be the main mechanism for the human gastric fundus relaxation. PMID:27589594

  15. Sinularin Induces Apoptosis through Mitochondria Dysfunction and Inactivation of the pI3K/Akt/mTOR Pathway in Gastric Carcinoma Cells

    PubMed Central

    Wu, Yu-Jen; Wong, Bing-Sang; Yea, Shu-Hao; Lu, Chi-I; Weng, Shun-Hsiang

    2016-01-01

    Sinularin is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinularin on two human gastric cancer cell lines, AGS and NCI-N87. Our results demonstrated that sinularin suppressed the proliferation of gastric cancer cells in a dose-dependent manner and induced apoptosis. In addition, the loss of mitochondrial membrane potential, the release of cytochrome C, the activation of Bax, Bad and caspase-3/9, and the suppression of p-Bad, Bcl-xL and Bcl-2 were observed in the cells treated with sinularin. This finding suggests that sinularin-induced apoptosis is associated with mitochondria-mediated apoptosis and occurs through caspase-dependent pathways. Furthermore, sinularin inhibited the phosphoinositol 3-kinase/Akt/mechanistic target of the rapamycin signaling pathway. Taken together, our results show that sinularin-induced apoptosis is mediated by activation of the caspase cascade and mitochondrial dysfunction. Our findings suggest that sinularin merits further evaluation as a chemotherapeutic agent for human gastric cancer. PMID:27472346

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

    PubMed Central

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

    2016-01-01

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

  17. Cisplatin and Etoposide or Temozolomide and Capecitabine in Treating Patients With Neuroendocrine Carcinoma of the Gastrointestinal Tract or Pancreas That Is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-01-05

    Colorectal Large Cell Neuroendocrine Carcinoma; Esophageal Large Cell Neuroendocrine Carcinoma; Gallbladder Large Cell Neuroendocrine Carcinoma; Gastric Large Cell Neuroendocrine Carcinoma; Pancreatic Large Cell Neuroendocrine Carcinoma; Small Intestinal Large Cell Neuroendocrine Carcinoma

  18. Hydrolysis of fluorescent pyrenetriacylglycerols by lipases from human stomach and gastric juice.

    PubMed

    Nègre, A; Salvayre, R; Dousset, N; Rogalle, P; Dang, Q Q; Douste-Blazy, L

    1988-11-25

    Fluorescent triacylglycerols containing pyrenedecanoic (P10) and pyrenebutanoic (P4) acids were synthesized and their hydrolysis by lipases from human gastric juice and stomach homogenate was investigated. The existence in stomach homogenate of four different lipolytic enzymes hydrolyzing fluorescent triacylglycerols is suggested by the comparison of various enzymatic properties: acyl chain length specificity, heat inactivation and effect of detergents (Triton X-100 and taurocholate), serum albumin, diethyl-para-nitrophenyl phosphate (E600) and other inhibitors. (1) The acid pH4-lipase hydrolyzes P10-triacylglycerols but not P4-triacylglycerol and exhibited the characteristic properties of the lysosomal lipase: the maximal activating effect of detergents occurs at relatively high concentrations (the substrate/detergent optimal molar ratios were 1:5 and 1:25 for triacylglycerols/taurocholate and triacylglycerols/Triton X-100, respectively); its activity was strongly inhibited by para-chloromercuribenzoate (2.5 mmol/l), but was not significantly affected by serum albumin and E600 (10(-2) mmol/l). (2) The neutral pH7-lipase hydrolyzes P10-triacylglycerols but not P4-triacylglycerol. It is resistant to E600 and heat-stable, similarly to the acid pH4-lipase, but it is well discriminated from the acid enzyme by its substrate/detergent optimal molar ratios (1:2 and 1:3 for triacylglycerols/taurocholate and triacylglycerols/Triton X-100, respectively), whereas higher detergent concentrations, optimal for the acid lipase, are strongly inhibitory for the neutral enzyme. (3) The pH5-lipase present in gastric juice as well as in stomach homogenate exhibited properties obviously discriminating it from the other lipolytic enzymes from stomach homogenate: broad substrate specificity for P10- as well as P4-triacylglycerols, activation by low concentrations of amphiphiles (with optimal ratios triacylglycerols/taurocholate, triacylglycerols/taurocholate and triacylglycerols

  19. MHC I-related chain a expression in gastric carcinoma and the efficacy of immunotherapy with cytokine-induced killer cells

    PubMed Central

    Chen, Yu; Lin, Jing; Guo, Zeng-Qing; Lin, Wan-Song; Zhou, Zhi-Feng; Huang, Chuang-Zhong; Chen, Qiang; Ye, Yun-Bin

    2015-01-01

    Cytokine-induced killer (CIK) cells have shown promising activity against gastric cancer in vitro and in vivo. Previous studies showed that cell signaling through MHC I-related Chain A (MICA)-Natural killer group 2, member D (NKG2D) results in CIK cell activation leading to cytolytic activities against tumor cells. In this study, we investigate the MICA status in patients with gastric carcinoma, and determine the potential relationship between MICA and clinical outcome of a CIK containing therapy. Two hundred and forty-three patients with gastric cancer who had received curative D2 gastrectomy were enrolled. The MICA expression of their tumors was determined by immunohistochemistry (IHC). Disease-free survival (DFS) and overall survival (OS) were evaluated. One hundred and forty-eight patients received adjuvant chemotherapy alone, and 95 patients received adjuvant chemotherapy combined with autologous CIK cell therapy. Patients who received adjuvant chemotherapy plus CIK had significantly longer DFS, 42.0 months vs. 32.0 months (P = 0.012), and OS, 45.0 months vs. 42.0 months (P = 0.039), by log-rank test. MICA high-expression, IHC scores of 5-7, was found in tumors from 89 of 243 patients (36.6%). The MICA expression was significantly correlated with the stage (P = 0.007) and there was a borderline association with histological grade (P = 0.054). In the adjuvant chemotherapy plus CIK group (n = 95), patients with high MICA expression had longer DFS, 46.0 months vs. 41.0 months (P = 0.027), and OS, 48.0 months vs. 42.0 months (P = 0.031). In the adjuvant chemotherapy alone group (n = 148), the median DFS and OS had no significant correlation with the MICA status. In a multivariate analysis stage, CIK therapy, and the interaction of MICA status and CIK therapy were independent prognostic factors for DFS and OS. Our study indicated that adjuvant chemotherapy plus CIK immunotherapy is a promising modality for treating gastric cancer patients after D2 gastrectomy. MICA

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

    PubMed

    Yang, Yang; Jiang, Man; Hu, Jing; Lv, Xin; Yu, Lixia; Qian, Xiaoping; Liu, Baorui

    2015-01-01

    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.

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

    PubMed

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

    2016-01-01

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

  2. Downregulation of microRNA-193-3p inhibits tumor proliferation migration and chemoresistance in human gastric cancer by regulating PTEN gene.

    PubMed

    Jian, Bin; Li, Zhongfu; Xiao, Dachun; He, Gan; Bai, Lian; Yang, Qiang

    2016-07-01

    In this study, we investigated the functional mechanisms of microRNA-193-3p (miR-193-3p) in human gastric cancer. Quantitative RT-PCR (qRT-PCR) was used to assess whether miR-193-3p was aberrantly expressed in gastric cancer cells and clinical samples from gastric cancer patients. Gastric cancer cell line AGS and MKN-45 cells were stably transduced with lentivirus to downregulate endogenous miR-193-3p. The modulation of miR-193-3p downregulation on gastric cancer proliferation, migration, chemo-drug responses, and tumor explant were assessed by MTT, wound-healing, 5-FU chemoresistance and in vivo tumorigenicity assays, respectively. Downstream target of miR-193-3p, phosphatase and tensin homolog (PTEN) in gastric cancer, was assessed by dual-luciferase reporter assay, qRT-PCR, and western blot. PTEN was knocked down by siRNA in AGS and MKN-45 cells to assess its direct impact on miR-193-3p modulation in gastric cancer. MiR-193-3p was aberrantly upregulated in both gastric cell lines and human gastric tumors. In AGS and MKN-45 cells, miR-193-3p downregulation reduced cancer proliferation, migration and 5-FU chemoresistance in vitro, and tumorigenicity in vivo. PTEN was confirmed to be targeted by miR-193-3p in gastric cancer. PTEN inhibition in AGS and MKN-45 cells directly reversed the anti-tumor modulations of miR-193-3p downregulation on gastric cancer proliferation, migration, and 5-FU chemoresistance. We presented clear evidence showing miR-193-3p played critical role in regulating human gastric cancer through direct targeting on PTEN gene.

  3. Gastrin and Gastric Cancer

    PubMed Central

    Waldum, Helge L.; Sagatun, Liv; Mjønes, Patricia

    2017-01-01

    Gastric cancer although occurring in reduced frequency is still an important disease, partly because of the bad prognosis when occurring in western countries. This decline in occurrence may mainly be due to the reduced prevalence of Helicobacter pylori (Hp) infection, which is the most important cause of gastric cancer. There exist many different pathological classifications of gastric carcinomas, but the most useful seems to be the one by Lauren into intestinal and diffuse types since these types seldom transform into the other and also have different epidemiology. During the nearly 30 years that have passed since the groundbreaking description of Hp as the cause of gastritis and gastric cancer, a continuous search for the mechanism by which Hp infection causes gastric cancer has been done. Interestingly, it is mainly atrophic gastritis of the oxyntic mucosa that predisposes to gastric cancer possibly by inducing hypoacidity and hypergastrinemia. There are many arguments in favor of an important role of gastrin and its target cell, the enterochromaffin-like cell, in gastric carcinogenesis. The role of gastrin in gastric carcinogenesis implies caution in the long-term treatment with inhibitors of gastric acid secretion inducing secondary hypergastrinemia, in a common disease like gastroesophageal reflux disease. PMID:28144230

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

    PubMed

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

    2014-08-01

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

  5. Cantharidin induces G2/M phase arrest and apoptosis in human gastric cancer SGC-7901 and BGC-823 cells

    PubMed Central

    ZHANG, CHENJING; CHEN, ZHONGTING; ZHOU, XINGLU; XU, WEN; WANG, GANG; TANG, XIAOXIAO; LUO, LAISHENG; TU, JIANGFENG; ZHU, YIMIAO; HU, WEN; XU, XIANG; PAN, WENSHENG

    2014-01-01

    The aim of the present study was to investigate the effect of cantharidin (CTD) on human gastric cancer cells and to explore the underlying mechanisms of these effects. The human gastric cancer SGC-7901 and BGC-823 cell lines were treated with CTD. MTS assays were then employed to examine cellular proliferation, flow cytometry was used to analyze the cell cycle and apoptosis, and western blot analysis was used to determine protein expression levels. It was found that CTD inhibited the proliferation of the human gastric cancer SGC-7901 and BGC-823 cells in a dose- and time-dependent manner in vitro. CTD also induced G2/M phase arrest and cellular apoptosis in a dose-dependent manner. In addition, CTD increased the levels of p21, caspase-7, -8 and -9, activated caspase-3, poly ADP ribose polymerase and Bad, but decreased the levels of cyclin-dependent kinase 1, cyclin A and B, B-cell lymphoma-2 (Bcl-2) and Bid. The present results suggested that CTD may inhibit the proliferation of human gastric cancer SGC-7901 and BGC-823 cells in vitro by inducing G2/M phase arrest and cell apoptosis. CTD may induce cellular G2/M phase arrest by regulating cycle-associated proteins and induce apoptosis by activating a caspase cascade or regulating the Bcl-2 family proteins. PMID:25364455

  6. Cellular systems for studying human oral squamous cell carcinomas.

    PubMed

    Patel, Vyomesh; Iglesias-Bartolome, Ramiro; Siegele, Bradford; Marsh, Christina A; Leelahavanichkul, Kantima; Molinolo, Alfredo A; Gutkind, J Silvio

    2011-01-01

    The human oral squamous epithelium plays an important role in maintaining a barrier function against mechanical, physical, and pathological injury. However, the self-renewing cells residing on the basement membrane of the epithelium can give rise to oral squamous cell carcinomas (OSCC), now the sixth most common cancer in the developed world, which is still associated with poor prognosis. This is due, in part, to the limited availability of well-defined culture systems for studying oral epithelial cell biology, which could advance our understanding of the molecular basis of OSCC. Here, we describe methods to successfully isolate large cultures of human oral epithelial cells and fibroblasts from small pieces of donor tissues for use in techniques such as three-dimensional cultures and animal grafts to validate genes suspected of playing a role in OSCC development and progression. Finally, the use of isolated oral epithelial cells in generating iPS cells is discussed which holds promise in the field of oral regenerative medicine.

  7. Zebrafish as a disease model for studying human hepatocellular carcinoma

    PubMed Central

    Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

    2015-01-01

    Liver cancer is one of the world’s most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury. PMID:26576090

  8. Enantiomeric CopA3 dimer peptide suppresses cell viability and tumor xenograft growth of human gastric cancer cells.

    PubMed

    Lee, Joon Ha; Kim, In-Woo; Shin, Yong Pyo; Park, Ho Jin; Lee, Young Shin; Lee, In Hee; Kim, Mi-Ae; Yun, Eun-Young; Nam, Sung-Hee; Ahn, Mi-Young; Kang, Dongchul; Hwang, Jae Sam

    2016-03-01

    The CopA3 dimer peptide is a coprisin analog that has an anticancer effect against human cancer cells in vitro. In this study, we investigated the anticancer activity of the enantiomeric CopA3 dimer peptide in human gastric cancer cell lines as well as in an in vivo tumor xenograft model. Enantiomeric CopA3 reduced gastric cancer cell viability and exhibited cytotoxicity against cancer cells. Enantiomeric CopA3-induced cell death was mediated by specific interactions with phosphatidylserine and phosphatidylcholine, membrane components that are enriched in cancer cells, in a calcein leakage assay. Moreover, acridine orange/ethidium bromide staining, flow cytometric analysis, and Western blot analysis showed that enantiomeric CopA3 induced apoptotic and necrotic gastric cancer cell death. The antitumor effect was also observed in a mouse tumor xenograft model in which intratumoral inoculation of the peptide resulted in a significant decrease in the SNU-668 gastric cancer tumor volume. In addition, periodic acid-Schiff and hematoxylin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed apoptotic and necrotic cell death in tumor masses treated with greater than 150 μg CopA3. Collectively, these results indicate that the enantiomeric CopA3 dimer peptide induces apoptosis and necrosis of gastric cancer cells in vitro and in vivo, indicating that the peptide is a potential candidate for the treatment of gastric cancer, which is a common cause of cancer and cancer deaths worldwide.

  9. Downregulation of NDRG1 promotes invasion of human gastric cancer AGS cells through MMP-2.

    PubMed

    Liu, Yan-Li; Bai, Wen-Tao; Luo, Wen; Zhang, De-Xin; Yan, Yan; Xu, Zhi-Kai; Zhang, Fang-Lin

    2011-02-01

    The N-myc downstream-regulated gene-1 (NDRG1) has recently been proposed as a metastasis suppressor, but its precise role remains unclear. To investigate whether NDRG1 can indeed influence the metastasis progress, expression of endogenous NDRG1 was knocked down in human AGS gastric adenocarcinoma cells using RNA interference. Stable NDRG1 "silenced" transfectants showed similar growth rates as their control counterparts. By contrast, invasive ability in Matrigel invasion activity and Gelatinolytic activity by matrix metalloproteinase-2 (MMP-2) were markedly increased in NDRG1 "silenced" cells. Moreover, re-expression of NDRG1 by recombinant adenovirus Ad-NDRG1 in NDRG1 "silenced" cells inhibited the increased invasive ability. Further study, we found the induction of MMP-2 by downregulation of NDRG1 was mediated by MT1-MMP. Altogether, our results imply that NDRG-1 could play a key role in the regulation of cellular invasion and metastasis, which may involve the upregulation of matrix metalloproteinases.

  10. Autophagy Protects from Raddeanin A-Induced Apoptosis in SGC-7901 Human Gastric Cancer Cells

    PubMed Central

    Liu, Shen-lin; Fang, Liang-hua; Zhou, Jin-yong; Wu, Jian; Xi, Song-yang; Chen, Yan; Zhang, Ying-ying; Xu, Song

    2016-01-01

    Raddeanin A (RA) is an extractive from Anemone raddeana Regel, a traditional Chinese medicine. The aim of this study is to assess the efficacy of RA against human gastric cancer (GC) cells (SGC-7901) and explore its mechanism. MTT assay showed that RA inhibition of proliferation of SGC-7901 cells increased in a dose-dependent manner. Flow cytometry analysis and Hoechst 33258 staining showed that RA induced apoptosis on SGC-7901 cells. Meanwhile, it induced autophagy. Western blotting analysis showed that the RA induces apoptosis and autophagy by activating p38 MAPK pathway and inhibiting mTOR pathway. Further studies showed that autophagy inhibition could protect from RA-induced apoptosis in SGC-7901 cells. In conclusion, RA can induce SGC-7901 cell apoptosis and autophagy by activating p38 MAPK pathway. And autophagy can protect SGC-7901 cells from apoptosis induced by RA. PMID:27974905

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

    PubMed

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

    2015-07-01

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

  12. Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells.

    PubMed

    Li, Yang; Liu, Xiaokang; Jiang, Dan; Lin, Yingjia; Wang, Yushi; Li, Qing; Liu, Linlin; Jin, Ying-Hua

    2016-09-01

    Betulin, an abundant natural compound, significantly inhibited the cell viability of advanced human gastric cancer SGC7901 cells. Mechanism study demonstrated that betulin induced apoptosis through mitochondrial Bax and Bak accumulation-mediated intrinsic apoptosis pathway. Downregulation of the anti-apoptosis proteins Bcl-2 and XIAP was involved during betulin-induced cell apoptosis. Reactive oxygen species (ROS) was generated in cells after betulin treatment in a time- and dose-dependent manner. Addition of antioxidant N-acetyl-L-cysteine (NAC) significantly attenuated betulin-induced ROS generation as well as Bcl-2 and XIAP downregulation. The mitochondrial accumulation of Bax and Bak, as well as caspase activity, was also remarkably inhibited by NAC treatment, indicating that ROS are important signaling intermediates that lead to betulin-induced apoptosis by modulating multiple apoptosis-regulating proteins in SGC7901 cells.

  13. Human papillomavirus detection in head and neck squamous cell carcinoma

    PubMed Central

    Vietía, Dayahindara; Liuzzi, Juan; Ávila, Maira; De Guglielmo, Zoraya; Prado, Yrneh; Correnti, María

    2014-01-01

    Introduction Human Papillomavirus (HPV) has been associated with benign and malignant lesions in different epitheliums. The relationship between specific genotypes of high-risk HPV and some human cancers is well established. The aim of this work was to detect the HPV genotypes present in head and neck squamous cell carcinoma (HNSCC). Methods We evaluated 71 samples of patients with histopathological diagnosis of HNSCC. The DNA extraction was conducted with the QIAGEN commercial kit. HPV detection and genotyping were performed by reverse hybridisation (INNO-LiPA) following the commercial specifications. Results The mean age of the patients evaluated was 60.7 ± 13.11 years. The distribution of the lesions included 25 (35.20%) cases of squamous cell carcinoma (SCC) of the oral cavity, 23 (32.39%) of larynx, 16 (22.50%) of the oropharynx, 4 (5.63%) of paranasal sinus, and 2 (2. 80%) cases of SCC of the nostril. Of the patients, 78.9% were males, and of these 76% were tobacco users and 67.6% were alcohol consumers. The viral DNA was detected in 67.6% of the samples. The oral cavity and the larynx were the highest HPV-positivity sites with 35.40% and 29.10% respectively. The most frequent genotype was 16 as single infection (18.70%), or in combination with another HPV types. In the oral cavity and larynx the genotypes 16 or the combination 6 and 51 were present in 11.76% and 14.28%, respectively; and in the oropharynx the most frequent genotype was 16 in 22.50% of the cases, and in the paranasal sinus 50% presented infection with HPV-6. We observed that tumours with most advanced size and stage presented greater HPV positivity. Conclusions This study shows a high percentage of HPV positivity in SCC is mainly associated with high-risk HPV. It is important to highlight that viral infection, especially HPV-16, could be a risk factor in HNSCC progression. PMID:25374623

  14. Blueberry proanthocyanidins against human norovirus surrogates in model foods and under simulated gastric conditions.

    PubMed

    Joshi, Snehal; Howell, Amy B; D'Souza, Doris H

    2017-05-01

    Blueberry proanthocyanidins (B-PAC) are known to decrease titers of human norovirus surrogates in vitro. The application of B-PAC as therapeutic or preventive options against foodborne viral illness needs to be determined using model foods and simulated gastric conditions in vitro. The objective of this study was to evaluate the antiviral effect of B-PAC in model foods (apple juice (AJ) and 2% reduced fat milk) and simulated gastrointestinal fluids against cultivable human norovirus surrogates (feline calicivirus; FCV-F9 and murine norovirus; MNV-1) over 24 h at 37 °C. Equal amounts of each virus (5 log PFU/ml) was mixed with B-PAC (1, 2 and 5 mg/ml) prepared either in AJ, or 2% milk, or simulated gastric fluids and incubated over 24 h at 37 °C. Controls included phosphate buffered saline, malic acid (pH 7.2), AJ, 2% milk or simulated gastric and intestinal fluids incubated with virus over 24 h at 37 °C. The tested viruses were reduced to undetectable levels within 15 min with B-PAC (1, 2 and 5 mg/ml) in AJ (pH 3.6). However, antiviral activity of B-PAC was reduced in milk. FCV-F9 was reduced by 0.4 and 1.09 log PFU/ml with 2 and 5 mg/ml B-PAC in milk, respectively and MNV-1 titers were reduced by 0.81 log PFU/ml with 5 mg/ml B-PAC in milk after 24 h. B-PAC at 5 mg/ml in simulated intestinal fluid reduced titers of the tested viruses to undetectable levels within 30 min. Overall, these results show the potential of B-PAC as preventive and therapeutic options for foodborne viral illnesses.

  15. Atrial natriuretic peptide modulates the proliferation of human gastric cancer cells via KCNQ1 expression

    PubMed Central

    ZHANG, JIA; ZHAO, ZHILONG; ZU, CHAO; HU, HAIJIAN; SHEN, HUI; ZHANG, MINGXIN; WANG, JIANSHENG

    2013-01-01

    Atrial natriuretic peptide (ANP) and brain NP (BNP) belong to the NP family that regulates mammalian blood volume and blood pressure. ANP signaling through NP receptor A (NPR-A)/cyclic guanosine 3′5′-monophosphate (cGMP)/ cGMP-dependent protein kinase (PKG) activates various downstream effectors involved in cell growth, apoptosis, proliferation and inflammation. Evidence has shown the critical role of plasma K+ channels in the regulation of tumor cell proliferation. However, the role of ANP in the proliferation of gastric cancer cells is not clear. In the present study, the expression of NPR-A in the human gastric cancer cell line, AGS, and the effect of ANP on the proliferation of AGS cells were investigated using western blotting, immunofluorescence, qPCR and patch clamp assays. The K+ current was also analyzed in the effect of ANP on the proliferation of AGS cells. NPR-A was expressed in the human gastric cancer AGS cell line. Lower concentrations of ANP promoted the proliferation of the AGS cells, although higher concentrations decreased their proliferation. Significant increases in the levels of cGMP activity were observed in the AGS cells treated with 10−10, 10−9 and 10−8 M ANP compared with the controls, but no significant differences were observed in the 10−7 and 10−6 M ANP groups. The patch clamp results showed that 10−9 M ANP significantly increased the tetraethylammonium (TEA)- and 293B-sensitive K+ current, while 10−6 M ANP significantly decreased the TEA- and 293B-sensitive K+ current. The results showed that 10−10 and 10−9 M ANP significantly upregulated the expression of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) at the protein and mRNA levels, although 10−7 and 10−6 M ANP significantly downregulated the expression of KCNQ1. The data indicated that lower and higher concentrations of ANP have opposite effects on the proliferation of AGS cells through cGMP-dependent or -independent pathways. KCNQ1

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

    SciTech Connect

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

    2014-01-03

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

  17. NOTCH1 and NOTCH2 regulate epithelial cell proliferation in mouse and human gastric corpus.

    PubMed

    Demitrack, Elise S; Gifford, Gail B; Keeley, Theresa M; Horita, Nobukatsu; Todisco, Andrea; Turgeon, D Kim; Siebel, Christian W; Samuelson, Linda C

    2017-02-01

    The Notch signaling pathway is known to regulate stem cells and epithelial cell homeostasis in gastrointestinal tissues; however, Notch function in the corpus region of the stomach is poorly understood. In this study we examined the consequences of Notch inhibition and activation on cellular proliferation and differentiation and defined the specific Notch receptors functioning in the mouse and human corpus. Notch pathway activity was observed in the mouse corpus epithelium, and gene expression analysis revealed NOTCH1 and NOTCH2 to be the predominant Notch receptors in both mouse and human. Global Notch inhibition for 5 days reduced progenitor cell proliferation in the mouse corpus, as well as in organoids derived from mouse and human corpus tissue. Proliferation effects were mediated through both NOTCH1 and NOTCH2 receptors, as demonstrated by targeting each receptor alone or in combination with Notch receptor inhibitory antibodies. Analysis of differentiation by marker expression showed no change to the major cell lineages; however, there was a modest increase in the number of transitional cells coexpressing markers of mucous neck and chief cells. In contrast to reduced proliferation after pathway inhibition, Notch activation in the adult stomach resulted in increased proliferation coupled with reduced differentiation. These findings suggest that NOTCH1 and NOTCH2 signaling promotes progenitor cell proliferation in the mouse and human gastric corpus, which is consistent with previously defined roles for Notch in promoting stem and progenitor cell proliferation in the intestine and antral stomach.

  18. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    SciTech Connect

    Wu Xiaofeng; Fan Jia; E-mail: jiafan99@yahoo.com; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-04-20

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment.

  19. Natural flavonoid derivatives as oral human epidermoid carcinoma cell inhibitors.

    PubMed

    Gunda, Shravan Kumar; Kongaleti, Sofia Florence; Shaik, Mahmood

    2015-01-01

    Natural flavonoid derivatives against cancer for selective KB cell lines (oral human epidermoid carcinoma) are analysed to determine the relationship between biological activities and structural properties of these molecules. Molecular alignment was performed for 88 natural flavonoid derivatives; out of these 88 molecules, 69 molecules were taken into training set and rest of the 19 molecules were used in test set prediction. We describe our elucidation of their structure activity relation (SAR) using three-dimensional quantitative structure activity relationship (3D-QSAR) models. A predictive comparative molecular field analysis (CoMFA) model of q² = 0.888 and r² = 0.940 was obtained and a comparative molecular similarity indices analysis (CoMSIA) model q² = 0.778 and r² = 0.971 was used to describe the non-linearly combined affinity of each functional group in the inhibitors. The contour maps obtained from 3D-QSAR studies were evaluated for the activity trends of the molecules analysed.

  20. Increased EGF receptors on human squamous carcinoma cell lines.

    PubMed Central

    Cowley, G. P.; Smith, J. A.; Gusterson, B. A.

    1986-01-01

    Characterisation and quantitation of epidermal growth factor receptors (EGFR) have been carried out on eight human squamous carcinoma cell lines and the results compared with those from simian virus transformed keratinocytes and normal keratinocytes grown under similar conditions. All cells tested possess both high and low affinity receptors with dissociation constants ranging from 2.4 X 10(-10) M to 5.4 X 10(-9) M. When epidermal growth factor (EGF) binds to its receptor it is internalised and degraded and the receptor is down regulated. Malignant cells and virally transformed cells possess 5-50 times more EGF receptors than normal keratinocytes and one cell line LICR-LON-HN-5 possesses up to 1.4 X 10(7) receptors per cell, which is the highest number yet reported for a cell line. These results are discussed in the context of recent data that suggest that the increased expression of EGF receptors in epidermoid malignancies may be an important component of the malignant phenotype in these tumours. PMID:2420349

  1. Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion.

    PubMed

    Yan, Xia; Zhou, Huiling; Zhang, Tingting; Xu, Pan; Zhang, Shusen; Huang, Wei; Yang, Linlin; Gu, Xingxing; Ni, Runzhou; Zhang, Tianyi

    2015-12-01

    Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion.

  2. Differential gene expression of the key signalling pathway in para-carcinoma, carcinoma and relapse human pancreatic cancer.

    PubMed

    Chang, Zheng-Yan; Sun, Ran; Ma, Yu-Shui; Fu, Da; Lai, Xiao-Long; Li, Yu-Sheng; Wang, Xing-Hong; Zhang, Xiao-Ping; Lv, Zhong-Wei; Cong, Xian-Ling; Li, Wen-Ping

    2014-04-01

    Pancreatic cancer (PC) has a high rate of mortality and a poorly understood mechanism of progression. Investigation of the molecular mechanism of PC and exploration of the specific markers for early diagnosis and specific targets of therapy are key points to prevent and treat PC effectively and to improve their prognosis. In our study, expression profiles experiment of para-carcinoma, carcinoma and relapse human PC was performed using Agilent human whole genomic oligonucleotide microarrays with 45 000 probes. Differentially expressed genes related with PC were screened and analysed further by Gene Ontology term analysis and Kyoto encyclopaedia of genes and genomes pathway analysis. Our results showed that there were 3853 differentially expressed genes associated with pancreatic carcinogenesis and relapse. In addition, our study found that PC was related to the Jak-STAT signalling pathway, PPAR signalling pathway and Calcium signalling pathway, indicating their potential roles in pancreatic carcinogenesis and progress.

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2013-09-20

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

  6. Density-dependent gastroretentive microparticles motion in human gastric emptying studied using computer simulation.

    PubMed

    Hao, Shilei; Wang, Bochu; Wang, Yazhou

    2015-04-05

    Density-dependent gastroretentive drug delivery systems have been used to prolong the gastric retention time of drugs since the 1960s. The design of density-dependent gastroretentive dosage forms, however, usually focuses on specific parameters rather than combines with the fluid dynamics of dosage form in the gastric emptying. Therefore, the purpose of the present study was to develop a 2-D model of multiple-phase flows for the simulation of gastric emptying and gastroretentive microparticles motion, and the influence of microparticle density, microparticle viscosity, and gastric juice viscosity on the gastric retention were studied. The recirculating flows, formed in the gastric emptying, could mix the conventional-density microparticles and transport them to the pylorus. However, the low-density microparticles remained floating on the surface of gastric juice, while the high-density microparticles could sink and deposit in the bottom of the stomach. The remaining integral area of microparticles was higher than 90% after 18.33min of simulation when the density of microparticles was lower than 550kg/m(3) or higher than 2500kg/m(3), which was higher compared to conventional-density microparticles (67.05%). These results are in good agreement with experimental data previously reported. In addition, the viscosity of microparticle and gastric juice also influenced the remaining integral area of gastroretentive microparticles. This study shows that the multiple-phase computational fluid dynamics models could provide detailed insights into the fluid dynamics of density-dependent gastroretentive microparticles in gastric emptying, which offers a powerful tool to further understand the mechanism of gastric retention for gastroretentive dosage forms and study the influence of different parameters on their ability for gastric retention.

  7. Hypoxia-induced angiogenesis in human hepatocellular carcinoma.

    PubMed

    Kim, Kwang-Rok; Moon, Hyo-Eun; Kim, Kyu-Won

    2002-11-01

    Hepatocellular carcinoma is a typical hypervascular tumor. Generally, hepatocellular carcinoma is developed through liver cirrhosis induced by chronic liver injury. This chronic injury leads to changes in the cellular property of the liver and subsequently causes fibrogenesis to demolish normal liver blood system. The catastrophe of the normal liver blood system leads to the shortage of blood circulation in the liver and causes hypoxia. Moreover, the increased cellularity due to highly proliferative tumor cells also induces local hypoxia inside hepatocellular carcinoma. Hypoxia can stimulate angiogenesis to support tumor growth by induction of angiogenic factors. Thus hypoxia may be a major cause of hypervasculature of hepatocellular carcinoma. Recently it has been reported that several hypoxia-regulatory factors are closely involved in angiogenesis of hepatocellular carcinoma. The stability and function of these factors can be regulated by interaction with other protein factors and consequently modulate the expression of angiogenic factors depending on oxygen tension. Therefore induction mechanism of hypoxia and the role of hypoxia-regulatory factors could provide new insights into hepatocarcinogenesis and the treatment of hepatocellular carcinoma.

  8. Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma

    SciTech Connect

    Burmer, G.C.; Rabinovitch, P.S.; Loeb, L.A. )

    1991-06-01

    Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum of mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.

  9. Human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma.

    PubMed

    Dalianis, Tina

    2014-12-01

    Numerous reports in recent decades have shown that, in addition to smoking and alcohol, human papillomavirus (HPV) is also associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), predominantly in the tonsils and base of the tongue. In 2007, the International Agency on Research against Cancer (IARC) therefore declared HPV to be a risk factor for OPSCC and noted that 80% of those affected are men. In addition, patients with HPV-positive OPSCC, in particular never-smokers, have a much better clinical response to therapy than patients with HPV-negative OPSCC and other head and neck cancers. Most patients with HPV-positive OPSCC may thus not need the increasingly intensive chemo-radiotherapy currently administered today to most patients with head neck cancers and associated with many adverse effects. Furthermore, an increase in the incidence of OPSCC has been observed in many western countries, accompanied by a rise in the proportion of HPV-positive tumors. Patients with HPV-positive OPSCC, like those with cervical cancer, more often have an earlier sexual debut and have more sexual partners. It has therefore been proposed that the increased incidence of OPSCC observed might be due to an epidemic of sexually transmitted HPV. The important issues today regarding this growing cohort of patients with HPV-positive OPSCC are therefore individualized treatment and prevention. More specifically, selected HPV-positive OPSCC patients with biomarkers of good prognosis might be included in randomized trials with less intensive treatment. HPV vaccination should also be considered for boys, in addition to the current recommendations for immunization of girls.

  10. Increased FNDC5/Irisin expression in human hepatocellular carcinoma.

    PubMed

    Gaggini, Melania; Cabiati, Manuela; Del Turco, Serena; Navarra, Teresa; De Simone, Paolo; Filipponi, Franco; Del Ry, Silvia; Gastaldelli, Amalia; Basta, Giuseppina

    2017-02-01

    The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors. Hepatic mRNA expression of FNDC5/Irisin and stearoyl-CoA desaturase (SCD-1), main enzymatic regulator of DNL, were significantly higher in HCC patients than in donors (p<0.0001 and p=0.015, respectively). The hepatic mRNA expression of the neurogenic locus notch homolog protein 1 (NOTCH1) tended to be higher in HCC patients than in donors (p=0.06). Only in HCC patients, hepatic FNDC5/Irisin strongly correlated with the transcription factor sterol regulatory element-binding factor 1, SCD-1, NOTCH1, tumor necrosis factor-α and Interleukin-6 mRNA expression. Further, in HCC patients, FNDC5/Irisin mRNA tended to correlate to plasma lipid profile namely triglycerides, palmitic/linoleic acid and polyunsaturated fatty acid/saturated fatty acid ratios. In conclusion, HCC-liver tissue over-expressed FNDC5/Irisin in association with gene expression of mediators involved in lipogenesis, inflammation and cancer, suggesting a possible protective role of the hormone from the liver damage.

  11. Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

    PubMed Central

    Yeung, Bonnie H. Y.; Shek, Felix H.; Lee, Nikki P.; Wong, Chris K. C.

    2015-01-01

    Growing evidence has revealed high expression levels of stanniocalcin-1 (STC1) in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC) an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL)-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal ≥ 2) were significantly smaller than the lower level (tumor/normal<2) samples (p = 0.008). A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 overexpression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients. PMID:26469082

  12. Healing with basic fibroblast growth factor is associated with reduced indomethacin induced relapse in a human model of gastric ulceration.

    PubMed Central

    Hull, M A; Knifton, A; Filipowicz, B; Brough, J L; Vautier, G; Hawkey, C J

    1997-01-01

    BACKGROUND: Acid stable basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats and reduces subsequent non-steroidal anti-inflammatory drug (NSAID) induced relapse. AIMS: To test in a double blind, placebo controlled, three way crossover study whether bFGF promotes healing and reduces subsequent relapse in a human model of gastric ulceration. SUBJECTS: Twelve healthy volunteers. METHODS: Subjects took aspirin 900 mg twice daily (days 1-3) with bFGF 0.1 mg twice daily or cimetidine 400 mg twice daily or placebo (days 1-14) and then indomethacin 50 mg thrice daily (days 15-21). Endoscopy was performed on days 1, 4, 8, 15, and 22 during each treatment period. Eight antral biopsy specimens were taken on day 1 and the number of unhealed biopsy induced mini-ulcers and NSAID induced erosions counted during subsequent endoscopies. RESULTS: Basic FGF and cimetidine were protective against aspirin and indomethacin induced duodenal (but not gastric) injury compared with placebo. There was significant relapse of biopsy induced mini-ulcers after indomethacin only in the placebo group (0 (0-0) before v 1 (0-4.5) after; p > 0.05). TGP-580 was detected in serum of one volunteer. CONCLUSIONS: Healing with bFGF (and cimetidine) was associated with reduced NSAID induced ulcer relapse in this model of gastric ulceration. PMID:9071932

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

    PubMed Central

    GHONEUM, MAMDOOH; FELO, NOURAN

    2015-01-01

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

  14. Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases

    PubMed Central

    Gobert, Alain P.; Wilson, Keith T.

    2017-01-01

    The innate immune response is a critical hallmark of Helicobacter pylori infection. Epithelial and myeloid cells produce effectors, including the chemokine CXCL8, reactive oxygen species (ROS), and nitric oxide (NO), in response to bacterial components. Mechanistic and epidemiologic studies have emphasized that dysregulated and persistent release of these products leads to the development of chronic inflammation and to the molecular and cellular events related to carcinogenesis. Moreover, investigations in H. pylori-infected patients about polymorphisms of the genes encoding CXCL8 and inducible NO synthase, and epigenetic control of the ROS-producing enzyme spermine oxidase, have further proven that overproduction of these molecules impacts the severity of gastric diseases. Lastly, the critical effect of the crosstalk between the human host and the infecting bacterium in determining the severity of H. pylori-related diseases has been supported by phylogenetic analysis of the human population and their H. pylori isolates in geographic areas with varying clinical and pathologic outcomes of the infection. PMID:28124148

  15. Construction of METHFR shRNA/5-fluorouracil co-loaded folate-targeted chitosan polymeric nanoparticles and its anti-carcinoma effect on gastric cells growth

    NASA Astrophysics Data System (ADS)

    Xin, Lin; Fan, Ji-Chang; Le, Yi-Guan; Zeng, Fei; Cheng, Hua; Hu, Xiao-yun; Cao, Jia-Qing

    2016-05-01

    PEGylated and folate-targeted chitosan polymeric nanoparticles (FPNs) for the treatment of gastric carcinoma were prepared successfully. OQC-anchored folate conjugates were synthesized and used in assembling FPNs nano-system for enhancing intracellular uptake against folate receptor overexpressing cancer cells. The results indicated that folate-targeted chitosan polymeric nanoparticles (CPNs) can reverse drug-resistant SGC-7901 cells of 5-fluorouracil (5-FU) compared with non-targeted CPNs. Increased therapeutic efficiency of 5-FU/METHFR shRNA co-loaded PNs were also tested in SGC-7901 cells and compaed with 5-FU or METHFR shRNA in solution, which was associated with increased cell inhibition function for single drug group and synergistic effects of 5-FU and METHFR shRNA at 2.0 µg/mL FPNs concentration. In addition, the cell accumulation levels of 5-FU in SGC-7901 cells was time dependent for these nanoparticles. FPNs (effective diameter: 83.2 ± 1.1 nm; polydispersity index: 0.193) could significantly boost cellular accumulation of 5-FU and overcome the drug efflux mechanism of MDR than 5-FU-loaded NPNs and 5-FU in solution. In conclusion, ligand-targeted PNs can be used as a potentially effective drug delivery system.

  16. Human Papilloma Virus (HPV) Induced Head & Neck Squamous Cell Carcinoma: A Comprehensive Retrospect

    PubMed Central

    Nishat, Roquaiya; Ramachandra, Sujatha; Kumar, Harish; Bandyopadhyay, Alokenath

    2015-01-01

    Head and Neck Squamous Cell Carcinoma accounts for the sixth most common malignancy occurring worldwide with tobacco and alcohol being the two well established risk factors. In the recent years, substantial evidence has been obtained that Human Papilloma Virus (HPV) associated head and neck cancers are on the rise. This article provides an insight into the structure of HPV genome, molecular pathogenesis, detection methods and clinical implications of HPV positive Head and Neck Squamous Cell Carcinoma. PMID:26266234

  17. The effect of aloe emodin-encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells.

    PubMed

    Li, Kai-Ting; Duan, Qin-Qin; Chen, Qing; He, Juan-Wen; Tian, Si; Lin, Hai-Dan; Gao, Qing; Bai, Ding-Qun

    2016-02-01

    Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)-encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE-encapsulated nanoliposomes (nano-AE) were prepared by reverse evaporation method. Electron microscopy and nano-ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase-3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH-DA staining. Outcomes demonstrated that the nano-AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r-caspase-3 was transfected had higher protein expression of the caspase-3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano-AE-mediated PDT in an energy-dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm(2) ). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano-AE PDT group had quadrupled in SGC-7901 cells as early as 1 h after PDT, while it is similar to the group of nano-AE transfection and PDT. Nano-AE-mediated r-caspase-3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human

  18. A Vector-Based Short Hairpin RNA Targeting Aurora B Suppresses Human Prostatic Carcinoma Growth.

    PubMed

    Cao, Mei; Qi, Panpan; Chen, Chong; Song, Liju; Wang, Xuege; Li, Ningzhe; Wu, Daoyan; Hu, Guoku; Zhao, Jian

    2017-02-01

    Aurora kinase B, playing a vital, important role in mitosis, is frequently detected to be overexpressed in many cancer cell lines and various tumor tissues, including prostatic carcinoma. Given the essential function of Aurora kinase B in mitosis and its association with tumorigenesis, it might be a drug target for prostatic carcinoma treatment. In our study, short hairpin RNA targeting Aurora kinase B was cloned into a pGPU6 plasmid vector and then transfected into human prostatic carcinoma cells. The expression level of Aurora kinase B was verified by reverse transcription-polymerase chain reaction and Western blot. At the same time, cell apoptosis was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, fluorescent staining, and flow cytometric analysis. Furthermore, prostate carcinoma cells were injected into mice to establish a tumor xenograft model. Previous studies have shown the effect of pGPU6-shAURKB plasmid on tumor growth in a prostate carcinoma xenogenic implantation model. From the study, we knew that the Aurora kinase B was significantly downregulated in prostate carcinoma cells, and cell apoptosis was also detected higher in treated groups than that in control groups. Moreover, in the prostate carcinoma xenogenic implantation model, compared with the control groups, the tumor growth was inhibited about 78.7% in the pGPU6-shAURKB plasmid-treated group, and cell apoptosis in the experimental group was notably higher than that in control groups. The average duration of tumor-bearing mice was prolonged to about 35 days. The results of experiment indicated that specific knockdown of Aurora kinase B led to prostate carcinoma cells apoptosis and inhibited tumor growth. Our data clearly confirmed that specific knockdown of Aurora kinase B expression by vector-based short hairpin RNA/liposome may be a potential new approach to treat human prostatic carcinoma.

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

    SciTech Connect

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

    1985-08-01

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

  20. Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes

    PubMed Central

    Chowdhury, Sara; Reeds, Dominic N.; Crimmins, Dan L.; Patterson, Bruce W.; Laciny, Erin; Wang, Songyan; Tran, Hung D.; Griest, Terry A.; Rometo, David A.; Dunai, Judit; Wallendorf, Michael J.; Ladenson, Jack H.; Polonsky, Kenneth S.

    2013-01-01

    Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10–14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol·kg−1·min−1 was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions. PMID:24356886

  1. Galectin-1 induces invasion and the epithelial-mesenchymal transition in human gastric cancer cells via non-canonical activation of the hedgehog signaling pathway

    PubMed Central

    Chong, Yang; Tang, Dong; Gao, Jun; Jiang, Xuetong; Xu, Chuanqi; Xiong, Qingquan; Huang, Yuqin; Wang, Jie; Zhou, Huaicheng; Shi, Youquan; Wang, Daorong

    2016-01-01

    Galectin-1 (Gal-1) has been reported to be an independent prognostic indicator of poor survival in gastric cancer and overexpression of Gal-1 enhances the invasiveness of gastric cancer cells. However, the downstream mechanisms by which Gal-1 promotes invasion remains unclear. Moreover, the function of Gal-1 in the epithelial-mesenchymal transition (EMT) in gastric cancer has not yet been elucidated. In this study, we observed Gal-1 expression was upregulated and positively associated with metastasis and EMT markers in 162 human gastric cancer tissue specimens. In vitro studies showed Gal-1 induced invasion, the EMT phenotype and activated the non-canonical hedgehog (Hh) pathway in gastric cancer cell lines. Furthermore, our data revealed that Gal-1 modulated the non-canonical Hh pathway by increasing the transcription of glioma-associated oncogene-1 (Gli-1) via a Smoothened (SMO)-independent manner, and that upregulation of Gal-1 was strongly associated with gastric cancer metastasis. We conclude that Gal-1 promotes invasion and the EMT in gastric cancer cells via activation of the non-canonical Hh pathway, suggesting Gal-1 could represent a promising therapeutic target for the prevention and treatment of gastric cancer metastasis. PMID:27835885

  2. miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3.

    PubMed

    Li, Zhengrong; Cao, Yi; Jie, Zhigang; Liu, Yi; Li, Yingliang; Li, Junhe; Zhu, Guoming; Liu, Zhengren; Tu, Yi; Peng, Gen; Lee, Dong-woo; Park, Sung-soo

    2012-10-01

    The phosphatase of regenerating liver-3 (PRL-3) gene is associated with metastasis in gastric cancer, and is believed to play a causative role by promoting tumor cell motility, invasion, and metastasis, but little is known of the mechanisms involved. We previously reported that PRL-3 expression is significantly higher in the tissues of primary gastric carcinomas with peritoneal metastasis. In the present study, we found that two microRNAs (miRNAs), miR-495 and miR-551a, predicted to target PRL-3, are downregulated in gastric carcinoma samples. The validation of this interaction between those two miRNAs and PRL-3 was confirmed by western blotting and quantitative real-time PCR (qPCR) in GC cell lines transfected with miR-495 and miR-551a mimics. Furthermore, the migration and invasion of GC cells were significantly inhibited by transfection with miR-495 or -551a mimics, and the mRNA and protein levels of PRL-3 were reduced in cells overexpressing miR-495 or -551a. Collectively, our findings suggest that miR-495 and miR-551a both act as tumor suppressors by targeting the PRL-3 oncogene and inhibiting gastric cancer cell migration and invasion. The findings of this study contribute to current understanding of the functions of miRNA mimics in GC gene therapy.

  3. Notch1 directly induced CD133 expression in human diffuse type gastric cancers

    PubMed Central

    Konishi, Hidetomo; Asano, Naoki; Imatani, Akira; Kimura, Osamu; Kondo, Yutaka; Jin, Xiaoyi; Kanno, Takeshi; Hatta, Waku; Ara, Nobuyuki; Asanuma, Kiyotaka; Koike, Tomoyuki; Shimosegawa, Tooru

    2016-01-01

    CD133 is considered as a stem-like cell marker in some cancers including gastric cancers, and Notch1 signaling is known to play an important role in the maintenance and differentiation of stem-like cells. We aimed to investigate whether Notch1 signaling contributes to the carcinogenesis of gastric cancers and CD133 induction. CD133 expression was detected in 51.4% of diffuse type gastric cancers while it was not detected in intestinal type gastric cancers. Similarly, only poorly-differentiated gastric cancer cell lines expressed CD133 and activated-Notch1. Inhibiting Notch1 signaling resulted in decreased CD133 expression, side population cells, cell proliferation and anchorage independent cell growth. Chromatin immunoprecipitation suggested that this Notch1 dependent regulation of CD133 was caused by direct binding of activated-Notch1 to the RBP-Jκ binding site in the 5′ promoter region of CD133 gene. In addition, knocking down RBP-Jκ reduced CD133 induction in activated-Notch1 transfected cells. These findings suggested that Notch1 signaling plays an important role in the maintenance of the cancer stem-like phenotype in diffuse type gastric cancer through an RBP-Jκ dependent pathway and that inhibiting Notch1 signaling could be an effective therapy against CD133 positive diffuse type gastric cancers. PMID:27489358

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2013-01-01

    Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer. PMID:23450234

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

    SciTech Connect

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

    2015-09-01

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

  7. Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway.

    PubMed

    Li, Zhaocal; Huang, Yong; Dong, Feng; Li, Wei; Ding, Li; Yu, Gaoshui; Xu, Dan; Yang, Yuanyuan; Xu, Xingang; Tong, Dewen

    2012-12-01

    Swainsonine, a natural indolizidine alkaloid, has been reported to have antitumour effects, and can induce apoptosis in human gastric and lung cancer cells. In the present study, we evaluated the antitumour effects of swainsonine on several oesophageal squamous cell carcinoma cells and investigated relative molecular mechanisms. Swainsonine treatment inhibited the growth of Eca-109, TE-1 and TE-10 cells in a concentration-dependent manner as measured by MTT assay. Morphological observation, DNA laddering detection and flow cytometry analysis demonstrated that swainsonine treatment induced Eca-109 cell apoptosis in vitro. Further results showed that swainsonine treatment up-regulated Bax, downregulated Bcl-2 expression, triggered Bax translocation to mitochondria, destructed mitochondria integrity and activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c, which in turn activated caspase-9 and caspase-3, promoted the cleavage of PARP, resulting in Eca-109 cell apoptosis. Moreover, swainsonine treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activation in xenograft tumour cells, resulting in a significant decrease of tumour volume and tumour weight in the swainsoninetreated xenograft mice groups compared with that in the control group. Taken together, this study demonstrated that swainsonine inhibited Eca-109 cells growth through activation of mitochondria-mediated caspase-dependent pathway.

  8. Galectin-1 mediates TGF-β-induced transformation from normal fibroblasts into carcinoma-associated fibroblasts and promotes tumor progression in gastric cancer

    PubMed Central

    Zheng, Lingyan; Xu, Cong; Guan, Zhonghai; Su, Xingyun; Xu, Zhenzhen; Cao, Jiang; Teng, Lisong

    2016-01-01

    Rcinoma-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment. Cancer cells can induce the transformation from normal fibroblasts (NFs) into CAFs, reciprocally, CAFs promote tumor invasion and proliferation. TGF-β has been the mostly accepted factor to fuel NFs transformation into CAFs. Galectin-1 (Gal1) is highly upregulated in CAFs of multiple human cancers, and overexpression of Gal1 in CAFs promotes tumor progression. The effect of Gal1 on TGF-β-induced CAFs activation has not yet been established in gastric cancer (GC). In this study, we show that Gal1 expression in stroma is positively related to TGF-β in epithelial cells by retrospective analysis of GC patient samples. Meanwhile, conditioned media (CMs) from gastric cancer cells induce expression of both Gal1 and the CAFs marker alpha smooth muscle actin (α-SMA) in NFs via TGF-β secretion. Knockdown of Gal1 prevents TGF-β-induced the conversion of NFs to CAFs. CMs from fibroblasts overexpressing Gal1 inhibits cancer cells apoptosis, promotes migration and invasion in vitro. Thus, Gal1 is significantly involved in the development of tumor-promoting microenvironment by enhancing TGF-β signaling in a positive feedback loop. Targeting Gal1 in tumor stroma should be considered as a potential therapeutic target for GC. PMID:27186290

  9. Apoptotic effect of sodium acetate on a human gastric adenocarcinoma epithelial cell line.

    PubMed

    Xia, Y; Zhang, X L; Jin, F; Wang, Q X; Xiao, R; Hao, Z H; Gui, Q D; Sun, J

    2016-10-05

    The objective of this study was to investigate the effect of sodium acetate on the viability of the human gastric adenocarcinoma (AGS) epithelial cell line. AGS cells were exposed to a range of concentrations of sodium acetate for different periods of time, and the sodium acetate-induced cytotoxic effects, including cell viability, DNA fragmentation, apoptotic gene expression, and caspase activity, were assessed. The changes in these phenotypes were quantified by performing a lactate dehydrogenase cell viability assay, annexin V staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and several caspase activity assays. In vitro studies demonstrated that the cytotoxicity of sodium acetate on the AGS cell line were dose- and time-dependent manners. No differences were found between the negative control and sodium acetate-treated cells stained with annexin V and subjected to the TUNEL assay. However, caspase-3 activity was increased in AGS cells exposed to sodium acetate. Overall, it was concluded that sodium acetate exerted an apoptotic effect in AGS cells via a caspase-dependent apoptotic pathway.

  10. Solubility of indium-tin oxide in simulated lung and gastric fluids: Pathways for human intake.

    PubMed

    Andersen, Jens Christian Østergård; Cropp, Alastair; Paradise, Diane Caroline

    2017-02-01

    From being a metal with very limited natural distribution, indium (In) has recently become disseminated throughout the human society. Little is known of how In compounds behave in the natural environment, but recent medical studies link exposure to In compounds to elevated risk of respiratory disorders. Animal tests suggest that exposure may lead to more widespread damage in the body, notably the liver, kidneys and spleen. In this paper, we investigate the solubility of the most widely used In compound, indium-tin oxide (ITO) in simulated lung and gastric fluids in order to better understand the potential pathways for metals to be introduced into the bloodstream. Our results show significant potential for release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal fluid) and digestive tract, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree) is very low. Our study confirms that ITO is likely to remain as solid particles in the upper parts of the lungs, but that particles are likely to slowly dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung, this environment is likely to provide the major route for uptake of In and Sn from inhaled ITO nano- and microparticles. Although dissolution through digestion may also lead to some uptake, the much shorter residence time is likely to lead to much lower risk of uptake.

  11. Role of calcium in adaptive cytoprotection and cell injury induced by deoxycholate in human gastric cells.

    PubMed

    Kokoska, E R; Smith, G S; Wolff, A B; Deshpande, Y; Rieckenberg, C L; Banan, A; Miller, T A

    1998-08-01

    We have developed an in vitro model of adaptive cytoprotection induced by deoxycholate (DC) in human gastric cells and have shown that pretreatment with a low concentration of DC (mild irritant, 50 microM) significantly attenuates injury induced by a damaging concentration of DC (250 microM). This study was undertaken to assess the effect of the mild irritant on changes in intracellular Ca2+ and to determine if these perturbations account for its protective action. Protection conferred by the mild irritant was lost when any of its effects on intracellular Ca2+ were prevented: internal Ca2+ store release via phospholipase C and inositol 1,4, 5-trisphosphate sustained Ca2+ influx through store-operated Ca2+ channels or eventual Ca2+ efflux. We also investigated the relationship between Ca2+ accumulation and cellular injury induced by damaging concentrations of DC. In cells exposed to high concentrations of DC, sustained Ca2+ accumulation as a result of extracellular Ca2+ influx, but not transient changes in intracellular Ca2+ content, appeared to precede and induce cellular injury. We propose that the mild irritant disrupts normal Ca2+ homeostasis and that this perturbation elicits a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation.

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

    PubMed Central

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

    2017-01-01

    As microtubules have a vital function in the cell cycle, oncologists have developed microtubule inhibitors capable of preventing uncontrolled cell division, as in the case of cancer. The anthelmintic drug albendazole (ABZ) has been demonstrated to inhibit hepatocellular, ovarian and prostate cancer cells via microtubule targeting. However, its activity against human gastric cancer (GC) cells has remained to be determined. In the present study, ABZ was used to treat GC cells (MKN-45, SGC-7901 and MKN-28). A a CCK-8 cell proliferation assay was performed to assess the effects of ABZ on cell viability and cell cycle changes were assessed using flow cytometry. SGC-7901 cells were selected for further study, and flow cytometry was employed to determine the apoptotic rate, immunofluorescence analysis was employed to show changes of the microtubule structure as well as the subcellular localization and expression levels of cyclin B1, and western blot analysis was used to identify the dynamics of microtubule assembly. The expression levels of relevant proteins, including cyclin B1 and Cdc2, the two subunits of mitosis-promoting factor as well as apoptosis-asociated proteins were also assessed by western blot analysis. The results showed that ABZ exerted its anti-cancer activity in GC cell lines by disrupting microtubule formation and function to cause mitotic arrest, which is also associated with the accumulation of cyclin B1, and consequently induces apoptosis. PMID:28352336

  13. Different methylation of oestrogen receptor DNA in human breast carcinomas with and without oestrogen receptor.

    PubMed Central

    Piva, R.; Rimondi, A. P.; Hanau, S.; Maestri, I.; Alvisi, A.; Kumar, V. L.; del Senno, L.

    1990-01-01

    The methylation of the human oestrogen receptor (ER) gene was analysed by restriction enzymes in normal and neoplastic human breast tissues and cell lines. CCGG sequences in regions inside the gene, which are methylated both in normal breast and in tissues that are not the target of the oestrogen, are hypomethylated in 30% of tumours, both ER+ and ER- carcinomas. Moreover, 5' sequences of the gene, which are hypomethylated in normal breast and not in tissues not the target of oestrogen, are methylated to a lower degree in ER+ carcinomas, whereas they are methylated to a greater degree in ER- carcinomas. However, the same region is equally hypomethylated in both ER+ and ER- cancer cell lines. Our results indicate that in breast carcinomas ER DNA methylation is deranged, and in cancer cell lines is different from that observed in primary tumours. Furthermore, the abnormal methylation in the 5' end seems to be related to abnormal expression, namely diffuse hypomethylation in carcinomas with high ER content and hypermethylation in carcinomas without ER. These findings support our previous hypothesis that DNA methylation could be involved in the control of ER gene expression and demonstrate that abnormal ER gene methylation is a typical feature of breast cancers. Images Figure 1 Figure 2 Figure 3 PMID:2155643

  14. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells

    PubMed Central

    1991-01-01

    The ability of carcinomas to invade and to metastasize largely depends on the degree of epithelial differentiation within the tumors, i.e., poorly differentiated being more invasive than well-differentiated carcinomas. Here we confirmed this correlation by examining various human cell lines derived from bladder, breast, lung, and pancreas carcinomas. We found that carcinoma cell lines with an epithelioid phenotype were noninvasive and expressed the epithelium-specific cell- cell adhesion molecule E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80), as visualized by immunofluorescence microscopy and by Western and Northern blotting, whereas carcinoma cell lines with a fibroblastoid phenotype were invasive and had lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin mAbs. These findings indicate that the selective loss of E-cadherin expression can generate dedifferentiation and invasiveness of human carcinoma cells, and they suggest further that E-cadherin acts as an invasion suppressor. PMID:2007622

  15. Microarray profiling of circular RNAs in human papillary thyroid carcinoma

    PubMed Central

    Peng, Nianchun; Shi, Lixin; Zhang, Qiao; Hu, Ying; Wang, Nanpeng; Ye, Hui

    2017-01-01

    Background Non-coding circular RNAs (circRNAs) have displayed dysregulated expression in several human cancers. Here, we profiled the circRNA expression of papillary thyroid carcinoma (PTC) tumors to improve our understanding of PTC pathogenesis. Methods Microarray profiling was performed on 18 thyroid samples, consisting of six PTC tumors, six matching contralateral normal samples, and six benign thyroid lesions. After low-intensity filtering, hierarchical clustering revealed the circRNA expression patterns. Statistical analysis followed by qRT-PCR validation identified the differential circRNAs. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a network map of circRNA-miRNA interactions for the differential circRNAs. Bioinformatics platforms predicted cancer-related circRNA-miRNA associations and putative downstream target genes, respectively. Results A total of 88 circRNAs and 10 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to normal thyroid tissue, while 129 circRNAs and 226 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to benign thyroid lesions. A total of 12 upregulated and four downregulated circRNAs were overlapping between the foregoing comparisons. One downregulated circRNA (hsa_circRNA_100395) showed interactive potential with two cancer-related miRNAs (miR-141-3p and miR-200a-3p). From this analysis, we identified several promising cancer-related genes that may be targets of the dysregulated hsa_circRNA_100395/miR-141-3p/miR-200a-3p axis in PTC tumors. Conclusions circRNA dysregulation may play a role in PTC pathogenesis, and several key circRNAs show promise as candidate biomarkers for PTC. The hsa_circRNA_100395/miR-141-3p/ miR-200a-3p axis may be involved in the pathogenesis of PTC. PMID:28288173

  16. Comparison of Ultrasonic Scalpel versus Conventional Techniques in Open Gastrectomy for Gastric Carcinoma Patients: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Xiao-Long; Chen, Xin-Zu; Lu, Zheng-Hao; Wang, Li; Yang, Kun; Hu, Jian-Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang

    2014-01-01

    Objectives To compare surgical efficacy and postoperative recovery of ultrasonic scalpel (USS) with conventional techniques for the resection of gastric carcinoma. Methods A systematic search of major medical databases (PubMed, Embase, CCRT and CNKI) was conducted. Both randomized and non-randomized controlled trials (RCTs and nRCTs) were considered eligible. Operation time (OT), intraoperative blood loss (BL) and postoperative complications (POC) rates as well as postoperative hospitalization days, number of dissected lymph nodes, abdominal drainage volume and time for recovery of gastrointestinal functions were synthesized and compared. Results Nineteen studies were included (7 RCTs and 12 nRCTs), in which 1930 patients were enrolled totally (946 in the USS group and 984 in the conventional group). Monopolar electrocautery and ligation were used as the conventional methods. Comparative meta-analysis showed perioperative outcomes were significantly improved using USS compared with conventional surgical instrumentation. OT was reduced from a weighted mean of 185.3 min in the conventional group to 151.0 min in the USS group (MD = −33.30, 95% CI [−41.75, −24.86], p<0.001) and intraoperative BL was decreased from a weighted mean of 217.9 ml in the conventional group to 111.6 ml in the USS group (MD = −113.42, 95% CI [−142.05, −84.79], p<0.001). Results from RCTs subgroup were consistent with those from nRCTs subgroup. The weighted cumulative risk of POC accounted for 8.9% (0%–25%) and 12.9% (5.5%–45%) in the USS and conventional groups, respectively. Pooled estimated results from nRCTs (OR = 0.54, 95% CI [0.27, 1.06], p = 0.07) and RCTs (RR = 0.75, 95% CI [0.44, 1.26], p = 0.27) showed no significant difference between the USS and control groups. Analysis of secondary outcomes showed the improvements of the USS group over control group regarding the number of dissected lymph nodes, postoperative hospitalization days, abdominal

  17. Use of antibodies to carcinoembryonic antigen and human milk fat globule to distinguish carcinoma, mesothelioma, and reactive mesothelium.

    PubMed Central

    Marshall, R J; Herbert, A; Braye, S G; Jones, D B

    1984-01-01

    Antibodies raised against human milk fat globule (HMFG 1 and 2) and carcinoembryonic antigen were used in an immunoperoxidase technique to differentiate mesothelioma, carcinoma, and benign, reactive mesothelium. Sixteen mesotheliomas, 27 lung carcinomas, and 13 specimens of reactive mesothelium were examined. Staining for carcinoembryonic antigen was not seen in reactive mesothelium or mesothelioma but was present in 22 of 27 carcinomas. Mesothelioma and carcinoma usually stained with HMFG 1 and 2; reactive mesothelium did not. These three antibodies may help to distinguish carcinoma, mesothelioma, and reactive mesothelium. Images PMID:6094617

  18. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study

    PubMed Central

    2014-01-01

    Background In Europe, gastric cancer remains diagnosed at advanced stage (serosal and/or lymph node involvement). Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of T3 and/or N + patients remain under 30%. More than 50% of recurrences are peritoneal and/or locoregional. The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences, was extensively evaluated by several randomized trials conducted in Asia. Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival. As it was previously done for the evaluation of the extension of lymph node dissection, it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia. Methods/design GASTRICHIP is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing, treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy. Peroperatively, at the end of curative surgery, patients will be randomized after preoperatively written consent has been given for participation. Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up (5 years). Secondary endpoint will be 3- and 5-year recurrence-free survival, site of recurrence, morbidity, and quality of life. An ancillary study will compare the incidence of positive peritoneal cytology pre- and post-gastrectomy in two arms of the study

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

    PubMed Central

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

    2016-01-01

    Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC-6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S-1 and NC-6004 were compared with those of S-1 and CDDP in a human gastric cancer model. In vitro cytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC-6004 and 5-fluorouracil (5-FU) were compared with the effects of CDDP and 5-FU using the combination index method. The in vivo antitumor effects of S-1/NC-6004 and S-1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, the in vivo antitumor effects did not differ between the S-1/NC-6004 and S-1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S-1/CDDP-treated mice. Our data warrant a clinical evaluation of S-1/NC-6004 combination therapy. PMID:28101359

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

    PubMed

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

    2015-11-01

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

  1. H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO).

    PubMed

    Lee, Sang Eok; Kim, Dae Hoon; Kim, Young Chul; Han, Joung-Ho; Choi, Woong; Kim, Chan Hyung; Jeong, Hye Won; Park, Seon-Mee; Yun, Sei Jin; Choi, Song-Yi; Sung, Rohyun; Kim, Young Ho; Yoo, Ra Young; Sun, Park Hee; Kim, Heon; Song, Young-Jin; Xu, Wen-Xie; Yun, Hyo-Yung; Lee, Sang Jin

    2014-10-01

    This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K(+) channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.

  2. miR-186 affects the proliferation, invasion and migration of human gastric cancer by inhibition of Twist1

    PubMed Central

    Cao, Chunhong; Sun, Deguang; Zhang, Liang; Song, Lei

    2016-01-01

    Recent evidence shows that miRNAs are dysregulated in a variety of cancers including gastric cancer (GC), and emerging as key oncogenes or tumor suppressors. In this study, qRT-PCR was used to analyze the expression of miR-186 in GC tissues and adjacent non-cancerous tissues, and then more in-vitro experiments were used to investigate the role of miR-186 in GC cells. Here, we identified miR-186 was generally down-regulated in GC tissues; however, Twist1 was generally up-regulated in GC tissues. Moreover, miR-186 and Twist1 were associated with larger tumor size and advanced clinical stage of GC. In-vitro experiments demonstrated that ectopic overexpression of miR-186 inhibited GC cell proliferation, invasion and migration; however, inhibited expression of miR-186 enhanced cell proliferation, invasion and migration. Furthermore, the luciferase reporter assay demonstrated Twist1 as a direct target of miR-186. Finally, over-expression of Twist1 abrogated inhibitory impact of miR-186 on cell proliferation, invasion and migration. In conclusion, miR-186 affects the proliferation, invasion and migration of human gastric cancer by inhibition of Twist1, and could be a tumor suppressor in GC development. Thus, miR-186 may be served as a candidate prognostic biomarker and target for new therapies in human gastric cancer. PMID:27835599

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

    PubMed

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

    2016-12-01

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

  4. Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses

    PubMed Central

    Xia, Pu; Xu, Xiao-Yan

    2016-01-01

    CD44 is a well-recognized stem cell biomarker expressed in colon and gastric cancer. In order to identify whether CD44 mRNA could be used as a prognostic marker in colon and gastric cancer, bioinformatic analyses were used in this study. cBioPortal analysis and COSMIC analysis were used to explore the CD44 mutation. CD44 mRNA levels were evaluated by using SAGE Genie tools and Oncomine analysis. Kaplan-Meier Plotter was performed to identify the prognostic roles of CD44 mRNA in these two cancers. In this study, first, we found that low alteration frequency of CD44 mRNA in colon and gastric cancer. Second, the high CD44 mRNA level was found in colon and gastric cancer, and it correlated with a benign survival rate in gastric cancer. Third, CD4 and CD74 may be used as markers to predict the prognosis of colon and gastric cancer. However, the deep mechanism(s) of these results remains unclear, further studies have to be performed in the future. PMID:27323782

  5. Targeted therapy for Epstein-Barr virus-associated gastric carcinoma using low-dose gemcitabine-induced lytic activation.

    PubMed

    Lee, Hyun Gyu; Kim, Hyemi; Kim, Eun Jung; Park, Pil-Gu; Dong, Seung Myung; Choi, Tae Hyun; Kim, Hyunki; Chong, Curtis R; Liu, Jun O; Chen, Jianmeng; Ambinder, Richard F; Hayward, S Diane; Park, Jeon Han; Lee, Jae Myun

    2015-10-13

    The constant presence of the viral genome in Epstein-Barr virus (EBV)-associated gastric cancers (EBVaGCs) suggests the applicability of novel EBV-targeted therapies. The antiviral nucleoside drug, ganciclovir (GCV), is effective only in the context of the viral lytic cycle in the presence of EBV-encoded thymidine kinase (TK)/protein kinase (PK) expression. In this study, screening of the Johns Hopkins Drug Library identified gemcitabine as a candidate for combination treatment with GCV. Pharmacological induction of EBV-TK or PK in EBVaGC-originated tumor cells were used to study combination treatment with GCV in vitro and in vivo. Gemcitabine was found to be a lytic inducer via activation of the ataxia telangiectasia-mutated (ATM)/p53 genotoxic stress pathway in EBVaGC. Using an EBVaGC mouse model and a [125I] fialuridine (FIAU)-based lytic activation imaging system, we evaluated gemcitabine-induced lytic activation in an in vivo system and confirmed the efficacy of gemcitabine-GCV combination treatment. This viral enzyme-targeted anti-tumor strategy may provide a new therapeutic approach for EBVaGCs.

  6. Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans.

    PubMed

    Little, Tanya J; Gupta, Nili; Case, R Maynard; Thompson, David G; McLaughlin, John T

    2009-09-01

    In cell line and animal models, sweet and bitter tastants induce secretion of signaling peptides (e.g., glucagon-like peptide-1 and cholecystokinin) and slow gastric emptying (GE). Whether human GE and appetite responses are regulated by the sweetness or bitterness per se of ingested food is, however, unknown. We aimed to determine whether intragastric infusion of "equisweet" (Study A) or "equibitter" (Study B) solutions slow GE to the same extent, and whether a glucose solution made sweeter by the addition of saccharin will slow GE more potently than glucose alone. Healthy nonobese subjects were studied in a single-blind, randomized fashion. Subjects received 500-ml intragastric infusions of predetermined equisweet solutions of glucose (560 mosmol/kgH(2)O), fructose (290 mosmol/kgH(2)O), aspartame (200 mg), and saccharin (50 mg); twice as sweet glucose + saccharin, water (volumetric control) (Study A); or equibitter solutions of quinine (0.198 mM), naringin (1 mM), or water (Study B). GE was evaluated using a [(13)C]acetate breath test, and hunger and fullness were scored using visual analog scales. In Study A, equisweet solutions did not empty similarly. Fructose, aspartame, and saccharin did not slow GE compared with water, but glucose did (P < 0.05). There was no additional effect of the sweeter glucose + saccharin solution (P > 0.05, compared with glucose alone). In Study B, neither bitter tastant slowed GE compared with water. None of the solutions modulated perceptions of hunger or fullness. We conclude that, in humans, the presence of sweetness and bitterness taste per se in ingested solutions does not appear to signal to influence GE or appetite perceptions.

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

    PubMed

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

    2017-02-08

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

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

    PubMed

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

    2015-09-18

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

  9. Reduced expression of the long non-coding RNA AI364715 in gastric cancer and its clinical significance.

    PubMed

    Zhu, Shengqian; Mao, Jinqin; Shao, Yongfu; Chen, Fang; Zhu, Xiaoqin; Xu, Dingli; Zhang, Xinjun; Guo, Junming

    2015-09-01

    Long non-coding RNA (lncRNA), which is greater than 200 nucleotides, is a class of RNA molecules without protein coding function. In recent years, studies have shown that lncRNAs are associated with cancers. They are affecting the occurrence and development of cancers. However, the diagnostic significances of lncRNAs in gastric cancer are largely unknown. In this study, we focused on AI364715, one typical lncRNA. A total of 186 samples were collected from two cancer centers. To find the potential association between its level and gastric cancer, we first collected 75 paired gastric cancer tissues and normal tissues, which are 5 cm away from the edge of carcinoma. Besides, 18 human healthy gastric mucosa and 18 gastric precancerous lesions (dysplasia) were also collected. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was first used to detect the expression level of AI364715 at multiple stages of gastric tumorigenesis. Then, the relationships between AI364715 level and the clinicopathological factors of patients with gastric cancer were analyzed. The results showed that the expression level of AI364715 in gastric cancer tissues was downregulated. Meanwhile, its expression level was closely associated with tumor size and differentiation. More importantly, AI364715 expression level was significantly changed in dysplasia, the typical precancerous lesions. Taken together, AI364715 may be a potential biomarker for the diagnosis of gastric cancer.

  10. E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance

    PubMed Central

    Koriyama, Chihaya; Akiba, Suminori; Itoh, Tetsuhiko; Sueyoshi, Kazunobu; Minakami, Yoshie; Corvalan, Alejandro; Yonezawa, Suguru; Eizuru, Yoshito

    2007-01-01

    AIM: To examine the role of E-cadherin and beta-catenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas (EBV-GCs). METHODS: We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients' prognosis and the expressions of these proteins. RESULTS: Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta-catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 95% confidence interval (CI), 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequently in EBV-GCs than non-EBV-GCs (odds ratio = 2.23; 95% CI, 0.97-5.09), and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs (P = 0.024). Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis (P < 0.001). Among EBV-GCs, the depth of invasion (P = 0.005), lymph node metastasis (P = 0.004) and an intestinal type by Lauren classification (hazard ratio = 9.47; 95% CI, 2.67-33.6) were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC (hazard ratio = 0.32; 95% CI, 0.11-0.93). CONCLUSION: We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV-GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions. PMID:17663505

  11. Gastric metastasis of bilateral breast cancer

    PubMed Central

    Belaïd, Asma; Mghirbi, Fahmi; Béhi, Khalil; Doghri, Raoudha; Benna, Farouk

    2017-01-01

    Breast cancer is the most common malignancy in women. The most frequent metastatic sites are lung, bone, liver and brain. On the other hand, gastric metastases are rare. Synchronous bilateral breast cancer (SBBC) occurs rarely. Lobular carcinoma is the histological type most often associated with bilateral breast carcinomas and gastric metastases. We made a retrospective study including four patients followed in the Salah Azaiez Institute, for a bilateral breast cancer with gastric metastases. We analyzed the epidemiological, anatomoclinical and therapeutic particularities of this rare entity. Symptoms were unspecific. The diagnosis of gastric metastasis of the SBBC was confirmed by a histopathological examination of an endoscopic biopsy. The median age was 46.2 years (range, 36–51 years) and the median time until the gastric involvement was 19 months (range, 0–41 months). None of patients had a surgical treatment for the gastric location. All Patients received at least one line of chemotherapy and radiotherapy. Median survival following the detection of gastric involvement was 22 months (range, 1–56 months). Gastric metastases from breast cancer are rare and frequently associated with other distant metastasis. Symptoms are unspecific and endoscopy may not be contributive. Therefore, gastric involvement is underestimated. Lobular infiltrating carcinoma (LIC) is the most histological type incriminated in its occurrence. The supply of immunohistochemistry is crucial to distinguish between primary or metastatic gastric cancer. PMID:28280631

  12. The utility of MRI for pre-operative T and N staging of gastric carcinoma: a systematic review and meta-analysis

    PubMed Central

    Huang, Z; Guo, L; Hu, C H; Fang, X; Meng, Q; Ping, X X; Lu, Z W

    2015-01-01

    Objective: To perform a meta-analysis and literature review regarding the diagnostic accuracy of MRI for pre-operative tumour depth invasion (T) and regional lymph node invasion (N) staging of gastric carcinoma (GC). Methods: Articles were identified through systematic search of Medline, PubMed, Cochrane Library, Web of Science, Springerlink and several Chinese databases. The study quality was assessed by the quality assessment for studies of diagnostic accuracy. 2 reviewers independently extracted and assessed the data from 11 eligible studies. A meta-analysis was then carried out. Subgroup and sensitivity analyses were also performed. Results: 11 studies (439 patients) were finally included in the current review. Among these studies, the significant evidence of heterogeneity was only discovered for specificity in T4 stage (I2 = 59.8%). Pooled sensitivity and specificity of MRI to diagnose T stage tumour (T3–4 vs T1–2) were 0.93 [95% confidence interval (CI), 0.89–0.96] and 0.91 (95% CI, 0.87–0.95), respectively. Pooled estimates of sensitivity and specificity of MRI to diagnose N stage tumour (N0 vs N+) were 0.86 (95% CI, 0.80–0.92) and 0.67 (95% CI, 0.54–0.79), respectively. Subgroup analyses showed that diffusion-weighted imaging was more helpful for T staging. Conclusion: The present systematic review suggests that MRI has a good diagnostic accuracy for pre-operative T staging of GC and should be widely used in clinical work. However, the ability for N staging is relatively poor on MRI. Advances in knowledge: In the pre-operative staging of GC, MRI was a useful tool and may enhance accuracy for the T staging of advanced GC. PMID:25790060

  13. Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

    PubMed Central

    Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2015-01-01

    Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients. PMID:26497995

  14. Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population.

    PubMed

    Li, Wen-Qing; Hu, Nan; Hyland, Paula L; Gao, Ying; Wang, Zhao-Ming; Yu, Kai; Su, Hua; Wang, Chao-Yu; Wang, Le-Min; Chanock, Stephen J; Burdett, Laurie; Ding, Ti; Qiao, You-Lin; Fan, Jin-Hu; Wang, Yuan; Xu, Yi; Shi, Jian-Xin; Gu, Fangyi; Wheeler, William; Xiong, Xiao-Qin; Giffen, Carol; Tucker, Margaret A; Dawsey, Sanford M; Freedman, Neal D; Abnet, Christian C; Goldstein, Alisa M; Taylor, Philip R

    2013-07-01

    The DNA repair pathways help to maintain genomic integrity and therefore genetic variation in the pathways could affect the propensity to develop cancer. Selected germline single nucleotide polymorphisms (SNPs) in the pathways have been associated with esophageal cancer and gastric cancer (GC) but few studies have comprehensively examined the pathway genes. We aimed to investigate associations between DNA repair pathway genes and risk of esophageal squamous cell carcinoma (ESCC) and GC, using data from a genome-wide association study in a Han Chinese population where ESCC and GC are the predominant cancers. In sum, 1942 ESCC cases, 1758 GC cases and 2111 controls from the Shanxi Upper Gastrointestinal Cancer Genetics Project (discovery set) and the Linxian Nutrition Intervention Trials (replication set) were genotyped for 1675 SNPs in 170 DNA repair-related genes. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-level associations were determined using the resampling-based adaptive rank-truncated product approach. The DNA repair pathways overall were significantly associated with risk of ESCC (P = 6.37 × 10(-4)), but not with GC (P = 0.20). The most significant gene in ESCC was CHEK2 (P = 2.00 × 10(-6)) and in GC was CLK2 (P = 3.02 × 10(-4)). We observed several other genes significantly associated with either ESCC (SMUG1, TDG, TP53, GTF2H3, FEN1, POLQ, HEL308, RAD54B, MPG, FANCE and BRCA1) or GC risk (MRE11A, RAD54L and POLE) (P < 0.05). We provide evidence for an association between specific genes in the DNA repair pathways and the risk of ESCC and GC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.

  15. The effectiveness of intravenous 5-fluorouracil-containing chemotherapy after curative resection for gastric carcinoma: A systematic review of published randomized controlled trials.

    PubMed

    Hu, Jian-Kun; Li, Chun-Mei; Chen, Xin-Zu; Chen, Zhi-Xin; Zhou, Zong-Guang; Zhang, Bo; Chen, Jia-Ping

    2007-08-01

    This is a review of randomized controlled trials of intravenous 5-flurorouracil (5-FU)-containing chemotherapy after curative resection versus surgery alone in patients with gastric carcinoma to determine the impact on survival rate, safety and economics. Data sources were the Cochrane Library (2006, Issue 2), Pub-Medline and Chinese Biomedical Database. We included 22 randomized controlled trials comparing 4501 patients. Intravenous 5-FU-containing chemotherapy after curative resection had a slightly significant improvement in 3-, 5- and 7-year overall survival rate (OR 1.49, 1.41 and 1.32). No benefit of postoperative disease-free survival rate was induced by 5-FU-containing chemotherapy. Sensitivity analysis was restricted to trials with the highest methodological quality, and the result was similar when the studies with Jadad score less than 3' were excluded. Subgroup analyses found borderline improved overall survival rate in both Western and Eastern countries but the statistical significance was stronger in the Eastern subset. The combinations of 5-FU plus mitomycin C, 5-FU plus cytosine arabinoside and 5-FU plus adriamycin or epidoxorubicin induced potentially more improvement of 3- and 5-year overall survival rates. Severe toxicities were reported in 1629 patients from 15 included trials, and hematological and gastrointestinal toxicities were the most remarkable side effects, around 5%-15% respectively. The chemotherapy-related overall mortality was 1.1%. No trials mentioned cost-effectiveness analysis. Although the results provide some evidence of a beneficial effect of adjuvant chemotherapy with 5-FU-containing regimens, they are inconclusive due to the limitations of methodological quality of including randomized controlled trials. Large scale randomized controlled trials with a positive result are still mandatory before postoperative chemotherapy are recommended.

  16. A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer

    ClinicalTrials.gov

    2015-06-10

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  17. Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma.

    PubMed

    Chen, Jie; Fu, Ziyi; Ji, Chenbo; Gu, Pingqing; Xu, Pengfei; Yu, Ningzhu; Kan, Yansheng; Wu, Xiaowei; Shen, Rong; Shen, Yan

    2015-05-01

    The human uterine cervix carcinoma is one of the most well-known malignancy reproductive system cancers, which threatens women health globally. However, the mechanisms of the oncogenesis and development process of cervix carcinoma are not yet fully understood. Long non-coding RNAs (lncRNAs) have been proved to play key roles in various biological processes, especially development of cancer. The function and mechanism of lncRNAs on cervix carcinoma is still rarely reported. We selected 3 cervix cancer and normal cervix tissues separately, then performed lncRNA microarray to detect the differentially expressed lncRNAs. Subsequently, we explored the potential function of these dysregulated lncRNAs through online bioinformatics databases. Finally, quantity real-time PCR was carried out to confirm the expression levels of these dysregulated lncRNAs in cervix cancer and normal tissues. We uncovered the profiles of differentially expressed lncRNAs between normal and cervix carcinoma tissues by using the microarray techniques, and found 1622 upregulated and 3026 downregulated lncRNAs (fold-change>2.0) in cervix carcinoma compared to the normal cervical tissue. Furthermore, we found HOXA11-AS might participate in cervix carcinogenesis by regulating HOXA11, which is involved in regulating biological processes of cervix cancer. This study afforded expression profiles of lncRNAs between cervix carcinoma tissue and normal cervical tissue, which could provide database for further research about the function and mechanism of key-lncRNAs in cervix carcinoma, and might be helpful to explore potential diagnosis factors and therapeutic targets for cervix carcinoma.

  18. Familial Gastric Cancers

    PubMed Central

    Setia, Namrata; Clark, Jeffrey W.; Duda, Dan G.; Hong, Theodore S.; Kwak, Eunice L.; Mullen, John T.

    2015-01-01

    Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%–3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Implications for Practice: Although the majority of gastric adenocarcinomas are sporadic with many of those related to chronic Helicobacter pylori infection, approximately 10% of the cases show familial aggregation, and a specific hereditary cause is determined in 1%–3% cases. This review describes the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Ultimately, a better understanding of the biology of these conditions should allow early identification and intervention as part of a multidisciplinary approach involving oncologists, surgeons, genetic counselors, and pathologists. PMID:26424758

  19. Gastric cancer arising from the remnant stomach after distal gastrectomy: A review

    PubMed Central

    Takeno, Shinsuke; Hashimoto, Tatsuya; Maki, Kenji; Shibata, Ryosuke; Shiwaku, Hironari; Yamana, Ippei; Yamashita, Risako; Yamashita, Yuichi

    2014-01-01

    Gastric stump carcinoma was initially reported by Balfore in 1922, and many reports of this disease have since been published. We herein review previous reports of gastric stump carcinoma with respect to epidemiology, carcinogenesis, Helicobacter pylori (H. pylori) infection, Epstein-Barr virus infection, clinicopathologic characteristics and endoscopic treatment. In particular, it is noteworthy that no prognostic differences are observed between gastric stump carcinoma and primary upper third gastric cancer. In addition, endoscopic submucosal dissection has recently been used to treat gastric stump carcinoma in the early stage. In contrast, many issues concerning gastric stump carcinoma remain to be clarified, including molecular biological characteristics and the carcinogenesis of H. pylori infection. We herein review the previous pertinent literature and summarize the characteristics of gastric stump carcinoma reported to date. PMID:25320511

  20. Gastric cancer arising from the remnant stomach after distal gastrectomy: a review.

    PubMed

    Takeno, Shinsuke; Hashimoto, Tatsuya; Maki, Kenji; Shibata, Ryosuke; Shiwaku, Hironari; Yamana, Ippei; Yamashita, Risako; Yamashita, Yuichi

    2014-10-14

    Gastric stump carcinoma was initially reported by Balfore in 1922, and many reports of this disease have since been published. We herein review previous reports of gastric stump carcinoma with respect to epidemiology, carcinogenesis, Helicobacter pylori (H. pylori) infection, Epstein-Barr virus infection, clinicopathologic characteristics and endoscopic treatment. In particular, it is noteworthy that no prognostic differences are observed between gastric stump carcinoma and primary upper third gastric cancer. In addition, endoscopic submucosal dissection has recently been used to treat gastric stump carcinoma in the early stage. In contrast, many issues concerning gastric stump carcinoma remain to be clarified, including molecular biological characteristics and the carcinogenesis of H. pylori infection. We herein review the previous pertinent literature and summarize the characteristics of gastric stump carcinoma reported to date.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2012-03-01

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

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

    SciTech Connect

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

    2008-03-07

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

  4. Apoptosis of AGS human gastric adenocarcinoma cells by methanolic extract of Dictamnus

    PubMed Central

    Park, Hyun Soo; Hong, Noo Ri; Ahn, Tae Seok; Kim, Hyungwoo; Jung, Myeong Ho; Kim, Byung Joo

    2015-01-01

    Background: The root bark of Dictamnus dasycarpus Turcz has traditionally been used in East Asia to treat skin diseases such as eczema, atopic dermatitis, and psoriasis. However, it has also been reported to exhibit an anti-proliferative effect on cancer cells. Objective: To investigate the anti-cancer effects of a methanol extract of Dictamnus dasycarpus root bark (MEDD) on AGS cells (a human gastric adenocarcinoma cell-line). Materials and Methods: An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium assay, a caspase activity assay, cell cycle analysis, mitochondrial membrane potential (MMP) measurements, and western blotting were used to investigate the anti-cancer effects of MEDD on AGS cells. Results: Treatment with MEDD significantly and concentration-dependently inhibited AGS cell growth. MEDD treatment in AGS cells led to increased accumulation of apoptotic sub-G1 phase cells in a concentration-dependent manner. Also, MEDD reduced the expressions of pro-caspase-3, -8 and -9, and increased the active form of caspase-3. Furthermore, subsequent Western blotting revealed elevated levels of poly (ADP-ribose) polymerase protein. MEDD treatment reduced levels of MMP and anti-apoptotic Bcl-2 and Bcl-xL proteins. Pretreatment with SB203580 (a specific inhibitor of p38 mitogen-activated protein kinases), SP600125 (a potent inhibitor of C-Jun N-terminal kinases), or PD98059 (a potent inhibitor of extracellular signal-regulated kinases) did not modify the effects of MEDD treatment. However, pretreatment with LY294002 (a specific inhibitor of Akt) significantly enhanced MEDD-induced cell death. Conclusion: These results suggest that MEDD-mediated cell death is associated with the intrinsic apoptotic pathway and that inhibition of Akt signaling contributes to apoptosis induction by MEDD. PMID:26664023

  5. Helicobacter pylori infection does not reduce the viscosity of human gastric mucus gel.

    PubMed Central

    Markesich, D C; Anand, B S; Lew, G M; Graham, D Y

    1995-01-01

    The mechanism by which Helicobacter pylori undermines host defence mechanisms is unclear. Several in vitro studies using soluble mucins have suggested that H pylori may compromise mucus function. Gastric mucus gel was obtained from 13 H pylori infected patients; six untreated subjects and seven after eradication of the infection. Gastric mucus is a non-Newtonian substance in that its viscosity changes with changing rates of shear, requiring mucus viscosity to be measured in a rotational cone-plate microviscometer. Viscosity was measured at shear rates varying from 1.15 s-1 to 46 s-1. The gastric mucus viscosity was significantly higher in patients infected with H pylori compared with mucus gel obtained after eradication of the infection. The results of our study suggest that the previous studies using in vitro methods involving soluble mucins or its components may have lead to erroneous conclusions about the in vivo interactions of H pylori and gastric mucus gel. The present findings argue against the hypothesis that degradation of gastric mucus by H pylori is important in the pathogenesis of peptic ulcer. PMID:7698685

  6. Effect of Exercise Intensity on Subsequent Gastric Emptying Rate in Humans.

    PubMed

    Evans, Gethin H; Watson, Phillip; Shirreffs, Susan M; Maughan, Ronald J

    2016-04-01

    Previous investigations have suggested that exercise at intensities greater than 70% maximal oxygen uptake (VO2max) reduces gastric emptying rate during exercise, but little is known about the effect of exercise intensity on gastric emptying in the postexercise period. To examine this, 8 healthy participants completed 3 experimental trials that included 30 min of rest (R), low-intensity (L; 33% of peak power output) exercise, or high-intensity (H; 10 × 1 min at peak power output followed by 2 min rest) exercise. Thirty minutes after completion of exercise, participants ingested 595 ml of a 5% glucose solution, and gastric emptying rate was assessed via the double-sampling gastric aspiration method for 60 min. No differences (p > .05) were observed in emptying characteristics for total stomach volume or test meal volume between the trials, and the quantity of glucose delivered to the intestine did not differ between trials (p > .05). Half-emptying times did not differ (p = .902) between trials and amounted to 22 ± 9, 22 ± 9, and 22 ± 7 min (M ± SD) during the R, L, and H trials, respectively. These results suggest that exercise has little effect on postexercise gastric emptying rate of a glucose solution.

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

    PubMed

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

    2015-01-01

    The standard of care for chronic gastro-esophageal reflux disease (GERD), which affects up to 40% of the population, is the use of drugs such as proton pump inhibitors (PPIs) that block the production of stomach acid. Despite widespread use, the effects of PPIs on gastric fluid remain poorly characterized. In this study, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Various enzymatic and immunoassays as well as mass spectrometry were utilized to analyze the concentrations of bile, gastricsin, trypsin, and pepsin in the gastric fluid. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. In general, the concentrations of all analytes evaluated varied over several orders of magnitude, covering a minimum of a 2000-fold range (gastricsin) and a maximum of a 1 × 10(6) -fold range (trypsin). Furthermore, the concentrations of various analytes were poorly correlated with one another in the samples. For example, trypsin and bile concentrations showed a significant (P < 0.0001) but not strong correlation (r = 0.54). Finally, direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid. These results further delineate the profound effects that PPI usage has on the physiology of the stomach.

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

    PubMed

    Ortakci, F; Sert, S

    2012-12-01

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

  9. The expression patterns of tight junction protein claudin-1, -3, and -4 in human gastric neoplasms and adjacent non-neoplastic tissues

    PubMed Central

    Wang, Haiming; Yang, Xingwang

    2015-01-01

    Recently, there is growing evidence that tight junction proteins are often abnormally regulated in human tumors. The function of tight junction proteins in the maintenance of normal epithelial physiology has been well discussed, but their role in the tumorigenesis of gastric cancer is less well defined. To explore the expression distinction of the tight junction proteins claudin-1, -3, and -4 expression in the gastric cancer, the expression of claudin-1, -3, and -4 in 92 gastric cancer tissues and the non-neoplastic tissues adjacent to the tumors were examined by immunohistochemistry. Compared with adjacent non-neoplastic tissues, the expression of claudin-1 was down regulated. However, the expression of claudin-3 and claudin-4 were up-regulated in gastric cancer tissue. In addition, the expression of claudin-3 is correlated with claudin-4 expression in gastric cancer. Our present study reveals that claudin-1, -3, and -4 protein expression altered between human gastric cancers and adjacent non-neoplastic tissues. PMID:25755790

  10. Type II oestrogen binding sites in human colorectal carcinoma.

    PubMed Central

    Piantelli, M; Ricci, R; Larocca, L M; Rinelli, A; Capelli, A; Rizzo, S; Scambia, G; Ranelletti, F O

    1990-01-01

    Seven cases of colorectal adenocarcinomas were investigated for the presence of oestrogen receptors and progesterone receptors. The tumours specifically bound oestradiol. This binding almost exclusively resulted from the presence of high numbers of type II oestrogen binding sites. Oestrogen receptors were absent or present at very low concentrations. Immunohistochemical investigation of nuclear oestrogen receptors gave negative results. This indicates that antioestrogen receptor antibodies recognise oestrogen receptors but not type II oestrogen binding sites. The presence of specific type II oestrogen binding sites and progesterone binding offers further evidence for a potential role for these steroids and their receptors in colorectal carcinoma. PMID:2266171

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Activation of Ca(2+)-dependent K+ current by acetylcholine and histamine in a human gastric epithelial cell line

    PubMed Central

    1993-01-01

    The effects of acetylcholine (ACh) and histamine (His) on the membrane potential and current were examined in JR-1 cells, a mucin-producing epithelial cell line derived from human gastric signet ring cell carcinoma. The tight-seal, whole cell clamp technique was used. The resting membrane potential, the input resistance, and the capacitance of the cells were approximately -12 mV, 1.4 G ohms, and 50 pF, respectively. Under the voltage-clamp condition, no voltage-dependent currents were evoked. ACh or His added to the bathing solution hyperpolarized the membrane by activating a time- and voltage- independent K+ current. The ACh-induced hyperpolarization and K+ current persisted, while the His response desensitized quickly (< 1 min). These effects of ACh and His were mediated predominantly by m3- muscarinic and H1-His receptors, respectively. The K+ current induced by ACh and His was inhibited by charybdotoxin, suggesting that it is a Ca(2+)-activated K+ channel current (IK.Ca). The measurement of intracellular Ca2+ ([Ca2+]i) using Indo-1 revealed that both agents increased [Ca2+]i with similar time courses as they increased IK.Ca. When EGTA in the pipette solution was increased from 0.15 to 10 mM, the induction of IK.Ca by ACh and His was abolished. Thus, both ACh and His activate IK.Ca by increasing [Ca2+]i in JR-1 cells. In the Ca(2+)-free bathing solution (0.15 mM EGTA in the pipette), ACh evoked IK.Ca transiently. Addition of Ca2+ (1.8 mM) to the bath immediately restored the sustained IK.Ca. These results suggest that the ACh response is due to at least two different mechanisms; i.e., the Ca2+ release-related initial transient activation and the Ca2+ influx-related sustained activation of IK.Ca. Probably because of desensitization, the Ca2+ influx-related component of the His response could not be identified. Intracellularly applied inositol 1,4,5-trisphosphate (IP3), with and without inositol 1,3,4,5-tetrakisphosphate (IP4), mimicked the ACh response. IP4 alone

  14. Treatment of gastric cancer

    PubMed Central

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

    2014-01-01

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

  15. Pre-treatment of human umbilical cord-derived mesenchymal stem cells with interleukin-6 abolishes their growth-promoting effect on gastric cancer cells.

    PubMed

    Wang, Mei; Cai, Jie; Huang, Feng; Zhu, Mengchu; Zhang, Qiang; Yang, Tingting; Zhang, Xu; Qian, Hui; Xu, Wenrong

    2015-02-01

    The inflammatory microenvironment contributes to cancer development and progression. Mesenchymal stem cells (MSCs), as important stromal cells, may be 'educated' by the inflammatory microenvironment to support the development of gastric cancer. Cytokines are a key component of cancer-related inflammation. Interleukin (IL)-6, as an inflammatory cytokine, has multiple roles in cancer. However, whether MSCs can be 'educated' by IL-6 to support gastric cancer remains unknown. In the present study, we focused on the phenotype and function of human umbilical cord-derived MSCs hUC‑MSCs pre-treated with IL-6 in gastric cancer. We found that the protein levels of α-smooth muscle actin (α-SMA) were upregulated, and phosphorylated nuclear factor (NF)-κB protein levels were downregulated in the hUC‑MSCs pre-treated with IL-6, as shown by western blot analysis. The levels of tumor‑promoting cytokines, including chemokine (C-C motif) ligand 5 (CCL5), platelet-derived growth factor‑BB (PDGF‑BB), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α(TNFα), were markedly reduced in the hUC‑MSCs following treatment with IL-6, as shown by RT-qPCR. In in vitro experiments, we co-cultured MSCs with N-methyl‑N'‑nitro‑N‑nitrosoguanidine (MNNG)‑transformed GES-1 gastric epithelial cells or SGC-7901 gastric cancer cells. Transwell and colony-forming cell assays revealed that the hUC-MSCs significantly promoted gastric cellular migration and proliferation. However, following treatment with IL-6, the hUC-MSCs had no growth-promoting effect on the gastric epithelial cells and gastric cancer cells. In in vivo experiments, we co-transplanted MSCs and SGC-7901 cells into nude mice in order to establish a nude mouse model of gastric cancer. The hUC-MSCs significantly promoted the growth gastric tumors through the promotion of cell proliferation and the inhibition of cell apoptosis. On the contrary, pre-treatment with IL-6 provided the hUC‑MSCs with

  16. Survivin promotes the invasion of human colon carcinoma cells by regulating the expression of MMP‑7.

    PubMed

    Gao, Fei; Zhang, Yuqin; Yang, Feng; Wang, Peng; Wang, Wenjun; Su, Yan; Luo, Weiren

    2014-03-01

    Increased expression levels of survivin are crucial for invasion activity in several types of human cancer, including colon carcinoma. However, the molecular mechanisms whereby survivin regulates cancer invasion have not been completely elucidated. To the best of our knowledge, this study is the first to investigate the role of matrix metalloprotease‑7 (MMP‑7) in cell invasion that is induced by survivin by using in vitro assays, including western blot, immunofluorescence and qPCR analyses. The results demonstrated that the ectopic expression of survivin significantly promoted the invasive activity of colon carcinoma cells (SW620 and HCT‑116) and resulted in increased levels of MMP‑7 activation. By contrast, the small interfering RNA (siRNA)‑based knockdown of survivin markedly reduced cell migration and led to a dose‑dependent decrease in MMP‑7 expression levels. Compared with the controls, knockdown of MMP‑7 by siRNA in colon carcinoma cells led to reduced invasion ability, whereas no obvious changes were observed when MMP‑7 expression was silenced in survivin‑overexpressing colon carcinoma cells. These findings demonstrate that MMP‑7 is crucial for survivin‑mediated invasiveness, suggesting that the survivin‑mediated MMP‑7 signaling pathway is a potential therapeutic target for the treatment of colon carcinoma.

  17. Human papillomavirus-16 presence and physical status in lung carcinomas from Asia

    PubMed Central

    2010-01-01

    Background Although human papillomavirus (HPV) genome has been detected in lung cancer, its prevalence is highly variable around the world. Higher frequencies have been reported in far-east Asian countries, when compared with European countries. The present study analysed the HPV-16 presence in 60 lung carcinomas from the Asian countries China, Pakistan and Papua New Guinea. Results HPV-16 was present in 8/59 (13%) samples. According to histological type, HPV-16 was detected in 8/18 (44%) squamous cell carcinomas (SQCs), which were mainly from Pakistan; 0/38 (0%) adenocarcinomas (ACs), which were mainly from China; and in 0/4 (0%) small cell carcinomas (SCLCs). The observed histological difference was statistically significant (p < 0.001). HPV-16 viral load was also determined using real-time polymerase chain reaction (qRT-PCR); it ranged between 411 to 2345 copies/100 ng of genomic DNA. HPV-16 genome was found integrated into the host genome in every HPV-16 positive carcinoma. Conclusion These results support the notion that HPV-16 infection is highly associated with SQCs in Pakistan. Our results show a frequent HPV-16 integration in SQCs, although the low viral load casts doubt respect a direct etiological role of HPV in lung carcinomas from Asia. Additional HPV-16 characterization is necessary to establish a direct or indirect etiological role of HPV in this malignancy. PMID:21080966

  18. Expression of alpha-crystallins in human sebaceous carcinoma of the eyelid

    PubMed Central

    RIGAS, PANAYOTA K.; KASE, SATORU; RAO, NARSING A.

    2010-01-01

    Purpose α-Crystallins are molecular chaperones that protect various cells from apoptosis. This study used immunohistochemistry to examine the expression of αA-crystallin and αB-crystallin in human sebaceous carcinoma tissues. Methods Nine patients with sebaceous carcinoma of the eyelid underwent excision of the eyelid or orbital exenteration. Formalin-fixed, paraffin-embedded tissue sections were submitted for hematoxylin-eosin staining and immunohistochemistry with anti-αA- and αB-crystallin antibodies. Results In the noncancerous eyelid, α-crystallins were weakly and homogeneously expressed in the Meibomian gland lobules. In eyelids with sebaceous carcinoma, αA-crystallin and αB-crystallin were highly expressed in 4 cases, where the cytoplasmic immunoreactivity was heterogeneously detected in the tumor cells. Three and 2 cases were shown to express low levels of αA-crystallin and αB-crystallin, respectively. A statistically significant correlation was observed between expression levels of αA-crystallin and αB-crystallin in sebaceous carcinomas (p=0.012). All sebaceous carcinoma tissues contained mitotic tumor cells, which showed predominantly perinuclear immunoreactivity of αB-crystallin. The mitotic rate of tumor cells was 5.85±1.76 and 10.72±1.64 in high and moderate/low αB-crystallin-expressing cases, respectively The number of mitotic cells was significantly higher in moderate/low αB-crystallin-positive than in high-positive cases (p<0.01). Conclusions α-Crystallins are expressed in human sebaceous carcinomas including mitotic cells. Expression of αB-crystallin correlated with low number of mitotic tumor cells, suggesting that αB-crystallin may play a potential role in the regulation of tumor cell proliferation. PMID:19787585

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

    SciTech Connect

    Schlosser, Paul M. Sasso, Alan F.

    2014-10-15

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

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

    SciTech Connect

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

    2011-08-12

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

  1. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma.

    PubMed

    Castellarin, Mauro; Warren, René L; Freeman, J Douglas; Dreolini, Lisa; Krzywinski, Martin; Strauss, Jaclyn; Barnes, Rebecca; Watson, Peter; Allen-Vercoe, Emma; Moore, Richard A; Holt, Robert A

    2012-02-01

    An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an invasive anaerobe that has been linked previously to periodontitis and appendicitis, but not to cancer. Fusobacteria are rare constituents of the fecal microbiota, but have been cultured previously from biopsies of inflamed gut mucosa. We obtained a Fusobacterium isolate from a frozen tumor specimen; this showed highest sequence similarity to a known gut mucosa isolate and was confirmed to be invasive. We verified overabundance of Fusobacterium sequences in tumor versus matched normal control tissue by quantitative PCR analysis from a total of 99 subjects (p = 2.5 × 10(-6)), and we observed a positive association with lymph node metastasis.

  2. Serum and urine biomarkers for human renal cell carcinoma.

    PubMed

    Pastore, A L; Palleschi, G; Silvestri, L; Moschese, D; Ricci, S; Petrozza, V; Carbone, A; Di Carlo, A

    2015-01-01

    Renal cell carcinoma (RCC) diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called "targeted therapies." The identification of molecular markers in body fluids (e.g., sera and urine), which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients.

  3. Ablation of human telomerase reverse transcriptase (hTERT) induces cellular senescence in gastric cancer through a galectin-3 dependent mechanism

    PubMed Central

    La, Sun-Hyuk; Kim, Seok-Jun; Kang, Hyeok-Gu; Lee, Han-Woong; Chun, Kyung-Hee

    2016-01-01

    The human Telomerase Reverse Transcriptase (hTERT) gene encodes a rate-limiting catalytic subunit of telomerase that maintains genomic integrity. Suppression of hTERT expression could induce cellular senescence and is considered a potent approach for gastric cancer therapy. However, control of hTERT expression and function remains poorly understood in gastric cancer. In this study, we demonstrated that high expression levels of hTERT in malignant tissues are correlated with poor survival probability in gastric cancer patients. Knockdown of hTERT expression retarded cell proliferation and cellular senescence, which was confirmed by increased protein expression levels of p21cip1 and p27kip1, and decreased phosphorylation of Rb. In contrast, overexpression of hTERT increased cell proliferation and decreased cellular senescence. Remarkably, the down-regulation of hTERT expression was detected in lgals3−/− mouse embryo fibroblasts (MEFs). Knockdown of galectin-3 decreased the expression of hTERT in gastric cancer cells. Galectin-3 ablation-induced cellular senescence was rescued by concomitant overexpression of hTERT. hTERT ablation-induced cellular senescence and p21cip1 and p27kip1 expression was rescued by concomitant overexpression of galectin-3. The size of tumor burdens was increased in hTERT-overexpressed gastric cancer cells xenografted mice, whereas it was repressed by concomitant depletion of galectin-3. Additionally, we determined that the N-terminal domain of galectin-3 directly interacted with hTERT. The telomeric activity of hTERT was also decreased by galectin-3 ablation. Taken together, ablation of hTERT induces cellular senescence and inhibits the growth of gastric cancer cells, suggesting that it could be a potent target in gastric cancer therapy. We also propose that galectin-3 is an important regulator of hTERT expression and telomeric activity in gastric tumorigenesis. PMID:27494887

  4. Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma

    PubMed Central

    Zhang, Li; Wu, Yong-Dong; Li, Peng; Tu, Jun; Niu, Ying-Lin; Xu, Cai-Min; Zhang, Shu-Tian

    2011-01-01

    AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells. METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay was used to evaluate cell growth, and flow cytometry was used to detect cell apoptosis. RESULTS: Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specific short interfering RNA (siRNA) but was increased in EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX-2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109 cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity, xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was 51.8% in the high-dose aspirin group. CONCLUSION: COX-2 plays a very critical role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC. PMID:22147962

  5. Labeling of human hepatocellular carcinoma cells by hexamethylene diamine modified fluorescent carbon dots

    NASA Astrophysics Data System (ADS)

    Dong, Wei; Dong, Yan; Wang, Ying; Zhou, Shiqi; Ge, Xin; Sui, Lili; Wang, Jingwen

    2013-12-01

    Fluorescent carbon dots (CDs) were synthesized by a solvothermal method with glucose as carbon source and surface-modified with 1,6-hexamethylene diamine. In this hybrid CDs, the modification played important role for improving the fluorescent performance by introducing nitrogenous compound to passivate CD's surface, making the CDs emit strong fluorescence. The as-prepared CDs were linked with mouse anti-human Alpha fetoprotein (AFP) antibody and goat anti-mouse immunoglobulin (IgG) to directly and indirectly label fixed human hepatocellular carcinoma cells, respectively. The cytotoxicity of these CDs were also tested using the human hepatocellular carcinoma cells. No apparent cytotoxicity was observed, which suggested the potential application of the as-prepared CDs in bioimaging.

  6. Gastric giardiasis.

    PubMed Central

    Doglioni, C.; De Boni, M.; Cielo, R.; Laurino, L.; Pelosio, P.; Braidotti, P.; 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 from patients harbouring G lamblia infection, who repeated endoscopy before treatment, were also examined electron microscopically. RESULTS: Forty one patients (0.37% of the population study) harboured gastric giardiasis. All patients underwent upper gastrointestinal endoscopy because of dyspepsia, epigastric pain, or abdominal distension. Only two patients had diarrhoea at the time of investigation. Giardiasis was clinically unsuspected in all cases, although the nine patients who also had duodenal biopsies performed had concomitant intestinal giardiasis. Gastric giardiasis was invariably associated with chronic atrophic gastritis. Intestinal metaplasia of the gastric mucosa and Helicobacter pylori infection were found in 32 and 37 of the 41 patients with gastric giardiasis, respectively. CONCLUSIONS: The invariable association of gastric giardiasis with chronic atrophic gastritis, most often showing intestinal metaplasia and H pylori infection, indicates that a decreased gastric acidity is a prerequisite for localisation of G lamblia to the gastric mucosa. Though its possible role as a gastric pathogen remains to be elucidated, these findings suggest that trophozoites should be carefully searched for when examining gastric biopsy specimens showing chronic atrophic gastritis. Images PMID:1452790

  7. S-1-Based Chemotherapy versus Capecitabine-Based Chemotherapy as First-Line Treatment for Advanced Gastric Carcinoma: A Meta-Analysis

    PubMed Central

    Wang, Zhi-qiang; Zhang, Dong-sheng; Luo, Hui-yan; Qiu, Miao-zhen; Wang, Feng-hua; Ren, Chao; Zeng, Zhao-lei; Xu, Rui-hua

    2013-01-01

    Background Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC. Methods PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model. Results Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There’re no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed. Conclusion S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared

  8. Mouse Models of Gastric Carcinogenesis

    PubMed Central

    Yu, Sungsook; Yang, Mijeong

    2014-01-01

    Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field. PMID:25061535

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

    PubMed Central

    Varro, Andrea; Pritchard, D. Mark; Barroso, Alicia; Oteo, Marta; Morcillo, Miguel Ángel; Vargiu, Pierfrancesco; Dodd, Steven; Garcia, Miriam; Reyes, José; Ortega, Sagrario; Benitez, Javier

    2016-01-01

    ABSTRACT By whole exome sequencing, we recently identified a missense mutation (p.R703C) in the human ATP4a gene, which encodes the proton pump responsible for gastric acidification. This mutation causes an aggressive familial type I gastric neuroendocrine tumor in homozygous individuals. Affected individuals show an early onset of the disease, characterized by gastric hypoacidity, hypergastrinemia, iron-deficiency anemia, gastric intestinal metaplasia and, in one case, an associated gastric adenocarcinoma. Total gastrectomy was performed as the definitive treatment in all affected individuals. We now describe the generation and characterization of a knockin mouse model for the ATP4aR703C mutation to better understand the tumorigenesis process. Homozygous mice recapitulated most of the phenotypical alterations that were observed in human individuals, strongly suggesting that this mutation is the primary alteration responsible for disease development. Homozygous mice developed premalignant condition with severe hyperplasia, dysplasia and glandular metaplasia in the stomach. Interestingly, gastric acidification in homozygous mice, induced by treatment with 3% HCl acid in the drinking water, prevented (if treated from birth) or partially reverted (if treated during adulthood) the development of glandular metaplasia and dysplasia in the stomach and partially rescued the abnormal biochemical parameters. We therefore suggest that, in this model, achlorhydria contributes to tumorigenesis to a greater extent than hypergastrinemia. Furthermore, our mouse model represents a unique and novel tool for studying the pathologies associated with disturbances in gastric acid secretion. PMID:27491072

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

    PubMed Central

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

    2016-01-01

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

  11. Tumor-Associated Monocytes/Macrophages Impair NK-Cell Function via TGFβ1 in Human Gastric Cancer.

    PubMed

    Peng, Liu-Sheng; Zhang, Jin-Yu; Teng, Yong-Sheng; Zhao, Yong-Liang; Wang, Ting-Ting; Mao, Fang-Yuan; Lv, Yi-Pin; Cheng, Ping; Li, Wen-Hua; Chen, Na; Duan, Mubing; Chen, Weisan; Guo, Gang; Zou, Quan-Ming; Zhuang, Yuan

    2017-03-01

    Natural killer (NK) cells are a major component of the host antitumor immune response in human cancer. However, the nature, functional regulation, and clinical relevance of NK cells in gastric cancer remain largely unknown. In this study, we showed that the percentages of NK cells in tumors were significantly decreased, and low percentages of tumor-infiltrating NK cells were positively correlated with poor survival and disease progression. Although the expression of activating and inhibitory receptors on NK cells was shown to be not different between tumor and nontumor tissues, NK cells in tumors had impaired effector functions, characterized by decreased IFNγ, TNFα, and Ki-67 expression. We found that tumor-infiltrating monocytes/macrophages were physically close to NK cells, and their percentages negatively correlated with IFNγ(+) and TNFα(+) NK-cell percentages. Ex vivo study showed that isolated tumor-associated monocytes/macrophages could impair NK-cell expression of IFNγ, TNFα, and Ki-67. Blockade of TGFβ1 attenuated such monocytes/macrophages-mediated impairment of NK-cell function. Our data suggest that human NK-cell function was impaired by tumor-associated monocytes/macrophages, and that restoring NK-cell function may be an important therapeutic strategy to prevent tumor immune escape in gastric cancer. Cancer Immunol Res; 5(3); 248-56. ©2017 AACR.

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

    PubMed

    Schlosser, Paul M; Sasso, Alan F

    2014-10-15

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

  13. Filamin C, a dysregulated protein in cancer revealed by label-free quantitative proteomic analyses of human gastric cancer cells.

    PubMed

    Qiao, Jie; Cui, Shu-Jian; Xu, Lei-Lei; Chen, Si-Jie; Yao, Jun; Jiang, Ying-Hua; Peng, Gang; Fang, Cai-Yun; Yang, Peng-Yuan; Liu, Feng

    2015-01-20

    Gastric cancer (GC) is the fourth and fifth most common cancer in men and women, respectively. We identified 2,750 proteins at false discovery rates of 1.3% (protein) and 0.03% (spectrum) by comparing the proteomic profiles of three GC and a normal gastric cell lines. Nine proteins were significantly dysregulated in all three GC cell lines, including filamin C, a muscle-specific filamin and a large actin-cross-linking protein. Downregulation of filamin C in GC cell lines and tissues were verified using quantitative PCR and immunohistochemistry. Data-mining using public microarray datasets shown that filamin C was significantly reduced in many human primary and metastasis cancers. Transient expression or silencing of filamin C affected the proliferation and colony formation of cancer cells. Silencing of endogenous filamin C enhanced cancer cell migration and invasion, whereas ectopic expression of filamin C had opposing effects. Silencing of filamin C increased the expression of matrix metallopeptidase 2 and improved the metastasis of prostate cancer in a zebrafish model. High filamin C associated with better prognosis of prostate cancer, leukemia and breast cancer patients. These findings establish a functional role of filamin C in human cancers and these data will be valuable for further study of its mechanisms.

  14. Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression.

    PubMed

    Stewart, Jonathan; James, Jacqueline; McCluggage, Glenn W; McQuaid, Stephen; Arthur, Kenneth; Boyle, David; Mullan, Paul; McArt, Darragh; Yan, Benedict; Irwin, Gareth; Harkin, D Paul; Zhengdeng, Lei; Ong, Chee-Wee; Yu, Jia; Virshup, David M; Salto-Tellez, Manuel

    2015-03-01

    The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers. Immunohistochemical analysis using a TMA platform revealed WLS overexpression in a subset of ovarian, gastric, and breast tumors; this overexpression was associated with poorer clinical outcomes in gastric cancer (P=0.025). In addition, a strong correlation was observed between WLS expression and human epidermal growth factor receptor 2 (HER2) overexpression. Indeed, 100% of HER2-positive intestinal gastric carcinomas, 100% of HER2-positive serous ovarian carcinomas, and 64% of HER2-positive breast carcinomas coexpressed WLS protein. Although HER2 protein expression or gene amplification is an established predictive biomarker for trastuzumab response in breast and gastric cancers, a significant proportion of HER2-positive tumors display resistance to trastuzumab, which may be in part explainable by a possible mechanistic link between WLS and HER2.

  15. Prognostic Value of Focal Adhesion Kinase (FAK) in Human Solid Carcinomas: A Meta-Analysis

    PubMed Central

    Ma, Li-Li; Tseng, Yu-Jen; Zhao, Nai-Qing; Chen, Shi-Yao

    2016-01-01

    Background Recently, the number of reports on focal adhesion kinase (FAK) as a vital therapeutic target in solid carcinomas has increased; however, the prognostic role of FAK status remains poorly understood. This study aims to evaluate the prognostic effect of FAK by means of a meta-analysis. Methods We performed a systematic literature search in order to examine the correlation between expression of FAK and overall survival(OS). The hazard ratio (HR) of OS was used to measure survival. A random-effects model was used to pool study statistics. Sensitivity and publication bias analyses were also conducted. Results Thirty eligible studies involving 4702 patients were included. The median expression rate of FAK was 54%. Meta-analysis of the HRs demonstrated that high FAK expression was associated with worse OS (average HR = 2.073, 95%confidence interval[CI]:1.712–2.510, p = 0.000). Regarding cancer type, FAK was associated with worse OS in gastric cancer (HR = 2.646,95% CI:1.743–4.017, p = 0.000), hepatocellular carcinoma (HR = 1.788,95% CI:1.228–2.602, p = 0.002), ovarian cancer (HR = 1.815, 95% CI: 1.193–2.762, p = 0.005), endometrial cancer (HR = 4.149, 95% CI:2.832–6.079, p = 0.000), gliomas (HR = 2.650, 95% CI: 1.205–5.829, p = 0.015), and squamous cell carcinoma (HR = 1,696, 95% CI: 1.030–2.793, p = 0.038). No association was found between HR and disease staging according to our meta-regression analysis. Conclusions Our study shows that high expression of FAK is associated with a worse OS in patients with carcinomas, but the association between FAK and prognosis varies according to cancer type. The value of FAK status in clinical prognosis in cancer needs further research. PMID:27637100

  16. Protective effect of sulglycotide on human gastric mucosa exposed to taurocholic acid.

    PubMed

    Corinaldesi, R; Zurita, J; Cenedese, A; Stanghellini, V; Cavalli, G; Paparo, G; Barbara, L

    1987-01-01

    Sulglycotide is a non-systemic drug used in the treatment of peptic ulcer. It seems also to possess cytoprotective action. A double-blind cross-over study on the influence of oral sulglycotide on gastric mucosal cell loss induced by taurocholic acid (20 mM + HCl 7mM in 100 ml normal saline) was carried out in sixteen healthy volunteers by means of the DNA-loss technique. Each subject received either sulglycotide (400 mg thrice daily) or a placebo in random order on the basis of a double-blind cross-over design. Sulglycotide appeared to reduce the gastric cell loss induced by taurocholic acid. These results can explain the therapeutic effect of sulglycotide in peptic disease.

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

    PubMed Central

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

    2010-01-01

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

  18. Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma

    PubMed Central

    Chen, Yu-Jen; Chen, Chien-Chih; Huang, Huey-Lan

    2016-01-01

    Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine “Tianma”. Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alamarBlue® assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In conclusion, our study indicates the potential of armillarikin as an effective agent for hepatoma or leukemia therapies. PMID:27536140

  19. Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells

    PubMed Central

    Liang, Gai; Li, Shuang; Du, Wei; Ke, Qinghua; Cai, Jun; Yang, Jiyuan

    2017-01-01

    Hypoxia induces proliferation and invasion in cancer cells via hypoxia-inducible factor (HIF)-1α. The cell adhesion molecule cluster of differentiation (CD) 44 has been associated with increased cell invasion and metastasis. Whether hypoxia regulates the expression of CD44 in gastric cancer cells remains to be established. In the current study, the effects of hypoxia on HIF-1α and CD44 expression levels in human gastric cell lines SGC-7901 and BGC-823 were evaluated. The cells were cultured in 1% O2 for 1 week and then treated with 20 nM rapamycin for 72 h. Cell viability was evaluated using the Cell Counting kit-8 assay, and cell invasion was detected by the Transwell invasion assay. The protein and messenger (m) RNA expression levels of HIF-1α and CD44 were detected using western blotting and reverse transcription-quantitative polymerase chain reaction, respectively. The results revealed that cell viability and invasion increased under hypoxic conditions, but decreased following rapamycin treatment in SGC-7901 and BGC-823 cells. Hypoxia also increased the protein and mRNA expression levels of HIF-1α and CD44 in these two cell lines. However, this hypoxia-induced increase in HIF-1α and CD44 protein and mRNA expression levels was inhibited by rapamycin. These findings suggest that hypoxia induced the proliferation and invasion of SGC-7901 and BGC-823 cells. Furthermore, CD44 expression levels were potentially associated with HIF-1α expression levels. Therefore, in gastric cancer cells, hypoxia may regulate CD44 expression via HIF-1α in order to promote cell proliferation and invasion.

  20. Gastric cancer

    SciTech Connect

    Douglass, H.O. )

    1988-01-01

    This book contains 10 selections. Some of the titles are: Radiation therapy for gastric cancer; Experimental stomach cancer: Drug selection based on in vitro testing; Western surgical adjuvant trials in gastric cancers: Lessons from current trials to be applied in the future; and Chemotherapy of gastric cancer.

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

    PubMed

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

    2015-12-01

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

  2. Effect of oxaliplatin combined with polyenephosphatidylcholine on the proliferation of human gastric cancer SGC-7901 cells

    PubMed Central

    Jiang, Tao; Zhang, Hongjun; Liu, Xiguang; Song, Hao; Yao, Ruyong; Li, Jianbin; Zhao, Yuanyuan

    2016-01-01

    Oxaliplatin (L-OHP) is a platinum compound that is widely used to treat certain solid tumors, including gastric tumors. L-OHP is an effective anti-cancer treatment; however, its usage increases the probability of patients developing hepatic injury with inflammation, referred to as chemotherapy-associated steatohepatitis. The present study aimed to evaluate the outcome of L-OHP treatment combined with polyenephosphatidylcholine (PPC), a major component of essential phospholipids used to treat steatohepatitis, on SGC-7901 gastric cancer cell proliferation. This would help to determine whether combination therapy with L-OHP and PPC is clinically beneficial for patients with gastric cancer. The viability of SGC-7901 cells was verified by an MTT assay; flow cytometry was used to analyze the cell cycle and rates of cell apoptosis; oxidation-related indicators were measured by spectrophotometry, and the expression of cell cycle- and apoptosis-related proteins was determined by western blotting. The results demonstrated that L-OHP significantly inhibited SGC-7901 cell growth in a dose- and time-dependent manner (F=194.193, P<0.01 and F=12.428, P=0.01, respectively). Furthermore, PPC stimulated the growth of SGC-7901 cells and greatly promoted their apoptosis induced by L-OHP, which was supported by the upregulation of cytochrome c and the downstream activation of caspases 3 and 9. Finally, following treatment with a combination of PPC and L-OHP, the expression of cyclins D1 and E was downregulated; however, PPC did not alter the production of reactive oxygen species caused by L-OHP (P=0.88). The present study determined that the combination of L-OHP and PPC exerts a synergistic anti-tumor effect, suggesting that L-OHP and PPC combination therapy may be used as a treatment for patients with gastric cancer that reduces the side effects of L-OHP without inhibiting its efficacy. PMID:28101212

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

    PubMed Central

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

    2016-01-01

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

  4. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    2006-06-16

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

  7. Protective autophagy is involved in resistance towards MET inhibitors in human gastric adenocarcinoma cells.

    PubMed

    Humbert, Magali; Medová, Michaela; Aebersold, Daniel M; Blaukat, Andree; Bladt, Friedhelm; Fey, Martin F; Zimmer, Yitzhak; Tschan, Mario P

    2013-02-08

    MET, also known as hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase with an important role, both in normal cellular function as well as in oncogenesis. In many cancer types, abnormal activation of MET is related to poor prognosis and various strategies to inhibit its function, including small molecule inhibitors, are currently in preclinical and clinical evaluation. Autophagy, a self-digesting recycling mechanism with cytoprotective functions, is induced by cellular stress. This process is also induced upon cytotoxic drug treatment of cancer cells and partially allows these cells to escape cell death. Thus, since autophagy protects different tumor cells from chemotherapy-induced cell death, current clinical trials aim at combining autophagy inhibitors with different cancer treatments. We found that in a gastric adenocarcinoma cell line GTL-16, where MET activity is deregulated due to receptor overexpression, two different MET inhibitors PHA665752 and EMD1214063 lead to cell death paralleled by the induction of autophagy. A combined treatment of MET inhibitors together with the autophagy inhibitor 3-MA or genetically impairing autophagy by knocking down the key autophagy gene ATG7 further decreased cell viability of gastric cancer cells. In general, we observed the induction of cytoprotective autophagy in MET expressing cells upon MET inhibition and a combination of MET and autophagy inhibition resulted in significantly decreased cell viability in gastric cancer cells.

  8. Effects of ToxCast Phase I Chemicals on Steroidogenesis in H295R Human Adrenocortical Carcinoma cells (SOT)

    EPA Science Inventory

    Steroid hormones are essential for proper development and reproduction. Disruption of steroidogenesis by environmental toxicants results in altered hormone levels causing adverse reproductive and developmental effects. H295R human adrenocortical carcinoma cells were used to evalu...

  9. Crossing Paths in Human Renal Cell Carcinoma (hRCC)

    PubMed Central

    Gallego, Guadalupe Aparicio; Villaamil, Vanessa Medina; Grande, Enrique; Caínzos, Isabel Santamarina; Antón Aparicio, Luís M.

    2012-01-01

    Historically, cell-signaling pathways have been studied as the compilation of isolated elements into a unique cascade that transmits extracellular stimuli to the tumor cell nucleus. Today, growing evidence supports the fact that intracellular drivers of tumor progression do not flow in a single linear pathway, but disseminate into multiple intracellular pathways. An improved understanding of the complexity of cancer depends on the elucidation of the underlying regulatory networks at the cellular and intercellular levels and in their temporal dimension. The high complexity of the intracellular cascades causes the complete inhibition of the growth of one tumor cell to be very unlikely, except in cases in which the so-called “oncogene addiction” is known to be a clear trigger for tumor catastrophe, such as in the case of gastrointestinal stromal tumors or chronic myeloid leukemia. In other words, the separation and isolation of the driver from the passengers is required to improve accuracy in cancer treatment. This review will summarize the signaling pathway crossroads that govern renal cell carcinoma proliferation and the emerging understanding of how these pathways facilitate tumor escape. We outline the available evidence supporting the putative links between different signaling pathways and how they may influence tumor proliferation, differentiation, apoptosis, angiogenesis, metabolism and invasiveness. The conclusion is that tumor cells may generate their own crossroads/crosstalk among signaling pathways, thereby reducing their dependence on stimulation of their physiologic pathways. PMID:23202921

  10. Changes in arginase isoenzymes pattern in human hepatocellular carcinoma

    SciTech Connect

    Chrzanowska, Alicja; Krawczyk, Marek; Baranczyk-Kuzma, Anna

    2008-12-12

    Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide affecting preferentially patients with liver cirrhosis. The studies were performed on tissues obtained during surgery from 50 patients with HCC, 40 with liver cirrhosis and 40 control livers. It was found that arginase activity in HCC was nearly 5- and 15-fold lower than in cirrhotic and normal livers, respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic arginase) were identified by Western blotting in all studied tissues, however the amount of AI, as well as the expression of AI-mRNA were lower in HCC, in comparison with normal liver, and those of AII were significantly higher. Since HCC is arginine-dependent, and arginine is essential for cells growth, the decrease of AI may preserve this amino acid within tumor cells. Concurrently, the rise of AII can increase the level of polyamines, compounds crucial for cells proliferation. Thus, both arginase isoenzymes seem to participate in liver cancerogenesis.

  11. DNMT1 regulates human endometrial carcinoma cell proliferation

    PubMed Central

    Wang, Xinjing; Li, Bilan

    2017-01-01

    Endometrial carcinoma (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. This study aimed to investigate the role of DNA methyltransferase 1 (DNMT1), a member of DNA methyltransferases, in EC. AN3CA cells were transfected with DNMT1 siRNA. The proliferation, cell cycle, and apoptosis of AN3CA cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The expression of related genes was detected by polymerase chain reaction and Western blot analysis. Knockdown of DNMT1 inhibited the proliferation, induced apoptosis, and G0/G1 phase arrest of AN3CA cells. Furthermore, knockdown of DNMT1 upregulated the expression of nuclear factor kappa-B-inhibitor alpha (NF-κBIA) and Bax and downregulated the expression of Bcl-2 and CCND1/2 in AN3CA cells. In conclusion, this study provides the first evidence that knockdown of DNMT1 affects the expression of cell cycle- and apoptosis-associated proteins in EC cells, suggesting the potential of DNMT1 in EC therapy.

  12. Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2

    PubMed Central

    SHEN, YONGHUA; CHEN, MIN; HUANG, SHULING; ZOU, XIAOPING

    2016-01-01

    The Warburg effect is important in tumor growth. The human M2 isoform of pyruvate kinase (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells. Recent studies have demonstrated that PKM2 is a potential target for cancer therapy. The present study investigated the effects of pantoprazole (PPZ) treatment and PKM2 transfection on human gastric adenocarcinoma SGC-7901 cells in vitro. The present study revealed that PPZ inhibited the proliferation of tumor cells, induced apoptosis and downregulated the expression of PKM2, which contributes to the current understanding of the functional association between PPZ and PKM2. In summary, PPZ may suppress tumor growth as a PKM2 protein inhibitor. PMID:26870273

  13. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells

    PubMed Central

    Gong, Jianlin; Avigan, David; Chen, Dongshu; Wu, Zekui; Koido, Shigeo; Kashiwaba, Masahiro; Kufe, Donald

    2000-01-01

    We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs. Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules. The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors. PMID:10688917

  14. Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line.

    PubMed

    Ruffa, M J; Ferraro, G; Wagner, M L; Calcagno, M L; Campos, R H; Cavallaro, L

    2002-03-01

    Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts.

  15. Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid.

    PubMed

    Homann, Arne; Qamar, Riaz-Ul; Serim, Sevnur; Dersch, Petra; Seibel, Jürgen

    2010-03-08

    Sialic acids are located at the termini of mammalian cell-surface glycostructures, which participate in essential interaction processes including adhesion of pathogens prior to infection and immunogenicity. Here we present the synthesis and bioorthogonal metabolic incorporation of the sialic acid analogue N-(1-oxohex-5-ynyl)neuraminic acid (Neu5Hex) into the cell-surface glycocalyx of a human larynx carcinoma cell line (HEp-2) and its fluorescence labelling by click chemistry.

  16. Resistance of human squamous carcinoma cells to transforming growth factor beta 1 is a recessive trait.

    PubMed Central

    Reiss, M; Muñoz-Antonia, T; Cowan, J M; Wilkins, P C; Zhou, Z L; Vellucci, V F

    1993-01-01

    Because most human squamous carcinoma cell lines of the aerodigestive and genital tracts are refractory to the antiproliferative action of transforming growth factor beta 1 (TGF beta 1) in vitro, we have begun to identify the causes for resistance of squamous carcinoma cell lines to TGF beta 1 by using somatic cell genetics. Two stable hybrid cell lines (FaDu-HKc.1 and FaDu-HKc.2) were obtained by fusing a TGF beta 1-resistant human squamous carcinoma cell line, FaDu-HygR, with a human papilloma virus 16-immortalized, TGF beta 1-sensitive, human foreskin keratinocyte cell line, HKc-neoR. Whereas TGF beta 1 did not inhibit DNA synthesis in parental FaDu-HygR cells, it reduced DNA synthetic activity of HKc-neoR, FaDu-HKc.1, and FaDu-HKc.2 cells by 75-85% (IC50, 2-5 pM). Although squamous carcinoma cells express lower than normal levels of TGF beta 1 type II receptors on their cell surface, TGF beta 1 type II receptor mRNA was detected in all four cell lines. Recessive genes involved in TGF beta 1 signaling may be localized to the distal portion of chromosome 18q, as this was the sole chromosomal region of homozygous deletion in parental FaDu-HygR cells. Furthermore, our previous observation that mutant p53 decreases sensitivity of keratinocytes to TGF beta 1 was supported by the finding that the level of the mutant p53 protein expressed by the hybrid cell lines was greatly reduced. In summary, TGF beta 1 resistance of FaDu cells appears to be recessive and is presumably due to the loss of one or more post-receptor elements of the signaling pathway. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8327510

  17. Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression.

    PubMed

    Liu, Fu-Rong; Jiang, Cheng-Gang; Li, Yan-Shu; Li, Jia-Bin; Li, Feng

    2011-04-01

    Cimetidine has been shown to have anti-metastatic activity and improves the survival of patients with colorectal cancer. One hypothesis is its modulation of the expression of the cell adhesion molecule by target organ endothelial cells. Because of the inconclusive results in clinical trials of gastric cancer, we investigated the effects of cimetidine on the adhesion of gastric cancer cells to activated endothelial cells and on the expression of some cell adhesion molecules. Human endothelial cells were pre-incubated with cimetidine for 6 h, incubated with the cytokine tumor necrosis factor for 4 h, and the endothelial surface expression of E-selectin was evaluated by flow cytometry, immunostaining and ELISA. Further, we investigated E-selectin mRNA expression by RT-PCR. Three gastric cancer cell lines (SGC-7901, MGC-803, BGC-823) and a normal gastric epithelial cell line, GES-1, were studied for the surface expression of sialyl Lewis x by flow cytometry and immunostaining. Adherence of CFSE-labeled gastric cancer cells and GES-1 cells to endothelial cell monolayers was determined. Cimetidine significantly reduced E-selectin expression of activated endothelial cells, but did not influence E-selectin expression at the mRNA level. Three gastric cancer cell lines expressed high levels of sialyl Lewis x, whereas GES-1 did not. Cimetidine also significantly decreased gastric cancer cell adherence to stimulated endothelial cells. The inhibition of E-selectin expression corresponded to the reduction of tumor cell adherence. The effects of cimetidine on tumor adhesion were almost nullified by pre-incubation with E-selectin and sialyl Lewis x antibody. Furthermore, there was no significant change of GES-1 adherence to endothelial cells by TNF-α, cimetidine, E-selectin and sialyl Lewis x antibody. The inhibiton of gastric cancer cell adherence to cytokine-stimulated endothelial cells treated with cimetidine appears to result from blocking endothelial E-selectin expression

  18. Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells.

    PubMed

    Zou, Xue; Zhang, Mengxiao; Sun, Yiming; Zhao, Surong; Wei, Yingmei; Zhang, Xudong; Jiang, Chenchen; Liu, Hao

    2015-10-01

    Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

  2. Prostaglandin protection of human isolated gastric glands against indomethacin and ethanol injury. Evidence for direct cellular action of prostaglandin.

    PubMed Central

    Tarnawski, A; Brzozowski, T; Sarfeh, I J; Krause, W J; Ulich, T R; Gergely, H; Hollander, D

    1988-01-01

    Isolated human gastric glands from surgical specimens were preincubated in an oxygenated medium with placebo or 16,16 dimethyl prostaglandin E2 (dmPGE2) and incubated at 37 degrees C in either medium alone, medium containing 4.43 mM indomethacin or medium containing 8% ethanol. We assessed the viability of gland cells with fast green exclusion, release of lactate dehydrogenase (LDH) into the medium, and ultrastructural damage by scanning and transmission electron microscopy. Both indomethacin and ethanol significantly reduced the viability of placebo-pretreated glands, increased LDH release into the medium, and produced prominent ultrastructural damage. DmPGE2 significantly reduced both indomethacin and ethanol-induced injury, increased the number of viable cells, reduced LDH release, and diminished the extent of ultrastructural damage. These studies indicate that PG protection of gastric mucosal cells has a direct cellular action that is not limited to replacement of depleted endogenous PGs. PG protection in our experiments did not depend on PG's previously described systemic actions, such as protection of the microvessels, preservation of the mucosal blood flow, or stimulation of bicarbonate and mucus secretion. Images PMID:3350966

  3. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    SciTech Connect

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  4. Therapy of human pancreatic carcinoma based on suppression of HMGA1 protein synthesis in preclinical models.

    PubMed

    Trapasso, Francesco; Sarti, Manuela; Cesari, Rossano; Yendamuri, Sai; Dumon, Kristoffel R; Aqeilan, Rami I; Pentimalli, Francesca; Infante, Luisa; Alder, Hansjuerg; Abe, Nobutsugu; Watanabe, Takashi; Viglietto, Giuseppe; Croce, Carlo M; Fusco, Alfredo

    2004-09-01

    Pancreatic carcinoma is one of the most aggressive tumors, and, being refractory to conventional therapies, is an excellent target for new therapeutic approaches. Based on our previous finding of high HMGA1 expression in pancreatic cancer cells compared to normal pancreatic tissue, we evaluated whether suppression of HMGA1 protein expression could be a treatment option for patients affected by pancreatic cancer. Here we report that HMGA1 proteins are overexpressed in pancreatic carcinoma cell lines, and their downregulation through an adenovirus carrying the HMGA1 gene in an antisense orientation (Ad Yas-GFP) results in the death of three human pancreatic carcinoma cell lines (PANC1, Hs766T and PSN1). Pretreatment of PANC1 and PSN1 cells with Ad Yas-GFP suppressed and reduced, respectively, their ability to form xenograft tumors in nude mice. To further verify the role of HMGA1 in pancreatic tumorigenesis, we used a HMGA1 antisense phosphorothioate oligodeoxynucleotide (ODN); its addition induced a decrease in HMGA1 protein levels and a significant reduction of the proliferation rate of PANC1-, Hs766T- and PSN1-treated cells. Therefore, suppression of HMGA1 protein synthesis by an HMGA1 antisense approach seems to be a feasible treatment strategy in pancreatic carcinomas.

  5. Establishment and characterization of a human uterine endometrial undifferentiated carcinoma cell line, TMG-L.

    PubMed

    Hasegawa, Kiyoshi; Suzuki, Machiko; Ishikawa, Kunimi; Yasue, Akira; Kato, Rina; Nakamura, Azumi; Kuroki, Jun; Udagawa, Yasuhiro

    2003-03-01

    A new cell line of human uterine endometrial undifferentiated carcinoma, designated as TMG-L, was established from the metastatic lymph node of 56-year-old patient TMG-L cells have been cultured with Ham's F-12 medium supplemented with 10% FCS and grew as a loosely adherent monolayer with polygonal or spindle-shaped cells exhibiting poor cell-cell contact and piled up against each other, showing a tendency to grow as floating cells. The doubling time of this cell line was about 48 hours, and chromosomal analysis revealed aneuploidy at passage 25. The cells formed tumors in SCID mouse, the histology of which was similar to that of undifferentiated carcinoma component of primary tumor. TMG-L cells showed the loss of expression and membranous localization of either E-cadherin or alpha-catenin, implied corresponding loss of their adhesive function. And this dysfunction implicated the biological aggressive behavior of uterine endometrial undifferentiated carcinoma. This cell line appears to provide a useful system for studying uterine undifferentiated carcinoma in vivo and in vitro.

  6. In situ hybridization analysis of human papillomavirus in anal squamous cell carcinoma.

    PubMed

    Gal, A A; Saul, S H; Stoler, M H

    1989-09-01

    To investigate the association between human papillomavirus (HPV) infection and anal carcinoma, we applied a sensitive in situ hybridization technique to detect HPV messenger RNA (HPV m-RNA) in formalin-fixed, paraffin-embedded sections from 18 patients. Using tritium-labeled probes, HPV m-RNA was detected in 12/18 (67%) patients. HPV 6 was detected in four patients, coexisting with HPV 18 in two cases, and HPV 16 was found in eight patients. In six patients, hybridization failed to demonstrate the presence of HPV. With respect to histology, HPV 6 was detected in 1/4 cases of well differentiated invasive squamous cell carcinoma. Ten of thirteen moderately or poorly differentiated invasive squamous cell carcinomas demonstrated HPV m-RNA (HPV 16, eight cases; HPV 6, one case; HPV 6 and 18, one case). HPV 31 was not detected in any specimens. These results suggest that HPV infection may play an important role in the pathogenesis of anal carcinoma.

  7. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    PubMed

    Werner-Klein, Melanie; Proske, Judith; Werno, Christian; Schneider, Katharina; Hofmann, Hans-Stefan; Rack, Brigitte; Buchholz, Stefan; Ganzer, Roman; Blana, Andreas; Seelbach-Göbel, Birgit; Nitsche, Ulrich; Männel, Daniela N; Klein, Christoph A

    2014-01-01

    Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  8. An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer

    PubMed Central

    Li, Hongwen; Yu, Chao; Jiang, Jing; Huang, Changjiang; Yao, Xuejing; Xu, Qiaoyu; Yu, Fang; Lou, Liguang; Fang, Jianmin

    2016-01-01

    ABSTRACT Antibody-drug conjugate (ADC) is a novel class of therapeutics for cancer target therapy. This study assessed antitumor activity of ADC with an antimitotic agent, monomethyl auristatin E (MMAE) and a humanized monoclonal anti-HER2 antibody, hertuzumab, in gastric cancer. The efficacy of hertuzumab-MC-Val-Cit-PAB-MMAE (hertuzumab-vcMMAE) on human epidermal growth factor receptor 2 (HER2) positive human gastric cancer cells, NCI-N87, was evaluated in vitro and in vivo. The cytotoxicity of hertuzumab was significantly enhanced after conjugation with MMAE. Compared to trastuzumab, hertuzumab had a higher affinity to HER2 and had more potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro. After conjugation with MMAE, the binding specificity for HER2 was not affected. Furthermore, the internalization of hertuzumab-vcMMAE in HER2 positive gastric cancer cells was verified. Although the conjugation of hertuzumab and MMAE decreased the ADCC effect, the overall cytotoxicity was dramatically increased in HER2 positive gastric cancer cells. In vitro data on this hertuzumab-vcMMAE has exerted much stronger antitumor activity compared to trastuzumab-DM1 in HER2 positive gastric cancer cells. A single administration of hertuzumab-vcMMAE at 5 or 10 mg/kg showed high potency and a sustained tumor inhibitory effect on NCI-N87 xenografts in mice. In conclusion, hertuzumab-vcMMAE conjugate is a highly effective anti-HER2 targeted therapy for HER2-positive gastric cancer. PMID:26853765

  9. Runt-related transcription factor 2 in human colon carcinoma: a potent prognostic factor associated with estrogen receptor.

    PubMed

    Sase, Tomohiko; Suzuki, Takashi; Miura, Koh; Shiiba, Kenichi; Sato, Ikuro; Nakamura, Yasuhiro; Takagi, Kiyoshi; Onodera, Yoshiaki; Miki, Yasuhiro; Watanabe, Mika; Ishida, Kazuyuki; Ohnuma, Shinobu; Sasaki, Hiroyuki; Sato, Ryuichiro; Karasawa, Hideaki; Shibata, Chikashi; Unno, Michiaki; Sasaki, Iwao; Sasano, Hironobu

    2012-11-15

    Runt-related transcription factor 2 (RUNX2) belongs to the RUNX family of heterodimeric transcription factors, and is mainly associated with osteogenesis. Previous in vitro studies demonstrated that RUNX2 increased the cell proliferation of mouse and rat colon carcinoma cells but the status of RUNX2 has remained unknown in human colon carcinoma. Therefore, we examined clinical significance and biological functions of RUNX2 in colon carcinoma. RUNX2 immunoreactivity was examined in 157 colon carcinoma tissues using immunohistochemistry. RUNX2 immunoreactivity was evaluated as percentage of positive carcinoma cells [i.e., labeling index (LI)]. We used SW480 and DLD-1 human colon carcinoma cells, expressing estrogen receptor-β (ER) in subsequent in vitro studies. RUNX2 immunoreactivity was detected in colon carcinoma cells, and the median value of RUNX2 LI was 67%. RUNX2 LI was significantly associated with Dukes' stage, liver metastasis and ERβ status. In addition, RUNX2 LI was significantly associated with adverse clinical outcome of the colon carcinoma patients, and turned out an independent prognostic factor following multivariate analysis. Results of in vitro studies demonstrated that both SW480 and DLD-1 cells transfected with small interfering RNA against RUNX2 significantly decreased their cell proliferation, migration and invasive properties. In addition, RUNX2 mRNA level was significantly decreased by ER antagonist in these two cells. These findings all suggest that RUNX2 is a potent prognostic factor in human colon carcinoma patients through the promotion of cell proliferation and invasion properties, and is at least partly upregulated by estrogen signals through ERβ of carcinoma cells.

  10. Branchiogenic carcinoma with high-risk-type human papillomavirus infection: A case report

    PubMed Central

    Maeda, Hiroyuki; Deng, Zeyi; Ikegami, Taro; Matayoshi, Sen; Agena, Shinya; Kiyuna, Asanori; Yamashita, Yukashi; Uehara, Takayuki; Ganaha, Akira; Suzuki, Mikio

    2016-01-01

    Branchiogenic carcinoma (BC) usually appears as a mass lesion with a predominant cystic component. Since lymph node metastasis from oropharyngeal carcinoma (OPC) has a cystic appearance, it is occasionally difficult to distinguish between BC and nodal metastases from clinically silent OPC. Factors associated with the malignant transformation process in BC remain obscure. The present study reports the case of a 56-year-old man with a right cystic cervical mass that was diagnosed as squamous cell carcinoma based on examination by fine-needle aspiration biopsy. The primary tumor could not be detected despite several imaging examinations, a pan-endoscopy of the head and neck, esophagus and stomach, biopsies of the head and neck regions, and bilateral tonsillectomies. The pathological findings of the surgical specimens from a radical neck dissection were consistent with the histological characteristics of BC, with evidence of transition from dysplasia through intraepithelial carcinoma to invasive carcinoma. Normal squamous epithelium and dysplastic and cancerous portions in the BC showed strong p16INK4a immunoreactivity. The expression of p16INK4a was also observed in all 9 nodal metastases in the neck dissection specimens. The cystic formation observed in the BC was not observed in the nodal metastases. As the presence of human papillomavirus-16 in the tumor was confirmed by polymerase chain reaction, quantitative polymerase chain reaction was employed for the measurement of human papillomavirus-16 viral load and integration. The results showed that the viral load of human papillomavirus-16 was 3.01×107/50 ng genomic DNA, and the E2/E6 ratio was 0.13, so the integration state was judged to be the mixed type. To the best of our knowledge, this is the first report of BC associated with high-risk-type human papillomavirus infection. The study indicates that a human papillomavirus-positive neck mass may not necessarily be OPC, but that it could be BC with a poor prognosis

  11. Helicobacter pylori and early gastric cancer.

    PubMed Central

    Craanen, M E; Blok, P; Dekker, W; Tytgat, G N

    1994-01-01

    The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer (p < 0.05 and p < 0.001, respectively). H pylori was found in 61.3% of intestinal type early gastric cancer and in 54.5% of diffuse type early gastric cancer (NS). The age adjusted prevalence of intestinal metaplasia in the patients with antral gastritis was higher in H pylori positive patients in all age groups studied. Comparing gastritis patients with patients with intestinal type early gastric cancer showed the age adjusted prevalence of intestinal metaplasia to be significantly higher in the patients with early gastric cancer in all age groups studied. In conclusion, H pylori is associated with both types of early gastric carcinoma. Intestinal metaplasia formation seems to be a multifactorial process in which H pylori may play a part. These findings suggest that gastric cancer may be included in the spectrum of H pylori associated diseases, although many questions about causality remain to be answered. PMID:7959189

  12. Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

    PubMed Central

    Sobhani, I; Denizot, Y; Hochlaf, S; Rigaud, D; Vatier, J; Benveniste, J; Lewin, M J; Mignon, M

    1993-01-01

    The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes). Platelet activating factor was detected at low concentration in 4/13 subjects under basal condition (mean (SEM) 1.2 (0.6) pg/hr) while high concentrations of lyso platelet activating factor (6.1 (1.8) microgram/hr) and of alkyl-acyl-glycerophosphocholine (AAGPC) (11.5 (3) micrograms/hr) were found in 13 and 11 subjects, respectively. Platelet activating factor was not detected during pentagastrin infusion, while lyso platelet activating factor and alkyl-acyl-glycerophosphocholine were detected in 13 and in 12 subjects, respectively. Compared with the basal condition these platelet activating factor precursors increased significantly (p < 0.001) going up to fivefold baseline (31.8 (6.8) micrograms/hr and 53 (9.3) micrograms/hr respectively) in response to pentagastrin. There was a positive correlation between platelet activating factor precursors and acid or pepsin output but not between platelet activating factor precursors and sialic acid. As sialic acid may be considered an index of mucus glycoprotein degradation, it seems that gastrin stimulation of gastric epithelial cells results in a concomittant secretion of platelet activating factor precursors, acid, and pepsin irrespective of mucus glycoprotein degradation. PMID:8174952

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

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

    PubMed

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

    2006-04-01

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

  15. Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes.

    PubMed

    Matsusaka, Keisuke; Kaneda, Atsushi; Nagae, Genta; Ushiku, Tetsuo; Kikuchi, Yasuko; Hino, Rumi; Uozaki, Hiroshi; Seto, Yasuyuki; Takada, Kenzo; Aburatani, Hiroyuki; Fukayama, Masashi

    2011-12-01

    Epstein-Barr virus (EBV) is associated with Burkitt lymphoma, nasopharyngeal carcinoma, opportunistic lymphomas in immunocompromised hosts, and a fraction of gastric cancers. Aberrant promoter methylation accompanies human gastric carcinogenesis, though the contribution of EBV to such somatic methylation changes has not been fully clarified. We analyzed promoter methylation in gastric cancer cases with Illumina's Infinium BeadArray and used hierarchical clustering analysis to classify gastric cancers into 3 subgroups: EBV(-)/low methylation, EBV(-)/high methylation, and EBV(+)/high methylation. The 3 epigenotypes were characterized by 3 groups of genes: genes methylated specifically in the EBV(+) tumors (e.g., CXXC4, TIMP2, and PLXND1), genes methylated both in EBV(+) and EBV(-)/high tumors (e.g., COL9A2, EYA1, and ZNF365), and genes methylated in all of the gastric cancers (e.g., AMPH, SORCS3, and AJAP1). Polycomb repressive complex (PRC) target genes in embryonic stem cells were significantly enriched among EBV(-)/high-methylation genes and commonly methylated gastric cancer genes (P = 2 × 10(-15) and 2 × 10(-34), respectively), but not among EBV(+) tumor-specific methylation genes (P = 0.2), suggesting a different cause for EBV(+)-associated de novo methylation. When recombinant EBV was introduced into the EBV(-)/low-methylation epigenotype gastric cancer cell, MKN7, 3 independently established subclones displayed increases in DNA methylation. The promoters targeted by methylation were mostly shared among the 3 subclones, and the new methylation changes caused gene repression. In summary, DNA methylation profiling classified gastric cancer into 3 epigenotypes, and EBV(+) gastric cancers showed distinct methylation patterns likely attributable to EBV infection.

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2015-01-01

    Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotyp