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Sample records for ags gastric adenocarcinoma

  1. Magnesium sulfate induced toxicity in vitro in AGS gastric adenocarcinoma cells and in vivo in mouse gastric mucosa.

    PubMed

    Zhang, Xulong; Bo, Agula; Chi, Baofeng; Xia, Yuan; Su, Xiong; Sun, Juan

    2015-01-01

    Magnesium sulfate is widely used as a food additive and as an orally administered medication. The aim of this study was to evaluate the possible cytotoxicity of magnesium sulfate on AGS human gastric adenocarcinoma cells and gastric mucosa in mice. A trypan blue exclusion assay was used to determine the reduction in viability of AGS cells exposed to magnesium sulfate, and then effects on cell proliferation were quantified. The role of magnesium sulfate-mediated pro-inflammatory cytokine production in AGS cells was also investigated. mRNA expression for IL-1β, IL-6, IL-8, and TNF-α was determined by RT-PCR, and secretion of these cytokines was measured by ELISA. Immunohistochemical evaluation of IL-1β, IL-6, and TNF-α expression was conducted in mouse gastric mucosa. Addition of 3 to 50 mM magnesium sulfate to AGS cells inhibited both cell proliferation and cell viability in a dose-dependent manner. Magnesium sulfate had little effect on production of IL-1β or IL-6 but significantly inhibited production of IL-8. The animal model demonstrated that magnesium sulfate induced production of IL-1β, IL-6, and TNF-α. These preliminary data suggest that magnesium sulfate had a direct effect on the stomach and initiates cytotoxicity in moderate concentrations and time periods by inhibiting viability and proliferation of AGS cells and by regulating expression and/or release of pro-inflammatory cytokines.

  2. 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

  3. 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

  4. 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

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

    PubMed

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

    2016-05-01

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

  6. Gastric adenocarcinoma with prostatic metastasis.

    PubMed

    Roshni, S; Anoop, Tm; Preethi, Tr; Shubanshu, G; Lijeesh, Al

    2014-06-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  7. Gastric Adenocarcinoma with Prostatic Metastasis

    PubMed Central

    Roshni, S; Preethi, TR; Shubanshu, G; Lijeesh, AL

    2014-01-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  8. Scopadulciol, Isolated from Scoparia dulcis, Induces β-Catenin Degradation and Overcomes Tumor Necrosis Factor-Related Apoptosis Ligand Resistance in AGS Human Gastric Adenocarcinoma Cells.

    PubMed

    Fuentes, Rolly G; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2015-04-24

    Scopadulciol (1), a scopadulan-type diterpenoid, was isolated from Scoparia dulcis along with three other compounds (2-4) by an activity-guided approach using the TCF reporter (TOP) luciferase-based assay system. A fluorometric microculture cytotoxicity assay (FMCA) revealed that compound 1 was cytotoxic to AGS human gastric adenocarcinoma cells. The treatment of AGS cells with 1 decreased β-catenin levels and also inhibited its nuclear localization. The pretreatment of AGS cells with a proteasome inhibitor, either MG132 or epoxomicin, protected against the degradation of β-catenin induced by 1. The 1-induced degradation of β-catenin was also abrogated in the presence of pifithrin-α, an inhibitor of p53 transcriptional activity. Compound 1 inhibited TOP activity in AGS cells and downregulated the protein levels of cyclin D1, c-myc, and survivin. Compound 1 also sensitized AGS cells to tumor necrosis factor-related apoptosis ligand (TRAIL)-induced apoptosis by increasing the levels of the death receptors, DR4 and DR5, and decreasing the level of the antiapoptotic protein Bcl-2. Collectively, our results demonstrated that 1 induced the p53- and proteasome-dependent degradation of β-catenin, which resulted in the inhibition of TCF/β-catenin transcription in AGS cells. Furthermore, 1 enhanced apoptosis in TRAIL-resistant AGS when combined with TRAIL. PMID:25793965

  9. Dealcoholized Korean Rice Wine (Makgeolli) Exerts Potent Anti-Tumor Effect in AGS Human Gastric Adenocarcinoma Cells and Tumor Xenograft Mice.

    PubMed

    Shin, Eun Ju; Kim, Sung Hee; Kim, Jae Ho; Ha, Jaeho; Hwang, Jin-Taek

    2015-09-01

    Makgeolli is a traditional wine in Korea and has been traditionally believed to exhibit health benefits. However, the inhibitory effect of dealcoholized makgeolli (MK) on cancer has never been investigated scientifically. In this study, MK exhibited an anti-angiogenic effect by inhibiting tube formation in human umbilical vein endothelial cells, without cytotoxicity. Treatment with MK reduced the proliferation of AGS human gastric adenocarcinoma cells in a dose-dependent manner and increased the sub-G1 population. Next, we evaluated whether MK could induce apoptosis in AGS cells by using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay or Annexin V method. Treatment with MK at 500 and 1,000 μg/ml increased the number of TUNEL-positive AGS cells. Under the same conditions, MK-treated (500 and 1,000 μg/ml) cells showed significant induction of early or late apoptosis, compared with untreated cells (no induction). In addition, MK also induced phosphatase and tensin homolog (PTEN) expression in AGS cells. However, p53 expression in AGS cells was not changed by MK treatment. Furthermore, MK at 500 mg/kg·d reduced the tumor size and volume in AGS tumor xenografts. Taken together, MK may be useful for the prevention of cancer cell growth.

  10. Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

    ClinicalTrials.gov

    2013-06-03

    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

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

    PubMed Central

    Al-Hussaini, Abdulrahman; AlGhamdi, Salem; Al-Kasim, Fawaz; Habib, Zakaria; Ourfali, Nouri

    2014-01-01

    Gastric carcinoma is extremely rare in children representing only 0.05% of all gastrointestinal malignancies. Here, we report the first pediatric case of gastric cancer presenting with gastric outlet obstruction. Upper endoscopy revealed a markedly thickened antral mucosa occluding the pylorus and a clean base ulcer 1.5 cm × 2 cm at the lesser curvature of the stomach. The narrowed antrum and pylorus underwent balloon dilation, and biopsy from the antrum showed evidence of Helicobacter pylori gastritis. The biopsy taken from the edge of the gastric ulcer demonstrated signet-ring-cell type infiltrate consistent with gastric adenocarcinoma. At laparotomy, there were metastases to the liver, head of pancreas, and mesenteric lymph nodes. Therefore, the gastric carcinoma was deemed unresectable. The patient died few months after initiation of chemotherapy due to advanced malignancy. In conclusion, this case report underscores the possibility of gastric adenocarcinoma occurring in children and presenting with gastric outlet obstruction. PMID:24707411

  12. Protein profiling of alpha-fetoprotein producing gastric adenocarcinoma

    PubMed Central

    He, Liang; Ye, Fei; Qu, Linlin; Wang, Daguang; Cui, Miao; Wei, Chengguo; Xing, Yanpeng; Lee, Peng; Suo, Jian; Zhang, David Y.

    2016-01-01

    Alpha-fetoprotein (AFP) producing gastric adenocarcinoma is considered as a rare subtype of gastric adenocarcinoma. Compared with AFP non-producing gastric adenocarcinoma, our study and other previous studies showed that AFP producing gastric adenocarcinoma is more aggressive and prone to liver metastasis. Using the Protein Pathway Array, 11 of out of 286 proteins tested were found to be differentially expressed between AFP producing (n=32) and AFP non-producing (n=45) gastric adenocarcinoma tissues. In addition, the high level expression of XIAP and IGF-Irβ in gastric adenocarcinoma tissues was independent factors for poor prognosis in AFP producing gastric adenocarcinoma patients. A risk model based on the XIAP and IGF-Irβ expression levels can separate AFP producing gastric adenocarcinoma patients into 2 subgroups and each subgroup had a distinct set of signaling pathways involved. In conclusion, AFP producing gastric adenocarcinoma is a heterogeneous cancer with different clinical outcomes, biological behaviors and underlying molecular alterations. PMID:27057629

  13. 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

    2016-02-01

    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.

  14. 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

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

    ClinicalTrials.gov

    2016-06-03

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

  16. Catumaxomab for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas

    ClinicalTrials.gov

    2016-10-13

    Gastric Adenocarcinoma With Peritoneal Carcinomatosis; Siewert Type II Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis; Siewert Type III Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis

  17. Passive smoking and risk of oesophageal and gastric adenocarcinomas

    PubMed Central

    Duan, L; Wu, A H; Sullivan-Halley, J; Bernstein, L

    2009-01-01

    Few studies have examined the association between passive smoking and the risk of oesophageal and gastric adenocarcinomas. In a population-based case–control study with 2474 participants in Los Angeles County, there was no evidence that passive smoking had any appreciable effect on oesophageal or gastric adenocarcinomas. PMID:19352383

  18. 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.

  19. Comprehensive molecular characterization of gastric adenocarcinoma

    PubMed Central

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  20. 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. PMID:26585375

  1. Gastric Adenocarcinoma after Gastric Bypass for Morbid Obesity: A Case Report and Review of the Literature

    PubMed Central

    Ribeiro, Maxwel Capsy Boga; Lopes, Luiz Roberto; Coelho Neto, João de Souza; Tercioti, Valdir; Andreollo, Nelson Adami

    2013-01-01

    Gastric adenocarcinoma after gastric bypass for morbid obesity is rare but has been described. The diet restriction, weight loss, and difficult assessment of the bypassed stomach, after this procedure, hinder and delay its diagnosis. We present a 52-year-old man who underwent Roux-en-Y gastric bypass 2 years ago and whose previous upper digestive endoscopy was considered normal. He presented with weight loss, attributed to the procedure, and progressive dysphagia. Upper digestive endoscopy revealed stenosing tumor in gastric pouch whose biopsy showed diffuse-type gastric adenocarcinoma. He underwent total gastrectomy, left lobectomy, distal pancreatectomy and splenectomy, segmental colectomy, and bowel resection with esophagojejunal anastomosis. The histopathological analysis confirmed the presence of gastric cancer. The pathogenesis of gastric pouch adenocarcinoma is discussed with a literature review. PMID:23509467

  2. PINCH Expression and Its Clinicopathological Significance in Gastric Adenocarcinoma

    PubMed Central

    Zhu, Zhen-Long; Yan, Bao-Yong; Zhang, Yu; Yang, Yan-Hong; Wang, Zheng-Min; Zhang, Hong-Zhen; Wang, Ming-Wei; Zhang, Xiang-Hong; Sun, Xiao-Feng

    2012-01-01

    Objective: Particularly interesting new cysteine-histidine rich protein (PINCH) is an important component of the local adhesion complexes and upregulated in several types of malignancies, and involved in the incidence and development of tumours. PINCH expression is also independently correlated with poorer survival in patients with colorectal cancer. However, there is no study of PINCH in gastric cancer, therefore, the aim of this project was to investigate PINCH expression and its clinicopathological significance in gastric adenocarcinoma. Patients and methods: PINCH expression was immunohistochemically examined in normal gastric mucous (n = 30) and gastric adenocarcinoma (n = 73), from gastric cancer patients. Results: PINCH expression in the associated-stroma of gastric cancers was heterogeneous, and its positive rate (75%) was higher than that of normal gastric mucosa (43%, X2 = 9.711, p = 0.002). The stronger staining was observed at the invasive edge of tumour when compared to the inner area of tumour. The rate of positive PINCH (88%) in the cases with lymph node metastasis was higher than that (52%) in the cases without metastasis (X2 = 11.151, p = 0.001). PINCH expression was not correlated with patients’ gender, age, tumour size, differentiation and invasion depth (p > 0.05). Comclusion: PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma. PMID:22976000

  3. Numb chin syndrome secondary to leptomeningeal carcinomatosis from gastric adenocarcinoma.

    PubMed

    Riesgo, Vincent J; Delgado, Silvia R; Poveda, Julio; Rammohan, Kottil

    2015-04-01

    Numb chin syndrome (NCS) can be a sign of malignancy. Its association with gastric adenocarcinoma is rare. We report a case of a 27-year-old Hispanic female that presented with complaint of left sided headache associated with numbness of the left side of chin and lower gingiva. Initial brain MRI, whole body gallium scan, high resolution CT of chest and elevated protein in the CSF were suggestive of sarcoidosis. She was treated with IV steroids with transient clinical improvement. Two weeks later, her symptoms worsened and further evaluation revealed the diagnosis of a poorly differentiated metastatic gastric adenocarcinoma with leptomeningeal involvement. This case report aims to emphasize the importance of identifying NCS as a possible indication of an underlying malignant condition. Reported cases of NCS associated with metastatic gastric adenocarcinoma are very rare.

  4. Poorly Differentiated Gastric Adenocarcinoma Can Mimic Hilar Cholangiocarcinoma.

    PubMed

    Urasaki, Tetsuya; Kodaira, Makoto; Hibino, Masaki; Yamagata, Shingo; Watanabe, Yukihiro; Terazawa, Yasuyuki; Sano, Munetaka; Kuriki, Ken

    2016-01-01

    This report describes two cases with obstructive jaundice caused by poorly differentiated gastric adenocarcinoma. Computed tomography scans showed circumferential stenosis in the hilar bile ducts. Endoscopic retrograde cholangiopancreatography showed dilatation of the bilateral hepatic ducts and stenosis of the common hepatic ducts from the bifurcation of the bilateral hepatic ducts. The first diagnoses were hilar cholangiocarcinoma and biliary drainage decreased serum bilirubin; however, both patients died of cancer within a short period of time. Autopsies revealed lymphatic vessel invasion and possible subepithelial invasion by gastric adenocarcinoma into the hilar bile ducts. A differential diagnosis should thus be required in suspected cases of hilar cholangiocarcinoma.

  5. Opium: an emerging risk factor for gastric adenocarcinoma.

    PubMed

    Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Aghcheli, Karim; Sotoudeh, Masoud; Islami, Farhad; Pourshams, Akram; Pawlita, Michael; Boffetta, Paolo; Dawsey, Sanford M; Abnet, Christian C; Kamangar, Farin

    2013-07-15

    Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9-5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance.

  6. Nobiletin, a citrus flavonoid, suppresses invasion and migration involving FAK/PI3K/Akt and small GTPase signals in human gastric adenocarcinoma AGS cells.

    PubMed

    Lee, Yi-Chieh; Cheng, Tsan-Hwang; Lee, Jung-Shin; Chen, Jiun-Hwan; Liao, Yi-Chen; Fong, Yao; Wu, Cheng-Hsun; Shih, Yuan-Wei

    2011-01-01

    Nobiletin, a compound isolated from citrus fruits, is a polymethoxylated flavone derivative shown to have anti-inflammatory, antitumor, and neuroprotective properties. This study has investigated that nobiletin exerted inhibitory effects on the cell adhesion, invasion, and migration abilities of a highly metastatic AGS cells under non-cytotoxic concentrations. Data also showed nobiletin could inhibit the activation of focal adhesion kinase (FAK) and phosphoinositide-3-kinase/Akt (PI3K/Akt) involved in the downregulation of the enzyme activities, protein expressions, messenger RNA levels of matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-2 (MMP-9). Also, our data revealed that nobiletin inhibited FAK/PI3K/Akt with concurrent reduction in the protein expressions of Ras, c-Raf, Rac-1, Cdc42, and RhoA by western blotting, whereas the protein level of RhoB increased progressively. Otherwise, nobiletin-treated AGS cells showed tremendously decreased in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), the nuclear level of NF-κB, and the binding ability of NF-κB to NF-κB response element. Furthermore, nobiletin significantly decreased the levels of phospho-Akt and MMP-2/9 in Akt1-cDNA-transfected cells concomitantly with a marked reduction in cell invasion and migration. These results suggest that nobiletin can reduce invasion and migration of AGS cells, and such a characteristic may be of great value in the development of a potential cancer therapy.

  7. Functional Genetic Variants of TNFSF15 and Their Association with Gastric Adenocarcinoma: A Case-Control Study

    PubMed Central

    Lu, Jie; Zhai, Kan; Cao, Lei; Rao, Juan; Liu, Yingwen; Zhang, Xuemei; Guo, Yongli

    2014-01-01

    The purpose of this study was to identify functional genetic variants in the promoter of tumor necrosis factor superfamily member 15 (TNFSF15) and evaluate their effects on the risk of developing gastric adenocarcinoma. Forty DNA samples from healthy volunteers were sequenced to identify single nucleotide polymorphisms (SNPs) in the TNFSF15 promoter. Two TNFSF15 SNPs (−358T>C and −638A>G) were identified by direct sequencing. Next, genotypes and haplotypes of 470 gastric adenocarcinoma patients and 470 cancer-free controls were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Serologic tests for Helicobacter pylori infection were measured by enzyme-linked immuno-sorbent assay (ELISA). Subjects carrying the TNFSF15 −358CC genotype were at an elevated risk for developing gastric adenocarcinoma, compared with those with the −358TT genotype (OR 1.42, 95% CI, 1.10 to 2.03). H. pylori infection was a risk factor for developing gastric adenocarcinoma (OR 2.31, 95% CI, 1.76 to 3.04). In the H. pylori infected group, subjects with TNFSF15 −358CC genotype were at higher risks for gastric adenocarcinoma compared with those carrying −358TT genotype (OR: 2.01, 95%CI: 1.65 to 4.25), indicating that H. pylori infection further influenced gastric adenocarcinoma susceptibility. The −358 T>C polymorphism eliminates a nuclear factor Y (NF-Y) binding site and the −358C containing haplotypes showed significantly decreased luciferase expression compared with −358T containing haplotypes. Collectively these findings indicate that functional genetic variants in TNFSF15 may play a role in increasing susceptibility to gastric adenocarcinoma. PMID:25251497

  8. Cutaneous metastases from gastric adenocarcinoma 15 years after curative gastrectomy.

    PubMed

    Liu, Fang; Yan, Wen Liang; Liu, Haibo; Zhang, Min; Sang, Hong

    2015-01-01

    We report the case of a 38-year-old man, who developed cutaneous metastases in the left inguinal groove 15 years after curative gastrectomy for advanced gastric adenocarcinoma. Histopathologic examination revealed poorly differentiated adenocarcinoma cells. They were stained positive for villin, CDX-2, CKpan (AE1/ AE3), CEA, CK8/18, CK19, CK7, EMA, Ki-67 (50%), and negative for S-100, CK20, CD34, GCDFP-15 and TTF-1. The patient underwent local excision, after the presence of other metastases was excluded. Nevertheless, local recurrence developed at the surgical bed one year later and PET/CT revealed metastases to lymph nodes, bone and skin. He died 2 years after the appearance of cutaneous metastases. We have reviewed the literature and described the immunohistochemical characteristics of cutaneous metastases from gastric adenocarcinoma. PMID:26312672

  9. HER2 testing in gastric and gastroesophageal adenocarcinomas.

    PubMed

    Vakiani, Efsevia

    2015-05-01

    The human epidermal growth factor receptor 2 (HER2) is overexpressed in 10% to 35% of gastric and gastroesophageal junction (GEJ) adenocarcinomas. In 2010, the phase III Trastuzumab for Gastric Cancer (ToGA) trial showed that addition of the anti-HER2 monoclonal antibody trastuzumab to chemotherapy significantly improved survival of patients with advanced or metastatic tumors that were positive for HER2 overexpression. As a result, HER2 testing is now recommended for all patients with advanced or metastatic disease, although there is still some debate as to the optimal methods of assessment. HER2 expression in gastric and GEJ tumors shows several differences compared with breast tumors and, for this reason, the proposed criteria for scoring HER2 expression in biopsies and resections of gastric and GEJ carcinomas differ from those used in breast carcinomas. This review discusses what is currently known about the patterns of HER2 expression in gastric and GEJ adenocarcinomas, summarizes the findings of the ToGA trial and its clinical implications, and provides an overview of the recommended guidelines for the most accurate evaluation of HER2 status in gastric and GEJ cancer.

  10. Low SP1 Expression Differentially Affects Intestinal-Type Compared with Diffuse-Type Gastric Adenocarcinoma

    PubMed Central

    Oh, Ensel; Erkin, Özgür Cem; Jung, Hun Soon; Cho, Mi-Hyun; Kwon, Mi Jeong; Chae, Seoung Wan; Kim, Seok-Hyung; Wang, Li-Hui; Park, Min-Jeong; Lee, Su-Yeon; Yang, Ho Bin; Jia, Lina; Choi, Yoon-La; Shin, Young Kee

    2013-01-01

    Specificity protein 1 (SP1) is an essential transcription factor that regulates multiple cancer-related genes. Because aberrant expression of SP1 is related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. Although patient survival decreased as SP1 expression increased (P<0.05) in diffuse-type gastric cancer, the lack of SP1 expression in intestinal-type gastric cancer was significantly correlated with poor survival (P<0.05). The knockdown of SP1 in a high SP1-expressing intestinal-type gastric cell line, MKN28, increased migration and invasion but decreased proliferation. Microarray data in SP1 siRNA-transfected MKN28 revealed that the genes inhibiting migration were downregulated, whereas the genes negatively facilitating proliferation were increased. However, both migration and invasion were decreased by forced SP1 expression in a low SP1-expressing intestinal-type gastric cell line, AGS. Unlike the intestinal-type, in a high SP1-expressing diffuse-type gastric cell line, SNU484, migration and invasion were decreased by SP1 siRNA. In contrast to previous studies that did not identify differences between the 2 histological types, our results reveal that low expression of SP1 is involved in cancer progression and metastasis and differentially affects intestinal-type compared with diffuse-type gastric adenocarcinoma. PMID:23437057

  11. Gastric adenocarcinoma concurrent with paravertebral plasmacytoma: A case report

    PubMed Central

    Du, Fengcai; Jiang, Lixin; Zhu, Fangqing; Gong, Zhao Hua; Chen, Jian; Zhang, Liangming

    2016-01-01

    Here, we report the case of a 77-year-old male patient who was revealed to have an unsuspected case of gastric adenocarcinoma with paravertebral plasmacytoma following biopsy. Plasmacytoma may be classified into two main groups: Multiple myeloma and plasmacytoma without marrow involvement. It comprises isolated plasmacytoma of the bone and extramedullary plasmacytoma. Extramedullary plasmacytoma (EMP) accounts for 3% of all plasmacytomas; however, ~80% are located in the upper respiratory tract and upper gastrointestinal tract. It occurs extremely rarely in paravertebral areas. Case reports of EMP and other types of malignant tumor occurring at the same time have not been identified in searches of the literature. In the present study, we describe the diagnosis and treatment process of a case of gastric adenocarcinoma concurrent with paravertebral plasmacytoma. It may be helpful for early clinical diagnosis and treatment of such cases. PMID:27446469

  12. Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma.

    PubMed

    Tan, Patrick; Yeoh, Khay-Guan

    2015-10-01

    Gastric cancer (GC) is globally the fifth most common cancer and third leading cause of cancer death. A complex disease arising from the interaction of environmental and host-associated factors, key contributors to GC's high mortality include its silent nature, late clinical presentation, and underlying biological and genetic heterogeneity. Achieving a detailed molecular understanding of the various genomic aberrations associated with GC will be critical to improving patient outcomes. The recent years has seen considerable progress in deciphering the genomic landscape of GC, identifying new molecular components such as ARID1A and RHOA, cellular pathways, and tissue populations associated with gastric malignancy and progression. The Cancer Genome Atlas (TCGA) project is a landmark in the molecular characterization of GC. Key challenges for the future will involve the translation of these molecular findings to clinical utility, by enabling novel strategies for early GC detection, and precision therapies for individual GC patients.

  13. Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma

    PubMed Central

    Eivaz-Mohammadi, Sahar; Tarar, Omer; Malik, Khurram; Syed, Amer K.

    2014-01-01

    A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0–5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma. PMID:25349615

  14. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy.

    PubMed

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008-2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  15. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

    PubMed Central

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  16. Postoperative adjuvant radiotherapy for patients with gastric adenocarcinoma.

    PubMed

    Lim, Do Hoon

    2012-12-01

    In gastric adenocarcinoma, high rates of loco-regional recurrences have been reported even after complete resection, and various studies have been tried to find the role of postoperative adjuvant therapy. Among them, Intergroup 0116 trial was a landmark trial, and demonstrated the definite survival benefit in adjuvant chemoradiotherapy, compared with surgery alone. However, the INT 0116 trial had major limitation for global acceptance of the INT 0116 regimen as an adjuvant treatment modality because of the limited lymph node dissection. Lately, several randomized studies that were performed to patients with D2-dissected gastric cancer were published. This review summarizes the data about patterns of failure after surgical resection and the earlier prospective studies, including INT 0116 study. Author will introduce the latest studies, including ARTIST trial and discuss whether external beam radiotherapy should be applied to patients receiving extended lymph node dissection and adjuvant chemotherapy. PMID:23346491

  17. Salt-Inducible Kinase 1 (SIK1) Is Induced by Gastrin and Inhibits Migration of Gastric Adenocarcinoma Cells

    PubMed Central

    Selvik, Linn-Karina M.; Rao, Shalini; Steigedal, Tonje S.; Haltbakk, Ildri; Misund, Kristine; Bruland, Torunn; Prestvik, Wenche S.; Lægreid, Astrid; Thommesen, Liv

    2014-01-01

    Salt-inducible kinase 1 (SIK1/Snf1lk) belongs to the AMP-activated protein kinase (AMPK) family of kinases, all of which play major roles in regulating metabolism and cell growth. Recent studies have shown that reduced levels of SIK1 are associated with poor outcome in cancers, and that this involves an invasive cellular phenotype with increased metastatic potential. However, the molecular mechanism(s) regulated by SIK1 in cancer cells is not well explored. The peptide hormone gastrin regulates cellular processes involved in oncogenesis, including proliferation, apoptosis, migration and invasion. The aim of this study was to examine the role of SIK1 in gastrin responsive adenocarcinoma cell lines AR42J, AGS-GR and MKN45. We show that gastrin, known to signal through the Gq/G11-coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP early repressor (ICER). We demonstrate that gastrin-mediated signalling induces phosphorylation of Liver Kinase 1B (LKB1) Ser-428 and SIK1 Thr-182. Ectopic expression of SIK1 increases gastrin-induced phosphorylation of histone deacetylase 4 (HDAC4) and enhances gastrin-induced transcription of c-fos and CRE-, SRE-, AP1- and NF-κB-driven luciferase reporter plasmids. We also show that gastrin induces phosphorylation and nuclear export of HDACs. Next we find that siRNA mediated knockdown of SIK1 increases migration of the gastric adenocarcinoma cell line AGS-GR. Evidence provided here demonstrates that SIK1 is regulated by gastrin and influences gastrin elicited signalling in gastric adenocarcinoma cells. The results from the present study are relevant for the understanding of molecular mechanisms involved in gastric adenocarcinomas. PMID:25384047

  18. Salt-inducible kinase 1 (SIK1) is induced by gastrin and inhibits migration of gastric adenocarcinoma cells.

    PubMed

    Selvik, Linn-Karina M; Rao, Shalini; Steigedal, Tonje S; Haltbakk, Ildri; Misund, Kristine; Bruland, Torunn; Prestvik, Wenche S; Lægreid, Astrid; Thommesen, Liv

    2014-01-01

    Salt-inducible kinase 1 (SIK1/Snf1lk) belongs to the AMP-activated protein kinase (AMPK) family of kinases, all of which play major roles in regulating metabolism and cell growth. Recent studies have shown that reduced levels of SIK1 are associated with poor outcome in cancers, and that this involves an invasive cellular phenotype with increased metastatic potential. However, the molecular mechanism(s) regulated by SIK1 in cancer cells is not well explored. The peptide hormone gastrin regulates cellular processes involved in oncogenesis, including proliferation, apoptosis, migration and invasion. The aim of this study was to examine the role of SIK1 in gastrin responsive adenocarcinoma cell lines AR42J, AGS-GR and MKN45. We show that gastrin, known to signal through the Gq/G11-coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP early repressor (ICER). We demonstrate that gastrin-mediated signalling induces phosphorylation of Liver Kinase 1B (LKB1) Ser-428 and SIK1 Thr-182. Ectopic expression of SIK1 increases gastrin-induced phosphorylation of histone deacetylase 4 (HDAC4) and enhances gastrin-induced transcription of c-fos and CRE-, SRE-, AP1- and NF-κB-driven luciferase reporter plasmids. We also show that gastrin induces phosphorylation and nuclear export of HDACs. Next we find that siRNA mediated knockdown of SIK1 increases migration of the gastric adenocarcinoma cell line AGS-GR. Evidence provided here demonstrates that SIK1 is regulated by gastrin and influences gastrin elicited signalling in gastric adenocarcinoma cells. The results from the present study are relevant for the understanding of molecular mechanisms involved in gastric adenocarcinomas. PMID:25384047

  19. Adenocarcinoma of the GEJ: gastric or oesophageal cancer?

    PubMed

    Rüschoff, J

    2012-01-01

    According to WHO (2010) adenocarcinomas of the esophagogastric junction (GEJ) are defined as tumors that cross the most proximal extent of the gastric folds regardless of where the bulk of the tumor lies. In addition, these neoplasms are now classified as esophageal cancers by UICC (2010). Recent studies, however, revealed two types of carcinogenesis in the distal oesophagus and at the GEJ, one of intestinal type (about 80 %) and the other of gastric type (about 20 %). These are characterized by marked differences in morphology, tumor stage at diagnosis, and prognosis. Furthermore, both cancer types show different targetable biomarker expression profiles such as Her2 in the intestinal and EGFR in the non-intestinal pathway indicating new therapy options. Due to the fact that carcinomas of the intestinal pathway were typically associated with Barrett's mucosa which was not the case in the non-intestinal-type tumors, this challenges the paradigm "no goblets no Barrett's". Moreover, even the cancer risk of intestinal-type metaplasia has seriously been questioned by a Danish population-based study where Barrett's mucosa turned out to be only a weak indicator of esophageal and GEJ cancer (1 case in 860 patients years). Thus, two biologically different types of cancer arise at the GEJ-esophageal and gastric type that open distinctive targeted treatment options and also question our current concept about the diagnostics of potential precursor lesions as well as the associated screening and surveillance strategy.

  20. Distal Esophageal Adenocarcinoma and Gastric Adenocarcinoma: Time for a Shared Research Agenda.

    PubMed

    Jansen, Marnix; Wright, Nicholas A

    2016-01-01

    The key insight that sparked Darwin's theory of descent with modification was that he compared and contrasted differences between living and extinct species across time and space. He likely arrived on this theory in large part through his culinary experiences, set against the background of the rugged Patagonian landscape of Southern Argentina. We feel that further integration of research into gastric and esophageal adenocarcinoma may benefit both fields and similarly lead to a coherent understanding of cancer progression in the upper gastrointestinal tract across time and space. Although the environmental trigger differs between carcinogenesis of the stomach and distal esophagus, there remain many important lessons to be learned from comparing precursor stages, such as intestinal metaplasia, across anatomic borders. This analysis will absolutely require detailed sampling within and between these related species, but most importantly we need higher resolution clinical phenotyping to relate genomic differences to drivers of morphologic evolution. In the end, this may provide us with a new phylogeny showing key differences between esophageal and gastric adenocarcinoma. PMID:27573764

  1. Expression of Pdx-1 in human gastric metaplasia and gastric adenocarcinoma.

    PubMed

    Leys, Charles M; Nomura, Sachiyo; Rudzinski, Erin; Kaminishi, Michio; Montgomery, Elizabeth; Washington, Mary Kay; Goldenring, James R

    2006-09-01

    Metaplastic lineages represent critical putative preneoplastic precursors for gastrointestinal metaplasia. Two metaplastic processes are associated with gastric cancer: intestinal metaplasia (the presence of intestinal goblet cell containing lineages in the stomach) and spasmolytic polypeptide-expressing metaplasia (SPEM; antralization of the gastric fundus). The transcription factor Pdx-1 is expressed in the adult pancreatic islet cells as well as the gastric antrum and duodenum. We have previously noted the increase in Pdx-1 expression in models of TGFalpha overexpression in mice but not in other models of SPEM in rodents. We have therefore sought to examine the presence of Pdx-1 expression in gastric metaplasias and gastric adenocarcinoma in humans. Tissue microarrays containing gastric cancers from the fundus and antrum and samples of SPEM and intestinal metaplasia were immunostained for Pdx-1. Nuclear Pdx-1 expression was observed in only 50% of antral-derived cancers and was present in 40% of fundic tumors. Pdx-1 expression did not correlate with clinical outcome. Although SPEM lineages did not show any staining for Pdx-1, intestinal metaplasia showed strong nuclear staining for Pdx-1. Thus, Pdx-1 expression is not associated with antralizing metaplasia (SPEM) but is associated with intestinal metaplasia. Given the pattern of normal Pdx-1 expression in the duodenum, goblet cell metaplasia in the stomach may reflect the adoption of a duodenal lineage paradigm.

  2. Identification of Differentiation-Related Proteins in Gastric Adenocarcinoma Tissues by Proteomics.

    PubMed

    Zhou, Xin; Yao, Kun; Zhang, Lang; Zhang, Ying; Han, Yin; Liu, Hui-Ling; Liu, Xiang-Wen; Su, Gang; Yuan, Wen-Zhen; Wei, Xiao-Dong; Guan, Quan-Lin; Zhu, Bing-Dong

    2016-10-01

    There is a significant correlation between the degree of tumor differentiation and the survival of patients with gastric cancers. In this report, we compared proteomic differences between poorly differentiated gastric adenocarcinoma tissues and well-differentiated gastric adenocarcinoma tissues in order to identify differentiation-related proteins that may be closely correlated with differentiation of gastric cancer pathogenesis. We identified 7 proteins, of which calreticulin precursor, tapasinERP57 heterodimer, pyruvate kinase isozymes M1/M2 isoform M2, class Pi glutathione S-transferase, and chain A crystal structure of human enolase 1 were upregulated in poorly differentiated gastric adenocarcinoma compared with well-differentiated gastric adenocarcinoma, while myosin-11 isoform SM2A and actin alpha cardiac were downregulated. Two of them, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 are enzymes involved in glycolytic pathway. The upregulation of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 in poorly differentiated gastric adenocarcinoma was confirmed by Western blotting and immunohistochemistry. Furthermore, we observed 107 cases with gastric adenocarcinoma and found that the high expression of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 correlates with tumor size (P = .0001 and P = .0017, respectively), depth of invasion (P = .0024 and P = .0261, respectively), and poor prognosis of patients. In conclusion, with this proteomic analysis, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 were identified upregulated in poorly differentiated gastric adenocarcinoma comparing with well-differentiated gastric adenocarcinoma. The expression level of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 was significantly correlated with overall survival. Some of them would be differentiation-related cancer biomarkers and are associated with tumor metastasis, invasion, and prognosis. PMID:27624754

  3. CYR61 (CCN1) is a metastatic biomarker of gastric cardia adenocarcinoma

    PubMed Central

    Wei, Jing; Yu, Guanzhen; Shao, Genbao; Sun, Aiqin; Chen, Miao; Yang, Wannian; Lin, Qiong

    2016-01-01

    Gastric cardia adenocarcinoma (GCA) is the most aggressive subtype of gastric cancer with a high metastatic rate. In this report, we collected tumor tissue samples from 214 GCA cases and examined expression of CYR61, a target gene product of the Hippo-YAP/TAZ pathway, in the GCA tumors by immunohistochemical (IHC) staining using the tissue microarray assay (TMA). The results have shown that CYR61 is overexpressed in 44% of the GCA tumor samples. Expression of CYR61 is inversely correlated with cumulative survival of GCA patients (p<0.001) and significantly associated only with metastatic pathological categories (with N category, p=0.052; with TNM stage, p=0.001). Furthermore, knockdown of CYR61 in gastric cancer AGS cells impairs the cancer cell migration and invasion, suggesting a driver role of CYR61 in metastasis. Thus, our studies have established CYR61 as a metastatic biomarker for prediction of poor prognosis of GCA and provided a potential molecular target for anti-metastatic therapy of GCA. PMID:27105510

  4. [Gastric adenocarcinoma: approach to a complex biological reality].

    PubMed

    Sánchez-Fayos, Paloma; Martín Relloso, María Jesús; González Guirado, Agustina; Porres Cubero, Juan Carlos

    2007-01-13

    The authors review the complex biological reality of gastric adenocarcinoma from several viewpoints. It is a neoplasm histologically expressed as a dual process (intestinal and diffuse types) with a broad cytological diversity. From an epidemiological point of view, it behaves as an entity with a deep geographical asymmetry and a changing incidence, currently decreasing. There is a multifactorial etiology with a combination of genetic, infectious (H. pylori), nutritional and environmental factors. It might have a multiphasic gestation from precancerous lesions, though not always following a lineal sequence. We only know fragmentary portions of its pathogenesis whose common denominator is a potentially mutagenic mitogenic activation of the epithelial cells implicated. A good knowledge of this complex biological reality will allow the identification of better markers for an early diagnosis as well as vulnerable etiopathogenetic points for a useful prevention and therapy.

  5. Co-expressed miRNAs in gastric adenocarcinoma.

    PubMed

    Yepes, Sally; López, Rocío; Andrade, Rafael E; Rodriguez-Urrego, Paula A; López-Kleine, Liliana; Torres, Maria Mercedes

    2016-08-01

    Co-expression networks may provide insights into the patterns of molecular interactions that underlie cellular processes. To obtain a better understanding of miRNA expression patterns in gastric adenocarcinoma and to provide markers that can be associated with histopathological findings, we performed weighted gene correlation network analysis (WGCNA) and compare it with a supervised analysis. Integrative analysis of target predictions and miRNA expression profiles in gastric cancer samples was also performed. WGCNA identified a module of co-expressed miRNAs that were associated with histological traits and tumor condition. Hub genes were identified based on statistical analysis and network centrality. The miRNAs 100, let-7c, 125b and 99a stood out for their association with the diffuse histological subtype. The 181 miRNA family and miRNA 21 highlighted for their association with the tumoral phenotype. The integrated analysis of miRNA and gene expression profiles showed the let-7 miRNA family playing a central role in the regulatory relationships. PMID:27422560

  6. Helicobacter pylori-binding gangliosides of human gastric adenocarcinoma.

    PubMed

    Roche, N; Larsson, T; Angström, J; Teneberg, S

    2001-11-01

    Acidic and neutral glycosphingolipids were isolated from a human gastric adenocarcinoma, and binding of Helicobacter pylori to the isolated glycosphingolipids was assessed using the chromatogram binding assay. The isolated glycosphingolipids were characterized using fast atom bombardment mass spectrometry and by binding of antibodies and lectins. The predominating neutral glycosphingolipids were found to migrate in the di- to tetraglycosylceramide regions as revealed by anisaldehyde staining and detection with lectins. No binding of H. pylori to these compounds was obtained. The most abundant acidic glycosphingolipids, migrating as the GM3 ganglioside and sialyl-neolactotetraosylceramide, were not recognized by the bacteria. Instead, H. pylori selectively interacted with slow-migrating, low abundant gangliosides not detected by anisaldehyde staining. Binding-active gangliosides were isolated and characterized by mass spectrometry, proton nuclear magnetic resonance, and lectin binding as sialyl-neolactohexaosylceramide (NeuAcalpha3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer) and sialyl-neolactooctaosylceramide (NeuAcalpha3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer).

  7. Gastroduodenal Intussusception Caused by a Gastric Collision Tumor Consisting of Adenocarcinoma and Neuroendocrine Carcinoma

    PubMed Central

    Kadowaki, Yoshihiko; Nishimura, Takeshi; Komoto, Satoshi; Yuasa, Takeshi; Tamura, Ryuji; Okamoto, Takahiro; Ishido, Nobuhiro

    2014-01-01

    Adenocarcinoma is the most common histological type of gastric tumor. Gastric tumor arising from collision of an adenocarcinoma with a neuroendocrine carcinoma is extremely rare. Moreover, this uncommon gastric collision tumor in our case had prolapsed into the duodenum. A 77-year-old woman was admitted to our hospital complaining of vomiting and severe weight loss. Abdominal X-ray showed gastric distension, and computed tomography revealed a duodenal giant mass spreading from the bulb to the horizontal part of the duodenum. Upper gastrointestinal endoscopy was not helpful in confirming the diagnosis of the tumor. We suspected duodenal malignant tumor and performed laparotomy. The operative findings indicated that the gastric antrum was deeply invaginated into the duodenum because of the gastric tumor. Partial resection of the stomach and duodenum was performed because the tumor was irreducible. Intraoperative diagnosis of the frozen section was well-differentiated adenocarcinoma and undifferentiated carcinoma. Additional distal gastrectomy with lymphadenectomy was performed. We herein report the first case of gastroduodenal intussusception caused by a gastric collision tumor consisting of well-differentiated adenocarcinoma and poorly differentiated neuroendocrine carcinoma. PMID:24803892

  8. Overexpression of DEK is an indicator of poor prognosis in patients with gastric adenocarcinoma

    PubMed Central

    OU, YINGFU; XIA, RONGJUN; KONG, FANYONG; ZHANG, XIAOKANG; YU, SHENGJIN; JIANG, LILI; ZHENG, LINLIN; LIN, LIJUAN

    2016-01-01

    Increased expression of the human DEK proto-oncogene (DEK) gene has been associated with numerous human malignancies. The DEK protein is associated with chromatin reconstruction and gene transcription, and is important in cell apoptosis. The present study aimed to elucidate the role of DEK with regard to gastric adenocarcinoma tumor progression and patient prognosis. DEK protein expression was analyzed using immunohistochemistry in 192 tumors paired with adjacent non-cancerous gastric mucosa that had been surgically resected from patients with primary gastric adenocarcinoma. The association between DEK expression and the clinicopathological characteristics of the patients was evaluated using the χ2 test and Fisher's exact test. The survival rates of the patients were calculated using the Kaplan-Meier method. Cox analysis evaluated the association between the expression of DEK and the survival rate of the patients. The DEK protein was expressed in 84 patients with gastric adenocarcinoma (43.8%) and in 20 of the paired normal gastric mucosa tissues (11.5%). The DEK expression rate was found to be associated with tumor size (P=0.006), tumor grade (P=0.023), lymph node metastasis (P=0.018), serous invasion (P=0.026), tumor stage (P=0.001) and Ki-67 expression (P=0.003). Furthermore, patients with gastric adenocarcinoma that expressed DEK had decreased disease-free (log-rank, 16.785; P<0.0001) and overall (log-rank, 15.759; P<0.0001) survival rates compared with patients without DEK expression. Patients with late-stage gastric adenocarcinoma that expressed DEK exhibited a lower overall survival rate compared with patients without DEK expression (P=0.002). Additional analysis revealed that DEK expression was an independent prognostic factor for the prognosis of gastric adenocarcinoma (hazard ratio, 0.556; 95% confidence interval, 0.337–0.918; P=0.022). From the results of the present study, it can be concluded that the detection of DEK protein expression in gastric

  9. Genetic Mechanisms and Aberrant Gene Expression during the Development of Gastric Intestinal Metaplasia and Adenocarcinoma

    PubMed Central

    Holmes, K; Egan, B; Swan, N; O’Morain, C

    2007-01-01

    Gastric adenocarcinoma occurs via a sequence of molecular events known as the Correa’s Cascade which often progresses over many years. Gastritis, typically caused by infection with the bacterium H. pylori, is the first step of the cascade that results in gastric cancer; however, not all cases of gastritis progress along this carcinogenic route. Despite recent antibiotic intervention of H. pylori infections, gastric adenocarcinoma remains the second most common cause of cancer deaths worldwide. Intestinal metaplasia is the next step along the carcinogenic sequence after gastritis and is considered to be a precursor lesion for gastric cancer; however, not all patients with intestinal metaplasia develop adenocarcinoma and little is known about the molecular and genetic events that trigger the progression of intestinal metaplasia into adenocarcinoma. This review aims to highlight the progress to date in the genetic events involved in intestinal-type gastric adenocarcinoma and its precursor lesion, intestinal metaplasia. The use of technologies such as whole genome microarray analysis, immunohistochemical analysis and DNA methylation analysis has allowed an insight into some of the events which occur in intestinal metaplasia and may be involved in carcinogenesis. There is still much that is yet to be discovered surrounding the development of this lesion and how, in many cases, it develops into a state of malignancy. PMID:19412438

  10. Cancer Stem Cell Markers CD44, CD133 in Primary Gastric Adenocarcinoma.

    PubMed

    Nosrati, Anahita; Naghshvar, Farshad; Khanari, Somaieh

    2014-01-01

    Cancer stem cells (CSCs) are unique subpopulations that have the capacity to drive malignant progression with renewal abilities. Recently the role of some of CSCs in gastric adenocarcinoma has been studied. This study was performed in order to evaluate CD44 and CD133 expressions by immunohistochemistry in 95 primary gastric adenocarcinoma and their relation to clinical and pathological parameters of these tumors. There was a significant correlation between CD44 expression and cancer subtype (intestinal), tumor size (4-8 cm), depth of invasion, no lymphatic/vascular invasion and moderate differentiation. There was a significant correlation between CD133 expression and patient's age (> 65 years), cancer subtype (intestinal), tumor size (4-8 cm), depth of invasion and moderate differentiation. CSC markers like CD 44 and CD133 had high expression in primary gastric adenocarcinoma and had some relations to clinical and pathological parameters of tumors. PMID:25635255

  11. Cancer Stem Cell Markers CD44, CD133 in Primary Gastric Adenocarcinoma

    PubMed Central

    Nosrati, Anahita; Naghshvar, Farshad; Khanari, Somaieh

    2014-01-01

    Cancer stem cells (CSCs) are unique subpopulations that have the capacity to drive malignant progression with renewal abilities. Recently the role of some of CSCs in gastric adenocarcinoma has been studied. This study was performed in order to evaluate CD44 and CD133 expressions by immunohistochemistry in 95 primary gastric adenocarcinoma and their relation to clinical and pathological parameters of these tumors. There was a significant correlation between CD44 expression and cancer subtype (intestinal), tumor size (4-8 cm), depth of invasion, no lymphatic/vascular invasion and moderate differentiation. There was a significant correlation between CD133 expression and patient's age (> 65 years), cancer subtype (intestinal), tumor size (4-8 cm), depth of invasion and moderate differentiation. CSC markers like CD 44 and CD133 had high expression in primary gastric adenocarcinoma and had some relations to clinical and pathological parameters of tumors. PMID:25635255

  12. A Detailed Immunohistochemical Analysis of a Large Series of Cervical and Vaginal Gastric-type Adenocarcinomas.

    PubMed

    Carleton, Claire; Hoang, Lien; Sah, Shatrughan; Kiyokawa, Takako; Karamurzin, Yevgeniy S; Talia, Karen L; Park, Kay J; McCluggage, W Glenn

    2016-05-01

    Adenocarcinomas exhibiting gastric differentiation represent a recently described and uncommon subtype of non-human papillomavirus (HPV)-related cervical adenocarcinoma. They comprise a spectrum from a well-differentiated variant (adenoma malignum/mucinous variant of minimal deviation adenocarcinoma) to a more poorly differentiated overtly malignant form, generally referred to as gastric-type adenocarcinoma. Rarely, such tumors have also been described as primary vaginal neoplasms. Gastric-type adenocarcinomas exhibit considerable morphologic overlap with adenocarcinomas originating outside the female genital tract, especially mucinous adenocarcinomas arising in the pancreas and biliary tract. Moreover, they often metastasize to unusual sites, such as the ovary and peritoneum/omentum, where they can be mistaken for metastatic adenocarcinomas from other, nongynecologic sites. There is little information regarding the immunophenotype of gastric-type adenocarcinomas, and knowledge of this is important to aid in the distinction from other adenocarcinomas. In this study, we undertook a detailed immunohistochemical analysis of a large series of cervical (n=45) and vaginal (n=2) gastric-type adenocarcinomas. Markers included were cytokeratin (CK)7, CK20, CDX2, carcinoembryonic antigen, CA125, CA19.9, p16, estrogen receptor, progesterone receptor, MUC6, PAX8, PAX2, p53, hepatocyte nuclear factor 1 beta, carbonic anhydrase IX, human epidermal receptor 2 (HER2), and mismatch repair (MMR) proteins. All markers were classified as negative, focal (<50% of tumor cells positive), or diffuse (≥50% tumor cells positive) except for p53 (classified as "wild-type" or "mutation-type"), HER2 (scored using the College of American Pathologists guidelines for gastric carcinomas), and MMR proteins (categorized as retained or lost). There was positive staining with CK7 (47/47-45 diffuse, 2 focal), MUC6 (17/21-6 diffuse, 11 focal), carcinoembryonic antigen (25/31-12 diffuse, 13 focal

  13. OTUB1 promotes tumor invasion and predicts a poor prognosis in gastric adenocarcinoma

    PubMed Central

    Weng, Weiwei; Zhang, Qiongyan; Xu, Midie; Wu, Yong; Zhang, Meng; Shen, Chen; Chen, Xiaochen; Wang, Yiqin; Sheng, Weiqi

    2016-01-01

    Backgrounds: The deubiquitinating enzyme OTUB1 participates in multiple cellular processes. However, its expression and functions in gastric adenocarcinoma remains unknown. The aim of this study was to investigate the expression of OTUB1 and its biological role in gastric adenocarcinoma. Methods: We used immunohistochemistry to analyze OTUB1 expressions levels in 80 paired samples of gastric adenocarcinoma and adjacent normal tissue (ANT) and 30 samples of intraepithelial neoplasia (IN). We also analyzed the correlation between OTUB1 expression and clinicopathological parameters and patient survival status. Moreover, we performed wound-healing, transwell, RT-qPCR and Western blot assays to evaluate the impact of OTUB1 on tumor migration and invasion. Results: In gastric adenocarcinomas, staining for OTUB1 was localized in the cytoplasm. The proportion of samples that expressed OTUB1 and the intensity of its expression were much higher in gastric adenocarcinoma tissues (61 out of 80, 76.25%) than that in either IN (10 out of 30, 33.33%, p<0.001) or ANT (7 out of 80, 8.75%, p<0.001) samples. In malignant cases, higher expression OTUB1 levels were significantly associated with deeper tumor invasion depths (p=0.02), advanced lymph node status (p=0.008) and TNM stage (p=0.001), lymph duct invasion (p<0.001) and nerve invasion (p=0.013). Univariate and multivariate Cox regression analyses revealed that OTUB1 was an independent risk factor for disease-specific survival but not disease-free survival. In vitro wound-healing and transwell assays showed that OTUB1 overexpression promoted tumor cell migration and invasion in gastric cancer cells. Conclusion: OTUB1 contributes to gastric cancer development by enhancing tumor invasiveness. Targeting OTUB1 should be considered in future molecular therapies. PMID:27347330

  14. Coexistence of Gastric Adenocarcinoma and Choriocarcinoma: Complete Response to Trastuzumab and Chemotherapy

    PubMed Central

    Gunduz, Seyda; Elpek, Gulsum Ozlem; Uysal, Mukremin; Goksu, Sema Sezgin; Tatli, Murat; Arslan, Deniz; Coskun, Hasan Senol; Bozcuk, Hakan; Savas, Burhan; Ozdogan, Mustafa

    2012-01-01

    Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gonadotropin and overexpression of the cErbB2 proto-oncogene. Staging revealed multiple metastases in the liver. A complete response was obtained with a combination of trastuzumab and chemotherapy. The diagnosis of gastric choriocarcinomas without pathological examination is difficult due to their rare occurrence. A complete response can be obtained with trastuzumab in the treatment of cases with overexpression of the cErbB2 protein. PMID:23525369

  15. High expression of DEK predicts poor prognosis of gastric adenocarcinoma

    PubMed Central

    2014-01-01

    Background DEK, as an oncoprotein, plays an important role in cancer development and progression. This study aimed to investigate the clinicopathological significance of DEK overexpression in patients with gastric cancer. Materials and methods The expression of DEK protein was evaluated by immunohistochemical (IHC) staining of 172 gastric cancer samples with complete clinicopathological features, and the correlation between DEK expression and clinicopathological features was examined. Survival rates were also calculated using the Kaplan-Meier method in gastric cancer patients with complete survival data. Results DEK protein showed a strictly nuclear staining pattern in gastric cancers with IHC and immunofluorescence. The strongly positive rate of DEK protein was 60.5% (104/172) in gastric cancers, which was significantly higher than that in either gastric dysplasia (19.4%, 7/36) or adjacent normal mucosa (0%, 0/27). DEK expression in gastric cancer correlated to tumor size, differentiation, clinical stage, disease-free survival, and overall survival rates. Further analysis showed that patients with early-stage gastric cancer and high DEK expression had shorter disease-free survival and overall survival duration than those with low DEK expression. Conclusion High level of DEK protein expression predicts the poor prognosis of patients with gastric cancer. DEK expression might be potentially used as an independent effective biomarker for prognostic evaluation of gastric cancers. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5050145571193097 PMID:24650035

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

    PubMed

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

    2015-09-29

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

  17. In situ detection of Epstein-Barr virus in gastric and colorectal adenocarcinomas.

    PubMed

    Yuen, S T; Chung, L P; Leung, S Y; Luk, I S; Chan, S Y; Ho, J

    1994-11-01

    The association of Epstein-Barr virus (EBV) with lymphoepithelioma-like carcinoma in the nasopharynx, which is common in Chinese from the southern region, is well established. Recently, EBV has also been found to be associated with lymphoepithelioma-like carcinomas (LELCs) and carcinomas with prominent lymphoid infiltrates in the stomach. We investigated for the presence of EBV in 74 cases of gastric adenocarcinoma and 36 cases of colorectal adenocarcinoma from Chinese patients by in situ hybridization (ISH) using an antisense EBER probe. In seven cases (9.5%) of gastric carcinoma, EBER was highly expressed in the adenocarcinoma cells and metastatic tumor cells in regional lymph nodes. In all these cases, the normal gastric epithelium was EBV negative. None of the colorectal carcinomas showed a positive signal. Isolated positive lymphoid cells were frequently found in both tumors. Of the seven positive cases, only one was LELC, and the others were conventional adenocarcinomas of the intestinal type. Five showed expression of the viral RNA in all tumor cells as well as the surrounding dysplastic epithelium. Interestingly, the sixth case showed distinct negative islands of dysplastic glands adjacent to strongly positive dysplastic glands and invasive carcinoma cells. This pattern of positivity, together with negative normal gastric epithelium and positive metastatic tumor, suggested that EBV infection occurred in the dysplastic phase and that an apparent growth advantage was conferred by the EBV infection.

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

    PubMed

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

    2016-02-16

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

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

    PubMed Central

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

    2016-01-01

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

  20. Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

    2016-07-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

  1. Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

    2016-07-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

  2. Expression of secreted phospholipase A2-Group IIA correlates with prognosis of gastric adenocarcinoma

    PubMed Central

    ZHANG, CHENGWEI; YU, HAIPENG; XU, HAIYAN; YANG, LANLAN

    2015-01-01

    The present study investigated the expression of secretory phospholipase A2-Group IIA (sPLA2-II) in gastric adenocarcinoma, in order to evaluate the correlation between sPLA2-II expression, and the clinicopathological features and prognosis of patients with gastric adenocarcinoma. Between January 2007 and April 2010, data were collected from 65 patients (44 males, 21 females; age range, 30–79 years; mean 66.7 ± 10.7 years). All patients exhibited a pathologically confirmed diagnosis of gastric adenocarcinoma. Endoscopic biopsy specimens of normal gastric mucosa from 11 of these patients were used as controls. Patients were subsequently followed-up at 3-month intervals, and survival data were recorded until April 2010. Expression of sPLA2-II in 65 gastric adenocarcinoma and 11 normal gastric mucosa specimens was evaluated via immunohistochemistry. A semi-quantitative method, consisting of evaluation of staining percentage and intensity, was utilized for immunohistochemical scoring, and the receiver operating characteristic curve method was applied to select a cut-off score for high and low sPLA2-II expression. The value of 8 was selected as the cut-off score, with maximum sensitivity and specificity. High sPLA2-II expression was observed in stage III/IV cases (83.3%; 40/48) and poorly differentiated cells (94.1%; 32/34), while sPLA2-II expression levels were observed to be significantly lower in stage I/II cases (52.9%; 9/17) and well and moderately differentiated cells (54.8%; 17/31; P=0.021 and P<0.001, respectively). There were no significant correlations observed between sPLA2-II expression and any other clinicopathological parameters, including gender, age, tumor diameter and Helicobacter pylori infection. Patients exhibiting low sPLA2-II expression experienced significantly improved overall survival (OS) and disease-free survival (DFS), compared with those exhibiting high sPLA2-II expression (P=0.043 and P=0.035, respectively). Multivariate analysis

  3. Hypercalcemia as Initial Presentation of Metastatic Adenocarcinoma of Gastric Origin: A Case Report and Review of the Literature

    PubMed Central

    Kumar, Abhishek; Kumar, Vinod; Kaur, Supreet; Maroules, Michael

    2016-01-01

    Hypercalcemia of malignancy due to metastatic gastric adenocarcinoma is extremely rare; in fact, to the best of our knowledge, only three case reports of hypercalcemia associated with metastatic gastric adenocarcinoma have been published in the literature to date. Herein, we report a rare case involving a 61-year-old African-American female who had hypercalcemia at initial presentation and who was later diagnosed with poorly differentiated gastric adenocarcinoma with extensive liver metastases, without bone involvement. She was found to have elevated parathyroid hormone-related peptide and normal parathyroid hormone levels. Despite aggressive treatment, she died within a few months of diagnosis. PMID:27752397

  4. Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells.

    PubMed

    Kang, Seo-Hee; Kim, Yon-Suk; Kim, Eun-Kyung; Hwang, Jin-Woo; Jeong, Jae-Hyun; Dong, Xin; Lee, Jae-Woong; Moon, Sang-Ho; Jeon, Byong-Tae; Park, Pyo-Jam

    2016-01-01

    Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer. PMID:26437948

  5. Peritoneal metastatic adenocarcinoma possibly due to a gastric duplication cyst: a case report and literature review

    PubMed Central

    2014-01-01

    Background Gastric duplication cysts are rare congenital abnormalities, and malignant transformation of these duplications is also thought to be rare. Case presentation During a routine health checkup, a 28-year-old man underwent abdominal sonography followed by computed tomography (CT) with contrast agent, which revealed a cystic lesion with no enhancement. Laparoscopic surgery showed a 10 × 10 cm cyst adhering to the gastric corpus. However, attempts to remove the lesion en bloc were unsuccessful, and the ruptured cyst had contaminated the peritoneal cavity. Gastric duplication was diagnosed from microscopic examination of the cyst. Seven months later, the patient suffered a progressive increase in ascites, and repeated cytological analysis showed small nests of adenocarcinoma cells, with primary lesion unknown. Diagnostic laparoscopy showed multiple white nodules scattered over the surface of the liver, greater omentum, and peritoneum. Biopsy of the omental nodules confirmed adenocarcinoma, while carcinomatosis was diagnosed in the peritoneum. Conclusions Clinical presentation and chronological developments indicated that the malignancy probably originated from the gastric duplication cyst. This case highlights the importance of accurate preoperative diagnosis and optimal surgical management for gastric duplication as well as considering the potential existence of malignant transformation during surgical evaluation of adult patients with gastric duplication cysts. PMID:24641252

  6. Expression of tumoral FOXP3 in gastric adenocarcinoma is associated with favorable clinicopathological variables and related with Hippo pathway

    PubMed Central

    Suh, Jung-Ho; Won, Kyu Yeoun; Kim, Gou Young; Bae, Go Eun; Lim, Sung-Jig; Sung, Ji-Youn; Park, Yong-Koo; Kim, Youn Wha; Lee, Juhie

    2015-01-01

    FOXP3 is a transcription factor and well-known hallmark of immune suppressive T regulatory cells (Tregs). Recent studies indicate that, in addition to its association with Treg function in the immune system, FOXP3 plays an important role in tumor development. And important tumor suppressor relay between the FOXP3 and Hippo pathways was found in human cancer. Thus, we investigated tumoral FOXP3, infiltrated Tregs count, Lats2, and YAP expression in gastric adenocarcinoma, and the relationships between expression of these three proteins and p53, Ki67, and other clinicopathological variables. We used 118 gastric adenocarcinoma tissues via immunohistochemical analysis, using a tissue microarray, in relation to survival and other clinicopathological factors. We report the several novel observations about the relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Positive tumoral FOXP3 expression was significantly related with smaller tumor size, tubular tumor type, lower histological grade, lower T stage, lower recurrence rate, less lymphatic invasion, and less neural invasion. Furthermore, patients with positive tumoral FOXP3 experienced significantly better disease-free and overall survival compared to patients with negative tumoral FOXP3. These findings show that tumoral FOXP3 expression is associated with favorable clinicopathological variables in gastric adenocarcinoma. And we report the novel observation of a relationship between tumoral FOXP3 and Hippo pathway components in gastric adenocarcinoma. Tumoral FOXP3 expression, infiltrated Tregs count, and Lats2 expression were all positively correlated with YAP expression. These findings suggest that the Hippo pathway in gastric adenocarcinoma might be influenced by both tumoral FOXP3 and infiltrated Tregs. In conclusion, the loss of FOXP3 expression in cancer cells is thought to contribute to tumorigenesis and progression of gastric adenocarcinoma. The expression of FOXP3 in

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

    PubMed Central

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

    2015-01-01

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

  8. Association of tooth loss and oral hygiene with risk of gastric adenocarcinoma.

    PubMed

    Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Abedi-Ardekani, Behnoush; Khoshnia, Masoud; Islami, Farhad; Pourshams, Akram; Pawlita, Michael; Boffetta, Paolo; Dawsey, Sanford M; Kamangar, Farin; Abnet, Christian C

    2013-05-01

    Poor oral health and tooth loss have been proposed as possible risk factors for some chronic diseases, including gastric cancer. However, a small number of studies have tested these associations. We conducted a case-control study in Golestan Province, Iran, that enrolled 309 cases diagnosed with gastric adenocarcinoma (118 noncardia, 161 cardia, and 30 mixed-locations) and 613 sex, age, and neighborhood matched controls. Data on oral health were obtained through physical examination and questionnaire including tooth loss, the number of decayed, missing, and filled teeth, and frequency of tooth brushing. ORs and 95% confidence intervals (95% CI) were obtained using conditional logistic regression models adjusted for potential confounders. Standard one degree-of-freedom linear trend test and a multiple degree-of-freedom global test of the effect of adding oral hygiene variables to the model were also calculated. Our results showed apparent associations between tooth loss and decayed, missing, filled teeth (DMFT) score with risk of gastric cancer, overall and at each anatomic subsite. However, these associations were not monotonic and were strongly confounded by age. The results also showed that subjects who brushed their teeth less than daily were at significantly higher risk for gastric cardia adenocarcinoma ORs (95% CI) of 5.6 (1.6-19.3). We found evidence for an association between oral health and gastric cancer, but the nonmonotonic association, the relatively strong effect of confounder adjustment, and inconsistent results across studies must temper the strength of any conclusions.

  9. A Case of Long-Term Complete Remission of Advanced Gastric Adenocarcinoma with Liver Metastasis

    PubMed Central

    Rim, Ch'angbum; Lee, Jung-Ae; Gong, Soojung; Kang, Dong Wook; Yang, Heebum; Han, Hyun Young

    2016-01-01

    We report the case of a patient with gastric adenocarcinoma with multiple liver metastases. This patient showed complete remission for more than 68 months after S-1/cisplatin combination chemotherapy and radical total gastrectomy. The patient, a 63-year-old man, presented with dyspepsia and difficulty in swallowing. Endoscopic findings showed a huge ulcero-infiltrative mass at the lesser curvature of the mid-body, extending to the distal esophagus. Biopsy revealed a poorly differentiated tubular adenocarcinoma. An abdominal computed tomography scan demonstrated multiple hepatic metastases. S-1/cisplatin combination chemotherapy was initiated, and following completion of six cycles of chemotherapy, the gastric masses and hepatic metastatic lesions had disappeared on abdominal computed tomography. Radical total gastrectomy and D2 lymphadenectomy combined with splenectomy were performed. The patient underwent three cycles of S-1/cisplatin combination chemotherapy followed by tegafur-uracil therapy for 1 year. He remained in complete remission for more than 68 months after surgery. PMID:27433398

  10. A Case of Long-Term Complete Remission of Advanced Gastric Adenocarcinoma with Liver Metastasis.

    PubMed

    Rim, Ch'angbum; Lee, Jung-Ae; Gong, Soojung; Kang, Dong Wook; Yang, Heebum; Han, Hyun Young; Kim, Nae Yu

    2016-06-01

    We report the case of a patient with gastric adenocarcinoma with multiple liver metastases. This patient showed complete remission for more than 68 months after S-1/cisplatin combination chemotherapy and radical total gastrectomy. The patient, a 63-year-old man, presented with dyspepsia and difficulty in swallowing. Endoscopic findings showed a huge ulcero-infiltrative mass at the lesser curvature of the mid-body, extending to the distal esophagus. Biopsy revealed a poorly differentiated tubular adenocarcinoma. An abdominal computed tomography scan demonstrated multiple hepatic metastases. S-1/cisplatin combination chemotherapy was initiated, and following completion of six cycles of chemotherapy, the gastric masses and hepatic metastatic lesions had disappeared on abdominal computed tomography. Radical total gastrectomy and D2 lymphadenectomy combined with splenectomy were performed. The patient underwent three cycles of S-1/cisplatin combination chemotherapy followed by tegafur-uracil therapy for 1 year. He remained in complete remission for more than 68 months after surgery. PMID:27433398

  11. Esophagogastric junction and gastric adenocarcinoma: neoadjuvant and adjuvant therapy, and future directions.

    PubMed

    Sandler, Steven

    2014-06-01

    In North America, gastric cancer is the third most common gastrointestinal malignancy and the third most lethal neoplasm overall. In Asia, gastric cancer represents an even more serious problem: in Japan, it is the most common cancer in men. The standard primary therapy for gastric cancer is surgical resection; in esophagogastric-junction (EGJ) adenocarcinoma, which is often included in studies of gastric cancer, surgery is also typically the initial management strategy. However, the rates of locoregional and distant recurrence following surgery with curative intent have remained high. Investigators have explored a variety of ways of reducing these rates and improving survival in patients with gastric and EGJ cancers. These strategies have included explorations of the optimal extent of regional lymphadenectomy at the time of gastric resection; investigation of different neoadjuvant, perioperative, and adjuvant chemotherapy regimens; use of preoperative and postoperative radiation therapy; and the use of pre- and postoperative chemoradiotherapy (CRT).To date, benefit has been seen in gastric cancer patients with the use of what is called a"D2 resection"(which includes lymph nodes of stations 7 through 12) and with adjuvant CRT (in the West) or adjuvant chemotherapy with S-1 (in Japan); and neoadjuvant CRT has been shown to have a survival benefit in patients with EGJ cancers.

  12. Gastric adenocarcinoma presenting with thromboembolism in a 13-year-old boy.

    PubMed

    Hunter, Wendy L M

    2015-03-01

    Abdominal pain is a frequent complaint in the pediatric emergency department. A 13-year-old boy presented with complaints of abdominal pain, hematemesis, headache, and leg pain. Further investigation revealed an advanced-stage gastric adenocarcinoma with multiple thromboembolism including the greater saphenous vein and nonbacterial thrombotic endocarditis. This case points out the challenges of diagnosing this rare condition and treating the primary tumor and thromboembolism in the setting of both hypercoagulable state and gastrointestinal bleeding. PMID:25738239

  13. Risk of adenocarcinomas of the oesophagus and gastric cardia in patients hospitalized for asthma

    PubMed Central

    Ye, W; Chow, W-H; Lagergren, J; Boffetta, P; Boman, G; Adami, H-O; Nyrén, O

    2001-01-01

    In the first cohort study of the question we followed 92 986 (42 663 men and 50 323 women) adult patients hospitalized for asthma in Sweden from 1965 to 1994 for an average of 8.5 years to evaluate their risk of oesophageal and gastric cardia adenocarcinoma. Standardized incidence ratio (SIR) adjusted for gender, age and calendar year was used to estimate relative risk, using the Swedish nationwide cancer incidence rates as reference. Asthmatic patients overall had a moderately elevated risk for oesophageal adenocarcinoma (SIR = 1.5, 95% confidence interval CI, 0.9–2.5) and gastric cardia cancer (SIR = 1.4, 95% CI, 1.0–1.9). However, the excess risks were largely confined to asthmatic patients who also had a discharge record of gastro-oesophageal reflux (SIR = 7.5, 95% CI, 1.6–22.0 and SIR = 7.1, 95% CI, 3.1–14.0, respectively). No significant excess risk for oesophageal squamous-cell carcinoma or distal stomach cancer was observed. In conclusion, asthma is associated with a moderately elevated risk of developing oesophageal or gastric cardia adenocarcinoma. Special clinical vigilance vis-à-vis gastro-esophageal cancers seems unwarranted in asthmatic patients, but may be appropriate in those with clinically manifest gastro-oesophageal reflux.   http://www.bjcancer.com © 2001 Cancer Research Campaign PMID:11720467

  14. "Big IGF-II"-induced hypoglycemia secondary to gastric adenocarcinoma.

    PubMed

    Morbois-Trabut, L; Maillot, F; De Widerspach-Thor, A; Lamisse, F; Couet, C

    2004-06-01

    Non-islet cell tumor-related hypoglycemia is a rare phenomenon. We report the case of a 63 Year-old man admitted for hemiparesia and a capillary blood glucose of 20 mg/dL. The presence of an immature form of IGF-II that can mimic the effect of insulin, namely "big IGF-II", explained this patient's hypoglycaemia. A moderately differentiated adenocarcinoma of the cardia with metastatic extension to the stomach and the liver was demonstrated. Octreotide failed to control the hypoglycaemia, therefore prednisolone (2 mg/kg per day) and enteral feeding prevented new episodes of severe hypoglycaemia. PMID:15223980

  15. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma

    PubMed Central

    Chen, Jian; Yang, Wei-jun; Sun, Hai-jian; Wu, Yu-zhang

    2016-01-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma. PMID:26186252

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

    PubMed

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

    2002-01-01

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

  17. UCH-LI acts as a novel prognostic biomarker in gastric cardiac adenocarcinoma

    PubMed Central

    Yang, Honghong; Zhang, Chunhong; Fang, Shan; Ou, Rongying; Li, Wenfeng; Xu, Yunsheng

    2015-01-01

    Gastric cardiac adenocarcinoma (GCA) accounts for a majority of gastric cancer population and harbors unfavorable outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the deubiquitinating enzyme family, which could regulate cell growth in human cancers. In the present study, expression of UCH-L1 was evaluated in 196 GCAs by immunohistochemistry using tissue microarray and its function on gastric cancer cells was measured. UCH-L1 expression was increased in GCA specimens, compared with their normal tissues and UCH-L1 overexpression is tightly correlated with tumor size and overall TNM stage. Log-rank analysis showed that UCH-L1 positive is reversely associated with cumulative survival (P<0.001). Multivariate Cox regression model showed that UCH-L1 overexpression is a remarkably negative predictor in GCA prognosis (Hazard Ratio=0.53, P<0.01), along with advanced TNM stage that is a known negative factor in gastric cancers (Hazard Ratio=0.33, P<0.05). Silencing of UCH-L1 reduced the ability of cell proliferation, colony formation, migration and invasion of gastric cancer cells. Our findings suggest that UCH-L1 is a promising prognostic biomarker for GCAs and might play an important role in the carcinogenesis of gastric cancer. PMID:26823707

  18. HER 2 Expression in Gastric and Gastro-esophageal Junction (GEJ) Adenocarcinomas

    PubMed Central

    Rajagopal, Indu; Sahadev, R; Nagappa, Preethan Kamagere; Rajendra, Sowmya Goddanakoppal

    2015-01-01

    Introduction: Gastric cancer is one of the leading causes of cancer mortality in the world/India with majority being diagnosed at an advanced stage. Various chemotherapeutic regimens have modestly improved overall survival leading to quest for novel therapeutic agents. Overexpression of HER2 in many gastric cancers has lead to the advent of targeted therapy with anti HER2 antibody like Trastusumab which has improved the overall survival. Materials and Methods: Sixty cases of gastric adenocarcinomas (44 biopsies and 16 gastrectomies) over the past five years ( June 2009 to June 2014),were included in the study. Diagnosis was confirmed by review of slides and IHC with anti HER2 antibodies was performed using Dako Real Envision Detection system and scoring was done by Hoffmann et al., scoring system. Results: Of the 60 cases, majority were males (60%),with a mean age of 65.65 yrs. Tumours in antrum (76.7%) formed the major bulk. HER2 expression was observed in 26.7% of Tumours, predominantly in males (p=0.006) and intestinal type (p= 0.054). HER2 expression correlated with Tumour grade (moderately differentiated and well differentiated, p= 0.042). Tumours of gastro-esophageal junction (GEJ) showed HER2 expression in 45.5% as opposed to 22.4% in gastric location. Poorly differentiated and diffuse type of adenocarcinomas did not express HER2. Two of three Tumours from patients in the age group 31-40 y expressed HER2. Conclusion: Male gender, intestinal-type and moderately differentiated gastric cancers may be the ones that can be targeted for therapy using Herceptin. Though trastusumab is approved for advanced gastric and GEJ cancers, it’s role in adjuvant / neo-adjuvant setting in early stages needs to be evaluated with newer agents like Pertuzumab, Bevacizumab, especially in young patients. PMID:25954623

  19. Remnant cystic duct adenocarcinoma presenting as gastric outlet obstruction

    PubMed Central

    Lo, Samuel Tsoon Wuan; Cheng, Yue; Cheung, Frances; Tang, Chung Ngai

    2016-01-01

    Only a few case reports of remnant cystic duct carcinoma exist. The presented case of remnant cystic duct carcinoma with invasion to pylorus and bulbus of duodenum leading to gastric outlet obstruction was the first of its kind. We reviewed all cases of remnant cystic duct carcinoma that we found in the literature and summarized its definition, presentation, extent of invasion and clinical outcome after operation. The diagnosis can be difficult due to the rarity of disease, locally advanced nature of disease and distorted postoperative anatomy. A high index of suspicion can increase the likelihood of a preoperative diagnosis. PMID:27154747

  20. Age effects and temporal trends in adenocarcinoma of the esophagus and gastric cardia (United States).

    PubMed

    Jeon, Jihyoun; Luebeck, E Georg; Moolgavkar, Suresh H

    2006-09-01

    A number of hypotheses have been advanced to explain the rapid increase of the incidence of esophageal adenocarcinoma in the US. A major problem in identifying and understanding the nature of this increase is the difficulty in untangling age effects from temporal trends due to cohort and period effects. To address this problem, we have developed multi-stage carcinogenesis models that describe the age-specific incidence of adenocarcinoma of the esophagus and of the gastric cardia with separate adjustments for temporal trends. These models explicitly incorporate important features of the cancers, such as the metaplastic conversion of normal esophagus to Barrett's esophagus (BE). We fit these models separately to the incidence of adenocarcinoma of the esophagus and of the gastric cardia reported in the Surveillance Epidemiology and End Results (SEER) registry over the period 1973-2000. We conclude that the incidence of both cancers is consistent with a sequence that posits a tissue conversion step in the target organ followed by a multi-stage process with three rate-limiting events, the first two leading to an initiated cell that can expand clonally into a premalignant lesion, and the third converting an initiated cell into a malignant cell. Temporal trends in the incidence of both cancers are dominated by dramatically increasing period effects.

  1. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    SciTech Connect

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  2. D-SP5 Peptide-Modified Highly Branched Polyethylenimine for Gene Therapy of Gastric Adenocarcinoma.

    PubMed

    Li, Xue; Xie, Zuoxu; Xie, Cao; Lu, Weiyue; Gao, Chunli; Ren, Henglei; Ying, Man; Wei, Xiaoli; Gao, Jie; Su, Bingxia; Ren, Yachao; Liu, Min

    2015-08-19

    Peptide-mediated targeting of tumors has become an effective strategy for cancer therapy. Retro-inverso peptides resist protease degradation and maintain their bioactivity. We used the retro-inverso peptide D(PRPSPKMGVSVS) (D-SP5) as a targeting ligand to develop gene therapy for gastric adenocarcinoma. D-SP5 has a higher affinity for human gastric adenocarcinoma (SGC7901) cells compared with that of its parental peptide, L(SVSVGMKPSPRP) (L-SP5). Polyethylenimine (PEI)/pDNA, polyethylene glycol (mPEG)-PEI/pDNA and D-SP5-PEG-PEI/pDNA were prepared for further study. Quantitative luciferase assays showed the transfection efficiency of D-SP5-PEG-PEI/pGL(4.2) was larger compared with that of mPEG-PEI/pGL(4.2). Flow cytometry assays revealed that the apoptosis rates of SGC7901 cells treated with D-SP5-PEG-PEI/pTRAIL were larger than mPEG-PEI/pTRAIL. Western blot assays indicated that the expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in SGC7901 cells treated with D-SP5-PEG-PEI/pTRAIL was higher compared with that in cells treated with mPEG-PEI/pTRAIL. In vivo pharmacodynamics study revealed that D-SP5-PEG-PEI/pTRAIL could inhibit the growth of gastric adenocarcinoma SGC7901 xenografts in nude mice. Our results demonstrate that D-SP5-PEG-PEI is a safe and efficient gene delivery vector with potential applications in antitumor gene therapy. PMID:26052814

  3. Adenocarcinoma arising from a gastric duplication cyst with invasion to the stomach: a case report with literature review

    PubMed Central

    Kuraoka, K; Nakayama, H; Kagawa, T; Ichikawa, T; Yasui, W

    2004-01-01

    This report describes a rare case of adenocarcinoma arising from a gastric duplication cyst, with invasion to the stomach wall, in a 40 year old Japanese man. A cystic lesion was found between the stomach and the spleen. The cyst had a well circumscribed smooth muscle layer, corresponding to the muscularis propria of the stomach and the mucosa of the alimentary tract. A well differentiated adenocarcinoma was found within the duplication cyst, invading its serosa. Well differentiated adenocarcinoma was independently found in the fundus of the stomach; the tumour of the cyst was connected by fibrous tissue. Microscopically, there was neither adenocarcinoma in situ nor precancerous lesions, such as epithelial dysplasia, suggesting that the carcinoma derived from a gastric duplication cyst that invaded the stomach. Duplication cysts should be included in the differential diagnosis of cystic masses of the gastrointestinal tract, and the possibility of malignancy within these cysts should be considered. PMID:15047751

  4. Prognostic significance of Versican expression in gastric adenocarcinoma

    PubMed Central

    Shen, X-H; Lin, W-R; Xu, M-D; Qi, P; Dong, L; Zhang, Q-Y; Ni, S-J; Weng, W-W; Tan, C; Huang, D; Ma, Y-Q; Zhang, W; Sheng, W-Q; Wang, Y-Q; Du, X

    2015-01-01

    Gastric cancer (GC) is the leading malignancy in the digestive system. Versican is a ubiquitous component of the extracellular matrix and has a role in tumor progression. We aim to examine the expression of Versican in GC and the relationship between Versican levels and patient survival. We detected the mRNA expression of Versican in tumorous pairs and adjacent normal tissues (ANTs) of 78 GC patients by quantitative real-time polymerase chain reaction. The protein expression of Versican in 101 cases of matched GC and ANT, as well as in 27 intraepithelial neoplastic (IN) samples, was evaluated by immunohistochemistry. We analyzed the correlation between Versican levels and clinical outcomes. Finally, we performed CCK-8 cell counting assay and transwell assay in GC cell lines. Versican mRNA expression was significantly greater in tumor tissues (P<0.001) than in ANT. Versican was majorly expressed in the stroma surrounding tumor epithelium and minorly some areas of tumor epithelium. The Versican expression level was higher in GC than in ANT (P=0.004), but no significant difference was observed between ANT and IN (P=0.517). The Versican mRNA and protein levels were consistent in GC. High Versican mRNA and protein expression correlated with greater tumor invasion depth (P=0.030, P=0.027). Univariate and multivariate analysis revealed that patients with high Versican mRNA expression exhibited poor disease-specific survival (P<0.001). In vitro experiments showed that Versican overexpression promoted cell proliferation and invasion. Our data indicate that Versican may be a novel prognostic indicator in GC and may be a potential target for clinical diagnosis. PMID:26619403

  5. Ras gene activation in gastric adenocarcinoma of Chinese patients in Taiwan

    SciTech Connect

    Tzeng, C.C.; Lee, W.Y.; Jin, Y.T.

    1994-09-01

    In order to assess the implication of mutational activation of members of the ras family of cellular proto-oncogenes in the development of gastric cancers in Chinese patients, a series of 55 cases of gastric adenocarcinoma in Taiwan was studied. Genomic deoxyribonucleic acid obtained from formalin-fixed paraffin-embedded archival tumor tissue was amplified by polymerase chain reaction and then analyzed by dot blot hybridation assay with allele-specific oligonucleotide probes to detect mutations at codons 12, 13, and 61 of c-Ki-ras, c-Ha-ras, and c-N-ras. Twelve (12.8%) of the 55 carcinomas examined harbored a point mutation. Of the 12 mutations, 8 (66.6%) were detected in Ha-ras codon 12. Our result is consistent with reports from mainland China and Korea, but different from those of Japan and the United States. This difference is probably attributable to different eating and drinking habits.

  6. Correlation between expression of cyclooxygenase-2 and angiogenesis in human gastric adenocarcinoma

    PubMed Central

    Li, Hong-Xia; Chang, Xin-Ming; Song, Zheng-Jun; He, Shui-Xiang

    2003-01-01

    AIM: To evaluate the expression of cyclooxygenase (COX-2) and the relationship with tumor angiogenesis and advancement in gastric adenocarcinoma. METHODS: Immunohistochemical stain was used for detecting the expression of COX-2 in 45 resected specimens of gastric adenocarcinoma; the monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was detected by counting of CD34-positive vascular endothelial cells. Paracancerous tissues were examined as control. RESULTS: Immunohistological staining with COX-2-specific polyclonal antibody showed cytoplasmic staining in the cancer cells, some atypical hyperplasia and intestinal metaplasia, as well as angiogenic vasculature present within the tumors and prexisting vasculature adjacent to cancer lesions. The rate of expression of COX-2 and MVD index in gastric cancers were significantly increased, compared with those in the paracancerous tissues (77.78 vs 33.33%, 58.13 ± 19.99 vs 24.02 ± 10.28, P < 0.01, P < 0.05, respectively). In 36 gastric carcinoma specimens with lymph node metastasis, the rate of COX-2 expression and MVD were higher than those in the specimens without metostasis (86.11 vs 44.44%, 58.60 ± 18.24 vs 43.54 ± 15.05, P < 0.05, P < 0.05, respectively). The rate of COX-2 expression and MVD in the specimens with invasive serosa were significantly higher than those in the specimens without invasion to serosa (87.88 vs 50.0%, 57.01 ± 18.79 vs 42.35 ± 14.65, P < 0.05, P < 0.05). Moreover, MVD in COX-2-positive specimens was higher than that in COX-2-negative specimens (61.29 ± 14.31 vs 45.38 ± 12.42, P < 0.05). COX-2 expression was positively correlated with MVD (r = 0.63, P < 0.05). CONCLUSION: COX-2 expression might correlate with the occurance and advancement of gastric carcinoma and is involved in tumor angiogenesis in gastric carcinoma. It is likely that COX-2 by inducing angiogenesis can be one of mechanisms which promotes invasion and

  7. Lymph node revealing solution: a new method for lymph node sampling: results in gastric adenocarcinoma.

    PubMed

    Koren, R; Kyzer, S; Levin, I; Klein, B; Halpern, M; Rath-Wolfson, L; Paz, A; Melloul, M M; Mishali, M; Gal, R

    1998-01-01

    Staging of gastric carcinoma depends on exact lymph node status. However, very small nodes are not easily found as they are obscured by the surrounding adipose tissue. The purpose of the present study was to demonstrate the usefulness of a Olymph node revealing solutionO (LNRS) in gastric cancer. The perigastric adipose tissue of ten OproblematicO cases of gastric carcinoma, in which <10 lymph nodes were found using the traditional method, was immersed in LNRS for 6-12 h. Subsequently, the lymph nodes stood out as white chalky nodules. They were excised and processed routinely. The traditional method yielded a total of 30 lymph nodes with a mean size of 6.69 +/- 3.43 mm. The LNRS revealed 89 additional nodes with a mean size of 3.03 +/- 3.43 mm, which was significantly smaller. The Node (N) stage was changed in four cases from Nx to N0, in one case from N1 to N2, and in one case from N0 to N2. LNRS seems to be the technique of choice for staging of patients with gastric adenocarcinoma in whom <10 lymph nodes were found with the traditional method and accurate staging was not possible. PMID:9468553

  8. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

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

    PubMed

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

    2015-01-01

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

  10. Modulation of MUC1 and blood group antigen expression in gastric adenocarcinoma cells by cytokines.

    PubMed

    Grohmann, Georg P M; Schirmacher, Peter; Manzke, Oliver; Hanisch, Franz Georg; Dienes, Hans P; Baldus, Stephan E

    2003-08-01

    Immunohistological studies demonstrated that MUC1 expression in gastric cancer is associated with a poor prognosis. As a mediator of cell-cell interactions, MUC1 may also be involved in metastasis. However, these aspects are of relevance since cytokine levels are locally increased as a consequence of peritumorous inflammatory response and coexisting chronic gastritis. Therefore we analyzed the potential influence of several cytokines on the expression of tumor-associated MUC1 and Lewis blood group antigens in gastric carcinoma cells. Gastric cancer cell lines AGS and KATOIII were incubated with the cytokines interleukin-1beta, interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), and hepatocyte growth factor over a period of 72 h. Expressions of mucin antigens and cytokine secretion were measured by immunocytochemistry and/or enzyme-linked immunosorbent assay (ELISA). Analysis by fluorescence-activated cell sorter (FACS) demonstrated that MUC1 and sialyl Lewis A reactivities of AGS cells were increased significantly following TNF-alpha stimulation but not by other cytokines. Expression of mucin-associated antigens by cell line KATOIII was not affected by any of the employed cytokines. These data provide evidence that TNF-alpha can raise the expression of important mucin peptide as well as mucin-associated carbohydrate antigens and thereby potentially influence the progression of gastric carcinomas. PMID:12906871

  11. Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma

    SciTech Connect

    Lee, Na Keum; Lee, Jung Hwa; Park, Chan Hyuk; Yu, Dayeon; Lee, Yong Chan; Cheong, Jae-Ho; Noh, Sung Hoon; Lee, Sang Kil

    2014-08-22

    Highlights: • HOTAIR expression was tested in fifty patients with gastric cancer. • Cell proliferation was measured after HOTAIR silencing in gastric cancer cell line. • siRNA–HOTAIR suppresses cell invasiveness and capacity of migration. • Knock down of HOTAR leads to decreased expression of EMT markers. • Inhibition of HOTAIR induces apoptosis and cell cycle arrest. - Abstract: Gastric cancer is one of the major causes of cancer death worldwide; however, the mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of metastasis in various cancers including gastric cancer. Here we investigated the impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer. We examined the mechanism of invasion and metastasis and analyzed the clinical significance of HOTAIR. Downregulation of HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was significantly elevated in various gastric cancer cell lines and tissues compared to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74, and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III cells. Lymphovascular invasion and lymph node metastasis were more common in the high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and migration. si-HOTAIR led to differential expression of epithelial to mesenchymal transition markers. We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer.

  12. Laparoscopic Versus Open Gastrectomy for Gastric Adenocarcinoma in the West: A Case–Control Study

    PubMed Central

    Kelly, Kaitlyn J.; Selby, Luke; Chou, Joanne F.; Dukleska, Katerina; Capanu, Marinela; Coit, Daniel G.; Brennan, Murray F.; Strong, Vivian E.

    2016-01-01

    Introduction Data on laparoscopic gastrectomy in patients with gastric cancer in the Western hemisphere are lacking. This study aimed to compare outcomes following laparoscopic versus open gastrectomy for gastric adenocarcinoma at a Western center. Methods Eighty-seven consecutive patients who underwent laparoscopic gastrectomy from November 2005 to April 2013 were compared with 87 patients undergoing open resection during the same time period. Patients were matched for age, stage, body mass index, and procedure (distal subtotal vs. total gastrectomy). Endpoints were short- and long-term perioperative outcomes. Results Overall, 65 patients (37 %) had locally advanced disease, and 40 (23 %) had proximal tumors. The laparoscopic approach was associated with longer operative time (median 240 vs.165 min; p < 0.01), less blood loss (100 vs.150 mL; p < 0.01), higher rate of microscopic margin positivity (9 vs.1 %; p = 0.04), decreased duration of narcotic and epidural use (2 vs. 4 days, p = 0.04, and 3 vs. 4 days, p = 0.02, respectively), decreased minor complications in the early (27 vs. 16 %) and late (17 vs. 7 %) postoperative periods (p < 0.01), decreased length of stay (5 vs. 7 days; p = 0.01), and increased likelihood of receiving adjuvant therapy (82 vs. 51 %; p < 0.01). There was no difference in the number of lymph nodes retrieved (median 20 in both groups), major morbidity, or 30-day mortality. Conclusions Laparoscopic gastrectomy for gastric adenocarcinoma is safe and effective for select patients in the West. PMID:25631063

  13. Helicobacter pylori genotyping in gastric adenocarcinoma and MALT lymphoma by multiplex PCR analyses of paraffin wax embedded tissues

    PubMed Central

    Koehler, C I; Mues, M B; Dienes, H P; Kriegsmann, J; Schirmacher, P; Odenthal, M

    2003-01-01

    Background: Gastric infection with Helicobacter pylori is the major cause of chronic active gastritis and is associated with the pathogenesis of peptic ulcer and gastric carcinoma. Gastric mucosal damage involves both host and H pylori dependent factors, such as the presence of the cag pathogenicity island and allelic variations of the vacA and iceA genes. Aims: To evaluate the association of these virulence factors with the development of gastric malignancies, a retrospective study was performed on archived tissue routinely obtained for diagnostic histopathology. Methods: DNA was extracted from formalin fixed, paraffin wax embedded gastric tissue sections of 93 patients with chronic active gastritis (n = 39), adenocarcinoma (n = 28), or mucosa associated lymphoid tissue (MALT) lymphoma (n = 24). The extracted DNA was used to perform a polymerase chain reaction based, simultaneous analysis of the following: (1) cagA status, (2) allelic variation of the iceA genes (iceA1, iceA2), allelic variation of the signal peptide (s1a, s1b, s2) and the midregion (m1, m1a, m2) of the vacA gene. Results: The iceA1 gene showed a 3.6 fold and the vacA s1a variant a 4.2 fold higher prevalence in gastric adenocarcinoma than in gastritis. The combined presence of both the vacA s1a and iceA1 genes had a 5.6 fold higher frequency in adenocarcinoma. The vacA m2 allele was the predominant subtype in MALT lymphoma and the combination of the vacA m2 subtypes with the vacA s1 and the iceA1 variants occurred in MALT lymphoma nearly five times more often than in chronic active gastritis. Conclusions: Certain H pylori subtype combinations possess a differentiating and predictive value for the development of gastric adenocarcinoma and MALT lymphoma. PMID:12560462

  14. Gastric outlet obstruction due to adenocarcinoma in a patient with Ataxia-Telangiectasia syndrome: a case report and review of the literature

    PubMed Central

    Otabor, Iyore A; Abdessalam, Shahab F; Erdman, Steven H; Hammond, Sue; Besner, Gail E

    2009-01-01

    Background Ataxia-Telangiectasia syndrome is characterized by progressive cerebellar dysfunction, conjuctival and cutaneous telangiectasias, severe immune deficiencies, premature aging and predisposition to cancer. Clinical and radiographic evaluation for malignancy in ataxia-telangiectasia patients is usually atypical, leading to delays in diagnosis. Case presentation We report the case of a 20 year old ataxia-telangiectasia patient with gastric adenocarcinoma that presented as complete gastric outlet obstruction. Conclusion A literature search of adenocarcinoma associated with ataxia-telangiectasia revealed 6 cases. All patients presented with non-specific gastrointestinal complaints suggestive of ulcer disease. Although there was no correlation between immunoglobulin levels and development of gastric adenocarcinoma, the presence of chronic gastritis and intestinal metaplasia seem to lead to the development of gastric adenocarcinoma. One should consider adenocarcinoma in any patient with ataxia-telangiectasia who presents with non-specific gastrointestinal complaints, since this can lead to earlier diagnosis. PMID:19284625

  15. Cutaneous Metastasis from Signet-ring Gastric Adenocarcinoma in a Carcinoma En Cuirasse Pattern: An Unusual Clinical-diagnostic Sequence

    PubMed Central

    Kaur, Sarabjit; Aggarwal, Parul; Dayal, Surabhi; Sangwan, Ankita; Jain, Vijay Kumar; Jindal, Nidhi

    2015-01-01

    Cutaneous metastasis (CM) of gastric adenocarcinoma (ADC) is rare and usually presents late in the course of the disease. We report a rare case of carcinoma en cuirasse (CEC) pattern of CM secondary to gastric malignancy in a 55-year-old male patient—the interesting part being that CM was the first-presenting sign, which on further histopathological and immunohistochemical evaluation led to the diagnosis of hidden gastric carcinoma. The finding of signet ring cells (SRCs) on cutaneous biopsy further added a differential of the rare possibility of primary cutaneous tumors. PMID:26677305

  16. Significance of TFF3 protein and Her-2/neu status in patients with gastric adenocarcinoma.

    PubMed

    Xu, Cong-cong; Yue, Lu; Wei, Hong-jun; Zhao, Wen-wen; Sui, Ai-hua; Wang, Xiu-mei; Qiu, Wen-sheng

    2013-08-01

    Increased knowledge of molecular alterations involved in gastric carcinogenesis has provided useful information for diagnosis and prediction. In this study, we investigated the clinicopathological significance of TFF3 expression and Her-2/neu status in gastric adenocarcinoma and explored the correlation between TFF3 expression and Her-2/neu status. A hundred and twenty-six (126) patients having undergone curative gastrectomy were enrolled. Immunohistochemistry for TFF3 was performed on tumor tissues and non-neoplastic resection margins. Her-2/neu status was assessed by immunohistochemical staining and fluorescence in situ hybridization (FISH) on tumor tissues. As a result, TFF3 expression and Her-2/neu positivity were detected in 46.8% and 11.9% of the cases, respectively. Patients with negative TFF3 exhibited longer survival than the positive group (P=0.0142), while patients with positive Her-2/neu only showed a tendency toward longer overall survival (P>0.05). However, Her-2/neu was significantly associated with improved disease-free survival (P=0.0234). Multivariate analysis demonstrated Her-2/neu and TFF3 to be independent prognostic indicators of recurrence, and a significantly poor prognosis for expression of TFF3 in patients with Her-2/neu negative tumors. TFF3 is an independent indicator for overall survival in gastric cancer, while Her-2/neu, as a marker of long time survival prediction, seems to be limited.

  17. HER2 Testing in Gastric/Gastroesophageal Junction Adenocarcinomas: Unique Features of a Familiar Test.

    PubMed

    Ross, Jeffrey S; Mulcahy, Mary

    2011-03-01

    Using the standard slide-based techniques of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), it has been firmly established that human epidermal growth factor receptor 2 (HER2) is overexpressed in adenocarcinoma of the upper gastrointestinal tract. In the ToGA trial, the addition of the monoclonal antibody trastuzumab to a standard regimen of cisplatin and fluoropyrimidine resulted in a clinically and statistically significant benefit in terms of response rate, median progression-free survival, and median overall survival in HER2-positive patients. Major differences exist, however, between HER2 testing in gastric/gastroesophageal junction (GEJ) cancer versus breast cancer, and the ToGA trial employed a significant modification of the breast cancer scoring criteria. As trastuzumab approaches regulatory approval in the United States for gastric/GEJ cancer, it is critical that pathologists and diagnostic laboratories learn and apply the unique criteria for assessing gastric/GEJ tumors for their HER2 status defined by the ToGA investigators, as they ready themselves for the approximately 50,000 new specimens that will be tested for HER2 status by both IHC and FISH each year.

  18. Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2016-06-27

    Adenocarcinoma of the Gastroesophageal Junction; Gastric Cardia Adenocarcinoma; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer

  19. Association between the expression levels of tumor necrosis factor-α-induced protein 8 and the prognosis of patients with gastric adenocarcinoma

    PubMed Central

    CHEN, LING; YANG, XIGUI; YANG, XIANGSHAN; FAN, KAIXI; XIAO, PING; ZHANG, JING; WANG, XIUWEN

    2016-01-01

    The present study aimed to investigate the expression levels of tumor necrosis factor-α-induced protein 8 (TNFAIP8) in gastric adenocarcinoma. TNFAIP8 expression levels in gastric adenocarcinoma tissue samples (with and without lymph node metastasis), adjacent normal tissue samples and metastatic lymph node tissue samples were detected by immunohistochemistry. The correlation between TNFAIP8 expression levels and clinicopathological data and gastric adenocarcinoma prognosis was analyzed. The results demonstrated that TNFAIP8 expression in gastric adenocarcinoma tissue samples and metastatic lymph node tissue samples markedly increased at a rate of 47.2% (50/106) and 81.7% (49/60), respectively, as compared with the adjacent normal tissue samples in which no TNGFAIP8 expression was detected (0%). This increase in TNFAIP8 expression was statistically significant. TNFAIP8 expression rates in the primary tumors (60%, 36/60) of patients with lymph node metastasis were significantly higher compared with the primary tumors of patients without lymph node metastasis (30.4%, 14/46). TNFAIP8 expression was associated with an increase in the severity of TNM stage, tumor grade, vascular invasion, lymph node metastasis and serum CA72-4 levels. The overall survival rate of patients with gastric adenocarcinoma and high TNFAIP8 expression was poorer compared with patients with low TNFAIP8 expression, and TNFAIP8 expression was negatively correlated with patient prognosis. The results also demonstrated that TNFAIP8 was an independent prognostic marker in gastric adenocarcinoma (relative risk, 1.736; P=0.029). In conclusion, the results of the present study demonstrated that TNFAIP8 expression was associated with the occurrence, development and metastasis of gastric adenocarcinoma, and negatively correlated with the prognosis of patients with gastric adenocarcinoma. TNFAIP8 may therefore serve as a prognostic factor for gastric adenocarcinoma. PMID:27347043

  20. Intraoperative Gastroscopy for Tumor Localization in Laparoscopic Surgery for Gastric Adenocarcinoma.

    PubMed

    Hur, Hoon; Son, Sang-Yong; Cho, Yong Kwan; Han, Sang-Uk

    2016-01-01

    Determining resection margins for gastric cancer, which are not exposed to the serosal surface of the stomach, is the most important procedure during totally laparoscopic gastrectomy (TLG). The aim of this protocol is to introduce a procedure for intraoperative gastroscopy, in order to directly mark tumors during TLG for gastric cancer in the middle third of the stomach. Patients who were diagnosed with adenocarcinoma in the middle third of the stomach were enrolled in this case series. Before surgery, additional gastroscopy for tumor localization is not performed. Under general anesthesia, laparoscopic mobilization of the stomach is performed first. After the first portion of the duodenum is mobilized from the pancreas and clamped, the surgeon moves to the other side for the gastroscopic procedure. On the insertion of a gastroscope through the oral cavity into the stomach, 2 - 3 cc of indigo carmine is administered via an endoscopic injector into the gastric muscle layer at the proximal margin of the stomach. The location of stained serosa in the laparoscopic view is used to guide distal subtotal gastrectomy, however, total gastrectomy is performed if the tumor is too close to the esophagogastric junction. A specimen is sampled after distal gastrectomy to confirm sufficient length from resection margin to tumor before reconstruction. In our case series, all patients had tumor-free margins and required no additional resection. There was no morbidity related to the gastroscopic procedure, and the time required for the procedure has gradually decreased to about five minutes. Intraoperative gastroscopy for tumor localization is an accurate and tolerated method for gastric cancer patients undergoing totally laparoscopic distal gastrectomy. PMID:27584713

  1. Intraoperative Gastroscopy for Tumor Localization in Laparoscopic Surgery for Gastric Adenocarcinoma.

    PubMed

    Hur, Hoon; Son, Sang-Yong; Cho, Yong Kwan; Han, Sang-Uk

    2016-08-09

    Determining resection margins for gastric cancer, which are not exposed to the serosal surface of the stomach, is the most important procedure during totally laparoscopic gastrectomy (TLG). The aim of this protocol is to introduce a procedure for intraoperative gastroscopy, in order to directly mark tumors during TLG for gastric cancer in the middle third of the stomach. Patients who were diagnosed with adenocarcinoma in the middle third of the stomach were enrolled in this case series. Before surgery, additional gastroscopy for tumor localization is not performed. Under general anesthesia, laparoscopic mobilization of the stomach is performed first. After the first portion of the duodenum is mobilized from the pancreas and clamped, the surgeon moves to the other side for the gastroscopic procedure. On the insertion of a gastroscope through the oral cavity into the stomach, 2 - 3 cc of indigo carmine is administered via an endoscopic injector into the gastric muscle layer at the proximal margin of the stomach. The location of stained serosa in the laparoscopic view is used to guide distal subtotal gastrectomy, however, total gastrectomy is performed if the tumor is too close to the esophagogastric junction. A specimen is sampled after distal gastrectomy to confirm sufficient length from resection margin to tumor before reconstruction. In our case series, all patients had tumor-free margins and required no additional resection. There was no morbidity related to the gastroscopic procedure, and the time required for the procedure has gradually decreased to about five minutes. Intraoperative gastroscopy for tumor localization is an accurate and tolerated method for gastric cancer patients undergoing totally laparoscopic distal gastrectomy.

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

    PubMed

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

    2013-04-01

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

  3. Cell-type specificity of β-actin expression and its clinicopathological correlation in gastric adenocarcinoma

    PubMed Central

    Khan, Shafqat A; Tyagi, Monica; Sharma, Ajit K; Barreto, Savio G; Sirohi, Bhawna; Ramadwar, Mukta; Shrikhande, Shailesh V; Gupta, Sanjay

    2014-01-01

    AIM: To investigate cell type specific distribution of β-actin expression in gastric adenocarcinoma and its correlation with clinicopathological parameters. METHODS: β-actin is a housekeeping gene, frequently used as loading control, but, differentially expresses in cancer. In gastric cancer, an overall increased expression of β-actin has been reported using tissue disruptive techniques. At present, no histological data is available to indicate its cell type-specific expression and distribution pattern. In the present study, we analyzed β-actin expression and distribution in paired normal and tumor tissue samples of gastric adenocarcinoma patients using immunohistochemistry (IHC), a tissue non-disruptive technique as well as tissue disruptive techniques like reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Correlation of β-actin level with clinicopathological parameters was done using univariate analysis. RESULTS: The results of this study showed significant overexpression, at both mRNA and protein level in tumor tissues as confirmed by RT-PCR (1.47 ± 0.13 vs 2.36 ± 0.16; P < 0.001) and western blotting (1.92 ± 0.26 vs 2.88 ± 0.32; P < 0.01). IHC revealed that β-actin expression is majorly distributed between epithelial and inflammatory cells of the tissues. Inflammatory cells showed a significantly higher expression compared to epithelial cells in normal (2.46 ± 0.13 vs 5.92 ± 0.23, P < 0.001), as well as, in tumor tissues (2.79 ± 0.24 vs 6.71 ± 0.14, P < 0.001). Further, comparison of immunostaining between normal and tumor tissues revealed that both epithelial and inflammatory cells overexpress β-actin in tumor tissues, however, significant difference was observed only in inflammatory cells (5.92 ± 0.23 vs 6.71 ± 0.14, P < 0.01). Moreover, combined expression in epithelial and inflammatory cells also showed significant increase (4.19 ± 0.15 vs 4.75 ± 0.14, P < 0.05) in tumor tissues. In addition, univariate

  4. Claudin-1, but not claudin-4, exhibits differential expression patterns between well- to moderately-differentiated and poorly-differentiated gastric adenocarcinoma

    PubMed Central

    TOKUHARA, YASUNORI; MORINISHI, TATSUYA; MATSUNAGA, TORU; OHSAKI, HIROYUKI; KUSHIDA, YOSHIO; HABA, REIJI; HIRAKAWA, EIICHIRO

    2015-01-01

    Claudins are members of a large family of transmembrane proteins, which are essential in the formation of tight junctions and have previously been associated with the process of tumor progression. Studies have reported the aberrant expression of claudin-1 and claudin-4 in numerous types of cancer. The present study aimed to investigate the expression of claudin-1 and claudin-4 in gastric adenocarcinoma tissue. Surgically resected gastric adenocarcinoma tissue specimens were obtained from 94 patients. Protein expression levels of claudin-1 and claudin-4 were determined using immunohistochemical staining; the association between claudin-1 or claudin-4 expression and various clinicopathological parameters were then analyzed. In gastric adenocarcinoma specimens, the expression rates of claudin-1 and claudin-4 were 43.6 and 87.2%, respectively. Claudin-1 expression demonstrated a significant correlation with histological type (P<0.01) and was significantly higher in well- to moderately-differentiated gastric adenocarcinomas compared with poorly-differentiated tumors. However, no correlation was observed between claudin-4 expression in adenocarcinoma and clinicopathological parameters. In conclusion, downregulation of claudin-1 expression in poorly-differentiated gastric adenocarcinoma may be involved in the biological transformation of tumors. The present findings suggested that claudin-1 may be an important protein associated with histological type and therefore may have potential for use as a prognostic marker for gastric adenocarcinoma. Further studies are required to elucidate the precise mechanism of claudin expression and its involvement in tumor progression. PMID:26170982

  5. Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

    PubMed Central

    Liu, Shin-Yun; Shun, Chia-Tung; Hung, Kuan-Yu; Juan, Hsueh-Fen; Hsu, Chia-Lang; Huang, Min-Chuan; Lai, I-Rue

    2016-01-01

    Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression. PMID:26848976

  6. Intraoperative Radiotherapy Combined With Adjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma

    SciTech Connect

    Fu Shen; Lu Jiade; Zhang Qing Yang Zhe; Peng Lihua; Xiong, Fei

    2008-12-01

    Purpose: To evaluate the efficacy of intraoperative radiotherapy (IORT) followed by concurrent chemotherapy and external beam RT (EBRT) in the treatment of locally advanced gastric adenocarcinoma. Methods and Materials: A total of 97 consecutive and nonselected patients with newly diagnosed Stage T3, T4, or N+ adenocarcinoma of the stomach underwent gastrectomy with D2 lymph node dissection between March 2003 and October 2005. Of the 97 patients, 51 received adjuvant concurrent chemotherapy (5-fluorouracil, leucovorin, docetaxel, and cisplatin) and EBRT (EBRT group) and 46 received IORT (dose range, 12-15 Gy) immediately after gastrectomy and lymph node dissection before concurrent chemoradiotherapy (EBRT+IORT group). Results: After a median follow-up of 24 months, the 3-year locoregional control rate was 77% and 63% in the two groups with or without IORT, respectively (p = 0.05). The 3-year overall survival and disease-free survival rate was 47% and 36% in the EBRT group and 56% and 44% in the EBRT+IORT group, respectively (p > 0.05). Multivariate analyses revealed that the use of IORT, presence of residual disease after surgery, and pN category were independent prognostic factors for locoregional control and that IORT, pN, and pT categories were independent prognostic factors for overall survival (p < 0.05). Four patients experienced Grade 3 or 4 late complications, but no significant difference was observed between the two groups. Conclusions: Radical gastrectomy with D2 lymph node dissection and IORT followed by adjuvant chemoradiotherapy appeared to be feasible and well-tolerated in the treatment of locally advanced gastric cancer. The addition of IORT to the trimodality treatment significantly improved the 3-year locoregional control rate.

  7. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment.

    PubMed

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-08-01

    Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  8. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

    PubMed Central

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi

    2016-01-01

    Abstract Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear. In this study, the Kaplan–Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM. CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245–0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma. A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    SciTech Connect

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho . E-mail: keesh@korea.ac.kr

    2005-08-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear {beta}-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear {beta}-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3{beta} activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death.

  12. Concurrent Gastric Adenocarcinoma of Fundic Gland Type and Carcinoma with Lymphoid Stroma: A Rare Case Report

    PubMed Central

    Cha, Hee Jeong; Kim, Kyungbin; Kim, Misung; Choi, Hyejeong; Kim, Young Min; Suh, Jae Hee

    2016-01-01

    Both gastric adenocarcinoma of fundic gland type (ADC-FG) and carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma, LELC) are relatively rare. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of LELC. However, the pathogenesis of ADC-FG, as well as the role of EBV in the carcinogenesis of LELC, remain unclear and under debate. The current study presents a case of concurrent ADC-FG and LELC in the stomach in a 69-year-old man. Total gastrectomy was performed, and two separate masses were identified. Upon histological and immunohistochemical examination, the mass located in the lower body was determined to be LELC and the mass in the upper body was diagnosed as ADC-FG. The lesions were characterized by different mucin phenotypes and EBV in situ results. In the lower-body mass, EBV in situ hybridization expression was diffusely strongly positive, but MUC2, MUC5AC, MUC6, and CD10 were all negative. On the other hand, in the upper-body mass, the results were positive for MUC6 but negative for MUC2, MUC5AC, CD10, and EBV by in situ hybridization. The remaining gastric tissue was unremarkable, and perigastric lymph node metastases were absent. Seven months after the gastrectomy, a postoperative computed tomography scan revealed no recurrence or metastasis. PMID:27462199

  13. Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity

    PubMed Central

    Ooi, Wen Fong; Xing, Manjie; Xu, Chang; Yao, Xiaosai; Ramlee, Muhammad Khairul; Lim, Mei Chee; Cao, Fan; Lim, Kevin; Babu, Deepak; Poon, Lai-Fong; Lin Suling, Joyce; Qamra, Aditi; Irwanto, Astrid; Qu Zhengzhong, James; Nandi, Tannistha; Lee-Lim, Ai Ping; Chan, Yang Sun; Tay, Su Ting; Lee, Ming Hui; Davies, James O. J.; Wong, Wai Keong; Soo, Khee Chee; Chan, Weng Hoong; Ong, Hock Soo; Chow, Pierce; Wong, Chow Yin; Rha, Sun Young; Liu, Jianjun; Hillmer, Axel M.; Hughes, Jim R.; Rozen, Steve; Teh, Bin Tean; Fullwood, Melissa Jane; Li, Shang; Tan, Patrick

    2016-01-01

    Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments. Somatic gain super-enhancers are associated with complex chromatin interaction profiles, expression patterns correlated with patient outcome and dense co-occupancy of the transcription factors CDX2 and HNF4α. Somatic super-enhancers are also enriched in genetic risk SNPs associated with cancer predisposition. Our results reveal a genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis, contributing to dysregulated local and regional cancer gene expression. PMID:27677335

  14. Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma

    PubMed Central

    2014-01-01

    Background Yin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis. The function and clinical significance of YY1 in gastric adenocarcinoma (GAC) have not been elucidated. Methods In this study, the functional role of YY1 in gastric cancer was investigated by MTT proliferation assays, monolayer colony formation, cell cycle analysis, signaling pathway analysis, Western blot analysis and in vivo study through YY1 knockdown or overexpression. Immunohistochemical study with YY1 antibody was performed on tissue microarray consisting of 247 clinical GAC samples. The clinical correlation and prognosis significance were evaluated. Results YY1 expression was up-regulated in gastric cancer cell lines and primary gastric cancers. Knocking down YY1 by siYY1 inhibited cell growth, inducing G1 phase accumulation and apoptosis. Ectopic YY1 expression enhanced cell proliferation in vitro and in vivo. Knocking down YY1 in gastric cancer cells suppressed proliferation by inhibiting Wnt/β-catenin pathway, whereas its overexpression exerted oncogenic property by activating Wnt/β-catenin pathway. In primary GAC samples, YY1 nuclear expression correlated with shorter survival and predicted poor prognosis in early stage GACs. Conclusion Our data demonstrated that YY1 contributes to gastric carcinogenesis in gastric cancer. In early stage GACs YY1 might serve as a poor prognostic marker and possibly as a potential therapeutic target. PMID:24674326

  15. Gastric adenocarcinoma in the context of X-linked agammaglobulinemia: case report and review of the literature.

    PubMed

    Staines Boone, Aidé Tamara; Torres Martínez, María Guadalupe; López Herrera, Gabriela; de Leija Portilla, Julia O; Espinosa Padilla, Sara Elva; Espinosa Rosales, Francisco J; Lugo Reyes, Saúl Oswaldo

    2014-02-01

    The hallmarks of X-linked Agammaglobulinemia (XLA) are panhypogammaglobulinemia, absent B-cells, and recurrent sinopulmonary and gastrointestinal infections starting at an early age, as well as other infections like cellulitis, meningitis, arthritis and sepsis. A number of non-infectious complications have been reported in these patients, including autoimmune diseases and malignancy, especially lymphomas. Here, we report the case of a 30-year old man who developed gastric adenocarcinoma in the context of XLA. Previous reports of, and hypotheses addressing the development of cancer in patients with XLA, are also summarized. Solid cancer in XLA affects mainly the gastrointestinal tract and seems to be related to chronic infection. A natural evolution can be traced back from gastric adenocarcinoma to megaloblastic anemia due to achlorhydria in the context of chronic infection; periodic endoscopy thus seems justified to detect and treat carcinoma in early stages. PMID:24338562

  16. Expression of SPARC like protein 1 (SPARCL1), extracellular matrix-associated protein is down regulated in gastric adenocarcinoma

    PubMed Central

    Jakharia, Aniruddha; Borkakoty, Biswajyoti

    2016-01-01

    Background SPARC-like protein 1 (SPARCL1/Hevin), a member of the SPARC family is defined by the presence of a highly acidic domain-I, a follistatin-like domain, and an extracellular calcium (EC) binding domain. SPARCL1 has been shown to be down-regulated in many types of cancer and may serve as a negative regulator of cell growth and proliferation. Methods Both tumor and adjacent normal tissue were collected from patients with gastric adenocarcinoma. Monoclonal antibody developed against recombinant SPARCL1 was used to analyze the expression of SPARCL1 by immunohisto chemical and western blotting (WB) analysis. Results The expression of SPARCL1 was found to be significantly lower or negligible in gastric adenocarcinoma tissues in nearly all of the cases in comparison with adjacent normal tissue. This comparison was found to be independent of the patient’s age, sex, and stage of cancer. Conclusions We postulate that down regulation of SPARCL1 may be related to inactivation of its tumor suppressor functions and might play an important role in the development of gastric adenocarcinoma. PMID:27034797

  17. Inflammatory Serum Proteins Are Severely Altered in Metastatic Gastric Adenocarcinoma Patients from the Chinese Population

    PubMed Central

    Sharma, Ashok; He, Mingfang; Xue, Jing; Wu, Jianzhong; Dun, Boying; Li, Gang; Wang, Xiaoxiao; Ji, Minghua; She, Jin-Xiong; Tang, Jinhai

    2015-01-01

    Background Inflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups. Methods Serum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay. Results The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA. Conclusions These results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer. PMID:25884401

  18. Impact of capillary invasion on the prognosis of gastric adenocarcinoma patients: A retrospective cohort study

    PubMed Central

    Lin, Pan-Pan; Xu, Yuan-Wei; 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

    Capillary invasion (CI) has been found to play an important role in metastasis and recurrence of gastric adenocarcinoma (GAC). However, the prognostic significance of CI is still controversial. From January 2005 to December 2011, 1398 patients with GAC who underwent gastrectomy were retrospectively enrolled and divided into CI (+) and CI (−) groups. Clinicopathological features and survival outcomes were compared between these groups. In our study, 227 (16.2%) patients were CI (+). Patients with CI (+) had significantly more advanced tumors and worse prognosis than those with CI (−) (p < 0.001). CI was demonstrated as an independent prognostic factor (p = 0.023) in patients with GAC. When stratified by TNM stage, the prognosis of CI (+) group in stage III was remarkably worse than CI (−) group (p = 0.006), while the differences were not significant in stage I–II and stage IV (both p > 0.05). The nomograms indicated that CI was part of the individual prognostic prediction system. The predictive accuracy of CI and other characteristics was better than TNM alone (p < 0.001). Our finding suggested that CI was an independent prognostic factor in patients with GAC, and the nomogram based on CI and other clinicopathological factors was a valuable and accurate tool in individual prognostic prediction. PMID:27145279

  19. Increased expression of IDO associates with poor postoperative clinical outcome of patients with gastric adenocarcinoma.

    PubMed

    Liu, Hao; Shen, Zhenbin; Wang, Zhenglin; Wang, Xuefei; Zhang, Heng; Qin, Jing; Qin, Xinyu; Xu, Jiejie; Sun, Yihong

    2016-02-18

    Clinical significance of 2,3-dioxygenase (IDO) has been studied in types of tumors, but the role that IDO played in gastric adenocarcinoma (GAC) is still unclear. Here, we aim to investigate the prognostic value of IDO expression in patients with GAC. We examined intratumoral IDO expression in retrospectively enrolled 357 patients with GAC undergoing gastrectomy at Zhongshan Hospital of Fudan University in 2008 by immunohistochemical staining. The Kaplan-Meier method and Cox regression models were used to evaluate the prognostic value of IDO expression and its association with clinical pathological factors. We generated a predictive nomogram by integrating IDO expression with the TNM staging system for overall survival of GAC patients. High expression of intratumoral IDO predicted a dismal outcome. Intratumoral IDO expression gave a further discrimination for the prognosis of GAC patients. By Cox multivariate analysis, IDO expression was defined as an independent prognosticator. The generated nomogram performed well in predicting the 3- and 5-year overall survival of GAC patients. Conclusively, IDO is a potential prognostic biomarker for overall survival of patients with GAC after gastrectomy.

  20. Impact of marital status on survival of gastric adenocarcinoma patients: Results from the Surveillance Epidemiology and End Results (SEER) Database

    PubMed Central

    Qiu, Miaozhen; Yang, Dajun; Xu, Ruihua

    2016-01-01

    Marital status was found to be an independent prognostic factor for survival in various cancer types. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among different marital status in the United States. Gastric adenocarcinoma patients from 2004–2012 were enrolled for study. The 5-year cause specific survival (CSS) was our primary endpoint. Totally 29,074 eligible patients were identified. We found that more male patients were married than female. Asian patients had the highest percentages of married than the other races. More married patients were covered by the insurance. Married patients had better 5-year CSS than unmarried, 30.6% vs 25.7%, P < 0.001. The median overall CSS was 17.87 and 13.61 months for the married and unmarried patients, hazard ratio: 1.09 (95% confidence interval: 1.01–1.17), P = 0.027. The survival difference was significant in the insured but not in the uninsured patients. Widowed patients had the worst prognosis compared with other groups even though they had more stage I disease and more well / moderate differentiated tumors. These results indicated that unmarried gastric adenocarcinoma patients were at greater risk of cancer specific mortality. We recommend every patient should have access to best available gastric cancer therapy. PMID:26876653

  1. HER2 in situ hybridization in gastric and gastroesophageal adenocarcinoma: comparison of automated dual ISH to FISH.

    PubMed

    Grin, Andrea; Brezden-Masley, Christine; Bauer, Sharon; Streutker, Catherine J

    2013-12-01

    Patients with gastric and gastroesophageal junction (GEJ) adenocarcinomas that are HER2 positive by immunohistochemistry (IHC) or in situ hybridization show a significant survival benefit with trastuzumab therapy. In situ hybridization is traditionally done by fluorescence in situ hybridization (FISH), despite some limitations. An alternative is the dual in situ hybridization (Dual ISH) technique that is fully automated and uses differentially labeled CEP17 and HER2 probes that can be read by light microscopy on 1 slide. The aim of this study was to assess the utility of Dual ISH in gastric/GEJ cancer and to compare the results with those obtained by IHC and FISH. Cases of gastric/GEJ adenocarcinoma were analyzed by IHC, FISH, and Dual ISH and the correlation between methods calculated. Results for 50 patients were available. There was a 98% (49/50) concordance rate between Dual ISH and FISH. One discrepant case was nonamplified by FISH but showed focal amplification by Dual ISH. Discrepancy was attributed to tumor heterogeneity, which was a frequent finding (78% of HER2-positive cases). There was excellent correlation between Dual ISH and FISH for assessment of HER2 amplification. Dual ISH was rapid, easy to interpret, and maintained cell morphology, which was valuable in identifying tumor heterogeneity.

  2. Molecular effects of Lapatinib in the treatment of HER2 overexpressing oesophago-gastric adenocarcinoma

    PubMed Central

    De Silva, Nadeera; Schulz, Laura; Paterson, Anna; Qain, Wendi; Secrier, Maria; Godfrey, Edmund; Cheow, Heok; O'Donovan, Maria; Lao-Sirieix, Pierre; Jobanputra, Minesh; Hochhauser, Daniel; Fitzgerald, Rebecca; Ford, Hugo

    2015-01-01

    Background: Lapatinib, a dual EGFR and HER2 inhibitor has shown disappointing results in clinical trials of metastatic oesophago-gastric adenocarcinomas (OGAs), and in vitro studies suggest that MET, IGFR, and HER3 confer resistance. This trial applied Lapatinib in the curative neoadjuvant setting and investigated the feasibility and utility of additional endoscopy and biopsy for assessment of resistance mechanisms ex vivo and in vivo. Methods: Patients with HER2 overexpressing OGA were treated for 10 days with Lapatinib monotherapy, and then in combination with three cycles of Oxaliplatin and Capecitabine before surgery. Endoscopic samples were taken for molecular analysis at: baseline including for ex vivo culture +/− Lapatinib to predict in vivo response, post-Lapatinib monotherapy and at surgery. Immunohistochemistry (IHC) and proteomic analysis was performed to assess cell kinetics and signalling activity. Results: The trial closed early (n=10) due to an anastomotic leak in two patients for which a causative effect of Lapatinib could not be excluded. The reduction in Phosphorylated-HER2 (P-HER2) and P-EGFR in the ex vivo-treated biopsy demonstrated good correlation with the in vivo response at day 10. Proteomic analysis pre and post-Lapatinib demonstrated target inhibition (P-ERBB2, P-EGFR, P-PI3K, P-AKT, and P-ERK) that persisted until surgery. There was also significant correlation between the activation of MET with the level of P-Erk (P=0.0005) and P-PI3K : T-PI3K (total PI3K) ratio (P=0.0037). There was no significant correlation between the activation status of IGFR and HER3 with downstream signalling molecules. Conclusions: Additional endoscopy and biopsy sampling for multiple biomarker endpoints was feasible and confirmed in vitro data that MET is likely to be a significant mechanism of Lapatinib resistance in vivo. PMID:26484410

  3. Prognostic value of differential CCND1 expression in patients with resected gastric adenocarcinoma.

    PubMed

    Ma, Liqiang; Wang, Xiaoting; Lan, Fenghua; Yu, Yinghao; Ouyang, Xuenong; Liu, Wei; Xie, Feilai; Huang, Qiaojia

    2015-01-01

    Cyclin D1 (CCND1) plays essential roles in cancer progression. In this study, CCND1 expression patterns in 211 cases of resected gastric adenocarcinoma (RGA) tissue were determined by immunohistochemistry, and the association between CCND1 expression levels and RGA prognosis was analyzed. RGA tissues displayed differential CCND1 expression (high expression, 52.1 %; n = 110, and low expression, 47.9 %; n = 101). CCND1 expression levels were related with median overall survival time (MST). MST in patients with high CCND1 expression was 43 months, whereas with low CCND1 expression it was 62 months (P = 0.013). When data were stratified by postoperative treatments and CCND1 expression levels, the MST for patients treated with fluoropyrimidine plus platinum (n = 140) was significantly longer than for those treated with fluoropyrimidine only (n = 71) in both high and low CCND1 expression groups (65.0 vs. 29.0 months, P = 0.041; and 74.5 vs. 33.0 months, P = 0.003, respectively). Cox multivariate analyses further confirmed that high CCND1 expression was related with poor prognosis in both treatment groups [hazard ratio (HR) 1.91, 95 % confidence interval (CI) 1.12-3.23; P = 0.017, and HR 2.14, 95 % CI 1.08-4.25; P = 0.029] and that fluoropyrimidine plus platinum was more effective than fluoropyrimidine only in high CCND1 (HR 0.47, 95 % CI 0.28-0.78; P = 0.004) and low CCND1 (HR 0.44; 95 % CI 0.23-0.82; P = 0.01) expression patients. Therefore, CCND1 may be used as a prognostic biomarker for patients with RGA.

  4. 64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

    ClinicalTrials.gov

    2016-09-16

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

  5. Synchronous gastric and ampullary adenocarcinomas in a hairy cell leukemia patient treated with pentostatin eight years prior.

    PubMed

    Senatore, Frank J; Dasanu, Constantin A

    2016-06-01

    Hairy cell leukemia patients are at increased risk for second malignancies, including both solid and lymphoid neoplasms. Along with other factors, multiple immune defects present in hairy cell leukemia likely contribute to subsequent carcinogenesis. We report herein a case of synchronous high-grade gastric and ampullary adenocarcinomas in a patient with a history of hairy cell leukemia treated eight years prior with pentostatin. We include a review of immune alterations induced by both hairy cell leukemia and its therapies, and link them with the occurrence of second cancers in these patients. PMID:25712625

  6. Evaluation of Trastuzumab Anti-Tumor Efficacy and its Correlation with HER-2 Status in Patient-Derived Gastric Adenocarcinoma Xenograft Models.

    PubMed

    Chen, Hao; Ye, Qingqing; Lv, Jing; Ye, Peng; Sun, Yun; Fan, Shuqiong; Su, Xinying; Gavine, Paul; Yin, Xiaolu

    2015-09-01

    The aim of the study was to investigate trastuzumab anti-tumor efficacy and its correlation with HER-2 status in primary xenograft models derived from Chinese patients with gastric adenocarcinoma. Patient-derived gastric adenocarcinoma xenograft (PDGAX) mouse models were firstly generated by implanting gastric adenocarcinoma tissues from patients into immune deficient mice. A high degree of histological and molecular similarity between the PDGAX mouse models and their corresponding patients' gastric adenocarcinoma tissues was shown by pathological observation, HER-2 expression, HER-2 gene copy number, and mutation detection. Based on Hoffmann's criteria in gastric cancer, three models (PDGAX001, PDGAX003 and PDGAX005) were defined as HER-2 positive with fluorescence in situ hybridization (FISH) amplification or immunohistochemistry (IHC) 2+/ 3+, while two models (PDGAX002, PDGAX004) were defined as HER-2 negative. Upon trastuzumab treatment, significant tumor regression (105 % TGI) was observed in model PDGAX005 (TP53 wt), while moderate sensitivity (26 % TGI) was observed in PDGAX003, and resistance was observed in PDGAX001, 002 and 004. A significant increase in HER-2 gene copy number was only observed in PDGAX005 (TP53 wt). Interestingly, trastuzumab showed no efficacy in PDGAX001 (HER2 IHC 3+ and FISH amplification, but with mutant TP53). Consistent with this finding, phosphor-HER2 modulation by trastuzumab was observed in model PDGAX005, but not in PDGAX001.

  7. Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region

    PubMed Central

    Vilar e Silva, Adenielson; Junior, Mario Ribeiro da Silva; Vinagre, Ruth Maria Dias Ferreira; Santos, Kemper Nunes; da Costa, Renata Aparecida Andrade; Fecury, Amanda Alves; Quaresma, Juarez Antônio Simões; Martins, Luisa Caricio

    2014-01-01

    The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92–7.46, and P = 0.002). A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation. PMID:26904732

  8. Evaluation of the Pattern of EPIYA Motifs in the Helicobacter pylori cagA Gene of Patients with Gastritis and Gastric Adenocarcinoma from the Brazilian Amazon Region.

    PubMed

    Vilar E Silva, Adenielson; Junior, Mario Ribeiro da Silva; Vinagre, Ruth Maria Dias Ferreira; Santos, Kemper Nunes; da Costa, Renata Aparecida Andrade; Fecury, Amanda Alves; Quaresma, Juarez Antônio Simões; Martins, Luisa Caricio

    2014-01-01

    The Helicobacter pylori is associated with the development of different diseases. The clinical outcome of infection may be associated with the cagA bacterial genotype. The aim of this study was to determine the EPIYA patterns of strains isolated from patients with gastritis and gastric adenocarcinoma and correlate these patterns with the histopathological features. Gastric biopsy samples were selected from 384 patients infected with H. pylori, including 194 with chronic gastritis and 190 with gastric adenocarcinoma. The presence of the cagA gene and the EPIYA motif was determined by PCR. The cagA gene was more prevalent in patients with gastric cancer and was associated with a higher degree of inflammation, neutrophil activity, and development of intestinal metaplasia. The number of EPIYA-C repeats showed a significant association with an increased risk of gastric carcinoma (OR = 3.79, 95% CI = 1.92-7.46, and P = 0.002). A larger number of EPIYA-C motifs were also associated with intestinal metaplasia. In the present study, infection with H. pylori strains harboring more than one EPIYA-C motif in the cagA gene was associated with the development of intestinal metaplasia and gastric adenocarcinoma but not with neutrophil activity or degree of inflammation. PMID:26904732

  9. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Steffen, Annika; Huerta, José-Maria; Weiderpass, Elisabete; Bueno-de-Mesquita, H B As; May, Anne M; Siersema, Peter D; Kaaks, Rudolf; Neamat-Allah, Jasmine; Pala, Valeria; Panico, Salvatore; Saieva, Calogero; Tumino, Rosario; Naccarati, Alessio; Dorronsoro, Miren; Sánchez-Cantalejo, Emilio; Ardanaz, Eva; Quirós, J Ramón; Ohlsson, Bodil; Johansson, Mattias; Wallner, Bengt; Overvad, Kim; Halkjaer, Jytte; Tjønneland, Anne; Fagherazzi, Guy; Racine, Antoine; Clavel-Chapelon, Françoise; Key, Tim J; Khaw, Kay-Tee; Wareham, Nick; Lagiou, Pagona; Bamia, Christina; Trichopoulou, Antonia; Ferrari, Pietro; Freisling, Heinz; Lu, Yunxia; Riboli, Elio; Cross, Amanda J; Gonzalez, Carlos A; Boeing, Heiner

    2015-08-01

    General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.

  10. Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids.

    PubMed

    Mukaisho, Ken-Ichi; Nakayama, Takahisa; Hagiwara, Tadashi; Hattori, Takanori; Sugihara, Hiroyuki

    2015-01-01

    Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC) continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER), which predominantly occurs in patients without Helicobacter pylori (H. pylori) infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles non-cardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori-negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid), play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids. PMID:26029176

  11. Clinicopathologic characteristics and survival outcomes of patients with advanced esophageal, gastroesophageal junction, and gastric adenocarcinoma: a single-institution experience

    PubMed Central

    Dechaphunkul, A.; Mulder, K.; El-Gehani, F.; Ghosh, S.; Deschenes, J.; Spratlin, J.

    2012-01-01

    Most patients with gastric or gastroesophageal junction (gej) cancer are diagnosed with inoperable advanced or metastatic disease. In these cases, chemotherapy is the only treatment demonstrating survival benefit. The present study compares clinicopathologic characteristics and survival outcomes for patients with advanced esophageal, gej, and gastric adenocarcinoma treated with first-line chemotherapy [epirubicin–cisplatin–5-fluorouracil (ecf), epirubicin–cisplatin–capecitabine (ecx), or etoposide–leucovorin–5-fluorouracil (elf)] or best supportive care (bsc) at our institution with those for historical controls. Methods We retrospectively reviewed medical information for 401 patients with newly diagnosed advanced esophageal, gej, or gastric adenocarcinoma treated with first-line chemotherapy (ecf, ecx, or elf) or bsc from January 1, 2004, through December 31, 2010. Descriptive statistics were used to compare the data collected with data for historical control patients. Results Of the study patients, 93% were diagnosed with metastatic disease (n = 374), and 63% received bsc only (n = 251). The main reasons that patients received bsc only included poor Eastern Cooperative Oncology Group performance status (55%), patient decision (31%), and comorbidities (14%). Of the remaining patients, 98 (24%) received ecf or ecx and 52 (13%) received elf as first-line treatment. Median overall survival was significantly longer in patients treated with ecf or ecx or with elf than in those receiving bsc (12.7 months vs. 12.7 months vs. 5.5 months respectively). Chemotherapy also significantly reduced the risk of death (64% reduction with ecf or ecx, 58% with elf). Conclusions We confirmed the substantial overall survival benefit of combination chemotherapy compared with bsc, with better survival in our patient population than in historical controls. However, novel treatment options are still warranted to improve outcomes in this patient population. PMID:23300355

  12. Progressing Sclerosing Mesenteritis (Mesenteric Panniculitis) Mimics Progression of Malignancy After Neoadjuvant Chemotherapy for Gastric Adenocarcinoma on Serial 18F-FDG PET/CT.

    PubMed

    Makis, William

    2016-04-01

    A 62-year-old man was diagnosed with a moderately differentiated gastric adenocarcinoma in the proximal stomach. A staging 18F-FDG PET/CT showed an intensely FDG-avid gastric mass, as well as a mildly FDG-avid misty nodular mesentery. After 3 cycles of neoadjuvant chemotherapy, a follow-up PET/CT showed partial response of the gastric primary, with increase in the size of nodules in the mesentery and increased FDG uptake, raising concern of secondary malignancy. Biopsy of the mesentery revealed xanthogranulomatous inflammation, consistent with sclerosing mesenteritis. PMID:26359565

  13. HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population

    PubMed Central

    2013-01-01

    Background With varied immunohistochemistry scoring criteria and patient cohorts, HER2-positivity rates in gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma have been reported with a wide range. Recently standardized scoring criteria for GC and GEJ cancer has been established and recommended. In this study, the frequency of HER2 expression and the relationship between HER2 expression and clinicopathological features were examined in a large cohort of Chinese GC and GEJ cancer patients. Methods A total of 1463 patients, including 929 primary GCs and 534 primary GEJ adenocarcinomas, was retrospectively analyzed for HER2 overexpression by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) analysis was used in 308 GCs and GEJ adenocarcinoma cases to assess HER2 gene amplification. Results HER2 overexpression (3+) was detected in 9.8% of carcinomas and more frequently observed in GEJ cancer cases, in the intestinal type, and in the well or moderately differentiated type (P=0.003, 0.000, and 0.000, respectively). HER2 equivocal (2+) was detected in 14.4% of cases. As for the 308 cases analyzed by FISH, 39 (of 40, 97.5%) IHC 3+ cases, 11 (of 38, 28.9%) IHC 2+ cases, and 3 (of 230, 1.3%) IHC 1+/0 cases showed HER2 gene amplification. A high concordance rate (98.5%) between IHC and FISH was demonstrated. Conclusions Approximately 10% of Chinese patients with primary GC and GEJ adenocarcinoma were HER2-positive on IHC. HER2 overexpression was associated with GEJ site, intestinal cancer subtype, and well or moderately differentiated carcinomas. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1935951199941072. PMID:23656792

  14. Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma

    PubMed Central

    Subbannayya, Yashwanth; Syed, Nazia; Barbhuiya, Mustafa A; Raja, Remya; Marimuthu, Arivusudar; Sahasrabuddhe, Nandini; Pinto, Sneha M; Manda, Srikanth Srinivas; Renuse, Santosh; Manju, HC; Zameer, Mohammed Abdul Lateef; Sharma, Jyoti; Brait, Mariana; Srikumar, Kotteazeth; Roa, Juan Carlos; Vijaya Kumar, M; Kumar, KV Veerendra; Prasad, TS Keshava; Ramaswamy, Girija; Kumar, Rekha Vijay; Pandey, Akhilesh; Gowda, Harsha; Chatterjee, Aditi

    2015-01-01

    Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer. PMID:25756516

  15. Reduced MUTYH, MTH1, and OGG1 expression and TP53 mutation in diffuse-type adenocarcinoma of gastric cardia.

    PubMed

    Kohno, Yukiko; Yamamoto, Hidetaka; Hirahashi, Minako; Kumagae, Yoshiteru; Nakamura, Masafumi; Oki, Eiji; Oda, Yoshinao

    2016-06-01

    The effects of oxidative stress in adenocarcinomas of gastric cardia (AGCs) have not been fully elucidated. With a strict definition of AGC, we examined the immunohistochemical expressions of inducible nitric oxide synthase; 8-hydroxy-deoxyguanosine; and the base excision repair enzymes such as MUTYH, MTH1, and OGG1, and TP53 mutational status. Sixty-three cases of AGC were characterized by younger patient age (P = .0227) and more frequent venous invasion (P = .0106) compared with the adenocarcinomas of pylorus (APs). 8-hydroxy-deoxyguanosine was accumulated (P = .0011), whereas MUTYH (P = .0325) and OGG1 (P = .0007) were decreased, in the AGCs compared with the adjacent mucosa, but these differences were not detected in the APs. Among the AGCs, lower expressions of MUTYH (P = .0013) and MTH1 (P = .0059) were each significantly associated with diffuse-type histology. A lower expression of OGG1 was correlated with higher T-stage (P = .0011), lymphatic invasion (P = .004), and lymph node metastasis (P = .0094). In addition, the presence of TP53 mutation was associated with diffuse-type histology (P = .0153) and a lower level of MUTYH (P = .0221). The AGCs also showed a relatively high rate of a transversion-type mutation of TP53 (50%), whereas all TP53 mutations in the APs were transition type. Age 62years or older (P = .0073), diffuse-type histology (P = .0020), and TP53 mutation (P = .0066) were each associated with worse survival in the AGC patients. Our results indicate that oxidative stress accumulation and a downregulation of base excision repair enzymes may play an important role in the pathogenesis of AGC, in particular diffuse-type AGCs. Diffuse-type AGC might involve molecular pathways different from those of other subsets of gastric cancer. PMID:26980051

  16. Cellular responses induced in vitro by pestheic acid, a fungal metabolite, in a gastric adenocarcinoma cell line (PG100).

    PubMed

    Sousa, J M C; Matos, L A; Alcântara, D F A; Ribeiro, H F; Santos, L S; Oliveira, M N; Brito-Junior, L C; Khayat, A S; Guimarães, A C; Cunha, L A; Burbano, R R; Bahia, M O

    2013-01-01

    There is a constant search for new cancer treatments that are less aggressive and economically affordable. In this context, natural products extracted from plants, fungi, and microorganisms are of great interest. Pestheic acid, or dihidromaldoxin, is a chlorinated diphenylic ether extracted from the phytopathogenic fungus Pestalotiopsis guepinii (Amphisphaeriaceae). We assessed the cytotoxic, cytostatic, and genotoxic effects of pestheic acid in a gastric adenocarcinoma cell line (PG100). A decrease in clonogenic survival was observed. Pestheic acid also induced significant increases in both micronucleus and nucleoplasmic bridge frequency. However, we did not observe changes in cell cycle kinetics or apoptosis induction. Reactive oxygen species induced by diphenylic ethers may explain the genotoxicity and mutagenicity of pestheic acid. The absence of repair checkpoints that we observed is probably due to the fact that the PG100 cell line lacks the TP53 gene, which is common in gastric cancers. Even though pestheic acid has had a clear cytotoxic effect, the minimal inhibitory concentration was high, which shows that pestheic acid is not an active anticancer compound under these conditions. PMID:24114206

  17. Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy

    PubMed Central

    Palestro, Giorgio; Pellicano, Rinaldo; Fronda, Gian Ruggero; Valente, Guido; Giuli, Marco De; Soldati, Tito; Pugliese, Agostino; Taraglio, Stefano; Garino, Mauro; Campra, Donata; Cutufia, Miguel Angel; Margaria, Elena; Spinzi, Giancarlo; Ferrara, Aldo; Marenco, Giorgio; Rizzetto, Mario; Ponzetto, Antonio

    2005-01-01

    AIM: To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC). METHODS: Samples from 317 (184 males, 133 females, mean age 69±3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study. Five hundred and fifty-five (294 males, 261 females, mean age 57.3±4.1 years) patients consecutively admitted to the Emergency Care Unit served as control. Histological examination of tumor, lymph nodes and other tissues obtained at the time of surgery represented the diagnostic “gold standard”. An enzyme immunosorbent assay was used to detect serum anti-H pylori (IgG) antibodies and Western blotting technique was utilized to search for anti-CagA protein (IgG). RESULTS: Two hundred and sixty-one of three hundred and seventeen (82.3%) GC patients and 314/555 (56.5%) controls were seropositive for anti-H pylori (P<0.0001; OR, 3.58; 95%CI, 2.53-5.07). Out of the 317 cases, 267 (84.2%) were seropositive for anti-CagA antibody vs 100 out of 555 (18%) controls (P<0.0001; OR, 24.30; 95%CI, 16.5-35.9). There was no difference between the frequency of H pylori in intestinal type carcinoma (76.2%) and diffuse type cancer (78.8%). Intestinal metaplasia (IM) was more frequent but not significant in the intestinal type cancer (83.4% vs 75.2% in diffuse type and 72.5% in mixed type). Among the patients examined for IM, 39.8% had IM type I, 8.3% type II and 51.9% type III (type III vs others, P = 0.4). CONCLUSION: This study confirms a high seroprevalence of H pylori infection in patients suffering from gastric adenocarcinoma and provides further evidence that searching for CagA status over H pylori infection might confer additional benefit in identifying populations at greater risk for this tumor. PMID:16437659

  18. Proteasome inhibitor MG-132 lowers gastric adenocarcinoma TMK1 cell proliferation via bone morphogenetic protein signaling

    SciTech Connect

    Wu, William Ka Kei; Sung, Joseph Jao Yiu; Yu Le; Cho, C.H.

    2008-06-27

    Proteasome inhibitor is a novel class of cancer therapeutics, of which the mechanism of action is not fully understood. It is reported that proteasome inhibitor enhances bone morphogenetic protein (BMP) signaling in osteoblasts to stimulate bone formation. BMP signaling is also an important tumor-suppressing pathway in gastric carcinogenesis. We therefore sought to determine the anti-mitogenic effect of proteasome inhibition in relation to BMP signaling in gastric cancer cells. Results showed that proteasome inhibitor MG-132 significantly suppressed the proliferation and the colony-forming ability of gastric cancer TMK1 cells. In this connection, MG-132 activated BMP signaling, manifested as an increase in Smad1/5/8 phosphorylation and up-regulation of p21{sup Waf1/Cip1} mRNA and protein expression. Knockdown of BMP receptor II by RNA interference abolished Smad1/5/8 phosphorylation, p21{sup Waf1/Cip1} induction, and the inhibition of cell proliferation induced by MG-132. Further analysis revealed that MG-132 up-regulated the expression of BMP1 and BMP4 and suppressed the expression of Smad6. Knockdown of Smad6 also mimicked the effect of MG-132 on BMP signaling. Collectively, these findings suggest that inhibition of proteasome suppresses gastric cancer cell proliferation via activation of BMP signaling. This discovery may open up a novel therapeutic avenue to proteasome inhibitors for the management of gastric cancer.

  19. Frequency of Detectable HBsAg in Fluid Adherent to the Endoscope, Gastric Juice, and Saliva Collected during Endoscopy in Patients Positive for HBsAg

    PubMed Central

    Yang, Ung-Suk; Liu, Bang-Hyun

    1986-01-01

    Gastric juice, saliva, and fluid adherent to the endoscope were collected from 50 patients who were seropositive for hepatitis B surface antigen (HBsAg) during the endoscopic examination of the upper gastrointestinal tract, and examined for HBsAg, using the radioimmunoassay. A positive test was obtained from 42.0% of the saliva samples, in 32.0% of the gastric juice specimens, and in 31.3% of the fluid adherent to the scope. These results should be taken as a warning, that calls for a more careful screening of the patients and disinfection of the endoscope. PMID:3154614

  20. Contribution of H. pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model

    PubMed Central

    Yeh, Jennifer M.; Hur, Chin; Schrag, Deb; Kuntz, Karen M.; Ezzati, Majid; Stout, Natasha; Ward, Zachary; Goldie, Sue J.

    2013-01-01

    Background Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence. Methods and Findings We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%–58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%–21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%–100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men. Conclusions Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be

  1. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

    PubMed

    Li, Jun; Woods, Susan L; Healey, Sue; Beesley, Jonathan; Chen, Xiaoqing; Lee, Jason S; Sivakumaran, Haran; Wayte, Nicci; Nones, Katia; Waterfall, Joshua J; Pearson, John; Patch, Anne-Marie; Senz, Janine; Ferreira, Manuel A; Kaurah, Pardeep; Mackenzie, Robertson; Heravi-Moussavi, Alireza; Hansford, Samantha; Lannagan, Tamsin R M; Spurdle, Amanda B; Simpson, Peter T; da Silva, Leonard; Lakhani, Sunil R; Clouston, Andrew D; Bettington, Mark; Grimpen, Florian; Busuttil, Rita A; Di Costanzo, Natasha; Boussioutas, Alex; Jeanjean, Marie; Chong, George; Fabre, Aurélie; Olschwang, Sylviane; Faulkner, Geoffrey J; Bellos, Evangelos; Coin, Lachlan; Rioux, Kevin; Bathe, Oliver F; Wen, Xiaogang; Martin, Hilary C; Neklason, Deborah W; Davis, Sean R; Walker, Robert L; Calzone, Kathleen A; Avital, Itzhak; Heller, Theo; Koh, Christopher; Pineda, Marbin; Rudloff, Udo; Quezado, Martha; Pichurin, Pavel N; Hulick, Peter J; Weissman, Scott M; Newlin, Anna; Rubinstein, Wendy S; Sampson, Jone E; Hamman, Kelly; Goldgar, David; Poplawski, Nicola; Phillips, Kerry; Schofield, Lyn; Armstrong, Jacqueline; Kiraly-Borri, Cathy; Suthers, Graeme K; Huntsman, David G; Foulkes, William D; Carneiro, Fatima; Lindor, Noralane M; Edwards, Stacey L; French, Juliet D; Waddell, Nicola; Meltzer, Paul S; Worthley, Daniel L; Schrader, Kasmintan A; Chenevix-Trench, Georgia

    2016-05-01

    Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present.

  2. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

    PubMed

    Li, Jun; Woods, Susan L; Healey, Sue; Beesley, Jonathan; Chen, Xiaoqing; Lee, Jason S; Sivakumaran, Haran; Wayte, Nicci; Nones, Katia; Waterfall, Joshua J; Pearson, John; Patch, Anne-Marie; Senz, Janine; Ferreira, Manuel A; Kaurah, Pardeep; Mackenzie, Robertson; Heravi-Moussavi, Alireza; Hansford, Samantha; Lannagan, Tamsin R M; Spurdle, Amanda B; Simpson, Peter T; da Silva, Leonard; Lakhani, Sunil R; Clouston, Andrew D; Bettington, Mark; Grimpen, Florian; Busuttil, Rita A; Di Costanzo, Natasha; Boussioutas, Alex; Jeanjean, Marie; Chong, George; Fabre, Aurélie; Olschwang, Sylviane; Faulkner, Geoffrey J; Bellos, Evangelos; Coin, Lachlan; Rioux, Kevin; Bathe, Oliver F; Wen, Xiaogang; Martin, Hilary C; Neklason, Deborah W; Davis, Sean R; Walker, Robert L; Calzone, Kathleen A; Avital, Itzhak; Heller, Theo; Koh, Christopher; Pineda, Marbin; Rudloff, Udo; Quezado, Martha; Pichurin, Pavel N; Hulick, Peter J; Weissman, Scott M; Newlin, Anna; Rubinstein, Wendy S; Sampson, Jone E; Hamman, Kelly; Goldgar, David; Poplawski, Nicola; Phillips, Kerry; Schofield, Lyn; Armstrong, Jacqueline; Kiraly-Borri, Cathy; Suthers, Graeme K; Huntsman, David G; Foulkes, William D; Carneiro, Fatima; Lindor, Noralane M; Edwards, Stacey L; French, Juliet D; Waddell, Nicola; Meltzer, Paul S; Worthley, Daniel L; Schrader, Kasmintan A; Chenevix-Trench, Georgia

    2016-05-01

    Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present. PMID:27087319

  3. [Intramedullary spinal cord metastasis from gastric adenocarcinoma: Case report and review of literature].

    PubMed

    Pérez-Suárez, Javier; Barrio-Fernández, Patricia; Ibáñez-Plágaro, Francisco Javier; Ribas-Ariño, Teresa; Calvo-Calleja, Pablo; Mostaza-Saavedra, Antonio Luis

    2016-01-01

    Intramedullary spinal cord metastases are very rare and usually associated with lung or breast cancer, with gastric origin being exceptional. Their clinical onset tends to be faster than that of primary intramedullary tumours. The most common early symptoms of intramedullary spinal cord metastasis are motor deficit in one or more limbs, pain, sensory loss, and sphincter disturbances. The appearance of a rapidly progressive Brown-Séquard syndrome in an oncology patient should orientate the diagnosis of this condition. The prognosis is very poor, with a median survival of 4 months. However, recent research has shown that surgery could offer a slight benefit in survival and functionality. The case is reported of a 61-year-old man with an intramedullary spinal cord metastasis from a gastric carcinoma, as well as a literature review of this topic. It has been found that this case is the fourth one reported in the literature.

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

    PubMed

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

    2012-12-01

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

  5. An unusual presentation of tumor lysis syndrome in a patient with advanced gastric adenocarcinoma: case report and literature review.

    PubMed

    Vodopivec, Danica Maria; Rubio, Jose Enrique; Fornoni, Alessia; Lenz, Oliver

    2012-01-01

    Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications) identified through these searches were reviewed and included.

  6. THE PRESENCE OF METASTASES IN REGIONAL LYMPH NODES IS ASSOCIATED WITH TUMOR SIZE AND DEPTH OF INVASION IN SPORADIC GASTRIC ADENOCARCINOMA

    PubMed Central

    CAMBRUZZI, Eduardo; de AZEREDO, Andreza Mariane; KRONHART, Ardala; FOLTZ, Katia Martins; ZETTLER, Cláudio Galeano; PÊGAS, Karla Lais

    2014-01-01

    Background Gastric adenocarcinoma is more often found in men over 50 years in the form of an antral lesion. The tumor has heterogeneous histopathologic features and a poor prognosis (median survival of 15% in five years). Aim To estimate the relationship between the presence of nodal metastasis and other prognostic factors in sporadic gastric adenocarcinoma. Method Were evaluated 164 consecutive cases of gastric adenocarcinoma previously undergone gastrectomy (partial or total), without clinical evidence of distant metastasis, and determined the following variables: topography of the lesion, tumor size, Borrmann macroscopic configuration, histological grade, early or advanced lesions, Lauren histological subtype, presence of signet ring cell, degree of invasion, perigastric lymph node status, angiolymphatic/perineural invasion, and staging. Results Were found 21 early lesions (12.8%) and 143 advanced lesions (87.2%), with a predominance of lesions classified as T3 (n=99/60, 4%) and N1 (n=62/37, 8%). The nodal status was associated with depth of invasion (p<0.001) and tumor size (p<0.001). The staging was related to age (p=0.048), histological grade (p=0.003), and presence of signet ring cells (p = 0.007), angiolymphatic invasion (p = 0.001), and perineural invasion (p=0.003). Conclusion In gastric cancer, lymph node involvement, tumor size and depth of invasion are histopathological data associated with the pattern of growth/tumor spread, suggesting that a wide dissection of perigastric lymph nodes is a fundamental step in the surgical treatment of these patients. PMID:24676292

  7. MGr1-Ag/37LRP promotes growth and proliferation of gastric cancer in vitro and in vivo.

    PubMed

    Liu, L; Sun, L; Wu, K; Shi, Y; Wang, Y; Wang, Y; Zhang, N; Zhang, H; Zhang, H

    2014-09-01

    Gastric carcinoma (GC) is an aggressive cancer with a poor prognosis. We previously reported that MGr1-Ag was involved in multidrug resistance and anti-apoptosis in GC. However, the exact function of MGr1-Ag in GC proliferation is not clear. In this study, we found that MGr1-Ag was highly expressed in GC tissues and four GC cell lines compared with nontumor gastric tissues or gastric epithelial mucosa cells. The high expression of MGr1-Ag/37LRP was also consistent with the decreased median survival time of GC patients. We employed lenti-mediated RNA interference technique to knock down MGr1-Ag expression in SGC7901 and MKN45 cells, respectively, and observed its effects on GC cells growth in vitro and in vivo. Further study showed that knockdown of MGr1-Ag could inhibit GC cell proliferation by inhibiting the cell cycle S-phase entry and induced apoptosis. Soft agar colony formation assay indicated that the colony formation ability of SGC7901 and MKN45 cells decreased after lenti-MGr1-Ag small interfering RNA (siRNA) infection. Western blot revealed that cyclin D1 and Bcl-2 expression were downregulated whereas p27 and Bax were upregulated in lenti-MGr-siRNA-infected GC cells. Further study demonstrated that the proliferation effect of MGr1-Ag in GC is dependent on its laminin-binding region. Taken together, these data revealed a novel function of MGr1-Ag that can possibly be used as an independent prognostic factor and a potential therapeutic target for GC. PMID:25060631

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

    NASA Astrophysics Data System (ADS)

    Zhang, Yun-Peng; Sun, Peng; Zhang, Xu-Rui; Yang, Wu-Li; Si, Cheng-Shuai

    2013-06-01

    The purpose of this experiment was to investigate the visible imaging of gastric adenocarcinoma cells in vitro by targeting tumor-associated glycoprotein 72 (TAG-72) with near-infrared quantum dots (QDs). QDs with an emission wavelength of about 550 to 780 nm were conjugated to CC49 monoclonal antibodies against TAG-72, resulting in a probe named as CC49-QDs. A gastric adenocarcinoma cell line (MGC80-3) expressing high levels of TAG-72 was cultured for fluorescence imaging, and a gastric epithelial cell line (GES-1) was used for the negative control group. Transmission electron microscopy indicated that the average diameter of CC49-QDs was 0.2 nm higher compared with that of the primary QDs. Also, fluorescence spectrum analysis indicated that the CC49-QDs did not have different optical properties compared to the primary QDs. Immunohistochemical examination and in vitro fluorescence imaging of the tumors showed that the CC49-QDs probe could bind TAG-72 expressed on MGC80-3 cells.

  9. S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or gastro-esophageal junction adenocarcinoma patients: a pilot study.

    PubMed

    Li, Yu Hong; Qiu, Miao Zhen; Xu, Jian Ming; Sun, Guo Ping; Lu, Hui Shan; Liu, Yun Peng; Zhong, Mei Zuo; Zhang, He Long; Yu, Shi Ying; Li, Wei; Hu, Xiao Hua; Wang, Jie Jun; Cheng, Ying; Zhou, Jun Tian; Guo, Zeng Qing; Guan, Zhon Gzhen; Xu, Rui Hua

    2015-10-27

    The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China.

  10. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-09-15

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

  11. Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

    PubMed Central

    Yang, Shi Bin; Han, Fanghai; Wu, Jian Hai; Zhao, Zhi; Zhan, Wenhua

    2016-01-01

    C-X-C motif chemokine receptor type 2 (CXCR2), a key regulatory protein, has been associated with multiple roles in the progression of numerous tumors, including gastric adenocarcinoma (GA). However, the mechanism of CXCR2 in the development of tumors remains controversial and unclear. In a previous study, the expression of CXCR2 and interleukin-22 receptor 2 (IL-22BP) was observed in GA. This promoted the present study, which aimed to explore the association between the two proteins, and to further analyze their roles in GA. CXCR2 and IL-22BP protein expression was analyzed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assays in gastric cancer (GC) tissue, additionally confirmed via western blotting and immunocytochemical analysis in the MKN-45, BGC-823 and SGC-7901 cell lines. The association between expression levels and clinicopathological characteristics was evaluated by the Mann-Whitney U and Kruskal-Wallis tests. Using Kaplan-Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with non-cancerous tissue, CXCR2 and IL-22BP were over expressed (P<0.001 and P<0.001, respectively), and were observed mainly in the cytoplasm (P=0.022 and P=0.014, respectively) in GA. The associated protein and messenger RNA levels were analyzed, and coexpression was identified. Increased expression and more positive cases of CXCR2 and IL-22BP were observed with advanced pathological tumor-node-metastasis (p-TNM) stage in GC (P<0.001 and P<0.001, respectively), as well as the presence and absence of lymph node metastasis (LNM) (P=0.003 and P=0.041, respectively) and deep or superficial muscular invasion (P=0.002 and P=0.004, respectively). In addition, an association between IL-22BP and tumor diameter was indicated (P=0.021). In a Kaplan-Meier analysis, compared with negative expression, the two proteins identified a group of patients with the shortest OS. Cox proportional hazard models revealed that

  12. Association of HLA-G*01:01:02:01/G*01:04:01 polymorphism with gastric adenocarcinoma.

    PubMed

    Khorrami, Samaneh; Rahimi, Roghayeh; Mohammadpour, Hemn; Bahrami, Salahadin; Yari, Fatemeh; Poustchi, Hossein; Malekzadeh, Reza

    2016-02-01

    Human leukocyte antigen-G (HLA-G) plays an important role in tumor cell escape from immune surveillance and HLA-G polymorphisms might service as a potential risk factor for clinical outcomes in GAC (gastric adenocarcinoma). We investigated the association between HLA-G polymorphisms as well as soluble HLA-G level and accordance of GAC. This case-control study included 100 GAC patients and 102 unrelated Iranian individual's samples as control. The clinical stages ranged from I to IV. PCR-RFLP method was carried out in order to specify the genotypes of the HLA-G gene. Concentrations of sHLA-G in serum were determined with the sHLA-G-specific enzyme linked immunosorbent assay (ELISA) kit. The G*01:04:01 and G*01:01:02:01 alleles were the predominant alleles in GAC patients and healthy controls. The G*01:01:03:01 and G*01:01:08 allele distributions are significantly higher among controls comparing to cases and seem to have protective effect (P value=0.026 and 0.007 respectively). There is a substantial differences in G*01:01:02:01/G*01:04:01 genotype frequencies between cases and controls (OR=2.8, P value<0.001). The G*01:01:03:01/G*01:04:01 and G*01:01:02:01/G*01:01:08 genotypes frequency are higher among controls in comparison to patients (P value=0.028 and 0.007 respectively). The polymorphisms in HLA-G could affect GAC induction and its outcome. Also, increased sHLA-G levels in serum might be a useful biomarker for diagnosis.

  13. Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas

    PubMed Central

    Lin, Suling J; Gagnon-Bartsch, Johann A; Tan, Iain Beehuat; Earle, Sophie; Ruff, Louise; Pettinger, Katherine; Ylstra, Bauke; van Grieken, Nicole; Rha, Sun Young; Chung, Hyun Cheol; Lee, Ju-Seog; Cheong, Jae Ho; Noh, Sung Hoon; Aoyama, Toru; Miyagi, Yohei; Tsuburaya, Akira; Yoshikawa, Takaki; Ajani, Jaffer A; Boussioutas, Alex; Yeoh, Khay Guan; Yong, Wei Peng; So, Jimmy; Lee, Jeeyun; Kang, Won Ki; Kim, Sung; Kameda, Yoichi; Arai, Tomio; zur Hausen, Axel; Speed, Terence P; Grabsch, Heike I; Tan, Patrick

    2015-01-01

    Objective Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome. Design We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatistical method (RUV-4) to adjust for technical variation between cohorts. We further validated our findings by computerised immunohistochemical analysis on two independent tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665). Results Gene signatures differentially expressed between Asians and non-Asian GCs were related to immune function and inflammation. Non-Asian GCs were significantly enriched in signatures related to T-cell biology, including CTLA-4 signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant cohort differences (p<0.05). Exploratory analyses revealed a significant relationship between tumour immunity factors, geographic locality-specific prognosis, and postchemotherapy outcomes. Conclusions Analyses of >1600 GCs suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures related to T-cell function. These differences may influence geographical differences in clinical outcome, and the design of future trials particularly in immuno-oncology. PMID:25385008

  14. Analysis of detergent-resistant membranes of Helicobacter pylori infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b in CagA-mediated disruption of cellular polarity.

    PubMed

    Zeaiter, Zaher; Cohen, David; Müsch, Anne; Bagnoli, Fabio; Covacci, Antonello; Stein, Markus

    2008-03-01

    Detergent-resistant membranes of eukaryotic cells are enriched in many important cellular signalling molecules and frequently targeted by bacterial pathogens. To learn more about pathogenic mechanisms of Helicobacter pylori and to elucidate novel effects on host epithelial cells, we investigated how bacterial co-cultivation changes the protein composition of detergent-resistant membranes of gastric adenocarcinoma (AGS) tissue culture cells. Using iTRAQ (isobaric tags for relative and absolute quantification) analysis we identified several cellular proteins, which are potentially related to H. pylori virulence. One of the proteins, which showed a significant infection-dependent increase in detergent resistance, was the polarity-associated serine/threonine kinase MARK2 (EMK1/Par-1b). We demonstrate that H. pylori causes the recruitment of MARK2 from the cytosol to the plasma membrane, where it colocalizes with the bacteria and interacts with CagA. Using Mardin Darby Canine Kidney (MDCK) monolayers and a three-dimensional MDCK tissue culture model we showed that association of CagA with MARK2 not only causes disruption of apical junctions, but also inhibition of tubulogenesis and cell differentiation. PMID:18005242

  15. miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells

    SciTech Connect

    Zhang, Mingjun; Wang, Xiaolei; Li, Wanhu; Cui, Yongchun

    2015-05-08

    Although a series of oncogenes and tumor suppressors were identified in the pathological development of gastric adenocarcinoma (GAC), the underlying molecule mechanism were still not fully understood. The current study explored the expression profile of miR-107 and miR-25 in GAC patients and their downstream regulative network. qRT-PCR analysis was performed to quantify the expression of these two miRNAs in serum samples from both patients and healthy controls. Dual luciferase assay was conducted to verify their putative bindings with LATS2. MTT assay, cell cycle assay and transwell assay were performed to explore how miR-107 and miR-25 regulate proliferation and invasion of gastric cancer cells. Findings of this study demonstrated that total miR-107 or miR-25 expression might be overexpressed in gastric cancer patients and they can simultaneously and synchronically regulate LATS2 expression, thereby affecting gastric cancer cell growth and invasion. Therefore, the miR-25/miR-107-LATS2 axis might play an important role in proliferation and invasion of the gastric cancer cells. - Highlights: • Total miR-107 and miR-25 expression is significantly increased in GAC patients. • Both miR-107 and miR-25 can promote proliferation and invasion of GAC cells. • Both miR-107 and miR-25 can target LATS2 and regulate its expression. • miR-107 and miR-25 regulate proliferation and invasion of GAC cells though LATS2.

  16. Apoptotic-Like Tumor Cells and Apoptotic Neutrophils in Mitochondrion-Rich Gastric Adenocarcinomas: A Comparative Study With Light and Electron Microscopy Between These Two Forms of Cell Death

    PubMed Central

    Caruso, Rosario A.; Fedele, Francesco; Rigoli, Luciana; Branca, Giovanni; Bonanno, Anna; Quattrocchi, Emilia; Finocchiaro, Giuseppe; Venuti, Antonio

    2013-01-01

    Abstract Mitochondrion-rich adenocarcinomas represent a rare variant of gastric adenocarcinomas composed predominantly of columnar adenocarcinoma cells with eosinophilic cytoplasm, a strong supranuclear immunoreactivity for antimitochondrial antibody, and a marked neutrophil infiltration associated to tumor cell death. The purpose of this work is to investigate, using correlated light and electron microscopy, mitochondrion-rich gastric adenocarcinomas focusing on the nature of the death in neoplastic cells and in infiltrating neutrophils. Adenocarcinoma cells, single or in small clusters, showed convoluted nuclei, irregularly condensed chromatin, loss of microvilli, and nuclear envelope dilatation. No nuclear fragmentation was observed in these dying cells and the plasma membrane did not show signs of disruption. These ultrastructural findings represent intermediate aspects between apoptosis and necrosis and are compatible with apoptosis-like programmed cell death. By contrast, some infiltrating neutrophils showed ultrastructural signs of classic apoptosis such as chromatin condensation into compact geometric (globular, crescentshaped) figures, tightly packed cytoplasmic granules and intact cell membrane. Our study provides ultrastructural evidence of apoptosislike tumour cell death in mitochondrion-rich gastric carcinomas and confirms that stereotyped outcome either as apoptosis or necrosis of tumor cells cannot always be expected in human neoplasms. PMID:23888218

  17. MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer

    PubMed Central

    Sun, Li; Liu, Lili; Liu, Xiangqiang; Wang, Yafang; Li, Mengbin; Yao, Liping; Yang, Jianjun; Ji, Genlin; Guo, Changcun; Pan, Yanglin; Liang, Shuhui; Wang, Biaoluo; Ding, Jie; Zhang, Hongwei; Shi, Yongquan

    2014-01-01

    It is well known that tumor microenvironment plays a vital role in drug resistance and cell adhesion-mediated drug resistance (CAM-DR), a form of de novo drug resistance. In our previous study, we reported that MGr1-Ag/37LRP ligation-induced adhesion participated in protecting gastric cancer cells from a number of apoptotic stimuli caused by chemotherapeutic drugs. Further study suggested that MGr1-Ag could prompt CAM-DR through interaction with laminin. However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown. In this study, our experimental results showed that gastric cancer MDR cell lines mediated CAM-DR through upregulation of Bcl-2 by MGr1-Ag interaction with laminin. Further study found that, as a receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK. Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1-Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide. According to these results, we concluded that the FAK/PI3K and MAPK signal pathway plays an important role in MGr1-Ag-mediated CAM-DR in gastric cancer. MGr1-Ag/37LRP might be a potential effective reversal target to MDR in gastric cancer. PMID:24703465

  18. Inhibition of {beta}-catenin-mediated transactivation by flavanone in AGS gastric cancer cells

    SciTech Connect

    Park, Chi Hoon; Hahm, Eun Ryeong; Lee, Ju Hyung; Jung, Kyung Chae; Yang, Chul Hak . E-mail: chulyang@plaza.snu.ac.kr

    2005-06-17

    Recently, data which prove that Wnt pathway activation may be an early event in multistep carcinogenesis in the stomach have been accumulating. We examined the effect of flavanone against {beta}-catenin/Tcf signaling in AGS gastric cancer cells. Reporter gene assay showed that flavanone inhibited {beta}-catenin/Tcf signaling efficiently. In addition, the inhibition of {beta}-catenin/Tcf signaling by flavanone in HEK293 cells transiently transfected with constitutively mutant {beta}-catenin gene, whose product is not phosphorylated by GSK3{beta}, indicates that its inhibitory mechanism was related to {beta}-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that there is no change of {beta}-catenin distribution and of nuclear {beta}-catenin levels through flavanone. In addition, the binding of Tcf complexes to DNA is not influenced by flavanone. The {beta}-catenin/Tcf transcriptional target gene cyclinD1 was downregulated by flavanone. These data suggest that flavanone inhibits the transcription of {beta}-catenin/Tcf responsive genes, by modulating Tcf activity without disrupting {beta}-catenin/Tcf complex formation.

  19. A Phase II Study of Sequential Capecitabine Plus Oxaliplatin Followed by Docetaxel Plus Capecitabine in Patients With Unresectable Gastric Adenocarcinoma: The TCOG 3211 Clinical Trial.

    PubMed

    Chen, Ming-Huang; Lin, Johnson; Hsiao, Chin-Fu; Shan, Yan-Shen; Chen, Yeu-Chin; Chen, Li-Tzong; Liu, Tsang-Wu; Li, Chung-Pin; Chao, Yee

    2016-01-01

    Fluorouracil and platinum are considered the standard treatment options for advanced gastric cancer. Docetaxel is also an effective agent and it shows no cross-resistance with fluorouracil and platinum. The combination treatment of docetaxel with fluorouracil and platinum has been explored, but it demonstrated intolerable toxicities. An alternative approach in the first-line treatment of gastric adenocarcinoma may be to use these agents sequentially. We aimed to evaluate the activity and safety profile of sequential chemotherapy with capecitabine plus oxaliplatin, followed by docetaxel plus capecitabine in the first-line treatment of unresectable gastric cancer.We conducted a phase II study of sequential first-line chemotherapy in advanced gastric cancer. Treatment consisted of 6 cycles of capecitabine plus oxaliplatin (capecitabine 1000 mg/m bid on days 1-10 and oxaliplatin 85 mg/m on day 1, every 2 weeks), followed by 4 cycles of docetaxel plus capecitabine (docetaxel 30 mg/m on days 1 and 8, capecitabine 825 mg/m bid on days 1-14, every 3 weeks). The primary end-point was the objective response rate.Fifty-one patients were enrolled: median age, 63 years; male/female: 37/14. The main grade 3 to 4 toxicities were a decreased absolute neutrophil count (25.4%), diarrhea (9.8%), and hand-foot syndrome (15.7%). The objective response rate was 61.7%. The median progression-free survival and overall survival were 8.6 and 11.0 months, respectively. Six patients (11.8%) received surgery after chemotherapy and 5 are still disease-free.This sequential treatment demonstrated feasibility with a favorable safety profile and produced encouraging results in terms of activity and efficacy. PMID:26817912

  20. Glutamine Deprivation Causes Hydrogen Peroxide-induced Interleukin-8 Expression via Jak1/Stat3 Activation in Gastric Epithelial AGS Cells

    PubMed Central

    Lee, Yun Mi; Kim, Mi Jung; Kim, Youngha; Kim, Hyeyoung

    2015-01-01

    Background: The Janus kinase (Jak)/Signal transducers of activated transcription (Stat) pathway is an upstream signaling pathway for NF-κB activation in Helicobacter pylori-induced interleukin (IL)-8 production in gastric epithelial AGS cells. H. pylori activates NADPH oxidase and produces hydrogen peroxide, which activates Jak1/Stat3 in AGS cells. Therefore, hydrogen peroxide may be critical for IL-8 production via Jak/Stat activation in gastric epithelial cells. Glutamine is depleted during severe injury and stress and contributes to the formation of glutathione (GSH), which is involved in conversion of hydrogen peroxide into water as a cofactor for GSH peroxidase. Methods: We investigated whether glutamine deprivation induces hydrogen peroxide-mediated IL-8 production and whether hydrogen peroxide activates Jak1/Stat3 to induce IL-8 in AGS cells. Cells were cultured in the presence or absence of glutamine or hydrogen peroxide, with or without GSH or a the Jak/Stat specific inhibitor AG490. Results: Glutamine deprivation decreased GSH levels, but increased levels of hydrogen peroxide and IL-8, an effect that was inhibited by treatment with GSH. Hydrogen peroxide induced the activation of Jak1/Stat3 time-dependently. AG490 suppressed hydrogen peroxide- induced activation of Jak1/Stat3 and IL-8 expression in AGS cells, but did not affect levels of reactive oxygen species in AGS cells. Conclusions: In gastric epithelial AGS cells, glutamine deprivation increases hydrogen peroxide levels and IL-8 expression, which may be mediated by Jak1/Stat3 activation. Glutamine supplementation may be beneficial for preventing gastric inflammation by suppressing hydrogen peroxide-mediated Jak1/Stat3 activation and therefore, reducing IL-8 production. Scavenging hydrogen peroxide or targeting Jak1/Stat3 may also prevent oxidant-mediated gastric inflammation. PMID:26473156

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

    SciTech Connect

    Yi, Ho-Keun; Kim, Sun-Young; Hwang, Pyoung-Han; Kim, Chan-Young; Yang, Doo-Hyun; Oh, Youngman; Lee, Dae-Yeol . E-mail: leedy@chonbuk.ac.kr

    2005-05-13

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

  2. Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns.

    PubMed

    Treece, Amanda L; Duncan, Daniel L; Tang, Weihua; Elmore, Sandra; Morgan, Douglas R; Dominguez, Ricardo L; Speck, Olga; Meyers, Michael O; Gulley, Margaret L

    2016-06-01

    MicroRNA expression in formalin-fixed paraffin-embedded tissue (FFPE) or plasma may add value for cancer management. The GastroGenus miR Panel was developed to measure 55 cancer-specific human microRNAs, Epstein-Barr virus (EBV)-encoded microRNAs, and controls. This Q-rtPCR panel was applied to 100 FFPEs enriched for adenocarcinoma or adjacent non-malignant mucosa, and to plasma of 31 patients. In FFPE, microRNAs upregulated in malignant versus adjacent benign gastric mucosa were hsa-miR-21, -155, -196a, -196b, -185, and -let-7i. Hsa-miR-18a, 34a, 187, -200a, -423-3p, -484, and -744 were downregulated. Plasma of cancer versus non-cancer controls had upregulated hsa-miR-23a, -103, and -221 and downregulated hsa-miR-378, -346, -486-5p, -200b, -196a, -141, and -484. EBV-infected versus uninfected cancers expressed multiple EBV-encoded microRNAs, and concomitant dysregulation of four human microRNAs suggests that viral infection may alter cellular biochemical pathways. Human microRNAs were dysregulated between malignant and benign gastric mucosa and between plasma of cancer patients and non-cancer controls. Strong association of EBV microRNA expression with known EBV status underscores the ability of microRNA technology to reflect disease biology. Expression of viral microRNAs in concert with unique human microRNAs provides novel insights into viral oncogenesis and reinforces the potential for microRNA profiles to aid in classifying gastric cancer subtypes. Pilot studies of plasma suggest the potential for a noninvasive addition to cancer diagnostics. PMID:26950485

  3. [Atrophy in the mucosa neighboring an intestinal-type gastric adenocarcinoma by comparing the Sydney vs. OLGA systems].

    PubMed

    Ramírez-Mendoza, Pablo; Hernández-Briseño, Liliana; Casarrubias-Ramírez, Moisés; Alvarado-Cabrero, Isabel; Ángeles-Garay, Ulises

    2015-01-01

    Introducción: el carcinoma gástrico ocasiona al año unas 700 000 muertes en el mundo. El objetivo de este artículo es evaluar la atrofia en la mucosa vecina al adenocarcinoma gástrico tipo intestinal comparando los sistemas Sídney y OLGA. Diferencias en el rendimiento diagnóstico impulsarían el empleo de alguno. Métodos: estudiamos 28 sujetos con adenocarcinoma gástrico tipo intestinal (Lauren), que comparamos con 32 casos sin neoplasia, ambos grupos con gastrectomía total. Dos patólogos evaluaron la atrofia en el epitelio de cuerpo y antro no neoplásico con los sistemas Sídney y OLGA. Se obtuvieron la media, mediana y distribución de frecuencias por escala de medición, así como la distribución de las variables del estudio. Se calculó la sensibilidad, especificidad y los valores predictivos para cáncer gástrico gracias a dicotomizar las escalas con resultado positivo y negativo para atrofia avanzada. Resultados: veinticuatro de 28 casos con adenocarcinoma gástrico tipo intestinal mostraron atrofia avanzada con OLGA con una sensibilidad y especificidad de 77 y 85 % respectivamente. Con el sistema Sídney, 4 de 28 mostraron atrofia avanzada con una sensibilidad y especificidad de 14 y 100 % respectivamente. Conclusiones: el sistema OLGA tiene elevada sensibilidad y especificidad (77 y 85 % respectivamente) para reconocer cambios preneoplásicos en la mucosa vecina al cáncer gástrico. Empero, OLGA no mostró atrofia avanzada en adenomas foveolares con displasia de alto grado, ni en adenocarcinomas en las porciones proximales del estómago.

  4. Claudin-4 expression in gastric cancer cells enhances the invasion and is associated with the increased level of matrix metalloproteinase-2 and -9 expression

    PubMed Central

    HWANG, TSANN-LONG; CHANGCHIEN, TZU-TSUNG; WANG, CHEE-CHAN; WU, CHI-MING

    2014-01-01

    Claudin-4 is a member of a large family of transmembrane proteins known as claudins, which are essential for the formation and maintenance of tight junctions. Our previous studies have revealed that claudin-4 proteins are overexpressed in metastatic gastric cancer. To clarify the roles of claudin-4 in gastric cancer metastasis, human gastric adenocarcinoma (AGS) cells constitutively expressing wild-type claudin-4 were generated. Expression of claudin-4 in AGS cells was found to increase cell invasion and migration, as measured by Boyden invasion chamber assays. Moreover, the claudin-4-expressing AGS cells were found to have increased matrix metalloproteinase (MMP)-2 and -9 expression, indicating that claudin-mediated increased invasion may be mediated through the activation of the MMP protein. Overall, the results suggest that claudin-4 overexpression may promote gastric cancer metastasis through the increased invasion of gastric cancer cells. PMID:25120725

  5. Tissue Inhibitor of Metalloproteinase-1 Is Confined to Tumor-Associated Myofibroblasts and Is Increased With Progression in Gastric Adenocarcinoma.

    PubMed

    Alpízar-Alpízar, Warner; Laerum, Ole Didrik; Christensen, Ib J; Ovrebo, Kjell; Skarstein, Arne; Høyer-Hansen, Gunilla; Ploug, Michael; Illemann, Martin

    2016-08-01

    The tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the extracellular matrix-degrading activity of several matrix metalloproteinases, thereby regulating cancer cell invasion and metastasis. Studies describing the expression pattern and cellular localization of TIMP-1 in gastric cancer are, however, highly discordant. We addressed these inconsistencies by performing immunohistochemistry and in situ hybridization analyses in a set of 49 gastric cancer lesions to reexamine the TIMP-1 localization. In addition, we correlated these findings to clinicopathological parameters. We show that strong expression of TIMP-1 protein and mRNA was observed in a subpopulation of stromal fibroblast-like cells at the periphery of the cancer lesions. In a few cases, a small fraction of cancer cells showed weak expression of TIMP-1 protein and mRNA. The stromal TIMP-1-expressing cells were mainly tumor-associated myofibroblasts. In the normal-appearing mucosa, scattered TIMP-1 protein was only found in chromogranin A positive cells. TIMP-1-positive myofibroblasts at the invasive front of the tumors were more frequently seen in intestinal than in diffuse histological subtype cases (p=0.009). A significant trend to a higher number of cases showing TIMP-1 staining in myofibroblasts with increasing tumor, node, metastasis (TNM) stage was also revealed (p=0.041). In conclusion, tumor-associated myofibroblasts are the main source of increased TIMP-1 expression in gastric cancer. PMID:27370797

  6. Not all gastric masses are gastric cancer.

    PubMed

    Del Rosario, Michael; Tsai, Henry

    2016-01-01

    Lung cancer metastasising to the gastrointestinal tract normally does not occur. However, as clinicians, we must be aware that lung adenocarcinoma, as in all cancers, can and will metastasise to any part of the body. We describe a case of a patient with a presumed primary gastric adenocarcinoma who presented with shortness of breath due to pleural effusion. Pathology from the pleural effusion was positive for primary lung adenocarcinoma. Further investigation revealed that the patient's gastric mass was misdiagnosed as gastric adenocarcinoma. We correctly diagnosed the mass as metastatic lung adenocarcinoma. This was very significant because the patient was transitioning to palliative care with possible tube feeding. After the correct diagnosis, her management drastically changed and her health improved. Clinical, pathological and medical management of lung cancer metastasis to the stomach are discussed. PMID:26976833

  7. Cytostatic activity of the duplex drug linking 2'-deoxy-5-fluorouridine (5FdU) with 3'-C-ethynylcytidine (ECyd) against gastric adenocarcinoma cell lines.

    PubMed

    Weinreich, Jürgen; Schott, Sarah; Königsrainer, Ingmar; Zieker, Derek; Königsrainer, Alfred; Schott, Herbert

    2011-12-01

    The cytostatic potential of the new duplex drug 2'-deoxy-5-fluorouridylyl-(5'5')-3'-C-ethynylcytidine (5FdU(5'-5')ECyd) was evaluated in comparison to those of 5-fluorouracil (5FU), 2'-deoxy-5-fluorourindine (5FdU), 3'-C-ethynylycytidine (ECyd), cisplatin, an equimolar mixture of 5FdU + ECyd and a three component-mixture of 0.75 μM epirubicin/0.90 μM cisplatin/3.0 μM 5FU (ECF) by incubation of the two human gastric adenocarcinoma cell lines 23132/87 and MKN-45. The molar composition of ECF was taken from data of a triple combination chemotherapy for human gastric cancer. Time and dose depending inhibition of cell growth was determinated using the CASY technology. A growth decrease of both cell lines from 100% to about 20% was observed by treatment with ECF over a course of 14 days. This result provided basis to estimate the cytostatic potential of all tested drugs and combinations thereof. Corresponding high activities in respect to ECF were achieved by incubation of 23132/87 cells with single drugs 49 μM 5FU, 10 μM cisplatin, 3.4 μM 5FdU, 0.65 μM ECyd, the mixture 0.32 μM 5FdU + 0.32 μM ECyd and 0.32 μM 5FdU(5'-5')ECyd. The less sensitive MKN-45 cells require a 1.5-4 fold higher dose of the standard chemotherapeutics in order to achieve an equivalent cytostatic effect, in respect to the 23132/87 cell line,. However, the effect of the duplex drugs on MKN-45 cells was gained with a 5-fold lower dose than ECF. Due to its high cytostatic potential the duplex drug, which covalently links two active anticancer compounds, could be a new therapeutic alternative for chemotherapy in gastric cancer, currently treated with different combinations.

  8. Neoadjuvant therapy for gastroesophageal adenocarcinoma

    PubMed Central

    Samalin, Emmanuelle; Ychou, Marc

    2016-01-01

    Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions. PMID:27298768

  9. Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells.

    PubMed

    Cao, Ai-Li; Tang, Qing-Feng; Zhou, Wen-Chao; Qiu, Yan-Yan; Hu, Song-Jiao; Yin, Pei-Hao

    2015-01-01

    Curcumin, the biologically active compound from the rhizome of Curcuma longa, could inhibit cell growth and induce apoptosis in gastric carcinoma. However, the underlying mechanism of curcumin on gastric carcinoma cells still needs further investigation. In this study, morphological observation indicated that curcumin inhibited the proliferation of AGS cells in a dose-dependent manner. According to the flow cytometric analysis, curcumin treatment resulted in G2/M arrest in AGS cells, accompanied with an increased expression of cyclin B1 and a decreased expression of cyclin D1. In addition, DNA ladders were observed by gel electrophoresis. Meanwhile, the activities of caspase-3, -8, and -9 were also enhanced in curcumin-treated AGS cells. Nevertheless, the increased activities could be inhibited by benzyloxycarbonyl-Val-Ala-Asp (OME)-fluoromethylketone (z-VAD-fmk), which suggested that the apoptosis was caspase-dependent. Furthermore, downregulation of rat sarcoma (Ras) and upregulation of extracellular-signal-regulated kinase (ERK) were also observed in AGS cells treated with curcumin by Western blot. U0126, an ERK inhibitor, blocked curcumin-induced apoptosis. The results suggested that curcumin inhibited the growth of the AGS cells and induced apoptosis through the activation of Ras/ERK signaling pathway and downstream caspase cascade, and curcumin might be a potential target for the treatment of gastric carcinoma.

  10. A Prognostic Model Using Inflammation- and Nutrition-Based Scores in Patients With Metastatic Gastric Adenocarcinoma Treated With Chemotherapy

    PubMed Central

    Hsieh, Meng-Che; Wang, Shih-Hor; Chuah, Seng-Kee; Lin, Yu-Hung; Lan, Jui; Rau, Kun-Ming

    2016-01-01

    Abstract The outcomes of patients with metastatic gastric cancer (mGC) are poor. Recent studies have identified the prognostic impact of inflammatory response and nutritional status on survival for patients with gastric cancer. This study aims to create a prognostic model using inflammatory- and nutrition-based scores to predict survival in patients with mGC treated with chemotherapy. After institutional review board approval, patients who had mGC and were treated with chemotherapy from 2007 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regression analyses. Based on these variables, a prognostic model using inflammatory- and nutrition-based scores was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The c-statistic values with 95% confidence interval (CI) were also calculated to access their predicting performances. Our study consisted of 256 patients with a median age of 60 years and a median follow-up visit of 18.5 months. Multivariate analyses showed that neutrophil to lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and Patient-Generated Subjective Global Assessment (PG-SGA) were independently related to survival. After computing these scores, patients were classified into favorable-, intermediate-, and poor-risk groups. The median overall survival were 27.6 versus 13.2 versus 8.2 months in favorable, intermediate, and poor-risk groups, respectively. The 2-year survival rate was 52% versus 16% versus 3% in favorable-, intermediate-, and poor-risk groups, respectively. (P < 0.001). The c-statistic value of our model at 2 years is 0.8 (95% CI, 0.75–0.86). NLR, mGPS, and PG-SGA were independently related to survival. Our prognostic model using inflammatory- and nutrition-based scores could provide prognostic information to patients and physicians. PMID:27124056

  11. Identification of TRAK1 (Trafficking protein, kinesin-binding 1) as MGb2-Ag: a novel cancer biomarker.

    PubMed

    Zhang, Faming; Ren, Gui; Lu, Yuanyuan; Jin, Bin; Wang, Jun; Chen, Xiong; Liu, Zhenxiong; Li, Kai; Nie, Yongzhan; Wang, Xin; Fan, Daiming

    2009-02-18

    The present study aimed to describe the characterization of an antibody MGb2 that reacts with an epitope on gastric cancer cells, and identification of MGb2 antigen (MGb2-Ag). Immunostaining revealed its distribution in human tissues and demonstrated that the positive rate of MGb2-Ag was 81.48% in gastric cancer, 100% in gastric signet-ring cell carcinoma and mucinous adenocarcinoma, 13.16% in precancerous conditions, and 0% in chronic superficial gastritis. Using Western blotting, immunoprecipitation and MALDI-TOF MS (matrix assisted laser desorption/ionization time-of-flight mass spectrometry), MGb2-Ag was identified as TRAK1 (Trafficking protein, kinesin-binding 1), a new molecular gained limited recognition. Both MGb2 and commercial anti-TRAK1 Ab recognized prokaryotic expressed TRAK1. Immunostaining characteristics of TRAK1 were identical with MGb2-Ag in continuous sections of paraffin-embedded tissues of gastric tissues. This is the first report that TRAK1/MGb2-Ag is a promising diagnostic marker for gastric cancer and may help to detect signet-ring cell carcinoma and mucinous adenocarcinoma.

  12. Association between TLR4 (+896A/G and +1196C/T) Polymorphisms and Gastric Cancer Risk: An Updated Meta-Analysis

    PubMed Central

    Zhou, Quan; Wang, Chenchen; Wang, Xiaofeng; Wu, Xiongyan; Zhu, Zhenggang; Liu, Bingya; Su, Liping

    2014-01-01

    Background Toll-like receptor 4 (TLR4) is a receptor of lipopolysaccharide in the signaling transduction of gastric epithelial cell. It plays a pivotal role in activation of innate immunity and pathogen recognition and thus acts as a modulator in the development and progression of gastric cancer. Growing studies explored the association of polymorphisms in TLR4 with susceptibility to gastric cancer, but the results have remained controversial and conflicting. To investigate the effect of two selected TLR4 (+896A/G and +1196C/T) polymorphisms on gastric cancer, we performed a meta-analysis. Methods A comprehensive search was conducted to identify all eligible case-control publications investigating the association between TLR4 polymorphisms and gastric cancer risk. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to assess such association. Results Up to March 26 2014, 10 published case-control studies from PubMed and EMBase were available, involving a total of 1888 gastric cancer patients and 3433 control subjects. In the overall meta-analyses, a significantly increased gastric cancer risk was detected in TLR4 +896A/G polymorphism (heterozygous model, AG vs. AA: OR = 1.67, 95% CI, 1.39–2.01; additive model, G vs. A: OR = 1.64, 95% CI, 1.37–1.95) and TLR4 +1196C/T polymorphism (heterozygous model, CT vs. CC: OR = 1.42, 95% CI, 1.11–1.81; additive model, T vs. C: OR = 1.36, 95% CI, 1.08–1.72), similar results were obtained in the subgroup analyses of Caucasian, whereas no associations were detected in any genetic models of non-Caucasian. Conclusions The overall results suggest that TLR4 polymorphisms (+896A/G and +1196C/T) may be associated with a significantly increased gastric cancer risk in Caucasian. PMID:25290654

  13. Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

    PubMed Central

    Jenab, M; Riboli, E; Ferrari, P; Friesen, M; Sabate, J; Norat, T; Slimani, N; Tjønneland, A; Olsen, A; Overvad, K; Boutron-Ruault, M-C; Clavel-Chapelon, F; Boeing, H; Schulz, M; Linseisen, J; Nagel, G; Trichopoulou, A; Naska, A; Oikonomou, E; Berrino, F; Panico, S; Palli, D; Sacerdote, C; Tumino, R; Peeters, P H; Numans, M E; Bueno-de-Mesquita, H B; Büchner, F L; Lund, E; Pera, G; Chirlaque, M D; Sánchez, M-J; Arriola, L; Barricarte, A; Quirós, J R; Johansson, I; Johansson, A; Berglund, G; Bingham, S; Khaw, K-T; Allen, N; Key, T; Carneiro, F; Save, V; Giudice, G Del; Plebani, M; Kaaks, R; Gonzalez, C A

    2006-01-01

    Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and α- and γ-tocopherol, with the risk of gastric adenocarcinoma in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and α-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma β-cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30–0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22–0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33–0.93, Ptrend=0.005) and lipid-unadjusted α-tocopherol (OR=0.59, 95% CI=0.37–0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted α-tocopherol (OR=0.26, 95% CI=0.11–0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and α-tocopherol are associated with reduced risk

  14. Silencing of FRAT1 by siRNA inhibits the proliferation of SGC7901 human gastric adenocarcinoma cells

    PubMed Central

    YU, QINGGONG; SHANG, LU; YU, HONGBO; YANG, ZIRONG; XU, DEKUI

    2016-01-01

    Frequently rearranged in advanced T cell lymphomas-1 (FRAT1) positively regulates the Wnt/β-catenin signaling pathway by inhibiting glycogen synthase kinase-3 mediated phosphorylation of β-catenin. FRAT1 is a proto-oncogene, implicated in tumorigenesis. The present study aimed to investigate the effects of FRAT1 silencing on the proliferation and apoptosis of SGC7901 cells. FRAT1 in SGC7901 cells was silenced by RNA interference. Reverse transcription-quantitative polymerase chain reaction was used for the analysis of FRAT1 mRNA and western blotting was used to evaluate FRAT1 and β-catenin protein levels. Cell proliferation was analyzed by the MTT assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression of FRAT1 mRNA, FRAT1 and β-catenin protein in FRAT1-silenced SGC7901 cells were reduced significantly compared to untreated cells. The proliferation of FRAT1 silenced SGC7901 cells decreased significantly The FRAT1 silenced SGC7901 cells were arrested at G0/G1 stage to a greater degree, and apoptosis was increased. In summary, silencing of FRAT1 inhibits SGC7901 cell proliferation and induces apoptosis, possible through a reduction in β-catenin expression. FRAT1 may serve as a prognostic biomarker and therapeutic target for gastric cancer. PMID:26893843

  15. Phase II Trial of Preoperative Irinotecan-Cisplatin Followed by Concurrent Irinotecan-Cisplatin and Radiotherapy for Resectable Locally Advanced Gastric and Esophagogastric Junction Adenocarcinoma

    SciTech Connect

    Rivera, Fernando; Galan, Maica; Tabernero, Josep; Cervantes, Andres; Vega-Villegas, M. Eugenia; Gallego, Javier; Laquente, Berta; Rodriguez, Edith; Carrato, Alfredo; Escudero, Pilar; Massuti, Bartomeu; Alonso-Orduna, Vicente; Cardenal, Adelaida; Saenz, Alberto; Giralt, Jordi; Yuste, Ana Lucia

    2009-12-01

    Purpose: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). Patients and Methods: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{sup 2} on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{sup 2} on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. Results: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. Conclusions: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.

  16. Elevated Preoperative Serum Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST) Ratio Is Associated with Better Prognosis in Patients Undergoing Curative Treatment for Gastric Adenocarcinoma

    PubMed Central

    Chen, Shu-Lin; Li, Jian-Pei; Li, Lin-Fang; Zeng, Tao; He, Xia

    2016-01-01

    The level of anine aminotransferase/aspartate aminotransferase (ALT/AST) ratio in the serum was often used to assess liver injury. Whether the ALT/AST ratio (LSR) was associated with prognosis for gastric adenocarcinoma (GA) has not been reported in the literature. Our aim was to investigate the prognostic value of the preoperative LSR in patients with GA. A retrospective study was performed in 231 patients with GA undergoing curative resection. The medical records collected include clinical information and laboratory results. We investigated the correlations between the preoperative LSR and overall survival (OS). Survival analysis was conducted with the Kaplan–Meier method, and Cox regression analysis was used to determine significant independent prognostic factors for predicting survival. A p value of <0.05 was considered to be statistically significant. A total of 231 patients were finally enrolled. The median overall survival was 47 months. Multivariate analysis indicated that preoperative LSR was an independent prognostic factor in GA. Patients with LSR ≤ 0.80 had a greater risk of death than those with LSR > 0.80. The LSR was independently associated with OS in patients with GA (hazard ratio: 0.610; 95% confidence interval: 0.388–0.958; p = 0.032), along with tumor stages (hazard ratio: 3.118; 95% confidence interval: 2.044–4.756; p < 0.001) and distant metastases (hazard ratio: 1.957; 95% confidence interval: 1.119–3.422; p = 0.019). Our study first established a connection between the preoperative LSR and patients undergoing curative resection for GA, suggesting that LSR was a simple, inexpensive, and easily measurable marker as a prognostic factor, and may help to identify high-risk patients for treatment decisions. PMID:27294917

  17. Catechin-based procyanidins from Peumus boldus Mol. aqueous extract inhibit Helicobacter pylori urease and adherence to adenocarcinoma gastric cells.

    PubMed

    Pastene, Edgar; Parada, Víctor; Avello, Marcia; Ruiz, Antonieta; García, Apolinaria

    2014-11-01

    In this work, the anti-Helicobacter pylori effect of an aqueous extract from dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract displayed high inhibitory activity against H. pylori urease. Therefore, in order to clarify the type of substances responsible for such effect, a bioassay-guided fractionation strategy was carried out. The active compounds in the fractions were characterized through different chromatographic methods (RP-HPLC; HILIC-HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active against H. pylori urease with an IC50  = 15.9 µg gallic acid equivalents (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin-derived proanthocyanidins (LC-MS and phloroglucinolysis). The anti-adherent effect of boldo was assessed by co-culture of H. pylori and AGS cells. Both the aqueous extract and F5 showed an anti-adherent effect in a concentration-dependent manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In conjunction, our results suggest that boldo extract has a potent anti-urease activity and anti-adherent effect against H. pylori, properties directly linked with the presence of catechin-derived proanthocyanidins. PMID:24853276

  18. Catechin-based procyanidins from Peumus boldus Mol. aqueous extract inhibit Helicobacter pylori urease and adherence to adenocarcinoma gastric cells.

    PubMed

    Pastene, Edgar; Parada, Víctor; Avello, Marcia; Ruiz, Antonieta; García, Apolinaria

    2014-11-01

    In this work, the anti-Helicobacter pylori effect of an aqueous extract from dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract displayed high inhibitory activity against H. pylori urease. Therefore, in order to clarify the type of substances responsible for such effect, a bioassay-guided fractionation strategy was carried out. The active compounds in the fractions were characterized through different chromatographic methods (RP-HPLC; HILIC-HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active against H. pylori urease with an IC50  = 15.9 µg gallic acid equivalents (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin-derived proanthocyanidins (LC-MS and phloroglucinolysis). The anti-adherent effect of boldo was assessed by co-culture of H. pylori and AGS cells. Both the aqueous extract and F5 showed an anti-adherent effect in a concentration-dependent manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In conjunction, our results suggest that boldo extract has a potent anti-urease activity and anti-adherent effect against H. pylori, properties directly linked with the presence of catechin-derived proanthocyanidins.

  19. Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma.

    PubMed

    Garcia-Perez, Juan Carlos; Rodríguez-Perez, Rosa; Ballestero, Araceli; Zuloaga, Jaime; Fernandez-Puntero, Belen; Arias-Díaz, Javier; Caballero, María Luisa

    2015-10-01

    Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P < 0.001) and (42.55% vs 10.64%, P < 0.001, respectively). When disaggregated by type of tumor, the patients with gastric cancer showed a higher proportion of positive results for sIgA1 to rAni s 1 (P < 0.001), whereas a higher proportion of colon cancer patients were shown to be positive for sIgA1 to both rAni s 1 (P < 0.05) and rAni s 5 (P < 0.01). Earlier Anisakis infection might be a risk factor for the development of stomach or colon cancer. PMID:26448021

  20. Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma

    PubMed Central

    Garcia-Perez, Juan Carlos; Rodríguez-Perez, Rosa; Ballestero, Araceli; Zuloaga, Jaime; Fernandez-Puntero, Belen; Arias-Díaz, Javier; Caballero, María Luisa

    2015-01-01

    Abstract Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P < 0.001) and (42.55% vs 10.64%, P < 0.001, respectively). When disaggregated by type of tumor, the patients with gastric cancer showed a higher proportion of positive results for sIgA1 to rAni s 1 (P < 0.001), whereas a higher proportion of colon cancer patients were shown to be positive for sIgA1 to both rAni s 1 (P < 0.05) and rAni s 5 (P < 0.01). Earlier Anisakis infection might be a risk factor for the development of stomach or colon cancer. PMID:26448021

  1. H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2.

    PubMed

    Song, Xin; Chen, Hui-Xin; Wang, Xiao-Yan; Deng, Xi-Yun; Xi, Yin-Xue; He, Qing; Peng, Tie-Li; Chen, Jie; Chen, Wei; Wong, Benjamin Chun-Yu; Chen, Min-Hu

    2013-01-01

    Helicobacter pylori encoded CagA is presently the only known virulence factor that is injected into gastric epithelial cells where it destroys apical junctional complexes and induces dedifferentiation of gastric epithelial cells, leading to H. pylori-related gastric carcinogensis. However, little is known about the molecular mechanisms by which CagA mediates these changes. Caudal-related homeobox 2 (Cdx2) is an intestine-specific transcription factor highly expressed in multistage tissues of dysplasia and cancer. One specific target of Cdx2, Claudin-2, is involved in the regulation of tight junction (TJ) permeability. In this study, our findings showed that the activity of Cdx2 binding to Cdx binding sites of CdxA (GTTTATG) and CdxB (TTTTAGG) of probes corresponding to claudin-2 flanking region increased in AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain. Moreover, Cdx2 upregulated claudin-2 expression at transcriptional level and translational level. In the meantime, we found that TJs of AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain, were more severely destroyed, leading to wider cell gap, interference of contact, scattering and highly elevated migration of cells. Herein, this study is firstly demonstrated that H. pylori-encoded CagA disrupts TJs and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2. This provides a new mechanism whereby CagA induced dedifferentiation of AGS cells, leading to malignant behavior of biology. PMID:24287273

  2. Negative regulation of {beta}-catenin/Tcf signaling by naringenin in AGS gastric cancer cell

    SciTech Connect

    Lee, Ju Hyung; Park, Chi Hoon; Jung, Kyung Chae; Rhee, Ho Sung; Yang, Chul Hak . E-mail: chulyang@plaza.snu.ac.kr

    2005-09-30

    Functional activation of {beta}-catenin/Tcf signaling plays an important role in early events in carcinogenesis. We examined the effect of naringenin against {beta}-catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that naringenin inhibited {beta}-catenin/Tcf signaling efficiently. In addition, the inhibition of {beta}-catenin/Tcf signaling by naringenin in HEK293 cells transiently transfected with constitutively mutant {beta}-catenin gene, whose product is not phosphorylated by GSK3{beta}, indicates that its inhibitory mechanism was related to {beta}-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that the {beta}-catenin distribution and the levels of nuclear {beta}-catenin and Tcf-4 proteins were unchanged after naringenin treatment. Moreover, the binding activities of Tcf complexes to consensus DNA were not affected by naringenin. Taken together, these data suggest that naringenin inhibits {beta}-catenin/Tcf signaling in gastric cancer with unknown mechanisms.

  3. Adenocarcinoma arising in a gastrocystoplasty

    PubMed Central

    Balachandra, B; Swanson, P E; Upton, M P; Yeh, M M

    2007-01-01

    Gastrocystoplasty is a form of surgical bladder augmentation or neobladder used to restore bladder capacity and compliance in children and in patients with neurogenic bladder. Other forms of bladder augmentation include ileocystoplasty and colocystoplasty. Reported complications of gastrocystoplasty include post‐operative bleeding, haematuria, stricture, metabolic alkalosis and rupture of the gastric segment. There are reports of adenocarcinomas arising in the setting of ileocystoplasty and colocystoplasty. However, the first case of adenocarcinoma arising in the setting of a gastrocystoplasty is reported. PMID:17213351

  4. Adenocarcinoma arising in a gastrocystoplasty.

    PubMed

    Balachandra, B; Swanson, P E; Upton, M P; Yeh, M M

    2007-01-01

    Gastrocystoplasty is a form of surgical bladder augmentation or neobladder used to restore bladder capacity and compliance in children and in patients with neurogenic bladder. Other forms of bladder augmentation include ileocystoplasty and colocystoplasty. Reported complications of gastrocystoplasty include post-operative bleeding, haematuria, stricture, metabolic alkalosis and rupture of the gastric segment. There are reports of adenocarcinomas arising in the setting of ileocystoplasty and colocystoplasty. However, the first case of adenocarcinoma arising in the setting of a gastrocystoplasty is reported.

  5. [Effects of CPUY013, a novel Topo I inhibitor, on human gastric adenocarcinoma BGC823 cells in vitro and in vivo].

    PubMed

    Ji, Yu-Bin; Zhou, Jian-Hua; Zuo, Ming-Xin; You, Qi-Dong

    2008-08-01

    Antitumor activity and the mechanism of CPUY013, a novel Topo I inhibitor, on gastric adenocarcinoma BGC823 cells were studied in vitro and in vivo. The proliferation was investigated by MTT assay and colony formation assay. Apoptosis was determined by both dual fluorescence staining with AO and EB and DNA agarose gel electrophoresis analysis methods. Nude mice model of BGC823 xenograft tumor was established by subcutaneous inoculation. The suppression activity of the CPUY013 by intragastric administration on xenograft mice model was detected. The change of cell cycle was studied by flow cytometry assay. The expressions of Topo I, widetype p53, active caspase-3, bcl-2 and bax proteins were analyzed by Western blotting assay. Results showed that CPUY013 could inhibit BGC823 cell proliferation at a certain range of dose. The flow cytometry analysis showed that CPUY013 and topoecan (TPT) led to a decrease in the proportion of G1 phase cells and an increase in the proportion of S phase cells, suggesting that they arrested the transition of tumor cells from S phase to G2 phase. The sub-G1 group was analyzed by flow cytometry. Compared with control, after 48 h treatment with CPUY013 or TPT, the sub-G1 group significantly increased in a dose-dependent manner. CPUY013 and TPT induced apoptosis in tumor cells. Cells treated with CPUY013 for 48 h were stained with AO/EB mixture. Then the cells were observed under fluorescence microscope. And it was found that early and late apoptosis cells were identified by perinuclear condensation of chromatin stained by AO/EB, respectively. Necrotic cells were identified by uniform labeling with EB. With the increase of concentration of CPUY013 and TPT, these morphological changes under the fluorescence microscope become clearer, indicating that the proportion of apoptosis cells increased gradually. By using JC-1 kit, loss of deltapsim was also detected in BGC823 cells treated with CPUY013 and TPT, which represent mitochondria function

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

    PubMed Central

    WANG, JINLIN; WANG, ZHIYONG; MO, YANXIA; ZENG, ZHAOHUI; WEI, PEI; LI, TAO

    2015-01-01

    The aim of the present study was to determine the antitumor effects of hyperthermic CO2 (HT-CO2)-treated dendritic cell (DC)-derived exosomes (Dex) on human gastric cancer AGS cells. Mouse-derived DCs were incubated in HT-CO2 at 43°C for 4 h. The exosomes in the cell culture supernatant were then isolated. Cell proliferation was analyzed using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was observed using flow cytometry, Hoechst 33258 staining and the analysis of caspase-3 activity. In addition, the proliferation of tumor cells was evaluated in xenotransplant nude mice. HT-CO2 markedly inhibited cell proliferation, as assessed by the CCK-8 assay, and also induced apoptosis in a time-dependent manner, as demonstrated by Annexin V/propidium iodide flow cytometry, caspase-3 activity and morphological analysis using Hoechst fluorescent dye. It was also revealed that HT-CO2-treated Dex decreased the expression of heat shock protein 70 and inhibited tumor growth in nude mice. In conclusion, HT-CO2 exerted an efficacious immune-enhancing effect on DCs. These findings may provide a novel strategy for the elimination of free cancer cells during laparoscopic resection. However, the potential cellular mechanisms underlying this process require further investigation. PMID:26170979

  7. Anti-proliferative role and prognostic implication of miR-141 in gastric cancer

    PubMed Central

    Huang, Mingwei; Wu, Liucheng; Qin, Yuzhou; Li, Zhao; Luo, Shanshan; Qin, Haiquan; Yang, Yang; Chen, Jiansi

    2016-01-01

    Gastric cancer is a prevalent disease causing a high annual death rate worldwide. Recent studies suggest the pivotal regulatory role of microRNAs in gastric cancer and the aberrant expression of microRNA-141 (miR-141) in gastric cancer cells. This study aims to explore the role and possible mechanism of miR-141 in gastric cancer prognosis and cell proliferation. A total of 30 gastric cancer patients were recruited for miR-141 level detection and a follow up of 115 weeks. Human adenocarcinoma cell line AGS was transfected with miR-141 mimic or inhibitor for cell viability, colony formation and cell cycle assays. A gastric cancer mouse model was constructed by implantation of transfected AGS cells. Insulin-like growth factor 1 receptor (IGF1R) was overexpressed in AGS cells to investigate miR-141 mechanism. Results showed that miR-141 was significantly down-regulated in gastric cancer tissue (P < 0.001). The patients with lower miR-141 levels exhibited poorer prognosis. miR-141 inhibited AGS cell viability (P < 0.01), colony formation (P < 0.01) and cell cycle (P < 0.05), and the mice implanted with miR-141 mimic cells showed an obvious smaller tumor size (P < 0.01), suggesting the anti-proliferative role of miR-141. Both the phosphorylated and total IGF1R protein levels were inhibited by miR-141, while IGF1R overexpression reversed the effects of miR-141 in AGS cell proliferation. These results indicate the potential roles of miR-141 as a prognostic factor and as a therapeutic alternative for gastric cancer. Its mechanism may be associated with IGF1R, and further research is necessary for more detail information. PMID:27648145

  8. Anti-proliferative role and prognostic implication of miR-141 in gastric cancer.

    PubMed

    Huang, Mingwei; Wu, Liucheng; Qin, Yuzhou; Li, Zhao; Luo, Shanshan; Qin, Haiquan; Yang, Yang; Chen, Jiansi

    2016-01-01

    Gastric cancer is a prevalent disease causing a high annual death rate worldwide. Recent studies suggest the pivotal regulatory role of microRNAs in gastric cancer and the aberrant expression of microRNA-141 (miR-141) in gastric cancer cells. This study aims to explore the role and possible mechanism of miR-141 in gastric cancer prognosis and cell proliferation. A total of 30 gastric cancer patients were recruited for miR-141 level detection and a follow up of 115 weeks. Human adenocarcinoma cell line AGS was transfected with miR-141 mimic or inhibitor for cell viability, colony formation and cell cycle assays. A gastric cancer mouse model was constructed by implantation of transfected AGS cells. Insulin-like growth factor 1 receptor (IGF1R) was overexpressed in AGS cells to investigate miR-141 mechanism. Results showed that miR-141 was significantly down-regulated in gastric cancer tissue (P < 0.001). The patients with lower miR-141 levels exhibited poorer prognosis. miR-141 inhibited AGS cell viability (P < 0.01), colony formation (P < 0.01) and cell cycle (P < 0.05), and the mice implanted with miR-141 mimic cells showed an obvious smaller tumor size (P < 0.01), suggesting the anti-proliferative role of miR-141. Both the phosphorylated and total IGF1R protein levels were inhibited by miR-141, while IGF1R overexpression reversed the effects of miR-141 in AGS cell proliferation. These results indicate the potential roles of miR-141 as a prognostic factor and as a therapeutic alternative for gastric cancer. Its mechanism may be associated with IGF1R, and further research is necessary for more detail information. PMID:27648145

  9. The role of additional chemotherapy with oral UFT in intravenous combination chemotherapy with cisplatin and 5-fluorouracil for human gastric cancer xenograft lines of well- and poorly- differentiated adenocarcinomas transplanted in nude mice.

    PubMed

    Tseng, C C; Nio, Y; Tsubono, M; Kawabata, K; Masai, Y; Hayashi, H; Fukumoto, M; Tobe, T

    1992-01-01

    In order to assess the role of maintenance chemotherapy with the oral anticancer agent UFT, a mixture of uracil and futraful, in the intensive intravenous chemotherapy for gastric cancer, nude mice transplanted with human gastric cancer xenografts were treated with intravenous 5-fluorouracil (5-FU) and cisplatin (CDDP), alone or in combination, with or without the oral anticancer agent UFT. UFT was given at its maximal clinical dose of 10 mg/kg of body weight daily for 2 weeks, while 5-FU and/or CDDP was intravenously administered at the dose of 20 mg/kg and 1.8 mg/kg of body weight respectively once a week, alone or in combination, for two weeks. The results revealed that 5-FU or CDDP alone were ineffective for both GC-YN, a well differentiated adenocarcinoma line, and GC-SF, a poorly differentiated adenocarcinoma line; however, UFT was effective for GC-SF. In combinations, only the three-agent combination 5-FU + CDDP + UFT (FPU) was effective for GC-YN; however, all the two-agent combinations and FPU were effective for GC-SF. FPU significantly suppressed the growth of GC-YN much more than all the other treatment groups. In contrast, although all combinations as well as UFT alone were effective for GC-SF, there was no significant difference among these effective groups. Moreover, no side effects were noted in combined use of UFT. This study suggests that oral UFT as a maintenance treatment may be beneficial in the combination chemotherapy for human gastric cancer.

  10. CpG island promoter hypermethylation of Ras association domain family 1A gene contributes to gastric carcinogenesis.

    PubMed

    Joo, Moon Kyung; Kim, Key Hyeon; Park, Jong-Jae; Yoo, Hyo Soon; Choe, Jungwan; Kim, Hyo Jung; Lee, Beom Jae; Kim, Jae Seon; Bak, Young-Tae

    2015-04-01

    Methylation rates of the Ras association domain family 1A gene (RASSF1A) have been variously reported as between 7.5 and 66.7% in gastric carcinoma tissues. The role of this gene in gastric cancer also remains to be fully elucidated. The present study aimed to investigate whether promoter hypermethylation of RASSF1A occurs in gastric adenocarcinoma tissues and gastric cancer cell lines, and to determine the effects of RASSF1A in gastric carcinoma cell lines. The results showed a methylation‑specific band only in SNU‑719, MKN28 and AGS human gastric cancer cells (indicating full methylation), none of which exhibited RASSF1A expression. By contrast, SNU‑16, MKN‑45 and KATO‑III human gastric carcinoma cells exhibited methylation as well as unmethylation‑specific bands (indicating partial methylation), and all displayed positive or weakly positive expression of RASSF1A. Bisulfite sequencing in AGS and SNU‑719 cells revealed that virtually all CpG sites were densely methylated. When SNU‑719, MKN‑28 and AGS cells were treated with the demethylating agent 5‑aza‑2'‑deoxycytidine, RASSF1A gene expression was restored and the methylation‑specific polymerase chain reaction pattern was altered in all three cell lines. Transfection of a plasmid expressing RASSF1A into AGS and SNU‑719 cells significantly inhibited cell proliferation. Exogenous RASSF1A also reduced the expression of cyclin D1 and phospho‑retinoblastoma protein, and increased that of p27 as demonstrated by western blot analysis. Furthermore, RASSF1A expression was significantly reduced (P=0.048) and the methylation rate was elevated in gastric adenocarcinoma tissues, compared with those in adjacent healthy intestinal metaplasia (34.6 vs. 66.7%, P=0.029). The present study indicated that epigenetic silencing of RASSF1A is frequently caused by promoter hypermethylation in gastric cancer cell lines as well as in gastric adenocarcinoma tissues, which may contribute to gastric

  11. Induction of apoptosis by genipin inhibits cell proliferation in AGS human gastric cancer cells via Egr1/p21 signaling pathway.

    PubMed

    Ko, Hyeonseok; Kim, Jee Min; Kim, Sun-Joong; Shim, So Hee; Ha, Chang Hoon; Chang, Hyo Ihl

    2015-10-01

    Natural compounds are becoming important candidates in cancer therapy due to their cytotoxic effects on cancer cells by inducing various types of programmed cell deaths. In this study, we investigated whether genipin induces programmed cell deaths and mediates in Egr1/p21 signaling pathways in gastric cancer cells. Effects of genipin in AGS cancer cell lines were observed via evaluation of cell viability, ROS generation, cell cycle arrest, and protein and RNA levels of p21, Egr1, as well as apoptotic marker genes. The cell viability of AGS cells reduced by genipin treatment via induction of the caspase 3-dependent apoptosis. Cell cycle arrest was observed at the G2/M phase along with induction of p21 and p21-dependent cyclins. As an upstream mediator of p21, the transcription factor early growth response-1 (Egr1) upregulated p21 through nuclear translocation and binding to the p21 promoter site. Silencing Egr1 expression inhibited the expression of p21 and downstream molecules involved in apoptosis. We demonstrated that genipin treatment in AGS human gastric cancer cell line induces apoptosis via p53-independent Egr1/p21 signaling pathway in a dose-dependent manner.

  12. Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer

    PubMed Central

    Kim, Seok-Jun; Hwang, Jung-Ah; Ro, Jae Y.; Lee, Yeon-Su; Chun, Kyung-Hee

    2013-01-01

    Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Therefore, the basic mechanisms underlying gastric tumorigenesis deserve investigation. Although regulation of the galactoside-binding lectin galectin-7 in cancer has been studied, its role in tumor formation and progression remains controversial. In this study, we investigated galectin-7 expression and its role in gastric cancer. Immunohistochemical staining using a tissue microarray of gastric cancer patients revealed significantly low expression levels of galectin-7 in malignant tissues compared with matched normal tissues, and decreased expression of galectin-7 in malignant tissues was associated with advanced TMN stage disease (p =0.034). Importantly, low expression of galectin-7 in normal tissues was associated with a poor survival rate (p =0.0561). Over-expression of galectin-7 in AGS gastric adenocarcinoma cells suppressed cell proliferation, migration, and invasion, whereas ablation of galectin-7 in KATO III gastric carcinoma cells reversed these properties. AGS cells that overexpressed galectin-7 could not form gastric tumors in xenografted mice. More than 70% hypermethylation was observed in 7 of 9 gastric cancer cell lines tested and 5-aza-cytidine treatment lowered galectin-7 expression by reducing methylation in 24 cancer cell lines from five different organ origins. We analyzed CpG islands in the galectin-7 genomic region and detected hypermethylation at +1566bp of exon 2, the predicted p53 binding region. DNA hypermethylation of this region was also detected in gastric cancer tissues from 20 patients. Taken together, our data indicate that galectin-7 has a tumor suppressive function, and that the gene is epigenetically modified by DNA methylation and significantly down-regulated in gastric cancer. Further study of galectin-7 regulation may lead to improved gastric cancer diagnosis and therapy. PMID

  13. Effect of Di(2-ethylhexyl)phthalate on Helicobacter pylori-Induced Apoptosis in AGS Cells

    PubMed Central

    Wu, Chien-Yi; Kou, Hwang-Shang; Chen, Chiao-Yun; Huang, Meng-Chuan; Hu, Huang-Ming; Wu, Meng-Chieh; Lu, Chien-Yu; Wu, Deng-Chyang; Wu, Ming-Tsang; Kuo, Fu-Chen

    2013-01-01

    Plastic products are wildly used in human life. Di(2-ethylhexyl)phthalate (DEHP) is an essential additive in plastic manufacturing and is used as plasticizer for many products including plastic food packaging. DEHP is a teratogenic compound and can cause potent reproductive toxicity. DEHP can also cause liver damage, peroxisome proliferation, and carcinogenesis. DEHP is also strongly associated with peptic ulcers and gastric cancer; however, the underlying effect and mechanism of DEHP on the gastrointestinal tract are not entirely clear. The oral infection route of H. pylori parallels the major ingestion route of DEHP into the human body. Therefore, we wanted to study the effect of DEHP and H. pylori exposure on the human gastric epithelial cell line, AGS (gastric adenocarcinoma). The viability of the AGS cell line was significantly lower in 80 μM-DEHP and H. pylori (MOI = 100 : 1) coexposure than DEHP or H. pylori alone. DEHP and H. pylori coexposure also induced caspase-3 activation, and increased Bax/Bcl-2 ratio and DNA fragmentation in AGS cells. These results indicate that DEHP can enhance H. pylori cytotoxicity and induce gastric epithelial cell apoptosis. Therefore, it is possible that DEHP and H. pylori coexposure might enhance the disruption of the gastric mucosa integrity and potentially promote the pathogenesis of gastric carcinogenesis. PMID:24454344

  14. Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

    PubMed Central

    Bain, G H; Collie-Duguid, E; Murray, G I; Gilbert, F J; Denison, A; Mckiddie, F; Ahearn, T; Fleming, I; Leeds, J; Phull, P; Park, K; Nanthakumaran, S; Grabsch, H I; Tan, P; Welch, A; Schweiger, L; Dahle-Smith, A; Urquhart, G; Finegan, M; Petty, R D

    2014-01-01

    Background: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy. Methods: Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations. Results: We identified 520 genes with differential expression (Mann–Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant

  15. DAG/PKCδ and IP3/Ca²⁺/CaMK IIβ Operate in Parallel to Each Other in PLCγ1-Driven Cell Proliferation and Migration of Human Gastric Adenocarcinoma Cells, through Akt/mTOR/S6 Pathway.

    PubMed

    Dai, Lianzhi; Zhuang, Luhua; Zhang, Bingchang; Wang, Fen; Chen, Xiaolei; Xia, Chun; Zhang, Bing

    2015-12-01

    Phosphoinositide specific phospholipase Cγ (PLCγ) activates diacylglycerol (DAG)/protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)/Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) axes to regulate import events in some cancer cells, including gastric adenocarcinoma cells. However, whether DAG/PKCδ and IP3/Ca(2+)/CaMK IIβ axes are simultaneously involved in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells and the underlying mechanism are not elucidated. Here, we investigated the role of DAG/PKCδ or CaMK IIβ in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells, using the BGC-823 cell line. The results indicated that the inhibition of PKCδ and CaMK IIβ could block cell proliferation and migration of BGC-823 cells as well as the effect of inhibiting PLCγ1, including the decrease of cell viability, the increase of apoptotic index, the down-regulation of matrix metalloproteinase (MMP) 9 expression level, and the decrease of cell migration rate. Both DAG/PKCδ and CaMK IIβ triggered protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/S6 pathway to regulate protein synthesis. The data indicate that DAG/PKCδ and IP3/Ca(2+)/CaMK IIβ operate in parallel to each other in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells through Akt/mTOR/S6 pathway, with important implication for validating PLCγ1 as a molecular biomarker in early gastric cancer diagnosis and disease surveillance.

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

    SciTech Connect

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

    2008-08-22

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

  17. Helicobacter pylori associated gastric intestinal metaplasia: Treatment and surveillance

    PubMed Central

    Liu, Kevin Sze-Hang; Wong, Irene Oi-Ling; Leung, Wai K

    2016-01-01

    Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa’s cancer cascade, non-cardia GC is usually developed through a series of mucosal changes from non-atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori (H. pylori) infection is an important initiating and promoting step of this gastric carcinogenesis cascade. Emerging long-term data showed that eradication of H. pylori reduced the risk of subsequent cancer development. It however remains confusing whether eradication of the bacterium in individuals with pre-neoplastic gastric lesions could regress these changes as well as in preventing cancer. Whilst H. pylori eradication could likely regress AG, the presence of IM may be a point of no return in this cascade. Hence, surveillance by endoscopy may be indicated in those with extensive IM or those with incomplete IM, particularly in populations with high GC risk. The optimal interval and the best tool of surveillance endoscopy remains to be determined in future studies. PMID:26811668

  18. Computed tomography of gastric lymphoma.

    PubMed

    Buy, J N; Moss, A A

    1982-05-01

    The CT features in 12 patients with gastric lymphoma, four primary and eight secondary, were analyzed, correlated with other diagnostic studies, surgery, and pathologic features, and compared with the CT findings in 22 patients with gastric adenocarcinoma. An abnormally thickened gastric wall (mean, 4.0 cm) was found in all patients with gastric lymphoma. Lymphomas of the stomach often involved more than one region of the stomach (83%). The contour of the outer gastric wall was smooth or lobulated in 42%, perigastric lymph adenopathy was common (58%), extension into adjacent organs was found in 42%, and 42% had lymphadenopathy at or below the renal pedicle.

  19. [Urachal adenocarcinoma].

    PubMed

    Dakir, M; Dahami, Z; Sarf, I; Tahri, A; Elmrini, M; Benjelloun, S

    2001-09-01

    Cancer of the urachus is very unusual. The lesion is a mucosecretory adenocarcinoma. The diagnosis is usually established late, and has a serious prognosis because of a long clinical latency. We report a case of metastatic adenocarcinoma of the urachus revealed by hematuria. A review of the literature allows us to demonstrate the rarity of this tumour and to demonstrate its various clinical, histological, radiological and therapeutical aspects.

  20. The Phase 2 Study of "(TOX) Preoperative Chemotherapy" Response Rate and Side Effects in [Locally Advanced Operable Gastric Adenocarcinoma] Patients With Docetaxel, Oxaliplatin and Capcitabine

    PubMed Central

    Yahyazadeh-Jabbari, Seyyed-Hossein; Malekpour, Nasser; Salmanian, Bahram; Foodazi, Hossein; Salehi, Masoud; Noorizadeh, Farsad

    2013-01-01

    Background Early stage gastric cancer diagnosis has ensued different approaches in resection strategies. In order to increase the proportion of cases which have undergone radical resection or have reduced the recurrence rate, different pre-operative treatments have introduced. Here, we have verified an active preoperative chemotherapeutic regimen in locally advanced gastric cancer patients. Methods Forty nine patients who have found eligible to enter this phase 2 trial have treated with oxaliplatin 100 mg/m2 IV, docetaxel 50 mg/m2 IV, plus capecitabine 625 mg/m2 PO (TOX). Clinical staging has been following the first 2 cycles of induction chemotherapy. Patients that have further undergone radical surgery, have evaluated for pathological response rate. Results Anemia (10.2%), nausea (10.2%) and vomiting (6.1%) were the most frequent grade 3 or 4 adverse effects. Regarding the pathologic staging, 6 patients (12.2%) had complete response (95% CI 3% to 21.4%), 18 of them (36.7%) had partial response (95% CI 23.2% to 50.2%), then 3 patients (6.1%) had stable disease (95% CI 0%-12.8%). Among the patients who had surgery, 22% had pathologic complete response. Conclusion Preoperative chemotherapeutic regimen of TOX seems to be an active and safe neoadjuvant therapy in non metastatic gastric cancer. It should further be considered with concurrent radiotherapy. PMID:25250123

  1. A case of gastric adenocarcinoma of fundic gland type resected by combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET).

    PubMed

    Kato, Motohiko; Uraoka, Toshio; Isobe, Yoh; Abe, Keiichiro; Hirata, Tetsu; Takada, Yoshiaki; Wada, Michiko; Takatori, Yusaku; Takabayashi, Kaoru; Fujiyama, Yoichi; Sekiya, Kousuke; Kawaguchi, Yoshiki; Sukeda, Aoi; Shiraishi, Junichi

    2015-12-01

    A male in his eighties attended our hospital for further evaluation of gastric cancer. A gastroscopy revealed a whitish flat elevated lesion (Paris, 0-IIa) of 15 mm in diameter on the greater curvature of the proximal fornix. The preoperative diagnosis was intra-mucosal differentiated gastric cancer, and a novel therapeutic approach, combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) was applied and the lesion was resected in a single piece without any complications. Histopathological findings revealed atypical glandular epithelium proliferated in the mucosa and shallow layer (300 μm) of submucosa. These cells stained positive for pepsinogen-I and the final diagnosis was gastric cancer of fundic gland type (GAFT). There was no lymph-vascular involvement and free horizontal and vertical margins were confirmed. CLEAN-NET could be a therapeutic option for GAFT at low risk of lymph node metastasis because it prevents excess wall defect and exposure of cancer cells into the peritoneal cavity.

  2. Serum HER 2 Extracellular Domain Level Is Correlated with Tissue HER 2 Status in Metastatic Gastric or Gastro-Oesophageal Junction Adenocarcinoma

    PubMed Central

    Wang, Fang; Shao, Qiong; Chen, Yong-Chang; Kong, Ya-Nan; Chen, Cui; Li, Cong; Luo, Hui-Yan; Liang, Ying; Wang, Feng-Hua; Xu, Rui-Hua; Li, Yu- Hong

    2013-01-01

    Background To explore the association between serum human epidermal growth factor receptor 2 (HER 2) extracellular domain (ECD) levels and tissue HER 2 status in metastatic gastric cancer. Patients and Methods HER 2 status was retrospectively analyzed in 219 advanced gastric or gastroesophageal junction (GEJ) patients. Serum HER 2 ECD was measured by chemiluminescent assay and tissue HER 2 was assessed by fluorescent in situ hybridisation (FISH) and immunohistochemistry (IHC) assay. Results Significant associations were found between serum HER 2 ECD levels and tissue HER 2 status. Twenty-four patients had HER 2 ECD levels >16.35 ng/mL, which has a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER 2 status. When the cut-off value was increased to 22 ng/mL, then all 12 patients with serum HER 2 ECD levels>22 ng/mL were tissue HER 2 positive, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER 2 ECD levels were strongly associated with the intestinal histological type (Lauren’s classification), liver metastasis, multiple metastasis (>2) and increased LDH levels, but not with overall survival. Conclusions The high specificity of the serum HER 2 ECD assay in predicting tissue HER 2 status suggests its potential as a surrogate marker of the HER 2 status in gastric cancer. PMID:23691049

  3. Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up.

    PubMed

    Gonzalez, Carlos A; Lujan-Barroso, Leila; Bueno-de-Mesquita, H B; Jenab, Mazda; Duell, Eric J; Agudo, Antonio; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Touillaud, Marina; Teucher, Birgit; Kaaks, Rudolf; Boeing, Heiner; Steffen, Annika; Trichopoulou, Antonia; Roukos, Dimitrios; Karapetyan, Tina; Palli, Domenico; Tagliabue, Giovanna; Mattiello, Amalia; Tumino, Rosario; Ricceri, Fulvio; Siersema, Peter D; Numans, Mattijs E; Peeters, Petra P H; Parr, Christine L; Skeie, Guri; Lund, Eiliv; Quirós, J Ramón; Sánchez-Cantalejo, Emilio; Navarro, Carmen; Barricarte, Aurelio; Dorronsoro, Miren; Ehrnström, Roy; Regner, Sara; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Crowe, Francesca L; Blaker, Hendrik; Romieu, Isabelle; Riboli, Elio

    2012-12-15

    In a previous European prospective investigation into cancer and nutrition (EPIC) analysis, we found an inverse association between total intake of vegetables, onion and garlic, and risk of intestinal gastric cancer (GC) and between citrus fruit and risk of cardia GC. The aim of this study is to reanalyze the effect of fruit and vegetables (F&V), based on a longer follow-up and twice the number of GC cases. Subjects are 477,312 men and women mostly aged 35 to 70 years participating in the EPIC cohort, including 683 gastric adenocarcinomas with 11 years of follow-up. Information on diet and lifestyle was collected at baseline. A calibration study in a subsample was used to correct for dietary measurement errors. When comparing the highest vs. lowest quintile of intake, we found an inverse association between total intake of V&F and GC risk [hazard ratio (HR) 0.77; 95% confidence interval (CI) 0.57-1.04; p for trend 0.02], between fresh fruit and risk of the diffuse type (HR 0.59; 95% CI 0.36-0.97; p for trend 0.03) and an inverse association between citrus fruit and risk of cardia cancer (HR 0.61; 95% CI 0.38-1.00, p for trend 0.01). Although calibration revealed somewhat stronger inverse associations, none of the risks reached statistical significance. There was no association between total or specific vegetables intake and GC risk. The inverse association between fresh fruit and citrus fruits and risk of GC seems to be restricted to smokers and the Northern European countries. Fresh fruit and citrus fruit consumption may protect against diffuse and cardia GC, respectively.

  4. Adenocarcinoma

    Cancer.gov

    Compared to adenomas, adenocarcinomas show greater cytological atypia, increased frequency of mitoses, regional variation in growth pattern, more papillary structures, have size over 5 mm in diameter, show invasion of vessels, large airways or pleura, as well as lymphatic and hematogenous metastases.

  5. Conjugation of toll-like receptor-7 agonist to gastric cancer antigen MG7-Ag exerts antitumor effects

    PubMed Central

    Wang, Xiao-Dong; Gao, Ning-Ning; Diao, Yu-Wen; Liu, Yu; Gao, Dong; Li, Wang; Wan, Yan-Yan; Zhong, Jing-Jing; Jin, Guang-Yi

    2015-01-01

    AIM: To investigate the effects of our tumor vaccines on reversing immune tolerance and generating therapeutic response. METHODS: Vaccines were synthesized by solid phase using an Fmoc strategy, where a small molecule toll-like receptor-7 agonist (T7) was conjugated to a monoclonal gastric cancer 7 antigen mono-epitope (T7-MG1) or tri-epitope (T7-MG3). Cytokines were measured in both mouse bone marrow dendritic cells and mouse spleen lymphocytes after exposed to the vaccines. BALB/c mice were intraperitoneally immunized with the vaccines every 2 wk for a total of three times, and then subcutaneously challenged with Ehrlich ascites carcinoma (EAC) cells. Three weeks later, the mice were killed, and the tumors were surgically removed and weighed. Serum samples were collected from the mice, and antibody titers were determined by ELISA using an alkaline phosphate-conjugated detection antibody for total IgG. Antibody-dependent cell-mediated cytotoxicity was detected by the lactate dehydrogenase method using natural killer cells as effectors and antibody-labeled EAC cells as targets. Cytotoxic T lymphocyte activities were also detected by the lactate dehydrogenase method using lymphocytes as effectors and EAC cells as targets. RESULTS: Vaccines were successfully synthesized and validated by analytical high performance liquid chromatography and electrospray mass spectrometry, including T7, T7-MG1, and T7-MG3. Rapid inductions of tumor necrosis factor-α and interleukin-12 in bone marrow dendritic cells and interferon γ and interleukin-12 in lymphocytes occurred in vitro after T7, T7-MG1, and T7-MG3 treatment. Immunization with T7-MG3 reduced the EAC tumor burden in BALB/c mice to 62.64% ± 5.55% compared with PBS control (P < 0.01). Six or nine weeks after the first immunization, the monoclonal gastric cancer 7 antigen antibody increased significantly in the T7-MG3 group compared with the PBS control (P < 0.01). As for antibody-dependent cell-mediated cytotoxicity

  6. The A/G Allele of Rs16906252 Predicts for MGMT Methylation and Is Selectively Silenced in Premalignant Lesions from Smokers and in Lung Adenocarcinomas

    PubMed Central

    Leng, Shuguang; Bernauer, Amanda M.; Hong, Chibo; Do, Kieu C.; Yingling, Christin M.; Flores, Kristina G.; Tessema, Mathewos; Tellez, Carmen S.; Willink, Randall P.; Burki, Elizabeth A.; Picchi, Maria A.; Stidley, Christine A.; Prados, Michael D.; Costello, Joseph F.; Gilliland, Frank D.; Crowell, Richard E.; Belinsky, Steven A.

    2011-01-01

    Purpose To address the association between sequence variants within the MGMT promoter-enhancer region and methylation of MGMT in premalignant lesions from smokers and lung adenocarcinomas, their biological effects on gene regulation, and targeting MGMT for therapy. Experimental Design SNPs identified through sequencing a 1.9kb fragment 5' of MGMT were examined in relation to MGMT methylation in 169 lung adenocarcinomas and 1731 sputum samples from smokers. The effect of promoter haplotypes on MGMT expression was tested using a luciferase reporter assay and cDNA expression analysis along with allele-specific sequencing for methylation. The response of MGMT methylated lung cancer cell lines to the alkylating agent temozolomide was assessed. Results The A allele of rs16906252 and the haplotype containing this SNP were strongly associated with increased risk for MGMT methylation in adenocarcinomas (ORs ≥ 94). This association was observed to a lesser extent in sputum samples in both smoker cohorts. The A allele was selectively methylated in primary lung tumors and cell lines heterozygous for rs16906252. With the most common haplotype as the reference, a 20–41% reduction in promoter activity was seen for the haplotype carrying the A allele that correlated with lower MGMT expression. The sensitivity of lung cancer cell lines to temozolamide was strongly correlated with levels of MGMT methylation and expression. Conclusions These studies provide strong evidence that the A allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in lung carcinogenesis. Moreover, temozolamide treatment may benefit a subset of lung cancer patients methylated for MGMT. PMID:21355081

  7. Association between serum vitamin D levels and gastric cancer: A retrospective chart analysis

    PubMed Central

    Vyas, Neil; Companioni, Rafael Ching; Tiba, Melik; Alkhawam, Hassan; Catalano, Carmine; Sogomonian, Robert; Baum, Joel; Walfish, Aaron

    2016-01-01

    AIM To determine whether there is an increased risk of gastric adenocarcinoma associated with vitamin D deficiency (VDd). METHODS A retrospective case control study was performed of all patients diagnosed with gastric adenocarcinoma between 2005 and 2015. After we excluded the patients without a documented vitamin D level, 49 patients were included in our study. RESULTS The average age of patients with gastric adenocarcinoma and documented vitamin D level was 64 years old (95%CI: 27-86) and average vitamin D level was 20.8 mg/dL (95%CI: 4-44). Compared to a matched control group, the prevalence of VDd/insufficiency in patients with gastric adenocarcinoma was significantly higher than normal vitamin D levels (83.7% vs 16.3%). Forty-one patients (83.7%) with adenocarcinoma showed VDd/insufficiency compared to 18 (37%) patients with normal vitamin D level without gastric cancer (OR: 8.8, 95%CI: 5-22, P value < 0.0001). The average age of males with gastric adenocarcinoma diagnosis was 60 years old vs 68 years old for females (P = 0.01). Stage II gastric adenocarcinoma was the most prevalent in our study (37%). CONCLUSION We reported a positive relationship between VDd and gastric adenocarcinoma, that is to say, patients with decreased VDd levels have an increased propensity for gastric adenocarcinoma. PMID:27672427

  8. Association between serum vitamin D levels and gastric cancer: A retrospective chart analysis

    PubMed Central

    Vyas, Neil; Companioni, Rafael Ching; Tiba, Melik; Alkhawam, Hassan; Catalano, Carmine; Sogomonian, Robert; Baum, Joel; Walfish, Aaron

    2016-01-01

    AIM To determine whether there is an increased risk of gastric adenocarcinoma associated with vitamin D deficiency (VDd). METHODS A retrospective case control study was performed of all patients diagnosed with gastric adenocarcinoma between 2005 and 2015. After we excluded the patients without a documented vitamin D level, 49 patients were included in our study. RESULTS The average age of patients with gastric adenocarcinoma and documented vitamin D level was 64 years old (95%CI: 27-86) and average vitamin D level was 20.8 mg/dL (95%CI: 4-44). Compared to a matched control group, the prevalence of VDd/insufficiency in patients with gastric adenocarcinoma was significantly higher than normal vitamin D levels (83.7% vs 16.3%). Forty-one patients (83.7%) with adenocarcinoma showed VDd/insufficiency compared to 18 (37%) patients with normal vitamin D level without gastric cancer (OR: 8.8, 95%CI: 5-22, P value < 0.0001). The average age of males with gastric adenocarcinoma diagnosis was 60 years old vs 68 years old for females (P = 0.01). Stage II gastric adenocarcinoma was the most prevalent in our study (37%). CONCLUSION We reported a positive relationship between VDd and gastric adenocarcinoma, that is to say, patients with decreased VDd levels have an increased propensity for gastric adenocarcinoma.

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

    PubMed Central

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

    2009-01-01

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

  10. Effectiveness of Magnifying Narrow-Band Imaging Endoscopy for Differential Diagnosis between the High-Risk Mixed-Type and Low-Risk Simple-Type of Low-Grade, Well-Differentiated Gastric Tubular Adenocarcinoma.

    PubMed

    Saitoh, Takashi; Takamura, Asako; Watanabe, Gen; Sugitani, Suzuko; Ajioka, Yoichi

    2016-01-01

    Backgrounds. Magnifying endoscopy with narrow-band imaging (NBI-ME) is useful for diagnosing differentiated early gastric cancer (D-EGC). D-EGC is classified as high- or low-grade based on its glandular architectural and cytological atypia. Low-grade, well-differentiated tubular adenocarcinoma (LG-tub1) mixed with high-grade tub1 (HG-tub1) and/or other histological types (M-LG-tub1) may indicate a primitive high-risk malignant lesion compared to histologically simple-type LG-tub1 (S-LG-tub1). Because LG-tub1 is occasionally difficult to diagnose due to its unclear demarcation under conventional white light endoscopy, early precise diagnoses are important. Methods. We compared NBI-ME and postendoscopic submucosal dissection histological findings for 30 S-LG-tub1 and 15 M-LG-tub1 lesions. We classified the NBI-ME findings of S-LG-tub1 (and not D-EGC) into four patterns. The differential diagnosis between M-LG-tub1 and S-LG-tub1 depended on the presence of more than one of these patterns without or with other patterns (referred to as "limited-to-four-pattern [LFP] sign-positive" and "sign-negative", resp.). Result. The sensitivity, specificity, accuracy, positive and negative predictive values, and intraobserver and interobserver agreement, using the "LFP sign" for the differential diagnosis between M-LG-tub1 and S-LG-tub1, were 87.9%, 91.7%, 88.9%, 96.7%, 73.3%, and k = 0.842 and k = 0.737, respectively. Conclusion. NBI-ME may be useful in differentiating between high-risk M-LG-tub1 and low-risk S-LG-tub1. PMID:27127502

  11. Effectiveness of Magnifying Narrow-Band Imaging Endoscopy for Differential Diagnosis between the High-Risk Mixed-Type and Low-Risk Simple-Type of Low-Grade, Well-Differentiated Gastric Tubular Adenocarcinoma

    PubMed Central

    Takamura, Asako; Watanabe, Gen; Sugitani, Suzuko; Ajioka, Yoichi

    2016-01-01

    Backgrounds. Magnifying endoscopy with narrow-band imaging (NBI-ME) is useful for diagnosing differentiated early gastric cancer (D-EGC). D-EGC is classified as high- or low-grade based on its glandular architectural and cytological atypia. Low-grade, well-differentiated tubular adenocarcinoma (LG-tub1) mixed with high-grade tub1 (HG-tub1) and/or other histological types (M-LG-tub1) may indicate a primitive high-risk malignant lesion compared to histologically simple-type LG-tub1 (S-LG-tub1). Because LG-tub1 is occasionally difficult to diagnose due to its unclear demarcation under conventional white light endoscopy, early precise diagnoses are important. Methods. We compared NBI-ME and postendoscopic submucosal dissection histological findings for 30 S-LG-tub1 and 15 M-LG-tub1 lesions. We classified the NBI-ME findings of S-LG-tub1 (and not D-EGC) into four patterns. The differential diagnosis between M-LG-tub1 and S-LG-tub1 depended on the presence of more than one of these patterns without or with other patterns (referred to as “limited-to-four-pattern [LFP] sign-positive” and “sign-negative”, resp.). Result. The sensitivity, specificity, accuracy, positive and negative predictive values, and intraobserver and interobserver agreement, using the “LFP sign” for the differential diagnosis between M-LG-tub1 and S-LG-tub1, were 87.9%, 91.7%, 88.9%, 96.7%, 73.3%, and k = 0.842 and k = 0.737, respectively. Conclusion. NBI-ME may be useful in differentiating between high-risk M-LG-tub1 and low-risk S-LG-tub1. PMID:27127502

  12. Effectiveness of Magnifying Narrow-Band Imaging Endoscopy for Differential Diagnosis between the High-Risk Mixed-Type and Low-Risk Simple-Type of Low-Grade, Well-Differentiated Gastric Tubular Adenocarcinoma.

    PubMed

    Saitoh, Takashi; Takamura, Asako; Watanabe, Gen; Sugitani, Suzuko; Ajioka, Yoichi

    2016-01-01

    Backgrounds. Magnifying endoscopy with narrow-band imaging (NBI-ME) is useful for diagnosing differentiated early gastric cancer (D-EGC). D-EGC is classified as high- or low-grade based on its glandular architectural and cytological atypia. Low-grade, well-differentiated tubular adenocarcinoma (LG-tub1) mixed with high-grade tub1 (HG-tub1) and/or other histological types (M-LG-tub1) may indicate a primitive high-risk malignant lesion compared to histologically simple-type LG-tub1 (S-LG-tub1). Because LG-tub1 is occasionally difficult to diagnose due to its unclear demarcation under conventional white light endoscopy, early precise diagnoses are important. Methods. We compared NBI-ME and postendoscopic submucosal dissection histological findings for 30 S-LG-tub1 and 15 M-LG-tub1 lesions. We classified the NBI-ME findings of S-LG-tub1 (and not D-EGC) into four patterns. The differential diagnosis between M-LG-tub1 and S-LG-tub1 depended on the presence of more than one of these patterns without or with other patterns (referred to as "limited-to-four-pattern [LFP] sign-positive" and "sign-negative", resp.). Result. The sensitivity, specificity, accuracy, positive and negative predictive values, and intraobserver and interobserver agreement, using the "LFP sign" for the differential diagnosis between M-LG-tub1 and S-LG-tub1, were 87.9%, 91.7%, 88.9%, 96.7%, 73.3%, and k = 0.842 and k = 0.737, respectively. Conclusion. NBI-ME may be useful in differentiating between high-risk M-LG-tub1 and low-risk S-LG-tub1.

  13. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report

    PubMed Central

    Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-01-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  14. [Early gastric cancer--two case reports].

    PubMed

    Neziha, Belkahla; Houneida, Bouzi; Mohamed, Jouini; Hajer, Ouerghi; Nadia, Maamouri; Imed, Cheikh; Faouzi, Chebbi; Saadia, Bouraoui; Nidhameddine, Kchir; Ahmed, Ben Ammar

    2005-11-01

    Gastric cancer is a serious disease with a high mortality rate. Early diagnosis of the disease improves its prognosis. We report two cases of early gastric cancer and we specify the clinical, endoscopic, histologic and therapeutic aspects of the disease. This study is about two female patients, respectively, 36 and 70 years old. The diagnosis of early gastric cancer was based on pathologic examination of the resected stomach. The two patients are in remission 2 years and 6 months later, respectively. The diagnosis of early gastric cancer is often made on nonspecific symptoms. Oeso-gastro-duodenoscopy shows gastric mucosal anomalies. Pathologic examination of gastric biopsies confirm the diagnosis of adenocarcinoma. Endoscopic ultrasound is essential; it specifies the submucosal infiltration and evaluates the lymph node invasion. Surgery is the primary treatment but in some cases endoscopic mucosal resection provides good long-term results. Early diagnosis of adenocarcinoma improves the prognosis of the disease, which remains poor nowadays.

  15. Inhibitory effect of ibuprofen on tumor survival and angiogenesis in gastric cancer cell.

    PubMed

    Akrami, Hassan; Aminzadeh, Saman; Fallahi, Hossein

    2015-05-01

    Numerous epidemiological studies have suggested effectiveness of long-term and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and aspirin, in preventing and treatment of certain cancers including prostate, colon, breast, lung, and gastric cancers. We have studied the potential anti-turmeric effect of ibuprofen in adenocarcinoma gastric cell line (AGS). The effects of ibuprofen were investigated on cell proliferation, apoptosis, angiogenesis, and expression of stemness marker genes using real-time RT-PCR, DNA laddering, and tube formation assays via ECM gel and human umbilical vein endothelial cells (HUVECs). Annexin-V-FLUOS and propidium iodide (PI) were used to stain the apoptotic cells. Our findings indicate that ibuprofen at the concentrations of 100, 200, 300, 400, and 500 μM is able to reduce the cancerous characteristics of the AGS cells by inducing apoptosis, inhibition of cell proliferation, and angiogenesis. Real-time RT-PCR showed that ibuprofen altered the expression of several genes including Akt, P53, PCNA, Bax, and Bcl2 in the AGS cells. In addition, reduction in CD44 and OCT3/4 transcript levels revealed that ibuprofen reduces the stemness of the AGS cells and therefore it could be used as a potential anti-tumor drug.

  16. Food group intake and risk of subtypes of esophageal and gastric cancer

    PubMed Central

    SA, Navarro Silvera; ST, Mayne; H, Risch; MD, Gammon; T, Vaughan; W-H, Chow; R, Dubrow; J, Schoenberg; JL, Stanford; AB, West; H, Rotterdam; WJ, Blot; JF, Fraumeni

    2010-01-01

    Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non-cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multi-center, population-based case-control study in Connecticut, New Jersey, and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73), and non-cardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and non-cardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High-fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high-fat dairy was associated with increased risk of gastric cardia adenocarcinoma. PMID:18537156

  17. [Helicobacter pylori and gastric cancer].

    PubMed

    Ramírez Ramos, Alberto; Sánchez Sánchez, Rolando

    2008-01-01

    Since its discovery and identification in gastric tissue by Marshall and Warren in 1983, our knowledge about the effects of Helicobacter pylori infection has grown considerably. Its role in the multifactorial pathology of peptic ulcer disease (gastrodudodenal ulcer disease), gastric adenocarcinoma, and MALT lymphoma is now widely accepted while its involvement in extraintestinal disease is still controversial.The correlation between the colonization of the stomach by H. pylori and gastric lymphoma has been demonstrated in multiple studies. Between 65 and 80% of distal gastric adenocarcinomas are attributed to H. pylori infection. However, gastric carcinogenesis cannot be explained by H. pylori infection alone. Among those individuals infected by this bacteria, only a small percentage (2-5%) ever develops gastric cancer, the majority exhibit benign lesions. There is a wide individual variation in the outcome of this infection in patients. This individual and population specific variation is due to the intricate relationship between genetics, the environment, bacterial virulence, diet, and socio-economic status and it explains the multiple outcomes of this infection. In this article, we conduct a review of the widely accepted theories regarding gastric cancer, Helicobacter pylori, the correlations and enigmas between them, the reported geographical variations, and the various proposed hypotheses on the carcinogenic mechanism of Helicobacter pylori.

  18. Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction.

    PubMed

    Marsman, W A; Tytgat, G N J; ten Kate, F J W; van Lanschot, J J B

    2005-12-01

    During the last few decades there has been an alarming rise in the incidence of tumors originating at the esophagogastric junction (EGJ) [1]. The reason for this is unknown. Tumors of the EGJ can be categorized in two types of cancer divided according to their anatomical origin: distal esophageal adenocarcinoma and adenocarcinoma of the gastric cardia. However, due to their location, in the transitional zone of the esophagus and stomach, there is constant debate about the proper classification, staging, and management of these tumors. The etiology of distal esophageal adenocarcinoma is clearly related to gastroesophageal reflux disease (GERD) and the development of a Barrett's esophagus [2]. The etiology of adenocarcinoma of the gastric cardia is less well understood. In the present paper, we will discuss the clinical characteristics and clinical management of esophagogastric tumors. Special attention will be given to differences and similarities of adenocarcinomas of the gastric cardia and distal esophagus.

  19. Helicobacter pylori in gastric carcinogenesis.

    PubMed

    Ahn, Hyo Jun; Lee, Dong Soo

    2015-12-15

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981

  20. Gastric cáncer: Overview

    PubMed Central

    Correa, Pelayo

    2013-01-01

    Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidence in some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases being diagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations. Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and in a small percentage of patients, a familial genetic component. More than 95% of stomach cancer cases are adenocarcinomas, which are classified into two major histologic types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a sequence of gastric lesions known as Correa´s cascade and is the histologic type associated with the global decrease in gastric cancer rates. Diffuse type adenocarcinomas have a more aggressive behavior and worse prognosis than those of the intestinal type. According to the anatomical location, adenocarcinomas are classified as proximal (originating in the cardia) and distal (originating in the body and antrum). This classification seems to recognize two different clinical entities. Surgical resection of the tumor at an early stage is the only effective treatment method. Therefore, the identification and surveillance of patients at risk may play a significant role in survival rates. Anti-Helicobacter pylori therapy has been shown to be an effective measure in the prevention of gastric cancer. PMID:24892619

  1. Gastric cáncer: Overview.

    PubMed

    Piazuelo, M Blanca; Correa, Pelayo

    2013-07-01

    Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidence in some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases being diagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations. Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and in a small percentage of patients, a familial genetic component. More than 95% of stomach cancer cases are adenocarcinomas, which are classified into two major histologic types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a sequence of gastric lesions known as Correa´s cascade and is the histologic type associated with the global decrease in gastric cancer rates. Diffuse type adenocarcinomas have a more aggressive behavior and worse prognosis than those of the intestinal type. According to the anatomical location, adenocarcinomas are classified as proximal (originating in the cardia) and distal (originating in the body and antrum). This classification seems to recognize two different clinical entities. Surgical resection of the tumor at an early stage is the only effective treatment method. Therefore, the identification and surveillance of patients at risk may play a significant role in survival rates. Anti-Helicobacter pylori therapy has been shown to be an effective measure in the prevention of gastric cancer.

  2. Clinical Efficacy of Endoscopic Submucosal Dissection for Adenocarcinomas of the Esophagogastric Junction

    PubMed Central

    Nagami, Yasuaki; Machida, Hirohisa; Shiba, Masatsugu; Obayashi, Tomoko; Ominami, Masaki; Fukunaga, Shusei; Sugimori, Satoshi; Yamagami, Hirokazu; Tanigawa, Tetsuya; Watanabe, Kenji; Watanabe, Toshio; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2014-01-01

    Background and Study Aims There are a few reports about the efficacy of endoscopic submucosal dissection (ESD) for adenocarcinomas of the esophagogastric junction (EGJ). However, there is no detailed analysis that divides EGJ cancers into Barrett’s adenocarcinoma and gastric cardia adenocarcinoma. The aim of this study was to analyze the efficacy of ESD for EGJ cancers, comparing these two adenocarcinomas. Patients and Methods This study included 43 patients who underwent ESD for type II EGJ cancers between 2004 and 2011. Pathological examination of resected specimens confirmed 14 cases of Barrett’s adenocarcinoma and 29 cases of gastric cardia adenocarcinoma. Cutting margins on the oral side were placed 1 cm from the squamocolumnar junction, or 1 cm away from the slight elevation that is an endoscopic sign of subsquamous carcinoma extension. Clinical outcomes, prevalence and length of subsquamous carcinoma extension, and long-term outcomes were compared between these two types of adenocarcinoma. Results No significant differences in clinical outcomes were found between these two types of adenocarcinoma (en bloc, 100 % versus 100 %; complete, 100 % versus 89.7 %; curative, 85.7 % versus 75.9 %). No serious adverse events were encountered. The prevalence of subsquamous carcinoma extension was significantly higher in Barrett’s adenocarcinoma compared with gastric cardia adenocarcinoma. Local and distant recurrence were not observed in any cases with curative resection during the follow-up period (1.6 – 87.6 months). Conclusion ESD for EGJ cancers, including both Barrett’s adenocarcinoma and gastric cardia adenocarcinoma, was efficient and useful. ESD with a 1 cm safety margin may be acceptable for EGJ cancers. PMID:26134607

  3. Inhibition of Gastric Tumor Cell Growth Using Seed-targeting LNA as Specific, Long-lasting MicroRNA Inhibitors.

    PubMed

    Staedel, Cathy; Varon, Christine; Nguyen, Phu Hung; Vialet, Brune; Chambonnier, Lucie; Rousseau, Benoît; Soubeyran, Isabelle; Evrard, Serge; Couillaud, Franck; Darfeuille, Fabien

    2015-07-07

    MicroRNAs regulate eukaryotic gene expression upon pairing onto target mRNAs. This targeting is influenced by the complementarity between the microRNA "seed" sequence at its 5' end and the seed-matching sequences in the mRNA. Here, we assess the efficiency and specificity of 8-mer locked nucleic acid (LNA)-modified oligonucleotides raised against the seeds of miR-372 and miR-373, two embryonic stem cell-specific microRNAs prominently expressed in the human gastric adenocarcinoma AGS cell line. Provided that the pairing is perfect over all the eight nucleotides of the seed and starts at nucleotide 2 or 1 at the microRNA 5' end, these short LNAs inhibit miR-372/373 functions and derepress their common target, the cell cycle regulator LATS2. They decrease cell proliferation in vitro upon either transfection at nanomolar concentrations or unassisted delivery at micromolar concentrations. Subcutaneously delivered LNAs reduce tumor growth of AGS xenografts in mice, upon formation of a stable, specific heteroduplex with the targeted miR-372 and -373 and LATS2 upregulation. Their therapeutic potential is confirmed in fast-growing, miR-372-positive, primary human gastric adenocarcinoma xenografts in mice. Thus, microRNA silencing by 8-mer seed-targeting LNAs appears a valuable approach for both loss-of-function studies aimed at elucidating microRNA functions and for microRNA-based therapeutic strategies.

  4. [Hyperplastic polyp with neoplastic transformation in a patient with atrophic gastritis and multiple gastric neuroendocrine tumors].

    PubMed

    Moura, E G H; Domingos, T A; Alvarado, H; Iriya, K; Kishi, H S; Martins, B C; Moura, E T H; P, P Sakai

    2012-01-01

    Hyperplastic gastric polyps are often found at GI endoscopy and are not considered premalignant lesions, although some cases of malignancy have been reported. Neuroendocrine tumors, conversely, are rare and account for approximately 1% to 2% of gastric polyps. Both hyperplastic gastric polyps and neuroendocrine tumors are related to gastric atrophy. The case of a hyperplastic polyp with multifocal areas of adenocarcinoma within the polyp associated to multiple gastric neuroendocrine tumors is reported.

  5. Effect of Rumex Aquaticus Herba Extract Against Helicobacter pylori-Induced Inflammation in Gastric Epithelial Cells.

    PubMed

    Han, Jeong Hoon; Khin, Phyu Phyu; Sohn, Uy Dong

    2016-01-01

    The purposes of this study were to examine the characteristics of Helicobacter pylori and the effect of Rumex Aquaticus Herba extract on the expression of cytokines in H. pylori-infected gastric epithelial cells. Cultured human adenocarcinoma gastric cells (AGS) were infected by H. pylori in RPMI 1640 media. Cell growth was measured by trypan blue assay. Western blot analysis was performed to investigate effect of extract containing Quercetin-3-O-β-d-glucuronopyranoside (ECQ) on the expression of inflammatory factors and the inhibition on cell growth. Furthermore, we compared the inhibitory effects with various combinations of clarithromycin, amoxicillin, omeprazole, and ECQ. The urease test with Christensen's Urea Agar was performed to identify the urease activity of H. pylori and the effect ECQ has on urease activity. When the cells were exposed to H. pylori, the trypan blue assay revealed a decrease in the rate of cell growth. Western blot analysis showed that H. pylori-infected cells had increased levels of degraded IκB-α and inflammatory factors. Pretreatment with ECQ inhibited interleukin expression induced by H. pylori in a dose-dependent manner. A combination of ECQ and antibiotics inhibited cytokine expression more effectively than other treatments. H. pylori displayed significant urease activity. ECQ did not significantly inhibit urease activity. These data suggest that H. pylori infection has cytotoxic effects against AGS cells, and ECQ may inhibit the production of proinflammatory cytokines in H. pylori-infected AGS cells. PMID:26580421

  6. Effect of Rumex Aquaticus Herba Extract Against Helicobacter pylori-Induced Inflammation in Gastric Epithelial Cells.

    PubMed

    Han, Jeong Hoon; Khin, Phyu Phyu; Sohn, Uy Dong

    2016-01-01

    The purposes of this study were to examine the characteristics of Helicobacter pylori and the effect of Rumex Aquaticus Herba extract on the expression of cytokines in H. pylori-infected gastric epithelial cells. Cultured human adenocarcinoma gastric cells (AGS) were infected by H. pylori in RPMI 1640 media. Cell growth was measured by trypan blue assay. Western blot analysis was performed to investigate effect of extract containing Quercetin-3-O-β-d-glucuronopyranoside (ECQ) on the expression of inflammatory factors and the inhibition on cell growth. Furthermore, we compared the inhibitory effects with various combinations of clarithromycin, amoxicillin, omeprazole, and ECQ. The urease test with Christensen's Urea Agar was performed to identify the urease activity of H. pylori and the effect ECQ has on urease activity. When the cells were exposed to H. pylori, the trypan blue assay revealed a decrease in the rate of cell growth. Western blot analysis showed that H. pylori-infected cells had increased levels of degraded IκB-α and inflammatory factors. Pretreatment with ECQ inhibited interleukin expression induced by H. pylori in a dose-dependent manner. A combination of ECQ and antibiotics inhibited cytokine expression more effectively than other treatments. H. pylori displayed significant urease activity. ECQ did not significantly inhibit urease activity. These data suggest that H. pylori infection has cytotoxic effects against AGS cells, and ECQ may inhibit the production of proinflammatory cytokines in H. pylori-infected AGS cells.

  7. Gastric Cancer in the Excluded Stomach 10 Years after Gastric Bypass

    PubMed Central

    Tinoco, Augusto; Gottardi, Lorena F.; Boechat, Eduardo D.

    2015-01-01

    According to the Brazilian health authorities, around 2,000 new cases of gastric cancer emerge in Brazil per year (Instituto Nacional de Câncer José Alencar Gomes da Silva, 2014). Indeed, gastric cancer constitutes the second most common cause of cancer-related mortality worldwide and 95% of such malignancies are adenocarcinomas (De Roover et al., 2006, and Clark et al., 2006). Roux-en-Y gastric bypass (RYGB) is a procedure frequently employed in bariatric surgery but restricted access to the excluded stomach means that discovery of gastric lesions is difficult, and diagnosis and treatment may be delayed. We report herein a case of gastric adenocarcinoma in the excluded stomach of a patient submitted to RYGB with the purpose of illustrating the difficulty of diagnosing and treating this rare condition. PMID:26229705

  8. α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells.

    PubMed

    Choi, Ji Hyun; Cho, Soon Ok; Kim, Hyeyoung

    2016-01-01

    The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. α-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether α-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-κB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without α-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-κB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-κB in AGS cells, which was inhibited by α-lipoic acid. In conclusion, α-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation.

  9. α-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-κB in H. pylori-Infected Gastric Epithelial AGS Cells

    PubMed Central

    Choi, Ji Hyun; Cho, Soon Ok

    2016-01-01

    The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. α-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether α-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-κB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without α-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-κB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-κB in AGS cells, which was inhibited by α-lipoic acid. In conclusion, α-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation. PMID:26632410

  10. The clinicopathological features and prognostic factors of gastric squamous cell carcinoma.

    PubMed

    Dong, Caixia; Jiang, Mengjie; Tan, Yinuo; Kong, Yiyao; Yang, Ziru; Zhong, Chenhan; Li, Dan; Yuan, Ying

    2016-08-01

    Primary gastric squamous cell carcinoma (SCC) is an exceedingly rare disease. We increased the understanding of gastric SCC and evaluated prognostic factors of gastric SCC.In this large-population cohort study, we retrospectively collected 163 primary gastric SCC and 66,209 primary gastric adenocarcinoma cases from the surveillance, epidemiology, and end results program (SEER) database from 1988 to 2012. The Chi-squared test demonstrated the distributed differences. Cox proportional hazards regression model was used to evaluate the prognostic factors.Gastric SCC accounted for 0.2% of all the primary gastric cancer cases. The mean age of patients with gastric SCC was 69.6 years old, and the man-to-woman ratio was 2.3:1. The proportion of black was higher in gastric SCC than gastric adenocarcinoma (P < 0.001). Almost half of the gastric SCCs were diagnosed in stage IV and more than half were poorly differentiated. In gastric SCC, the median survival was 8.0 months and the 5-year overall survival (OS) was 32.7%; in gastric adenocarcinoma the median survival rate was 19.0 months and the 5-year OS was 35.4%. The multivariate analysis showed that number of primary lesions, tumor location, grade, and stage were independent prognostic factors in gastric SCC. The tumor stage was the most important prognostic factor.Primary gastric SCC is exceedingly rare. Compared with gastric adenocarcinoma, gastric SCC was more frequent in black patients and was usually diagnosed when it was poorly differentiated and at a later stage. On the whole, gastric SCC has a poorer outcome. Disease stage is likely a key determinant in survival. PMID:27559983

  11. Helicobacter pylori infection in patients with early gastric cancer by the endoscopic phenol red test

    PubMed Central

    Iseki, K; Tatsuta, M; Iishi, H; Baba, M; Ishiguro, S

    1998-01-01

    Background—An endoscopic procedure that uses a pH indicator called phenol red to assess Helicobacter pylori infected gastric mucosa has recently been developed. This test makes it possible to take biopsy specimens from H pylori infected areas. 
Aim—This test was applied to patients with early gastric cancers to clarify the role of H pylori in gastric carcinogenesis. 
Subjects—Sixty five patients with early gastric cancer (50 with differentiated adenocarcinoma and 15 with undifferentiated adenocarcinoma). 
Methods—Patients with early gastric cancer underwent the endoscopic phenol red test before their operation. In this test, areas infected with H pylori can be observed as "coloured" areas where phenol red was turned from yellow to red. 
Results—H pylori infection was significantly (p<0.001) more frequent in patients with differentiated adenocarcinomas than in those with undifferentiated adenocarcinomas. Differentiated adenocarcinomas were usually located in areas of mucosa infected with H pylori, but undifferentiated adenocarcinomas were frequently located in non-infected areas. 
Conclusion—H pylori may be a strong risk factor for differentiated early gastric cancer. 

 Keywords: endoscopic phenol red test; Helicobacter pylori; gastric cancer; differentiated adenocarcinoma; high risk factor PMID:9505880

  12. MicroRNA-373 is upregulated and targets TNFAIP1 in human gastric cancer, contributing to tumorigenesis.

    PubMed

    Zhang, Xiaoting; Li, Xiaofeng; Tan, Zhiwen; Liu, Xizhi; Yang, Celi; Ding, Xiaofeng; Hu, Xiang; Zhou, Jianlin; Xiang, Shuanglin; Zhou, Chang; Zhang, Jian

    2013-11-01

    The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Previous studies have shown that miRNA-372 plays crucial roles in gastric tumorigenesis by targeting the mRNA of tumor necrosis factor, α-induced protein 1 (TNFAIP1). The present study showed that miR-373 is upregulated in gastric adenocarcinoma tissue and gastric carcinoma cell lines when compared to normal gastric tissues. The overexpression of miR-373 in the gastric cancer cells increased cell proliferation. A bioinformatics search revealed a conserved target site within the 3' untranslated region (UTR) of TNFAIP1, an immediate-early response gene of the endothelium induced by TNF-α. The overexpression of miR-373 caused the suppression of a luciferase reporter containing the TNFAIP1 3'UTR in the HEK293 cells and reduced the levels of TNFAIP1 protein in the AGS cells. The mRNA levels of TNFAIP1 in the gastric cancer and normal gastric tissues were negatively correlated with the expression levels of miR-373 in these tissues. Moreover, the knockdown of TNFAIP1 had a similar effect to the overexpression of miR-373. The overexpression of TNFAIP1 may partly rescue the inhibition of proliferation caused by the inhibitor, miR-373-ASO. Taken together, these findings demonstrate an oncogenic role for miR-373, similar to that of miR-372, in controlling cell growth through the downregulation of TNFAIP1.

  13. Update on gastric lymphoma.

    PubMed Central

    Thomas, C. R.

    1991-01-01

    Primary gastrointestinal lymphoma is an uncommon entity that can often present like classic adenocarcinoma. The most common organ site involved is the stomach. Important prognostic indicators include location of lymph node involvement, histologic subtype, lymphocyte lineage, gross size, and location of the tumor. Surgical resection is the mainstay of curative therapy. Combination chemotherapy and radiotherapy may have a role either separately or as part of a multimodality treatment program. Clinicians are encouraged to enter patients with primary gastric lymphoma into multi-institutional, cooperative group clinical trials to more clearly define the best treatment strategy. PMID:1956083

  14. Gastric Perforation Following Prophylactic Embolization of Right Gastric and Gastroduodenal Arteries Prior to Selective Internal Radiation Therapy.

    PubMed

    Shukla, Pratik A; Ahuja, Jitesh; Kurli, Vineel; Patel, Rajesh I; Kozuch, Peter S

    2015-12-01

    Prophylactic gastroduodenal artery (GDA) and right gastric artery (RGA) embolization for prevention of gastric ulceration in patients with hepatic metastases from colorectal cancer undergoing Selective Internal Radiation Therapy (SIRT) are relatively safe. Herein, we present a case of gastric perforation following prophylactic embolization of the GDA and RGA for SIRT in a 43-year-old male with sigmoid colon adenocarcinoma and multiple hepatic metastases.

  15. [Lymphoma of the residual gastric stump].

    PubMed

    La Torre, F; Nicastro, A; Crescenzi, U; Persico Stella, L; Clarioni, A; Pontone, P; Montori, A

    1993-03-01

    The authors report a case of non-Hodgkin's lymphoma (lymphoplasmocytoid type) arisen on the gastric stump of a patient operated 18 years before according to Billroth II gastric resection for peptic ulcer. They underline the extraordinary rarity of the event because this type of neoplasia never arises on the gastric stump, where would be more likely to find, due to irritative chemical stimuli of the biliary reflux, phenomena of intestinal metaplasia or severe dysplasia highly predisposing to adenocarcinomas. Furthermore, they stress the importance of a "deep" bioptic examination for a diagnosis as early as possible of this type of pathology.

  16. PIVKA-II-producing advanced gastric cancer.

    PubMed

    Takano, Shigetsugu; Honda, Ichiro; Watanabe, Satoshi; Soda, Hiroaki; Nagata, Matsuo; Hoshino, Isamu; Takenouchi, Toshinao; Miyazaki, Masaru

    2004-08-01

    We describe the case of a 68-year-old man with primary advanced adenocarcinoma of the stomach, who displayed extremely high plasma levels of protein induced by vitamin K antagonist (PIVKA)-II (15 600 mAU/ml) and normal levels of alphafetoprotein (AFP) (4 ng/ml). Ultrasonography and dynamic computed tomography ruled out hepatocellular carcinoma (HCC) or liver metastasis. After preoperative chemotherapy, pancreatico-spleno total gastrectomy with D2 lymphadenectomy was performed. Postoperatively, plasma levels of PIVKA-II returned to within the normal range (29 mAU/ml). Microscopic examination revealed stomach adenocarcinoma showing various histological types, such as moderately to poorly differentiated mucinous adenocarcinoma, but hepatoid differentiation of gastric adenocarcinoma was not detected. Localization of PIVKA-II and AFP within tumor cells was demonstrated by immunohistochemical staining using monoclonal antibodies. These results indicate that tumor cells from gastric cancer may produce PIVKA-II. Some cases of PIVKA-II- and AFP-producing advanced gastric cancer with liver metastasis have been reported, but this is the first report of gastric cancer without liver metastasis producing PIVKA-II alone.

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

    PubMed Central

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

    2016-01-01

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

  18. CDX2 can be regulated through the signalling pathways activated by IL-6 in gastric cells.

    PubMed

    Cobler, Lara; Pera, Manuel; Garrido, Marta; Iglesias, Mar; de Bolós, Carme

    2014-09-01

    The inflammatory infiltrate of the gastric mucosa associated with Helicobacter pylori infection increases the presence of the pro-inflammatory cytokine IL-6 that activates both the SHP-2/ERK/MAPK and the JAK/STAT signalling pathways. Furthermore, the ectopic expression of CDX2 is detected in pre-neoplasic lesions associated with decreased levels of SOX2, and we found that in gastric adenocarcinomas their expression is inversely correlated. To determine the role of IL-6 in the regulation of CDX2, MKN45 that constitutively expresses p-STAT3, and NUGC-4 gastric cancer cell lines were treated with IL-6, which induced the CDX2 up-regulation and SOX2 down-regulation. ChIP assays determined that in IL-6-treated cells, c-JUN and p-STAT3 bound to CDX2 promoter in MKN45 cells whereas in NUGC-4 cells, p-STAT3 binds to and c-JUN releases from the CDX2 promoter. Specific inhibition of STAT3 and ERK1/2 phosphorylation through AG490 and U0126, respectively, and STAT3 down-regulation using shRNA verified that the SHP-2/ERK/MAPK pathway regulates the expression of CDX2 in basal conditions, and the CDX2 up-regulation by IL-6 is through the JAK/STAT pathway in NUGC-4 cells whereas in MKN45 cells both pathways contribute to the CDX2 up-regulation. In conclusion, the signalling pathways activated by IL-6 have a crucial role in the regulation of CDX2 that is a key factor in the process of gastric carcinogenesis, suggesting that the inflammatory infiltrate in the gastric mucosa is relevant in this process and a potential target for new therapeutic approaches. PMID:24953186

  19. Helicobacter pylori, Cancer, and the Gastric Microbiota.

    PubMed

    Wroblewski, Lydia E; Peek, Richard M

    2016-01-01

    Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer. PMID:27573782

  20. Association of MMP7 -181A→G Promoter Polymorphism with Gastric Cancer Risk: INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB).

    PubMed

    Kesh, Kousik; Subramanian, Lakshmi; Ghosh, Nillu; Gupta, Vinayak; Gupta, Arnab; Bhattacharya, Samir; Mahapatra, Nitish R; Swarnakar, Snehasikta

    2015-06-01

    Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to play a pivotal role in cancer invasion. The -181A→G (rs11568818) polymorphism in the MMP7 promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of -181A→G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n = 520). The GG genotype as compared with the AA genotype was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p = 0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis revealed that tobacco enhanced the risk for cancer more markedly in AG and GG carriers. Activity and expression of MMP7 were significantly higher in GG than in AA carriers. In support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine-induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the -181G than the -181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer.

  1. [Genetic factors in gastric carcinogenesis].

    PubMed

    Ohgaki, H

    1983-02-01

    Genetic control of susceptibility of rats to gastro-carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI strain rats, resistant Buffalo strain rats, and their F1 and F2 offsprings. Rats were given MNNG at a concentration of 83 micrograms/ml in drinking water for 32 weeks and sacrificed on week 72. The incidence of gastric adenocarcinomas in F1 was as low as that in Buffalo rats. The results showed that susceptibility to MNNG was controlled genetically and that the resistance of Buffalo strain rats was autosomal dominant. To clarify the mechanisms which determine susceptibility to MNNG, some biochemical parameters such as pH of gastric juice, glutathione content in the gastric mucosa and the binding of MNNG to DNA, were analysed. No difference was observed between ACI and Buffalo strains in regard to the events leading to the binding of MNNG to DNA.

  2. 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.

  3. A randomized Phase II trial of systemic chemotherapy with and without trastuzumab followed by surgery in HER2-positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301 (Trigger Study).

    PubMed

    Kataoka, Kozo; Tokunaga, Masanori; Mizusawa, Junki; Machida, Nozomu; Katayama, Hiroshi; Shitara, Kohei; Tomita, Toshihiko; Nakamura, Kenichi; Boku, Narikazu; Sano, Takeshi; Terashima, Masanori; Sasako, Mitsuru

    2015-11-01

    Pre-operative chemotherapy with S-1 plus cisplatin is considered to be acceptable as one of the standard treatment options for gastric cancer patients with extensive lymph node metastases in Japan. Addition of trastuzumab to chemotherapy is shown to be effective for HER2-positive advanced gastric cancer patients, and we have commenced a randomized Phase II trial in March 2015 to evaluate S-1 plus cisplatin plus trastuzumab compared with S-1 plus cisplatin alone in the neoadjuvant setting for HER2-positive gastric cancer patients with ELM, which are followed by adjuvant chemotherapy with S-1 for 1 year. A total of 130 patients will be accrued from 41 Japanese institutions over 3 years. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, proportion of patients with R0 resection, proportion of patients who complete the pre-operative chemotherapy and surgery, proportion of patients who complete the protocol treatment including post-operative chemotherapy, pathological response rate and adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN 000016920.

  4. Solitary AFP- and PIVKA-II-producing hepatoid gastric cancer with giant lymph node metastasis.

    PubMed

    Iso, Yukihiro; Sawada, Tokihiko; Shimoda, Mitsugi; Rokkaku, Kyu; Ohkura, Yasuo; Kubota, Keiichi

    2005-01-01

    A 61-year-old man was admitted to our hospital because of abdominal pain and an abdominal mass. The patient had anemia and elevated serum alpha-fetoprotein (AFP) (9630ng/mL) and PIVKA-II (91mAU/mL) levels. Roentgenographic examination revealed an extra-gastric tumor in the upper abdomen, and gastroscopy revealed Bormann type 2 gastric cancer in the lower portion of the stomach. The preoperative diagnosis was synchronous gastric cancer and hepatocellular carcinoma (HCC), and surgery was performed. The extra-gastric tumor appeared to be an extra-hepatically growing HCC because the tumor was fed by vessels ramifying from the umbilical portion of the liver. Distal gastrectomy with resection of the extra-gastric tumor was performed, and histological examination of the resected specimen revealed that the gastric cancer was an AFP-producing hepatoid gastric adenocarcinoma and that the extra-gastric tumor was a lymph node metastasis. AFP-producing hepatoid gastric adenocarcinoma tends to metastasize to the regional lymph nodes and form a giant tumor. A giant tumor in the upper abdomen associated with gastric cancer may therefore be a clinical manifestation of AFP-producing hepatoid gastric adenocarcinoma.

  5. PSMB8 and PBK as potential gastric cancer subtype-specific biomarkers associated with prognosis

    PubMed Central

    Kwon, Chae Hwa; Park, Hye Ji; Choi, Yu Ri; Kim, Ahrong; Kim, Hye Won; Choi, Jin Hwa; Hwang, Chung Su; Lee, So Jung; Choi, Chang In; Jeon, Tae Yong; Kim, Dae Hwan; Kim, Gwang Ha; Park, Do Youn

    2016-01-01

    Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers. PMID:26894977

  6. An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach

    SciTech Connect

    Kim, Sung; Lim, Do Hoon; Lee, Jeeyun; Kang, Won Ki . E-mail: wkkang@smc.samsung.co.kr; MacDonald, John S.; Park, Chan Hyung; Park, Se Hoon; Lee, Se-Hoon; Kim, Kihyun; Park, Joon Oh; Kim, Won Seog; Jung, Chul Won; Park, Young Suk; Im, Young-Hyuck; Sohn, Tae Sung; Noh, Jae Hyung; Heo, Jin Seok; Kim, Yong Il; Park, Chul Keun; Park, Keunchil

    2005-12-01

    Purpose: The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric-cancer patients has not been defined yet. We investigated the effect of postoperative chemoradiotherapy on the relapse rate and survival rate of patients with D2-resected gastric cancer. Methods and Materials: From August 1995 to April 2001, 544 patients received postoperative CRT after curative D2 resection. During the same period of time, 446 patients received surgery without further adjuvant treatment. The adjuvant CRT consisted of 400 mg/m{sup 2} of fluorouracil plus 20 mg/m{sup 2} of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy. Results: The median duration of overall survival was significantly longer in the CRT group than in the comparison group (95.3 months vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p = 0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year survival rates were consistently longer in the CRT group at Stages II, IIIA, IIIB, and IV than those in the comparison group. The CRT was associated with increases in the median duration of relapse-free survival (75.6 months vs. 52.7 months; hazard ratio for relapse, 0.80, p = 0.0160). Conclusion: Our results highly suggest that the postoperative chemoradiotherapy in D2-resected gastric-cancer patients can prolong survival and decrease recurrence.

  7. Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus?

    PubMed

    Khor, Tze Sheng; Alfaro, Eduardo E; Ooi, Esther M M; Li, Yuan; Srivastava, Amitabh; Fujita, Hiroshi; Park, Youn; Kumarasinghe, Marian Priyanthi; Lauwers, Gregory Yves

    2012-03-01

    Dysplasia in Barrett esophagus has been recognized to be morphologically heterogenous, featuring adenomatous, foveolar, and hybrid phenotypes. Recent studies have suggested a tumor suppressor role for CDX-2 in the metaplasia-dysplasia-carcinoma sequence. The phenotypic stability and role of CDX-2 in the neoplastic progression of different types of dysplasias have not been evaluated. Thirty-eight endoscopic mucosal resections with dysplasia and/or intramucosal carcinoma (IMC) arising in Barrett esophagus were evaluated for the expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2. The background mucosa was also evaluated. The results were correlated with morphologic classification and clinicopathologic parameters. Of 38 endoscopic mucosal resections, 23 had IMC and dysplasia, 8 had IMC only, and 7 had dysplasia only. Among dysplastic lesions, 73% were foveolar, 17% were adenomatous, and 10% were hybrid. Twenty of 23 cases with dysplasia and adjacent IMC showed an identical immunophenotype of dysplasia and IMC comprising 16 gastric, 3 intestinal, and 1 mixed immunophenotype. Three cases showed discordance of dysplasia and IMC immunophenotype. These findings suggest that most Barrett-related IMC cases are either gastric or intestinal, with phenotypic stability during progression supporting separate gastric and intestinal pathways of carcinogenesis. CDX-2 showed gradual downregulation of expression during progression in adenomatous dysplasia but not in foveolar or hybrid dysplasia, supporting a tumor suppressor role, at least in the intestinal pathway. CDX-2 was also found to be expressed to a greater degree in intestinal metaplasia compared with nonintestinalized columnar metaplasia. Consistent with CDX-2 as a tumor suppressor, this suggests that nonintestinalized columnar metaplasia may be an unstable intermediate state at risk for neoplastic progression.

  8. Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells

    PubMed Central

    Byun, Eunyoung; Park, Bohye; Lim, Joo Weon

    2016-01-01

    Purpose In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. Materials and Methods Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. Results H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. Conclusion H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells. PMID:26996564

  9. Laparoscopic gastric banding

    MedlinePlus

    ... adjustable gastric banding; Bariatric surgery - laparoscopic gastric banding; Obesity - gastric banding; Weight loss - gastric banding ... gastric banding is not a "quick fix" for obesity. It will greatly change your lifestyle. You must ...

  10. Endoscopic Submucosal Dissection for Early Gastric Cancers with Uncommon Histology

    PubMed Central

    Kim, Gwang Ha

    2016-01-01

    Endoscopic submucosal dissection (ESD) enables en bloc curative resection of early gastric cancers (EGCs) with a negligible risk of lymph node metastasis (LNM). Although ESD for EGCs with absolute and expanded indications is safe, the results differ between EGCs with specialized and common histologies. EGC with papillary adenocarcinoma is a differentiated-type adenocarcinoma. At present, it is treated with ESD according to the same criteria as other differentiated-type adenocarcinomas. The LNM rate under the current indication criteria is high, and over half of the patients who undergo ESD as a primary treatment for EGC with papillary adenocarcinoma achieve an out-of-ESD result. Gastric carcinoma with lymphoid stroma in EGC has a low LNM rate and a favorable outcome, despite deep submucosal invasion. Patients with this gastric cancer subtype may be good candidates for ESD, even with deep submucosal invasion. Large-scale prospective multi-center studies with longer follow-up periods are needed to set proper ESD criteria for these tumors. Clinicians should be aware of these disease entities and ESD should be more carefully considered for EGCs with papillary adenocarcinoma and gastric carcinoma with lymphoid stroma. PMID:27744663

  11. Fractal Analysis and the Diagnostic Usefulness of Silver Staining Nucleolar Organizer Regions in Prostate Adenocarcinoma

    PubMed Central

    Stepan, Alex; Simionescu, Cristiana; Pirici, Daniel; Ciurea, Raluca; Margaritescu, Claudiu

    2015-01-01

    Pathological diagnosis of prostate adenocarcinoma often requires complementary methods. On prostate biopsy tissue from 39 patients including benign nodular hyperplasia (BNH), atypical adenomatous hyperplasia (AAH), and adenocarcinomas, we have performed combined histochemical-immunohistochemical stainings for argyrophilic nucleolar organizer regions (AgNORs) and glandular basal cells. After ascertaining the pathology, we have analyzed the number, roundness, area, and fractal dimension of individual AgNORs or of their skeleton-filtered maps. We have optimized here for the first time a combination of AgNOR morphological denominators that would reflect best the differences between these pathologies. The analysis of AgNORs' roundness, averaged from large composite images, revealed clear-cut lower values in adenocarcinomas compared to benign and atypical lesions but with no differences between different Gleason scores. Fractal dimension (FD) of AgNOR silhouettes not only revealed significant lower values for global cancer images compared to AAH and BNH images, but was also able to differentiate between Gleason pattern 2 and Gleason patterns 3–5 adenocarcinomas. Plotting the frequency distribution of the FDs for different pathologies showed clear differences between all Gleason patterns and BNH. Together with existing morphological classifiers, AgNOR analysis might contribute to a faster and more reliable machine-assisted screening of prostatic adenocarcinoma, as an essential aid for pathologists. PMID:26366372

  12. Serum biomarker panels for diagnosis of gastric cancer

    PubMed Central

    Tong, Weihua; Ye, Fei; He, Liang; Cui, Lifeng; Cui, Miao; Hu, Yuan; Li, Wei; Jiang, Jing; Zhang, David Y; Suo, Jian

    2016-01-01

    Purpose Currently, serum biomarkers that are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinomas are not known. In this study, ten serum markers were assessed using the Luminex system and enzyme-linked immunosorbent assay for the diagnosis of gastric cancer and analysis of the relation between prognosis and metastases. Patients and methods A training set consisting of 228 gastric adenocarcinoma and 190 control samples was examined. A Luminex multiplex panel with nine biomarkers, consisting of three proteins discovered through our previous studies and six proteins previously reported to be cancer-associated, was constructed. One additional biomarker was detected using a commercial kit containing EDTA. Logistic regression, random forest (RF), and support vector machine (SVM) were used to identify the panel of discriminatory biomarkers in the training set. After selecting five proteins as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 57 gastric adenocarcinoma and 48 control samples. Results Serum pepsinogen I, serum pepsinogen II, A Disintegrin And Metalloproteinase domain-containing protein 8 (ADAM8), vascular endothelial growth factor (VEGF), and serum IgG to Helicobacter pylori were selected as classifiers in the three algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (RF 79.0%, SVM 83.8%, logistic regression 76.2%). These algorithms also differentiated the samples in the validation set (accuracy: RF 82.5%, SVM 86.1%, logistic regression 78.7%). Conclusion A panel of combinatorial biomarkers comprising VEGF, ADAM8, IgG to H. pylori, serum pepsinogen I, and pepsinogen II were developed. The use of biomarkers is a less invasive method for the diagnosis of

  13. Diagnosis and Management of High Risk Group for Gastric Cancer

    PubMed Central

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

  14. Diagnosis and management of high risk group for gastric cancer.

    PubMed

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval.

  15. Immunotherapy for gastric premalignant lesions and cancer.

    PubMed

    Zorzetto, Valerio; Maddalo, Gemma; Basso, Daniela; Farinati, Fabio

    2012-06-01

    Chronic atrophic gastritis, a precancerous change for gastric cancer, shows a loss of appropriate glands, Helicobacter pylori infection and autoimmune gastritis being the two main etiologic factors. While H. pylori eradication is the mandatory treatment for the former, no etiologic treatment is available for the latter, in which a Th1-type response, modulated by Tregs and Th17 cells, is involved. H. pylori-related atrophic gastritis is a risk factor for gastric adenocarcinoma, while autoimmune atrophic gastritis is also linked to a substantial risk of gastric type I carcinoid, related to the chronic stimulus exerted by hypergastrinemia on enterochromaffin-like cells. Several studies have been published on gastric cancer treatment through an active specific immunotherapy, aimed at improving the immunoregulatory response and increasing the circulating tumor-specific T cells. No study on immunotherapy of carcinoids is available but, in our experience, the administration of an antigastrin 17 vaccine induced carcinoid regression in two out of three patients treated.

  16. Regulation of Noxa-mediated apoptosis in Helicobacter pylori–infected gastric epithelial cells

    PubMed Central

    Rath, Suvasmita; Das, Lopamudra; Kokate, Shrikant Babanrao; Pratheek, B. M.; Chattopadhyay, Subhasis; Goswami, Chandan; Chattopadhyay, Ranajoy; Crowe, Sheila Eileen; Bhattacharyya, Asima

    2015-01-01

    Helicobacter pylori induces the antiapoptotic protein myeloid cell leukemia 1 (Mcl1) in human gastric epithelial cells (GECs). Apoptosis of oncogenic protein Mcl1-expressing cells is mainly regulated by Noxa-mediated degradation of Mcl1. We wanted to elucidate the status of Noxa in H. pylori–infected GECs. For this, various GECs such as AGS, MKN45, and KATO III were either infected with H. pylori or left uninfected. The effect of infection was examined by immunoblotting, immunoprecipitation, chromatin immunoprecipitation assay, in vitro binding assay, flow cytometry, and confocal microscopy. Infected GECs, surgical samples collected from patients with gastric adenocarcinoma as well as biopsy samples from patients infected with H. pylori showed significant up-regulation of both Mcl1 and Noxa compared with noninfected samples. Coexistence of Mcl1 and Noxa was indicative of an impaired Mcl-Noxa interaction. We proved that Noxa was phosphorylated at Ser13 residue by JNK in infected GECs, which caused cytoplasmic retention of Noxa. JNK inhibition enhanced Mcl1-Noxa interaction in the mitochondrial fraction of infected cells, whereas overexpression of nonphosphorylatable Noxa resulted in enhanced mitochondria-mediated apoptosis in the infected epithelium. Because phosphorylation-dephosphorylation can regulate the apoptotic function of Noxa, this could be a potential target molecule for future treatment approaches for H. pylori–induced gastric cancer.—Rath, S., Das, L., Kokate, S. B., Pratheek, B. M., Chattopadhyay, S., Goswami, C., Chattopadhyay, R., Crowe, S. E., Bhattacharyya, A. Regulation of Noxa-mediated apoptosis in Helicobacter pylori–infected gastric epithelial cells. PMID:25404713

  17. Lymphoepithelioma-like gastric carcinoma: A case report and review of the literature

    PubMed Central

    Wang, Zhao-Hui; Zhao, Jun-Jun; Yuan, Zhao

    2016-01-01

    Lymphoepithelioma-like gastric carcinoma is a rare type of gastric cancer characterized by a carcinoma with intense stromal lymphocytic infiltration. Although lymphocytic infiltration is closely associated with Epstein-Barr virus (EBV) infection, concomitant occurrence with differentiated adenocarcinoma is relatively rare. The clinical manifestations of lymphoepithelioma-like gastric carcinoma (including EBV-positive and -negative forms) are similar to those of gastric cancer, and the diagnosis is based on pathologic, histologic, and immunohistochemical findings. This report describes the case of a 55-year-old female patient who presented with a 10-year history of recurrent and worsening abdominal pain and melena that had been occurring for 2 mo. An ulcerative lesion was detected in the stomach by endoscopic examination, which raised suspicion of early gastric cancer. A subsequent preoperative endoscopic biopsy showed adenocarcinoma, but the postoperative pathologic, histologic, and immunohistochemical analyses of the resected specimen revealed a final diagnosis of lymphoepithelioma-like gastric carcinoma. PMID:26973402

  18. Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells.

    PubMed

    Yuan, Chun-Xiu; Zhou, Zhi-Wei; Yang, Yin-Xue; He, Zhi-Xu; Zhang, Xueji; Wang, Dong; Yang, Tianxing; Pan, Si-Yuan; Chen, Xiao-Wu; Zhou, Shu-Feng

    2015-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide, with a poor response to current chemotherapy. Danusertib is a pan-inhibitor of the Aurora kinases and a third-generation Bcr-Abl tyrosine kinase inhibitor with potent anticancer effects, but its antitumor effect and underlying mechanisms in the treatment of human gastric cancer are unknown. This study aimed to investigate the effects of danusertib on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition and the molecular mechanisms involved in human gastric cancer AGS and NCI-N78 cells. The results showed that danusertib had potent growth-inhibitory, apoptosis-inducing, and autophagy-inducing effects on AGS and NCI-N78 cells. Danusertib arrested AGS and NCI-N78 cells in G2/M phase, with downregulation of expression of cyclin B1 and cyclin-dependent kinase 1 and upregulation of expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib induced mitochondria-mediated apoptosis, with an increase in expression of proapoptotic protein and a decrease in antiapoptotic proteins in both cell lines. Danusertib induced release of cytochrome c from the mitochondria to the cytosol and triggered activation of caspase 9 and caspase 3 in AGS and NCI-N78 cells. Further, danusertib induced autophagy, with an increase in expression of beclin 1 and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3-I) to LC3-II in both cell lines. Inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways as well as activation of 5' AMP-activated protein kinase contributed to the proautophagic effect of danusertib in AGS and NCI-N78 cells. SB202191 and wortmannin enhanced the autophagy-inducing effect of danusertib in AGS and NCI-N78 cells. In addition, danusertib inhibited epithelial to mesenchymal transition with an increase in expression of E-cadherin and a decrease in expression of

  19. Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells

    PubMed Central

    Yuan, Chun-Xiu; Zhou, Zhi-Wei; Yang, Yin-Xue; He, Zhi-Xu; Zhang, Xueji; Wang, Dong; Yang, Tianxing; Pan, Si-Yuan; Chen, Xiao-Wu; Zhou, Shu-Feng

    2015-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide, with a poor response to current chemotherapy. Danusertib is a pan-inhibitor of the Aurora kinases and a third-generation Bcr-Abl tyrosine kinase inhibitor with potent anticancer effects, but its antitumor effect and underlying mechanisms in the treatment of human gastric cancer are unknown. This study aimed to investigate the effects of danusertib on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition and the molecular mechanisms involved in human gastric cancer AGS and NCI-N78 cells. The results showed that danusertib had potent growth-inhibitory, apoptosis-inducing, and autophagy-inducing effects on AGS and NCI-N78 cells. Danusertib arrested AGS and NCI-N78 cells in G2/M phase, with downregulation of expression of cyclin B1 and cyclin-dependent kinase 1 and upregulation of expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib induced mitochondria-mediated apoptosis, with an increase in expression of proapoptotic protein and a decrease in antiapoptotic proteins in both cell lines. Danusertib induced release of cytochrome c from the mitochondria to the cytosol and triggered activation of caspase 9 and caspase 3 in AGS and NCI-N78 cells. Further, danusertib induced autophagy, with an increase in expression of beclin 1 and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3-I) to LC3-II in both cell lines. Inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways as well as activation of 5′ AMP-activated protein kinase contributed to the proautophagic effect of danusertib in AGS and NCI-N78 cells. SB202191 and wortmannin enhanced the autophagy-inducing effect of danusertib in AGS and NCI-N78 cells. In addition, danusertib inhibited epithelial to mesenchymal transition with an increase in expression of E-cadherin and a decrease in expression

  20. Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer

    PubMed Central

    Mizrak, Dilsa; Alkan, Ali; Erdogdu, Batuhan; Utkan, Gungor

    2015-01-01

    Osteogenesis imperfecta (OI) is a rare, inherited skeletal disorder characterized by abnormalities of type 1 collagen. Malignancy is rarely reported in patients with OI and it was suggested that this disease can protect against cancer. Here, we report a 41-year-old woman with symptoms of achalasia where repeated treatment of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy was given after assessing dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can be deficient in OI patients. This is the first report of gastric cancer mimicking achalasia in a patient with OI. PMID:25874139

  1. [Gastric lymphosarcoma associated with early carcinoma (type IIa)--a case report].

    PubMed

    Sawa, S; Kawaura, Y; Hirano, M; Yamada, T; Iwa, T

    1984-04-01

    We report a case of gastric lymphosarcoma associated with early carcinoma (type IIa). Lymphosarcoma was also seen in the small intestine, but there were no metastatic lesions in the lymph nodes , liver, and peritoneum. This suggest that lymphosarcoma was the primary cancer in both the stomach and small intestine. Microscopically, the early carcinoma was a moderately differentiated tubular adenocarcinoma . Only two earlier cases of coexistent gastric lymphosarcoma and early gastric carcinoma have been reported in the literature. PMID:6547189

  2. Immunomodulatory Effects of Psyllium Extract on Helicobacter pylori Interaction With Gastric Epithelial Cells.

    PubMed

    Yakoob, Javed; Jafri, Wasim; Mehmood, Malik Hassan; Abbas, Zaigham; Tariq, Kanwal

    2016-10-01

    Natural plant product Psyllium has anti-inflammatory activity that can modulate the function of cytokines. We determined the effect of Psyllium husk extract on interleukin (IL)-8 and NF-κB secretion by gastric epithelial cells in response to Helicobacter pylori Human gastric adenocarcinoma cell line (AGS) cells were pretreated with Psyllium extract in different concentrations before H pylori infection. Cell culture supernatant was analyzed for IL-8 and NF-κB by ELISA. RNA from cells was used for real-time polymerase chain reaction for messenger RNA expression of IL-8. Psyllium extract 5 and 10 μg/mL markedly (P < .001) lowered basal IL-8 by 64.71% and 74.51%, respectively, and H pylori-stimulated IL-8 was also (P < .001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10 μg/mL also reduced (P < .0001) cagA-positive H pylori-induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced (P = .0001) NF-κB in response to H pylori strains confirming its role as an anti-inflammatory agent.

  3. Syndromic Gastric Polyps: At the Crossroads of Genetic and Environmental Cancer Predisposition.

    PubMed

    Brosens, Lodewijk A A; Giardiello, Francis M; Offerhaus, G Johan; Montgomery, Elizabeth A

    2016-01-01

    Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare not primarily gastrointestinal syndromes. In addition, Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a recently described heritable syndrome characterized by isolated gastric polyposis and risk of gastric cancer.Some of these syndromes are associated with an increased risk of gastric cancer, whereas others are not. However, the neoplastic potential and the precursor status of these gastric polyps are not always clear, even in syndromes with a well-established risk of gastric cancer. For instance, the neoplastic potential of Peutz-Jeghers polyps is debatable, despite the well-established risk of gastric cancer in this syndrome. Also fundic gland polyps and gastric foveolar-type adenomas in FAP carry a low risk of malignant transformation. In contrast, gastric juvenile polyps are precursor lesions of gastric cancer in juvenile polyposis syndrome through neoplastic progression of juvenile polyps in these patients.Although these hereditary syndromes with gastric polyps are rare, recognition is important for individual patient management. Furthermore, the initiation and progression of these lesions can be influenced by environmental factors such as Helicobacter Pylori infection. This makes these rare lesions an appropriate model for understanding the clonal evolution of early gastric cancer in the wider population. PMID:27573780

  4. Role of PTCH1 gene methylation in gastric carcinogenesis.

    PubMed

    Zuo, Yun; Song, Yu; Zhang, Min; Xu, Zhen; Qian, Xiaolan

    2014-08-01

    The present study aimed to investigate the role of PTCH1 methylation in gastric carcinogenesis and the therapeutic effect of the methylation inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), in the treatment of gastric cancer. Total RNA was extracted from 20 gastric cancer tissues, their corresponding adjacent normal tissues and a gastric cancer AGS cell line. PTCH1 mRNA expression was detected by quantitative PCR, and the PTCH1 methylation of the promoter was examined by methylation-specific PCR. The AGS cells were treated with 5-Aza-dC; apoptosis and the cell cycle were examined by flow cytometry, and the PTCH1 methylation level was observed. PTCH1 expression was negatively correlated with promoter methylation in the gastric cancer tissues, their corresponding adjacent normal tissues and the gastric cancer AGS cell line (r=-0.591, P=0.006). 5-Aza-dC treatment caused apoptosis and the G0/G1 phase arrest of the AGS cells, and also induced the demethylation and increased expression of PTCH1. In conclusion, the study found that the hypermethylation of the PTCH1 gene promoter region is one of the main causes of low PTCH1 expression in AGS cells. Demethylation agent 5-Aza-dC can reverse the methylation status of PTCH1 and regulate the expression of PTCH1, indicating its potential role in gastric cancer treatment. PMID:25013484

  5. Isoprenaline Induces Periostin Expression in Gastric Cancer

    PubMed Central

    Liu, Guo-Xiao; Xi, Hong-Qing; Sun, Xiao-Yan; Geng, Zhi-Jun; Yang, Shao-Wei; Lu, Yan-Jie

    2016-01-01

    Purpose Periostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression. Materials and Methods Normal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting. Results Periostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of α-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress-related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. Conclusion These findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. PMID:26996552

  6. First reports of esophageal adenocarcinoma with white globe appearance in Japanese and Caucasian patients

    PubMed Central

    Tonai, Yusuke; Ishihara, Ryu; Yamasaki, Yasushi; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Tomita, Yasuhiko; Iishi, Hiroyasu

    2016-01-01

    Background and study aims: Better endoscopic diagnosis in case of Barrett’s esophagus is still needed. White globe appearance (WGA) is a novel endoscopic marker for gastric adenocarcinoma, with high sensitivity for differentiating between gastric cancer/high-grade dysplasia and other lesions. We report 2 cases of esophageal adenocarcinoma with WGA. In Case 1, esophagogastroduodenoscopy (EGD) revealed a 10-mm esophageal adenocarcinoma in a 48-year-old Japanese woman with short-segment Barrett’s esophagus. A small (< 1 mm) white globular lesion, typical of WGA, was observed under the epithelium by magnifying narrow-band imaging. A dilated neoplastic gland with eosinophilic material and necrotic epithelial fragments was identified at the site of the WGA by histologic examination. In Case 2, EGD revealed a 5-mm esophageal adenocarcinoma in a 60-year-old Caucasian man with long-segment Barrett’s esophagus. A typical WGA was observed by magnifying narrow-band imaging and similar histologic findings were identified at the site of the WGA. WGA could be a reliable endoscopic finding for target biopsy in esophageal adenocarcinoma, if its specificity is as high as in gastric cancer. The clinical implications of WGA in patients with Barrett’s esophagus should be investigated further. PMID:27747281

  7. Solid adenocarcinoma

    Cancer.gov

    Uniformly solid character of the lesions is usually indicative of a well differentiated tumor. No solid adenocarcinomas have observed in our series. However, rare cases have been described by others. In human pathology this diagnosis is usually based on detection of mucin after periodic acid-Schiff reaction with diastase (α-amylase) digestion.

  8. Adenocarcinoma of the prostrate

    SciTech Connect

    Bruce, A.W.; Trachtenberg, J.

    1987-01-01

    This books contains 13 chapters. Some of the chapter titles are: Imaging Techniques in the Diagnosis and Pelvic Staging of Prostatic Cancer; Interstitial Radiotherapy; The Case for External Beam Radiotherapy of Certain Adenocarcinomas of the Prostate; and Chemotherapy of Prostatic Cancer.

  9. 13-acetoxysarcocrassolide induces apoptosis on human gastric carcinoma cells through mitochondria-related apoptotic pathways: p38/JNK activation and PI3K/AKT suppression.

    PubMed

    Su, Ching-Chyuan; Chen, Jeff Yi-Fu; Din, Zhong-Hao; Su, Jui-Hsin; Yang, Zih-Yan; Chen, Yi-Jen; Wang, Robert Y L; Wu, Yu-Jen

    2014-10-01

    13-acetoxysarcocrassolide (13-AC), an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells) gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ΔΨm, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor) and SP600125 (a JNK-specific inhibitor) led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways. PMID:25342459

  10. Anti-tumor Activity of Ferulago angulata Boiss. Extract in Gastric Cancer Cell Line via Induction of Apoptosis

    PubMed Central

    Heidari, Shafagh; Akrami, Hassan; Gharaei, Roghaye; Jalili, Ali; Mahdiuni, Hamid; Golezar, Elham

    2014-01-01

    Ferulago angulata Boiss. known in Iran as Chavir, has some bioactive compounds having antioxidant activity. Because of its antioxidant activities, it sounded Chavir extract can be a good candidate for finding chemopreventive agents having inductive apoptosis properties on cancer cells. In this study, the cytotoxic effects and proapoptotic activities of Chavir’s leaf and flower extracts were investigated on human adenocarcinoma gastric cell line (AGS). The ferric reducing antioxidant power (FRAP) assay was used to determine antioxidant activity of the extract. Cytotoxic effects of the extract were performed by trypan blue and neutral red assays. For apoptosis detection, we used Annexin V staining, flow cytometry and DNA fragmentation assays. The FRAP assay results showed that antioxidant activity of leaf extract was higher than flower extract. Cytotoxicity and apoptosis–inducing activity of flower and leaf extracts changed coordinately, indicating the cytotoxicity of chavir extracts is due probably to induce apoptosis. Our results revealed that the cytotoxic effects of F. angulate Boiss. extracts on AGS cell line is close to some other plant extracts such as Rhus verniciflua Stokes (RVS) and Scutellaria litwinowii. This is the first study on cytotoxic and apoptosis–inducing effects of chavir leaf and flower extracts against AGS cell line. The Further investigation can be identification of the agent(s) by which these effects is observed. PMID:25587323

  11. Genetic control of susceptibility of rats to gastric carcinoma.

    PubMed

    Ohgaki, H; Kawachi, T; Matsukura, N; Morino, K; Miyamoto, M; Sugimura, T

    1983-08-01

    Genetic control of the induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI rats, resistant Buffalo rats, and their F1 and F2 offspring. Both sexes of all strains, initially 7 to 9 weeks old, were given MNNG at a concentration of 83 micrograms/ml in their drinking water for 32 weeks and were sacrificed at experimental Week 72. The incidence of gastric adenocarcinoma in ACI rats was 80% in males and 47% in females; in Buffalo rats, the incidence was 18% in males and 0% in females. F1 hybrids showed the same resistance to MNNG as did Buffalo rats; the incidence of gastric adenocarcinoma was 17% in males and 8% in females. These results suggest that resistance to induction of gastric adenocarcinoma by MNNG is a dominant characteristic. The incidence of gastric adenocarcinoma in the F2 generation was 36% in males and 14% in females, which is close to the 3:1 ratio expected from the segregation of a single resistant gene. In ACI and Buffalo strains and their hybrids, males were more susceptible than females to induction of gastric carcinoma by MNNG. Intestinal tumors were observed mainly in the duodenum and jejunum in both strains and their hybrids, and the incidences were as follows: ACI: males, 67% and females 42%; Buffalo: males, 12% and females, 18%; F1: males, 18% and females, 15%; and F2: males, 15% and females, 19%. Thus, there seems to be a common genetic basis for both gastric and intestinal carcinogenesis by MNNG.

  12. Gastric bypass surgery

    MedlinePlus

    ... Y gastric bypass; Gastric bypass - Roux-en-Y; Weight-loss surgery - gastric bypass; Obesity surgery - gastric bypass ... Weight-loss surgery may be an option if you are very obese and have not been able to ...

  13. [Analysis of the Cochrane Review: Helicobacter pylori Eradication for the Prevention of Gastric Neoplasia. Cochrane Database Syst Rev. 2015;7:CD005583].

    PubMed

    Libãnio, Diogo; Azevedo, Luís Filipe

    2015-01-01

    Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. Identification of individuals with this infection and its eradication may be considered as a primary prevention strategy to reduce the incidence of gastric adenocarcinoma; however, the magnitude of benefit and the effectiveness of this strategy are still unclear. A systematic review and meta-analysis of randomized clinical trials was conducted comparing the incidence of gastric adenocarcinoma in infected individuals submitted to Helicobacter pylori eradication and individuals not submitted to this therapy. The results of the six included randomized clinical trials (all conducted in countries with high gastric cancer incidence) suggest that Helicobacter pylori eradication is associated with a relative risk reduction of 34% in gastric cancer incidence. However, generalization of the results to countries with lower gastric cancer incidence should be cautious and the cost-effectiveness of this strategy in this context remains uncertain.

  14. Gastric Banding

    MedlinePlus

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

  15. Gastric suction

    MedlinePlus

    ... al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila) . 2013;51(3); 140-146. ... 2012:chap 49. Zeringe M, Fowler GC. Gastrointesinal decontamination. In: Pfenninger JL, Fowler GC, eds. Pfenninger & Fowler's ...

  16. Polymorphisms in TLR9 but not in TLR5 increase the risk for duodenal ulcer and alter cytokine expression in the gastric mucosa.

    PubMed

    Trejo-de la O, Alejandra; Torres, Javier; Sánchez-Zauco, Norma; Pérez-Rodríguez, Martha; Camorlinga-Ponce, Margarita; Flores-Luna, Lourdes; Lazcano-Ponce, Eduardo; Maldonado-Bernal, Carmen

    2015-10-01

    Colonization of the gastric mucosa by Helicobacter pylori can lead to peptic ulcer and gastric adenocarcinoma. TLRs are signaling receptors involved in the recognition of microorganisms, and polymorphisms in their genes may influence the innate and adaptive immune response to H. pylori, affecting the clinical outcomes of the infection. We assessed the association between single nucleotide polymorphisms in TLR9 and TLR5 and gastroduodenal diseases. All patients were genotyped by allelic discrimination in regions 1174C>T and 1775A>G of TLR5 and -1237T>C and 2848G>A of TLR9. The 2848A allele of TLR9 was more frequent in duodenal ulcer and showed an association of risk with this pathology. Polymorphisms in TLR5 were not found to be associated with disease. Patients with polymorphisms in TLR9 and TLR5 expressed significantly lower levels of IL-1β and TNF-α, whereas polymorphisms in TLR5 also decreased the expression of IL-6 and IL-10. Our findings suggest that 2848G>A polymorphism in TLR9 increases the risk for the development of duodenal ulcer probably by modifying the inflammatory response to H. pylori infection. This is the first study to show an association of 2848A allele of TLR9 with duodenal ulcer and with altered expression of inflammatory cytokines in the gastric mucosa.

  17. [Current standards in the treatment of gastric cancer].

    PubMed

    Hacker, Ulrich; Lordick, Florian

    2015-08-01

    Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option.

  18. Akt Inhibitor MK2206, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With Locally Advanced or Metastatic HER2-Positive Breast , Gastric, or Gastroesophageal Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2013-09-27

    Adenocarcinoma of the Gastroesophageal Junction; HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Breast Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  19. Immunohistochemical detection of gastric mucin in normal and disease states.

    PubMed

    Taylor, K L; Mall, A S; Barnard, R A; Ho, S B; Cruse, J P

    1998-01-01

    At least seven human mucin genes have been described, which express glycoproteins MUC1-7 in various tissues. It has been shown that different mucins are expressed in various gastric disease states compared to the normal. In this study we used histochemical and immunohistochemical methods to determine the type and pattern of mucin in 54 patients with a variety of gastric conditions [i.e., normal controls, fetal stomachs, gastritis, low-grade dysplasia, intestinal metaplasia (associated with gastritis, benign ulcers, dysplasia, and cancer), early and advanced intestinal type adenocarcinoma, and diffuse adenocarcinoma]. We report for the first time the use of all seven MUC antibodies in the various conditions. Normal controls were immunoreactive for MUC4, 5, and 6 , and gastritis specimens showed similar results, although the latter showed more MUC1 immunoreactivity. Whereas early fetal stomach showed no MUC immunoreactivity, MUC4, 5, and 6 were present from the early second trimester onwards. There was no significant difference between dysplasia and intestinal metaplasia, both categories showing the presence of MUC2 and 3 predominantly. Early intestinal type adenocarcinomas did not show any mucins in the majority of cases. Advanced intestinal type adenocarcinomas showed immunoreactivity predominantly for MUC1, 5, and 6, as well as MUC2 in some cases. Diffuse adenocarcinomas showed strong positive MUC2 and 6 staining, and in some cases MUC5 and 7. In conclusion, we have shown different patterns of mucin immunoreactivity in various gastric disease states. Specimens with dysplasia, intestinal metaplasia, late intestinal type adenocarcinoma, and diffuse gastric cancer were characterized by increased diversity of mucin types, whereas early intestinal cancer showed loss of mucin immunoreactivity.

  20. Prognostic Role of Lemur Tyrosine Kinase-3 germline polymorphisms in Adjuvant Gastric Cancer in Japan and the United States

    PubMed Central

    Wakatsuki, Takeru; LaBonte, Melissa J; Bohanes, Pierre O; Zhang, Wu; Yang, Dongyun; Azuma, Mizutomo; Brazi, Afsaneh; Ning, Yan; Loupakis, Fotios; Saadat, Siamak; Volz, Nico; Stintzing, Sebastian; El-Khoueiry, Rita; Koizumi, Wasaburo; Watanabe, Masahiko; Shah, Manish; Stebbing, Justin; Giamas, Georgios; Lenz, Heinz-Josef

    2013-01-01

    Lemur tyrosine kinase-3 (LMTK3) was recently identified as estrogen receptor (ER) -α modulator related to endocrine therapy resistance, and its polymorphisms rs9989661 (T>C) T/T genotype and rs8108419 (G>A) G/G or A/G genotype predicted improved outcomes in breast cancer. Since different predominant ERs distributions link to breast and gastric cancer and little is known of the prognostic role of LMTK3 in gastric cancer, this study was conducted to clarify the prognostic role of these polymorphisms in gastric cancer. One-hundred and sixty-nine Japanese and one-hundred and thirty-seven United States (US) patients with localized gastric adenocarcinoma were enrolled. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA-sequencing. Overall, these polymorphisms were not associated with survival in both cohorts. When gender was considered, in multivariate analysis, harboring rs9989661 T/T genotype was associated with disease-free survival (HR 4.37; 95% CI, 2.08–9.18; p<0.0001) and overall survival (OS) (HR 3.69; 95% CI, 1.65–8.24; p=0.0014) in the Japanese males and time to recurrence (HR 7.29; 95% CI, 1.07–49.80; p=0.043) in the US females. Meanwhile, harboring rs8108419 G/G genotype was associated with OS in the Japanese females (HR 3.04; 95% CI, 1.08–8.56; p=0.035) and the US males (HR 3.39; 95% CI, 1.31–8.80; p=0.012). The prognostic role of these polymorphisms may be negative in gastric cancer. These findings suggest that the estrogen pathway may play a prognostic role in patient with gastric cancer but this may be dependent on the regional differences both in physiology and genetic alterations of gastric cancer. PMID:23918832

  1. Helicobacter Pylori associated global gastric cancer burden

    PubMed Central

    Mbulaiteye, Sam M.; Hisada, Michie; El-Omar, Emad M.

    2008-01-01

    1. Abstract Helicobacter pylori infection is ubiquitous, infecting close to one-half of the world's population, but its prevalence is declining in developed countries. Chronic H. pylori infection is etiologically linked to gastric adenocarcinoma, especially non-cardia type (63% of all stomach cancer or ∼5.5% of the global cancer burden: ∼25% of cancers associated with infectious etiology), and to gastric mucosal associated lymphoid tissue (MALT) lymphoma, which accounts for up to 8% of all non-Hodgkin lymphoma. Epidemiological, clinical, and animal studies have established a central role for H. pylori in gastric carcinogenesis and provided insights into the mechanisms and biologic relationships between bacterial infection, host genetics, nutrition, and environmental factors. These discoveries invite strategies to prevent infection to be the logical primary goals in a multi-pronged effort to curtail suffering and death from H. pylori infection-associated cancers. PMID:19273142

  2. [Low grade sinonasal adenocarcinoma].

    PubMed

    Sayilgan, Ayşe Tülay; Kamali, Gülçin; Ozcan, Deniz; Emre, Funda; Hatıpoğlu, Ayşe

    2012-01-01

    Sinonasal adenocarcinoma is a rare neoplasm which is classified as 'intestinal' or 'nonintestinal' type, depending on its resemblance to gastrointestinal mucosa. These tumors are associated with occupational and environmental carcinogens. In this study, a fifty-year-old oil-painter male patient with a low-grade nonintestinal type sinonasal adenocarcinoma originating from the left middle concha and ethmoid sinus is presented. Microscopical examination revealed many infiltrative glandular structures, most of which were cystically dilated and some of which were smaller in diameter, arranged back to back in loose fibrous stroma as well as intraglandular papillary and micropapillary structures forming complex branches or a cribriform pattern. The glands were lined by epithelial cells that were faintly eosinophilic and relatively abundant cubical/ cylinderical cytoplasms and mildly pleomorphic round/oval nuclei, with rare mitotic figures. Intraluminal and focally intracytoplasmic mucin was demonstrated with Alcian Blue, mucicarmin and PAS stains. Immunohistochemically, tumor cells were strongly and diffusely positive with CK7; focally and weakly positive with CK20 and negative with CDX2 in accordance with the nonintestinal type. S-100, Actin and p63, applied for investigating the myoepithelial and salivary glandular origins, were all negative. Prognostic markers, TTF-1 and p53 were negative; while the Ki-67 index was 2%. The fact that intestinal type sinonasal adenocarcinomas are generally high grade, while nonintestinal tumors are histologically low grade makes this morphological and immunohistochemical-based classification valuable in predicting the prognosis of the disease. In addition to the morphological and immunohistochemical findings, clinical information stands out in the differentiation of the tumor from benign or malignant primary lesions or metastatic adenocarcinoma.

  3. Cytoprotective effect of American ginseng in a rat ethanol gastric ulcer model.

    PubMed

    Huang, Chi-Chang; Chen, Yi-Ming; Wang, Dean-Chuan; Chiu, Chien-Chao; Lin, Wan-Teng; Huang, Chih-Yang; Hsu, Mei-Chich

    2013-12-27

    Panax quinquefolium L. (American Ginseng, AG) is one of the most popular herbal medicines in the World. We aimed to investigate whether chronic (28-day) supplementation with AG could protect against ethanol-induced ulcer in gastric tissue. Furthermore, we investigated the possible molecular mechanisms leading to AG-mediated gastric mucosal protection. We randomized 32 male Wistar rats into four groups for treatment (n=8 per group): supplementation with water (vehicle) and low-dose (AG-1X), medium-dose (AG-2X) and high-dose (AG-5X) AG at 0, 250, 500, and 1250 mg/kg, respectively. In the first experiment, animals were fed vehicle or AG treatments for 4 weeks. At day 29, 75% ethanol was given orally to each animal at 10 mL/kg to induce gastric ulceration for 2 h. In a second experiment, animals were pretreated orally with each treatment for 1 hr before a single oral administration of ethanol (70%, 10 mL/kg). Trend analysis revealed that AG treatments inhibited ethanol-induced gastric mucosal damage. AG supplementation dose-dependently decreased the pro-inflammatory levels of interleukin 1β and cyclooxygenase 2 and the expression of pro-apoptotic proteins tBid, cytochrome C, and caspases-9 and -3 and increased the levels of anti-apoptotic proteins Bcl-2, Bcl-xL and p-Bad. AG could have pharmacological potential for treating gastric ulcer.

  4. Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma.

    PubMed

    Bayraktar, Ulas Darda; Bayraktar, Soley; Hosein, Peter; Chen, Emerson; Koniaris, Leonidas G; Rocha-Lima, Caio Max S; Montero, Alberto J

    2012-09-01

    Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

  5. [Gastric cancer].

    PubMed

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

    1991-11-01

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

  6. Review of Atrophic Gastritis and Intestinal Metaplasia as a Premalignant Lesion of Gastric Cancer

    PubMed Central

    Park, Yo Han; Kim, Nayoung

    2015-01-01

    Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor lesions of gastric cancer as the incidence of gastric cancer increases in the gastric mucosa involved with AG and IM. The prevalence of AG and IM vary depending on countries, even it represents diverse results in the same nation. Usually AG is antecedent of IM but the etiologies of AG and IM are not always the same. The sensitivity and specificity of diagnostic methods to detect AG and IM are different. Furthermore, the management strategy of AG and IM has not been established, yet. Helicobacter pylori infection has been proved as the most important cause of AG and IM. Thus the eradication of H. pylori is very important to prevent the progression to gastric cancer which is still placed in the high rank in morbidity and mortality among cancers. However, the reversibility of AG and IM by eradication of H. pylori which was assumed to be certain by meta-analysis is; however, controversial now. Therefore, the understanding and early diagnosis of AG and IM are very important, especially, in high incidence area of gastric cancer such as Republic of Korea. PMID:25853101

  7. Helicobacter pylori Update: Gastric Cancer, Reliable Therapy, and Possible Benefits

    PubMed Central

    Graham, David Y.

    2015-01-01

    Helicobacter pylori infection contributes to development of diverse gastric and extra-gastric diseases. The infection is necessary but not sufficient for development of gastric adenocarcinoma. Its eradication would eliminate a major worldwide cause of cancer death, so there is much interest in identifying how, if, and when this can be accomplished. There are several mechanisms by which H pylori contributes to development of gastric cancer. Gastric adenocarcinoma is one of many cancers associated with inflammation, which is induced by H pylori infection, yet the bacteria also cause genetic and epigenetic changes that lead to genetic instability in gastric epithelial cells. H pylori eradication reduces both. However, many factors must be considered in determining whether treating this bacterial infection will prevent cancer or only reduce its risk—these must be considered in designing reliable and effective eradication therapies. Furthermore, H pylori infection has been proposed to provide some benefits, such as reducing the risks of obesity or childhood asthma, although there are no convincing data to support the benefits of H pylori infections. PMID:25655557

  8. Epidemiology of Helicobacter pylori and gastric cancer.

    PubMed

    Kikuchi, Shogo

    2002-01-01

    Findings in epidemiological studies of the relationship between Helicobacter pylori and gastric cancer have been inconsistent: many studies have yielded a positive relationship, whereas several studies have shown no relationship. The inconsistency arises because of the occurrence of seroreversion during the period between the time that H. pylori exerts a carcinogenic effect and the time of blood sampling. When this seroreversion is taken into account, there is an epidemiologically positive association between H. pylori status and the risk for gastric cancer. In addition to the epidemiological evidence, experimental studies using Mongolian gerbils have shown that H. pylori infection elevates the risk for gastric cancer. It is concluded that H. pylori is a causal factor for gastric cancer. In the creation of preventive strategies against gastric cancer by the eradication of H. pylori, determination of the time at which H. pylori plays a role as a carcinogen is important. Three hypotheses have been proposed in regard to this timing: that H. pylori infection in childhood or the teenage years acts as a factor that produces precancerous lesions with irreversible damage in the gastric mucosa, that in adulthood it acts as an initiator, and also in adulthood, that it acts as a promoter. As these hypotheses are not mutually exclusive, the extent to which each hypothesis plays a part in explaining gastric carcinogenesis should be evaluated. Only a small proportion of subjects infected with H. pylori have gastric cancer during their lifetime. Interleukin-1 polymorphism, a host factor, and CagA, a virulence factor of H. pylori, are suspected to be risk factors for gastric cancer in subjects with H. pylori infection. Dietary factors, especially vitamin C, and patterns of precancerous lesions also seem to influence the relationship between H. pylori and gastric cancer. H. pylori seems to reduce the risk for esophageal and for some gastric cardia adenocarcinomas. This finding, as

  9. Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study

    PubMed Central

    Xiao, Q; Freedman, N D; Ren, J; Hollenbeck, A R; Abnet, C C; Park, Y

    2014-01-01

    Background: Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer. Methods: We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492 293 men and women. Results: We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer. Conclusion: Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma. PMID:24481406

  10. Endoscopic and operative palliation strategies for pancreatic ductal adenocarcinoma.

    PubMed

    Stark, Alexander; Hines, O Joe

    2015-02-01

    Malignant biliary obstruction, duodenal, and gastric outlet obstruction, and tumor-related pain are the complications of unresectable pancreatic adenocarcinoma that most frequently require palliative intervention. Surgery involving biliary bypass with or without gastrojejunostomy was once the mainstay of treatment in these patients. However, advances in non-operative techniques-most notably the widespread availability of endoscopic biliary and duodenal stents-have shifted the paradigm of treatment away from traditional surgical management. Questions regarding the efficacy and durability of endoscopic stents for biliary and gastric outlet obstruction are reviewed and demonstrate high rates of therapeutic success, low rates of morbidity, and decreased cost. Surgery remains an effective treatment modality, and still produces the most durable relief in appropriately selected patients.

  11. Clinicopathological significance of gastric poorly differentiated medullary carcinoma.

    PubMed

    Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Haga, Toshihiro; Wu, Yunyan; Ota, Rie; Takatsuna, Masafumi; Akasaka, Harue; Hakamada, Kenichi; Kijima, Hiroshi

    2016-01-01

    Poorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients' prognosis. PMID:27108877

  12. Pancreatic adenocarcinoma: Outstanding problems

    PubMed Central

    Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I

    2012-01-01

    Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary. PMID:22655124

  13. Gastric mycosis following gastric resection and vagotomy.

    PubMed Central

    Rehnberg, O; Faxen, A; Haglund, U; Kewenter, J; Stenquist, B; Olbe, L

    1982-01-01

    In a prospective five-year follow-up study of 289 consecutive patients subjected to antrectomy and gastroduodenostomy with or without vagotomy, 130 patients underwent gastroscopy. Gastric mycosis was present almost exclusively in patients subjected to combined antrectomy and vagotomy (36%). Gastric acidity seemed to be of only minor or no importance in the development of the mycosis. The residual volume in the gastric remnant was significantly higher in patients with gastric mycosis. The impaired emptying of the gastric remnant is most likely a vagotomy effect and may be the main reason for the development of gastric mycosis. A simple but effective method was developed to evacuate gastric yeast cell aggregates. Gastric mycosis seems to give rise to only slight symptoms, mainly nausea and foul-smelling belching, whereas the reflux of duodenal contents that often occurred in combination with gastric mycosis was more likely to cause gastritis and substantial discomfort. PMID:7092348

  14. Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

    PubMed Central

    Imamura, Taisuke; Komatsu, Shuhei; Ichikawa, Daisuke; Kobayashi, Hiroki; Miyamae, Mahito; Hirajima, Shoji; Kawaguchi, Tsutomu; Kubota, Takeshi; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Ogiso, Kiyoshi; Yagi, Nobuaki; Yanagisawa, Akio; Ando, Takashi; Otsuji, Eigo

    2015-01-01

    Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland (HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery (LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor (SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm into the submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG. PMID:26306144

  15. Laparoscopic gastric banding - discharge

    MedlinePlus

    ... laparoscopic gastric banding - discharge; Obesity gastric banding discharge; Weight loss - gastric banding discharge ... as your body gets used to your weight loss and your weight becomes stable. Weight loss may be slower after ...

  16. Gastric bypass surgery - discharge

    MedlinePlus

    ... bypass - discharge; Gastric bypass - Roux-en-Y - discharge; Obesity gastric bypass discharge; Weight loss - gastric bypass discharge ... al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised ...

  17. AURKA regulates JAK2-STAT3 activity in human gastric and esophageal cancers.

    PubMed

    Katsha, Ahmed; Arras, Janet; Soutto, Mohammed; Belkhiri, Abbes; El-Rifai, Wael

    2014-12-01

    Aurora kinase A is a frequently amplified and overexpressed gene in upper gastrointestinal adenocarcinomas (UGCs). Using in vitro cell models of UGCs, we investigated whether AURKA can regulate Signal Transducer and Activator of Transcription 3 (STAT3). Our data indicate that overexpression of AURKA in FLO-1 and AGS cells increase STAT3 phosphorylation at the Tyr705 site, whereas AURKA genetic depletion by siRNA results in decreased phosphorylation levels of STAT3 in FLO-1 and MKN45 cells. Immunofluorescence analysis showed that AURKA overexpression enhanced STAT3 nuclear translocation while AURKA genetic knockdown reduced the nuclear translocation of STAT3 in AGS and FLO-1 cells, respectively. Using a luciferase reporter assay, we demonstrated that AURKA expression induces transcriptional activity of STAT3. Pharmacological inhibition of AURKA by MLN8237 reduced STAT3 phosphorylation along with down-regulation of STAT3 pro-survival targets, BCL2 and MCL1. Moreover, by using clonogenic cells survival assay, we showed that MLN8237 single dose treatment reduced the ability of FLO-1 and AGS cells to form colonies. Additional experiments utilizing cell models of overexpression and knockdown of AURKA indicated that STAT3 upstream non-receptor tyrosine kinase Janus kinase 2 (JAK2) is mediating the effect of AURKA on STAT3. The inhibition of JAK2 using JAK2-specific inhibitor AZD1480 or siRNA knockdown, in presence of AURKA overexpression, abrogated the AURKA-mediated STAT3 activation. These results confirm that the AURKA-JAK2 axis is the main mechanism by which AURKA regulates STAT3 activity. In conclusion, we report, for the first time, that AURKA promotes STAT3 activity through regulating the expression and phosphorylation levels of JAK2. This highlights the importance of targeting AURKA as a therapeutic approach to treat gastric and esophageal cancers. PMID:24953013

  18. Resected tumor seeding in stomach wall due to endoscopic ultrasonography-guided fine needle aspiration of pancreatic adenocarcinoma

    PubMed Central

    Tomonari, Akiko; Katanuma, Akio; Matsumori, Tomoaki; Yamazaki, Hajime; Sano, Itsuki; Minami, Ryuki; Sen-yo, Manabu; Ikarashi, Satoshi; Kin, Toshifumi; Yane, Kei; Takahashi, Kuniyuki; Shinohara, Toshiya; Maguchi, Hiroyuki

    2015-01-01

    Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a useful and relatively safe tool for the diagnosis and staging of pancreatic cancer. However, there have recently been several reports of tumor seeding after EUS-FNA of adenocarcinomas. A 78-year-old man was admitted to our hospital due to upper gastric pain. Examinations revealed a 20 mm mass in the pancreatic body, for which EUS-FNA was performed. The cytology of the lesion was adenocarcinoma, and the stage of the cancer was T3N0M0. The patient underwent surgery with curative intent, followed by adjuvant chemotherapy with S-1. An enlarging gastric submucosal tumor was found on gastroscopy at 28 mo after surgery accompanied by a rising level of CA19-9. Biopsy result was adenocarcinoma, consistent with a pancreatic primary tumor. Tumor seeding after EUS-FNA was strongly suspected. The patient underwent surgical resection of the gastric tumor with curative intent. The pathological result of the resected gastric specimen was adenocarcinoma with a perfectly matched mucin special stain result with the previously resected pancreatic cancer. This is the first case report of tumor seeding after EUS-FNA which was surgically resected and inspected pathologically. PMID:26217099

  19. Ramucirumab: A Review in Advanced Gastric Cancer.

    PubMed

    Greig, Sarah L; Keating, Gillian M

    2015-10-01

    Ramucirumab (Cyramza(®)), an intravenously administered, monoclonal antibody against vascular endothelial growth factor receptor-2, is approved in the USA, EU and Japan (either as a single agent or in combination with paclitaxel) as second-line treatment in adults with advanced gastric or gastro-oesophageal junction adenocarcinoma. In two phase III trials (REGARD and RAINBOW) in this indication, overall survival and progression-free survival were significantly prolonged with ramucirumab 8 mg/kg every 2 weeks compared with placebo, and with ramucirumab 8 mg/kg every 2 weeks plus weekly paclitaxel compared with placebo plus paclitaxel. Ramucirumab had a generally acceptable tolerability profile in phase III trials; hypertension was the most common non-haematological adverse event of grade 3 or higher with ramucirumab (either alone or with paclitaxel). As the first antiangiogenic agent to provide significant survival benefit in patients with advanced gastric cancer, ramucirumab is a valuable option in the second-line treatment of advanced gastric or gastro-oesophageal junction adenocarcinoma.

  20. Spontaneous gastric squamous cell carcinomas and other neoplasms in Greenland collared lemmings (Dicrostonyx groenlandicus).

    PubMed Central

    Barker, I K; Mallory, F F; Brooks, R J

    1982-01-01

    Malignant neoplasms were present in 39/66 Dicrostonyx groenlandicus of varying ages, examined from a laboratory colony. The presence of multiple neoplasms in some resulted in an overall average of 1.15 tumors/affected animal. Gastric squamous papillomas were present in nine, and locally invasive or metastatic gastric squamous cell carcinomas in a further 36 animals. Three mammary adenocarcinomas, one pancreatic islet cell tumor, one probable pancreatic adenocarcinoma and one adrenal cortical adenoma were also seen in lemmings with gastric tumors. Two others had mammary adenocarcinoma alone, and one animal had bilateral Harderian gland adenocarcinoma. Lesions resembling glomerulonephrosis of rats were seen in 23/51 animals whose kidneys were examined. These findings were not considered artefacts of captivity since concurrent gastric squamous cell carcinoma, mammary adenocarcinoma and glomerulonephrosis were present in the single animal examined directly from the wild at Eskimo Point, Northwest Territories. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:6751508

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

    PubMed Central

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

    2014-01-01

    AIM: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells (CSCs) of gastric mucosa in an animal model. METHODS: In this study we investigated the effects of aging and Helicobacter pylori (H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old (young) with 22 mo (aged) old Fischer-344 rats. For human studies, gastric biopsies and resection specimens representing normal mucosa or different stages of H. pylori gastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells. RESULTS: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylori gastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylori gastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia. CONCLUSION: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pylori infection may have additive effects in progression to neoplasia. PMID:25133037

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

    PubMed

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

    2001-08-01

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

  3. Challenges of deciphering gastric cancer heterogeneity.

    PubMed

    Hudler, Petra

    2015-10-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  4. Challenges of deciphering gastric cancer heterogeneity

    PubMed Central

    Hudler, Petra

    2015-01-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  5. Aneuploidies, deletion, and overexpression of TP53 gene in intestinal metaplasia of patients without gastric cancer.

    PubMed

    César, Ana Cristina Gobbo; Borim, Aldenis Albaneze; Caetano, Alaor; Cury, Patrícia Maluf; Silva, Ana Elizabete

    2004-09-01

    Gastric carcinogenesis is attributable to interacting environmental and genetic factors, through a sequence of events including intestinal metaplasia. Using a fluorescence in situ hybridization technique, we investigated the occurrence of aneuploidies of chromosomes 3, 7, 8, 9, and 17, TP53 gene deletion, and expression of p53 in 21 intestinal metaplasia (IM) samples from cancer-free patients and in 20 gastric adenocarcinoma samples. Aneuploidies were found in 71% (15/21) of the IM samples. Trisomy of chromosomes 7 and 9 occurred mainly in complete-type IM; in the incomplete type, trisomy of chromosomes 7 and 8 were more commonly found. The TP53 gene deletion was observed in 60% (3/5) of the IM cases, and immunohistochemistry revealed p53 overexpression in 12% (2/17) of the analyzed IM cases. All gastric adenocarcinoma cases presented higher frequencies of trisomy or tetrasomy of chromosomes 3, 7, 8, 9, and 17. The TP53 deletion was found in all three of the gastric adenocarcinoma analyzed for it, and immunohistochemistry detected overexpression of protein p53 in 80% (12/15) of the analyzed cases. Our study revealed for the first time the presence of aneuploidies of chromosomes 7, 8, 9, and 17 and of TP53 gene deletion and overexpression in IM samples from cancer-free patients. These results suggest that IM and gastric adenocarcinoma may share the same genetic alterations. PMID:15350302

  6. [Synchronous adenocarcinoma and lymphoepithelioma-like carcinoma in the stomach: a case presentation and literature review].

    PubMed

    Aranguibel, D; Benítez, S; Guillen, I; Villarreal, L; Bandres, D; Bastidas, G

    2012-01-01

    Gastric cancer is one of the main causes of death in the world. In Venezuela, gastric tumors represent 37% of all malignant tumors of the digestive system, but only 1,6% to 3,1% of these cases are lymphoepithelioma-like carcinoma. Synchronous neoplastic lesions are also rare. The clinical case presented herein, a man with two synchronous tumor lesions, is the first of its kind in this country. Despite their incipient aspect, the histologic study reported two malignant tumors of epithelial origin: well-differentiated adenocarcinoma and lymphoepithelioma-like carcinoma.

  7. Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer

    PubMed Central

    Miike, Tadashi; Yamamoto, Shojiro; Miyata, Yoshifumi; Hirata, Tomoya; Noda, Yuko; Noda, Takaho; Suzuki, Sho; Takeda, Sachiko; Natsuda, Shuichiro; Sakaguchi, Mai; Maemura, Kosuke; Hashimoto, Kanna; Yamaji, Takumi; Abe, Hiroo; Iwakiri, Hisayoshi; Tahara, Yoshihiro; Hasuike, Satoru; Nagata, Kenji; Kitanaka, Akira; Shimoda, Kazuya

    2016-01-01

    Background and Aim. It is difficult to master the skill of discriminating gastric adenoma from early gastric cancer by conventional endoscopy or magnifying endoscopy combined with narrow-band imaging, because the colors and morphologies of these neoplasms are occasionally similar. We focused on the surrounding gastric mucosa findings in order to determine how to discriminate between early gastric cancer and gastric adenoma by analyzing the characteristics of the gastric background mucosa. Methods. We retrospectively examined 146 patients who underwent endoscopic submucosal dissection for gastric neoplasm between October 2009 and January 2015. The boundary of atrophic gastritis was classified endoscopically according to the Kimura-Takemoto classification system. Of 146 lesions, 63 early gastric cancers and 21 gastric adenomas were ultimately evaluated and assessed. Results. Almost all gastric adenomas were accompanied by open-type gastritis, whereas 47 and 16 early gastric cancers were accompanied by open-type and closed-type gastritis, respectively (p = 0.037). Conclusions. The evaluation of the boundary of atrophic gastritis associated with gastric neoplasms appears to be useful for discrimination between early gastric cancer and gastric adenoma. When gastric neoplasm is present in the context of surrounding localized gastric atrophy, gastric cancer is probable but not certain. PMID:26858751

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

    PubMed

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

    2016-01-01

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

  9. Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

    PubMed Central

    Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

    2015-01-01

    AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal

  10. Gastric infarction following gastric bypass surgery

    PubMed Central

    Do, Patrick H; Kang, Young S; Cahill, Peter

    2016-01-01

    Gastric infarction is an extremely rare occurrence owing to the stomach’s extensive vascular supply. We report an unusual case of gastric infarction following gastric bypass surgery. We describe the imaging findings and discuss possible causes of this condition. PMID:27200168

  11. Adenocarcinoma of the cervical stump

    SciTech Connect

    Goodman, H.M.; Niloff, J.M.; Buttlar, C.A.; Welch, W.R.; Marck, A.; Feuer, E.J.; Lahman, E.A.; Jenison, E.; Knapp, R.C. )

    1989-11-01

    Sixteen women with adenocarcinoma of the cervical stump were treated over a 15-year period. The median survivals of 40 months for stage IB and 17 months for stages II and III were significantly worse compared with those for patients treated for cervical adenocarcinoma of the intact uterus or squamous carcinoma of the cervical stump. The poor results were due to both local and distant failure. Implications regarding tumor radiosensitivity and adjuvant therapy in these high-risk patients are discussed.

  12. Current status of novel agents in advanced gastroesophageal adenocarcinoma

    PubMed Central

    Kothari, Nishi

    2015-01-01

    Gastroesophageal (GE) adenocarcinomas are highly lethal malignancies and despite multiple chemotherapy options, 5-year survival rates remain dismal. Chemotherapy is the mainstay of treatment but patients are often limited by toxicity and poor performance status. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and develop targeted therapies that act on individual tumors. Trastuzumab, a human epidermal growth factor receptor type 2 (HER2) monoclonal antibody, was the first such agent shown to improve response rate, progression free survival (PFS), and overall survival (OS) when added to cisplatin based chemotherapy in patients with HER2 over-expressing GE junction (GEJ) and gastric adenocarcinomas. However, HER2 over expressing GE tumors are in the minority and the need for additional targeted agents is urgent. Though many agents are in development, incorporating targeted therapy in the treatment of GE cancers comes with a unique set of challenges. In this review, we outline oncogenic pathways relevant to GE adenocarcinomas, including HER2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and c-Met, and discuss recent trials with agents targeting these pathways. PMID:25642339

  13. Angiogenesis inhibitors in gastric and gastroesophageal junction cancer.

    PubMed

    Roviello, Giandomenico; Petrioli, Roberto; Marano, Luigi; Polom, Karol; Marrelli, Daniele; Perrella, Armando; Roviello, Franco

    2016-01-01

    Despite significant improvements in systemic chemotherapy during the past two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. Unfortunately, although a number of molecular targets have been studied, very few of these agents can be used in a clinical setting. In this review, we summarize the available data on anti-angiogenic agents in advanced/metastatic gastric cancer. PMID:26329368

  14. Dieulafoy's disease associated with early gastric cancer.

    PubMed Central

    Leone, O; Zanelli, M; Santini, D; Minni, F; Marrano, D

    1995-01-01

    In the past different terms have been used to define the vascular malformations of Dieulafoy's disease--for example, calibre persistent artery of the stomach, cirsoid aneurysm and gastric atherosclerosis. A case of Dieulafoy's disease is described in a 41 year old man, who presented with symptoms of anaemia and melaena, with particular attention paid to the morphological characterisation of the vascular histological lesions. Intimal hyperplasia with a non-concentric proliferation of myointimal cells, areas of muscular degeneration, aspects of vascular neoformation of the arterial wall, and other findings are reported. An association between an early diffuse adenocarcinoma and parietal anomalies of Dieulafoy's disease is illustrated. Images PMID:7730491

  15. Helicobacter pylori inhibits gastric cell cycle progression.

    PubMed

    Ahmed, A; Smoot, D; Littleton, G; Tackey, R; Walters, C S; Kashanchi, F; Allen, C R; Ashktorab, H

    2000-08-01

    Helicobacter pylori infection of the gastric mucosa is associated with changes in gastric epithelial cell proliferation. In vitro studies have shown that exposure to H. pylori inhibits proliferation of gastric cells. This study sought to investigate the cell cycle progression of gastric epithelial cell lines in the presence and absence of H. pylori. Unsynchronized and synchronized gastric epithelial cell lines AGS and KatoIII were exposed to H. pylori over a 24-h period. Cell cycle progression was determined by flow cytometry using propidium iodide (PI), and by analysis of cyclin E, p21, and p53 protein expression using Western blots. In the absence of H. pylori 40, 45, and 15% of unsynchronized AGS cells were in G(0)-G(1), S, and G(2)-M phases, respectively, by flow cytometry analysis. When AGS cells were cultured in the presence of H. pylori, the S phase decreased 10% and the G(0)-G(1) phase increased 17% after 24 h compared with the controls. KatoIII cells, which have a deleted p53 gene, showed little or no response to H. pylori. When G1/S synchronized AGS cells were incubated with media containing H. pylori, the G(1) phase increased significantly (25%, P < 0.05) compared with controls after 24 h. In contrast, the control cells were able to pass through S phase. The inhibitory effects of H. pylori on the cell cycle of AGS cells were associated with a significant increase in p53 and p21 expression after 24 h. The expression of cyclin E was downregulated in AGS cells following exposure of AGS cells to H. pylori for 24 h. This study shows that H. pylori-induced growth inhibition in vitro is predominantly at the G(0)-G(1) checkpoint. Our results suggest that p53 may be important in H. pylori-induced cell cycle arrest. These results support a role for cyclin-dependent kinase inhibitors in the G(1) cell cycle arrest exerted by H. pylori and its involvement in changing the regulatory proteins, p53, p21, and cyclin E in the cell cycle. PMID:11008106

  16. 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).

  17. Discrimination of premalignant lesions and cancer tissues from normal gastric tissues using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Luo, Shuwen; Chen, Changshui; Mao, Hua; Jin, Shaoqin

    2013-06-01

    The feasibility of early detection of gastric cancer using near-infrared (NIR) Raman spectroscopy (RS) by distinguishing premalignant lesions (adenomatous polyp, n=27) and cancer tissues (adenocarcinoma, n=33) from normal gastric tissues (n=45) is evaluated. Significant differences in Raman spectra are observed among the normal, adenomatous polyp, and adenocarcinoma gastric tissues at 936, 1003, 1032, 1174, 1208, 1323, 1335, 1450, and 1655 cm-1. Diverse statistical methods are employed to develop effective diagnostic algorithms for classifying the Raman spectra of different types of ex vivo gastric tissues, including principal component analysis (PCA), linear discriminant analysis (LDA), and naive Bayesian classifier (NBC) techniques. Compared with PCA-LDA algorithms, PCA-NBC techniques together with leave-one-out, cross-validation method provide better discriminative results of normal, adenomatous polyp, and adenocarcinoma gastric tissues, resulting in superior sensitivities of 96.3%, 96.9%, and 96.9%, and specificities of 93%, 100%, and 95.2%, respectively. Therefore, NIR RS associated with multivariate statistical algorithms has the potential for early diagnosis of gastric premalignant lesions and cancer tissues in molecular level.

  18. Gastric leiomyoblastoma

    PubMed Central

    Bose, B.; Candy, J.

    1970-01-01

    This paper describes two cases of gastric leiomyoblastoma (bizarre smooth muscle tumour), one of them having evidence of metastases. Both patients remain well after seven years and three and a half years respectively. The literature is reviewed, and the clinical features, diagnosis, and treatment are discussed. The histological appearances are described in detail and an attempt is made to assess the criteria for the diagnosis of malignancy. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:5485837

  19. The descriptive epidemiology of gastric cancer in Central America and comparison with United States Hispanic populations

    PubMed Central

    Corral, Juan E.; Delgado Hurtado, Juan J.; Domínguez, Ricardo L.; de Cuéllar, Marisabel Valdez; Cruz, Carlos Balmore; Morgan, Douglas R.

    2015-01-01

    Purpose Delineate the epidemiology of gastric adenocarcinoma in Central America and contrast it with Hispanic-Latino populations in the U.S. Methods Published literature and Central America Ministry of Health databases were used as primary data sources, including national, population-based and hospital-based registries. U.S. data was obtained from the NCI-SEER registry. Incident gastric adenocarcinoma cases were analyzed for available data between 1985–2011, including demographic variables and pathology information. Results In Central America, 19,741 incident gastric adenocarcinomas were identified. Two-thirds of cases were male, 20.5% were under age 55, and 58.5% were from rural areas. In the SEER database (n=7,871), 57.8% were male, and 28.9% were under age 55. Among the U.S. Hispanics born in Central America with gastric cancer (n=1,210), 50.3% of cases were male, and 38.1% were under age 55. Noncardia gastric cancer was more common in Central America (83.3%), among U.S. Hispanics (80.2%), and Hispanics born in Central America (86.3%). Cancers of the antrum were more common in Central America (73.6%), whereas cancers of the corpus were slightly more common among U.S. Hispanics (54.0%). Adenocarcinoma of the diffuse subtype was relatively common, both in Central America (35.7%), and U.S. Hispanics (69.5%), although Lauren classification was reported in only 50% of cases. Conclusions A significant burden of gastric adenocarcinoma is observed in Central America based upon limited available data. Differences are noted between Central America and U.S. Hispanics. Strengthening population-based registries is needed for improved cancer control in Central America, which may have implications for the growing U.S. Hispanic population. PMID:25412859

  20. Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

    PubMed Central

    Silva, Tanielly Cristina Raiol; Andrade Junior, Edilson Ferreira; Rezende, Alexandre Pingarilho; Carneiro Muniz, José Augusto Pereira; Lacreta Junior, Antonio Carlos Cunha; Assumpção, Paulo Pimentel; Calcagno, Danielle Queiroz; Demachki, Samia; Rabenhorst, Silvia Helena Barem; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodriguez

    2011-01-01

    The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and

  1. Molecular Classification of Gastric Cancer: A new paradigm

    PubMed Central

    Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.

    2011-01-01

    Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

  2. Metastasis of Gastric Signet-Ring Cell Carcinoma to the Urinary Bladder: A Case Report and Review of the Literature

    PubMed Central

    Okutur, Kerem; Eren, Orhan Onder; Demir, Gokhan

    2015-01-01

    Although signet-ring cell (SRC) adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer. PMID:26346068

  3. Runx3 Expression Inhibits Proliferation and Distinctly Alters mRNA Expression of Bax in AGS and A549 Cancer Cells

    PubMed Central

    Torshabi, Maryam; Faramarzi, Mohammad Ali; Tabatabaei Yazdi, Mojtaba; Ostad, Seyyed Naser; Gharemani, Mohammad Hosein

    2011-01-01

    Runx3, a member of Runt-related transcription factor (Runx) proteins with tumor suppressor effect, is a tissue–restricted and cancer related transcription factor that regulate cell proliferation and growth, as well as differentiation. In the present study, exogenous Run3 was transiently expressed in AGS (human gastric adenocarcinoma), with undetectable Runx3 protein and in A549 (human lung carcinoma) with low levels of endogenous Runx3 protein. The GFP tagged Runx3 was transfected into AGS and A549 cells using fugene6 and PolyFect and Runx3 expression was confirmed by fluorescent microscopy and RT-PCR. The effect of Runx3 transfection on cell proliferation was determined by MTT assay and the results were confirmed by the trypan blue dye exclusion method. The effect of Runx3 expression on mRNA expression of BCL2-associated X protein (Bax) was evaluated using RT-PCR. In AGS and A549 cells, Runx3 expression inhibited cell proliferation (p < 0.01). The growth inhibition was less in A549 cells. We show that Runx3 expression increases Bax mRNA expression in AGS cells when compared with control (p < 0.05), but no significant differences in mRNA expression was observed in both examined cells. Runx3 expression has antiproliferative effect in AGS cell perhaps via increase in expression of Bax. The effect of Runx3 on A549 cells’ viability which has endogenous level of Runx3 is not related to Bax. These findings implicate a complex regulation by Runx3 in inhibition of cell proliferation utilizing Bax. PMID:24250365

  4. Gastric carcinoids and therapeutic options. Case report and review of the literature.

    PubMed

    Dobru, Daniela; Boeriu, Alina; Mocan, Simona; Pascarenco, Ofelia; Boeriu, Cristian; Molnar, Calin

    2013-03-01

    Neuroendocrine tumors (carcinoids) are tumors originating from neuroendocrine cells. The distinction between different types of gastric carcinoids is important for their management. We present the case of a 38-year old woman with type 1 gastric neuroendocrine tumors (NETs) associated with autoimmune atrophic gastritis. The management of these tumors has not been yet codified and different therapeutic strategies have been suggested. A proper evaluation before therapy is indicated in order to rule out both the malignant transformation as well as the presence of synchronous lesions, such as dysplasia or gastric adenocarcinoma. We describe our diagnostic and therapeutic strategies with references to previously published reports. PMID:23539397

  5. Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

    NASA Astrophysics Data System (ADS)

    Odenbreit, Stefan; Püls, Jürgen; Sedlmaier, Bettina; Gerland, Elke; Fischer, Wolfgang; Haas, Rainer

    2000-02-01

    The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA+) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

  6. Identification of differentially expressed serum proteins in gastric adenocarcinoma☆

    PubMed Central

    Subbannayya, Yashwanth; Mir, Sartaj Ahmad; Renuse, Santosh; Manda, Srikanth S.; Pinto, Sneha M.; Puttamallesh, Vinuth N.; Solanki, Hitendra Singh; Manju, H.C.; Syed, Nazia; Sharma, Rakesh; Christopher, Rita; Vijayakumar, M.; Kumar, K.V. Veerendra; Prasad, T.S. Keshava; Ramaswamy, Girija; Kumar, Rekha V.; Chatterjee, Aditi; Pandey, Akhilesh; Gowda, Harsha

    2015-01-01

    Gastric adenocarcinoma is an aggressive cancer with poor prognosis. Blood based biomarkers of gastric cancer have the potential to improve diagnosis and monitoring of these tumors. Proteins that show altered levels in the circulation of gastric cancer patients could prove useful as putative biomarkers. We used an iTRAQ-based quantitative proteomic approach to identify proteins that show altered levels in the sera of patients with gastric cancer. Our study resulted in identification of 643 proteins, of which 48 proteins showed increased levels and 11 proteins showed decreased levels in serum from gastric cancer patients compared to age and sex matched healthy controls. Proteins that showed increased expression in gastric cancer included inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Mannose-binding protein C (MBL2), sex hormone-binding globulin (SHBG), insulin-like growth factor-binding protein 2 (IGFBP2), serum amyloid A protein (SAA1), Orosomucoid 1 (ORM1) and extracellular superoxide dismutase [Cu–Zn] (SOD3). We used multiple reaction monitoring assays and validated elevated levels of ITIH4 and SAA1 proteins in serum from gastric cancer patients. Biological significance Gastric cancer is a highly aggressive cancer associated with high mortality. Serum-based biomarkers are of considerable interest in diagnosis and monitoring of various diseases including cancers. Gastric cancer is often diagnosed at advanced stages resulting in poor prognosis and high mortality. Pathological diagnosis using biopsy specimens remains the gold standard for diagnosis of gastric cancer. Serum-based biomarkers are of considerable importance as they are minimally invasive. In this study, we carried out quantitative proteomic profiling of serum from gastric cancer patients to identify proteins that show altered levels in gastric cancer patients. We identified more than 50 proteins that showed altered levels in gastric cancer patient sera. Validation in a large cohort of well

  7. Murine Models of Helicobacter (pylori or felis)-associated Gastric Cancer.

    PubMed

    Duckworth, Carrie A; Burkitt, Michael D; Williams, Jonathan M; Parsons, Bryony N; Tang, Joseph M F; Pritchard, D Mark

    2015-06-01

    Gastric adenocarcinoma is the fifth most common cancer and third most common cause of cancer-related death in the world. The majority of these cancers develop in genetically susceptible individuals who are chronically infected with the Gram-negative bacterium Helicobacter pylori. Often these individuals have also been exposed to certain environmental factors that increase susceptibility, such as dietary components. Murine models of Helicobacter-induced gastric cancer are valuable tools for investigating the mechanisms responsible for the stepwise pathological changes of chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric adenocarcinoma. Helicobacter felis colonization greatly accelerates the development of gastric neoplasia in mice, and causes pathologies similar to those observed with Helicobacter pylori-associated gastric carcinogenesis in humans. These mouse models are therefore useful for investigating genetic and environmental factors that may be involved in the pathogenesis and treatment of gastric cancer. Detailed in these protocols are procedures for inducing Helicobacter-associated carcinogenesis in mice as well as the histological analysis and interpretation of gastric pathology in these animals.

  8. [A surgically resected case of AFP and PIVKA-II producing gastric cancer with hepatic metastasis].

    PubMed

    Tomono, Ayako; Wakahara, Tomoyuki; Kanemitsu, Kiyonori; Toyokawa, Akihiro; Teramura, Kazuhiro; Iwasaki, Takeshi

    2013-05-01

    A 78-year-old man was admitted for workup for a liver tumor. Both serum AFP and PIVKA-II levels were high (2260ng/ml and 806mAU/ml, respectively). Contrast-enhanced CT scan and MRI using Gd-EOB-DTPA demonstrated a liver tumor in segment 6 resembling the imaging patterns of hepatocellular carcinoma (HCC), while the upper gastrointestinal endoscopy revealed a type 2 gastric cancer in the gastric antrum. Although the liver metastasis of the gastric cancer was undeniable, we performed partial resection of segment 6 of the liver and distal gastrectomy under a preoperative diagnosis of double cancer. Histopathologically, gastric tumor consisted of two components, such as well differentiated adenocarcinoma and hepatoid adenocarcinoma. The histology of the liver tumor was similar to that of the hepatoid component in the stomach lesion. Immunohistochemical staining revealed both the gastric and the liver tumors to be positive for AFP and PIVKA-II, yielding a definite diagnosis of AFP and PIVKA-II producing gastric cancer with liver metastasis. Because many cases of this disease have liver metastases at presentation with confusing images with HCC, the diagnosis of liver tumors should be carefully differentiated in the gastric cancer patients with liver tumors, high serum AFP and PIVKA-II levels.

  9. Membrane bile acid receptor TGR5 predicts good prognosis in ampullary adenocarcinoma patients with hyperbilirubinemia

    PubMed Central

    Chen, Min-Chan; Chen, Yi-Ling; Wang, Tzu-Wen; Hsu, Hui-Ping; Lai, Ming-Derg

    2016-01-01

    Bile acids are potential carcinogens in gastrointestinal cancer, and interact with nuclear and membrane receptors to initiate downstream signaling. The effect of TGR5 [also known as G protein-coupled bile acid receptor 1 (GPBAR1)] on cancer progression is dependent on the tissue where it is activated. In this report, the function of TGR5 expression in cancer was studied using a bioinformatic approach. TGR5 expression in ampullary adenocarcinoma and normal duodenum was compared by western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry (IHC). High GPBAR1 gene expression was found to be an indicator of worse prognosis in gastric and breast cancer patients, and an indication of better prognosis in ovarian cancer patients. The level of GPBAR1 gene expression was higher in bile-acid exposed cancer than in other types of cancer, and was increased in well-differentiated ampullary adenocarcinoma. Negative, weak or mild expression of TGR5 was correlated with younger age, higher plasma level of total/direct bilirubin, higher plasma concentration of CA-125, advanced tumor stage and advanced AJCC TNM stage. The disease-specific survival rate was highest in ampullary adenocarcinoma patients with high TGR5 expression and high total bilirubin level. In summary, TGR5 functions as a tumor-suppressor in patients with ampullary adenocarcinoma and preoperative hyperbilirubinemia. Further study of the suppressive mechanism may provide a new therapeutic option for patients with ampullary adenocarcinoma. PMID:27510297

  10. Membrane bile acid receptor TGR5 predicts good prognosis in ampullary adenocarcinoma patients with hyperbilirubinemia.

    PubMed

    Chen, Min-Chan; Chen, Yi-Ling; Wang, Tzu-Wen; Hsu, Hui-Ping; Lai, Ming-Derg

    2016-10-01

    Bile acids are potential carcinogens in gastrointestinal cancer, and interact with nuclear and membrane receptors to initiate downstream signaling. The effect of TGR5 [also known as G protein-coupled bile acid receptor 1 (GPBAR1)] on cancer progression is dependent on the tissue where it is activated. In this report, the function of TGR5 expression in cancer was studied using a bioinformatic approach. TGR5 expression in ampullary adenocarcinoma and normal duodenum was compared by western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry (IHC). High GPBAR1 gene expression was found to be an indicator of worse prognosis in gastric and breast cancer patients, and an indication of better prognosis in ovarian cancer patients. The level of GPBAR1 gene expression was higher in bile‑acid exposed cancer than in other types of cancer, and was increased in well-differentiated ampullary adenocarcinoma. Negative, weak or mild expression of TGR5 was correlated with younger age, higher plasma level of total/direct bilirubin, higher plasma concentration of CA-125, advanced tumor stage and advanced AJCC TNM stage. The disease-specific survival rate was highest in ampullary adenocarcinoma patients with high TGR5 expression and high total bilirubin level. In summary, TGR5 functions as a tumor-suppressor in patients with ampullary adenocarcinoma and preoperative hyperbilirubinemia. Further study of the suppressive mechanism may provide a new therapeutic option for patients with ampullary adenocarcinoma. PMID:27510297

  11. Stomach (Gastric) Cancer Screening

    MedlinePlus

    ... Treatment Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a ...

  12. Gastric Large Cell Neuroendocrine Carcinoma

    PubMed Central

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    with a platinum-based regimen. Discussion: In the current WHO classification of gastric tumors, only carcinoids and small cell carcinomas are included in the neuroendocrine (NE) tumor category. However, a new pathologic entity has recently been described by Jiang et al. High-grade gastric NE carcinomas of non-small cell type have been tentatively named large cell neuroendocrine carcinomas (LCNEC). Morphologically, these tumors differ from both carcinoids and small cell carcinomas, and are confirmed immunohistochemically using NE markers, chromogranin-A and synaptophysin. Gastric LCNEC is currently defined if > 50% of tumor cells demonstrate positivity for chromogranin-A and/or synaptophysin. LCNECs account for < 1.5% of all gastric cancers. LCNECs, which had been previously diagnosed as adenocarcinomas (ACs) are highly malignant and portend a significantly worse prognosis than ACs. Reported 5-year survival rates for LCNECs and ACs have are 31.1% and 69.3%, respectively. At the time of presentation, 70–75% of LCNECs have lymph node metastases and 5–10% also have metastases to liver. Clinical management of gastric LCNECs has not been clearly defined given the rarity of the malignancy and limited experience in its management. An overall regression rate of 67% was achieved in a small series of poorly differentiated gastroenteropancreatic NE carcinomas treated with cisplatin and etoposide.

  13. HER2 testing in gastric cancer.

    PubMed

    Albarello, Luca; Pecciarini, Lorenza; Doglioni, Claudio

    2011-01-01

    Molecular therapies targeting HER2 are part of the established drug armamentarium in breast carcinoma. Now the ToGA trial, an international multicenter phase III clinical study, involving 24 countries globally, has shown that the anti-HER2 humanized monoclonal antibody Trastuzumab is effective in prolonging survival in HER2-positive carcinoma of the stomach and the gastroesophageal junction (GEJ). Similarly to breast carcinoma, >20% of gastric cancers show HER2 overexpression and/or amplification, and this percentage increases to 33% in GEJ tumors. Thus, as in breast carcinoma, pathologists are now asked to evaluate HER2 status in gastric carcinoma samples. As validated in the ToGA trial, the HER2 testing criteria that must be used in evaluating both gastric carcinoma biopsies and surgical specimens significantly differ from those routinely applied in breast carcinoma. The main variations with regard to the pattern of reactivity in HER2-expressing cells are as follows: the completeness of membrane staining is not a "conditio sine qua non" and the number of stained cells necessary to consider a case as positive is different. We must also take note of the much more frequent heterogeneity of HER2 positivity in gastric cancer compared with breast carcinoma and the less stringent correlation between HER2 amplification and protein overexpression that is observed in gastric carcinoma, where more than 20% of cases may carry HER2 amplification, although of low level, without HER2 expression. In these patients, in the ToGA trial, there was no apparent benefit from adding Trastuzumab to chemotherapy: for this reason the European Medicines Agency, while approving usage of Trastuzumab for metastatic adenocarcinoma treatment, indicated HER2 testing by immunohistochemistry as first evaluation assay, followed by fluorescence in situ hybridization in 2+ equivocal cases. HER2 testing in gastric carcinoma is a new field, opening several opportunities: for patients with gastric cancer

  14. Heterotopic Gastric Mucosa in the Distal Part of Esophagus in a Teenager

    PubMed Central

    Lupu, Vasile Valeriu; Ignat, Ancuta; Paduraru, Gabriela; Mihaila, Doina; Burlea, Marin; Ciubara, Anamaria

    2015-01-01

    Abstract Heterotopic gastric mucosa (HGM) of the esophagus is a congenital anomaly consisting of ectopic gastric mucosa. It may be connected with disorders of the upper gastrointestinal tract, exacerbated by Helicobacter pylori. The diagnosis of HGM is confirmed via endoscopy with biopsy. Histopathology provides the definitive diagnosis by demonstrating gastric mucosa adjacent to normal esophageal mucosa. HGM located in the distal esophagus needs differentiation from Barrett's esophagus. Barrett's esophagus is a well-known premalignant injury for adenocarcinoma of the esophagus. Malignant progression of HGM occurs in a stepwise pattern, following the metaplasia–dysplasia–adenocarcinoma sequence. We present a rare case of a teenage girl with HGM located in the distal esophagus, associated with chronic gastritis and biliary duodenogastric reflux. Endoscopy combined with biopsies is a mandatory method in clinical evaluation of metaplastic and nonmetaplastic changes within HGM of the esophagus. PMID:26496283

  15. Lower expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) association with poor prognosis of gastric cancer

    PubMed Central

    Hou, Yachao; Deng, Jingyu; Zhang, Li; Xie, Xingming; Guo, Xiaofan; Sun, Changyu; Zhang, Rupeng; Liang, Han

    2015-01-01

    Background: The aim of this study was to investigate the expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) in gastric cancer (GC), and its potential influence on the prognosis of GC patients. Methods: At present study, we examined the immunohistochemical expression of PHLPP1 on tissue microarrays (TMAs) containing 135 gastric adenocarcinoma tissues and 135 matched adjacent non-tumor tissues. In addition, both semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis (WB) were adopted to detect of the expression of PHLPP1 in the GC cell lines (AGS, SUN-1, KATO-III, BGC-823, MGC-803, SGC-7901, and HGC-27) and the normal gastric cell line GES-1. Survival analysis was used to investigate the efficiency of the prognostic evaluation of PHLPP1 expression in GC patients. Results: Positive expression rate of PHLPP1 in the primary GC tissues was significantly lower than that in adjacent non-tumor tissues (55.6% vs. 87.4%, P<0.001). Both gene transcription (mRNA) and Protein expression of PHLPP1 in the GC cell lines were significantly lower than those in the GES-1 cell line, respectively. The Kaplan-Meier analysis showed that patients presented PHLPP1 negative expression in the GC tissues had significantly lower overall survival rate than those presented PHLPP1 positive expression in the GC tissues (P=0.008). With the multivariate survival analysis (Cox regression), PHLPP1 expression in the GC tissue was identified as an independent predictor of the survival of patients. Conclusions: This study indicated that aberrant PHLPP1 expression was observed in GC tissues, which was significantly associated with the poor prognostic outcomes of GC patients. PMID:26884964

  16. Cutaneous Metastases From Esophageal Adenocarcinoma

    PubMed Central

    Triantafyllou, Stamatina; Georgia, Doulami; Gavriella-Zoi, Vrakopoulou; Dimitrios, Mpistarakis; Stulianos, Katsaragakis; Theodoros, Liakakos; Georgios, Zografos; Dimitrios, Theodorou

    2015-01-01

    The aim of this study is to present 2 rare cases of cutaneous metastases originated from adenocarcinoma of the gastro-esophageal junction, thus, underline the need for early diagnosis and possible treatment of suspicious skin lesions among patients with esophageal malignancy. Metastatic cancer to the skin originated from internal malignancies, mostly lung cancer, breast cancer, and colorectal cancer, constitute 0.5 to 9% of all metastatic cancers.5,8,15 Skin metastases, mainly from squamous cell carcinomas of the esophagus, are rarely reported. Cutaneous metastasis is a finding indicating progressiveness of the disease.17 More precisely, median survival is estimated approximately 4.7 months.2,14 This study is a retrospective review of 2 cases of patients with adenocarcinoma of the esophagus and a review of the literature. Two patients aged 60 and 32 years old, respectively, underwent esophagectomy. Both pathologic reports disclosed adenocarcinoma of the gastro-esophageal junction staged T3 N2 M0 (stage IIIB). During follow-up time, the 2 patients were diagnosed with cutaneous metastases originated from the primary esophageal tumor 11 and 4 months after surgery, respectively. The first patient is alive 37 months after diagnosis, while the second one died 16 months after surgery. Cutaneous metastasis caused by esophageal adenocarcinoma is possible. Therefore, follow-up of patients who were diagnosed with esophageal malignancy and underwent esophagectomy is mandatory in order to reveal early surgical stages. PMID:25785344

  17. [Endolymphatic sac adenocarcinoma: case report].

    PubMed

    Silveira, Roberto Leal; Gusmão, Sebastião Silva; Pittella, José Eymard H; Santos, Sinval Pereira

    2002-09-01

    A case of endolymphatic sac adenocarcinoma is reported and the literature is reviewed. The clinical picture was presented by vertigo and progressive hearing loss caused by a tumor of the endolymphatic sac. The surgical removal was complete, via a retro and translabyrinthine approach. Endolymphatic sac tumors are locally invasive, involve the petrous bone and the mastoid. The radical surgery presents good outcome.

  18. Surgical resection of colorectal recurrence of gastric cancer more than 5 years after primary resection

    PubMed Central

    Noji, Takehiro; Yamamura, Yoshiyuki; Muto, Jun; Kuroda, Aki; Koinuma, Junkichi; Yoshioka, Tatsuya; Murakawa, Katsuhiko; Otake, Setsuyuki; Hirano, Satoshi; Ono, Koichi

    2014-01-01

    INTRODUCTION Intestinal metastasis from gastric cancer is rare, although the most common cause of secondary neoplastic infiltration of the colon is gastric cancer. However, little data is available on recurrence or death in patients with gastric cancer surviving >5 years post-gastrectomy. Here we report two cases of lower intestinal metastasis from gastric cancer >5 years after primary resection and discuss with reference to the literature. PRESENTATION OF CASE Case 1: A 61-year-old man with a history of total gastrectomy for gastric cancer 9 years earlier was referred to our hospital with constipation and abdominal distention. We diagnosed primary colon cancer and subsequently performed extended left hemicolectomy. Histological examination revealed poorly differentiated adenocarcinoma resembling the gastric tumor he had 9 years earlier. The patient refused postoperative adjuvant chemotherapy and remained alive with cancerous peritonitis and skin metastases as of 17 months later. Case 2: A 46-year-old woman with a history of total gastrectomy for gastric cancer 9 years earlier presented with constipation. She also had a history of Krukenberg tumor 3 years earlier. We diagnosed metastatic rectal cancer and subsequently performed low anterior resection and hysterectomy. Pathological examination revealed poorly differentiated tubular adenocarcinoma, resembling the gastric tumor. The patient remained alive without recurrence as of 17 months later. DISCUSSION We found 19 reported cases of patients with resection of colon metastases from gastric cancer. Median disease-free interval was 74 months. CONCLUSION Resection of late-onset colorectal recurrence from gastric cancer appears worthwhile for selected patients. PMID:25460445

  19. Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration

    PubMed Central

    Kumar, J. Dinesh; Steele, Islay; Moore, Andrew R.; Murugesan, Senthil V.; Rakonczay, Zoltan; Venglovecz, Viktoria; Pritchard, D. Mark; Dimaline, Rodney; Tiszlavicz, Laszlo; Varro, Andrea

    2015-01-01

    The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling. PMID:25977510

  20. The Prevalence of Gastric Intestinal Metaplasia and Distribution of Helicobacter pylori Infection, Atrophy, Dysplasia, and Cancer in Its Subtypes

    PubMed Central

    Olmez, Sehmus; Aslan, Mehmet; Erten, Remzi; Sayar, Suleyman; Bayram, Irfan

    2015-01-01

    Objectives. Gastric intestinal metaplasia (IM) is frequently encountered and is considered a precursor of gastric adenocarcinoma. In the Van region of Turkey, gastric adenocarcinoma incidence is high but the prevalence of gastric IM is not known. Helicobacter pylori (H. pylori) infection is a main factor leading to atrophy, IM, and cancer development in the stomach. The aim of the current study was to investigate the prevalence of IM and its subtypes and the prevalence of H. pylori infection, atrophy, dysplasia, and cancer in gastric IM subtypes. Materials and Methods. This retrospective study was conducted on 560 IM among the 4050 consecutive patients who were undergoing esophagogastroduodenoscopy (EGD) with biopsy between June 2010 and October 2014. Clinical records and endoscopic and histopathologic reports of patients with IM were analyzed. Results. The prevalence of gastric IM was 13.8%. The prevalence of incomplete IM was statistically significantly higher than complete IM. Type III IM was the most frequent subtype. Conclusions. Gastric IM is a common finding in patients undergoing EGD with biopsy in this region. High prevalence of incomplete type IM, especially type III, can be associated with the high prevalence of gastric cancer in our region. PMID:26635875

  1. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

    2016-01-01

    Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention. PMID:27331918

  2. Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma.

    PubMed

    Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng

    2016-02-01

    Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett's esophagus [BE]) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done, but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (ie, changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia-EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel therapeutic

  3. Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma.

    PubMed

    Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng

    2016-02-01

    Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett's esophagus [BE]) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done, but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (ie, changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia-EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel therapeutic

  4. The role of endoscopic ultrasound on the preoperative T staging of gastric cancer

    PubMed Central

    Han, Chaoqun; Lin, Rong; Shi, Huiying; Liu, Jun; Qian, Wei; Ding, Zhen; Hou, Xiaohua

    2016-01-01

    Abstract Endoscopic ultrasonography (EUS) is used for preoperative assessment of gastric cancer. However, recent studies suggested that EUS staging accuracy is lower than previously thought. We aimed to assess EUS efficacy and image characteristics in preoperative gastric cancer T staging. A retrospective review of clinical and imaging features of 232 gastric carcinoma patients who underwent preoperative EUS assessment of T stage was performed. Only cases with tumor-free resection margin status and no metastases were enrolled. Comparisons of preoperative EUS and postoperative histopathological stagings were also performed to identify vital EUS image features for evaluating gastric carcinoma. EUS accuracy for T staging was 64.2% (149/232) with the highest accuracy for T3 (75.0%). Enlarged lymph nodes, well differentiated histological type and Borrmann IV type were associated with diagnostic accuracy in predicting tumor invasion. Although no factors were associated with overstaging, circumferential lesions ≥1/2, signet ring cell adenocarcinoma, and Borrmann IV type had significantly higher risks of understaging. Gastric wall outer edge irregularity was also an indicator of serosal involvement with a sensitivity of 82.0%. The pancreas and colon were more frequent disease extension sites than previously predicted. Although EUS is likely the best and most accurate option that we have used to stage gastric cancer, the finding that factors including circumferential lesions, signet ring cell adenocarcinoma, and Borrmann IV type carcinoma were more frequently related to incorrect staging warrants attention. PMID:27603347

  5. The role of endoscopic ultrasound on the preoperative T staging of gastric cancer: A retrospective study.

    PubMed

    Han, Chaoqun; Lin, Rong; Shi, Huiying; Liu, Jun; Qian, Wei; Ding, Zhen; Hou, Xiaohua

    2016-09-01

    Endoscopic ultrasonography (EUS) is used for preoperative assessment of gastric cancer. However, recent studies suggested that EUS staging accuracy is lower than previously thought. We aimed to assess EUS efficacy and image characteristics in preoperative gastric cancer T staging.A retrospective review of clinical and imaging features of 232 gastric carcinoma patients who underwent preoperative EUS assessment of T stage was performed. Only cases with tumor-free resection margin status and no metastases were enrolled. Comparisons of preoperative EUS and postoperative histopathological stagings were also performed to identify vital EUS image features for evaluating gastric carcinoma.EUS accuracy for T staging was 64.2% (149/232) with the highest accuracy for T3 (75.0%). Enlarged lymph nodes, well differentiated histological type and Borrmann IV type were associated with diagnostic accuracy in predicting tumor invasion. Although no factors were associated with overstaging, circumferential lesions ≥1/2, signet ring cell adenocarcinoma, and Borrmann IV type had significantly higher risks of understaging. Gastric wall outer edge irregularity was also an indicator of serosal involvement with a sensitivity of 82.0%. The pancreas and colon were more frequent disease extension sites than previously predicted.Although EUS is likely the best and most accurate option that we have used to stage gastric cancer, the finding that factors including circumferential lesions, signet ring cell adenocarcinoma, and Borrmann IV type carcinoma were more frequently related to incorrect staging warrants attention. PMID:27603347

  6. Hepatoid Adenocarcinoma of the Urachus

    PubMed Central

    Jimenez, Carlos Andrés; Carrascal, Edwin

    2016-01-01

    Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI) reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP) and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis. PMID:27803830

  7. Oesophageal and gastric cancer in Scotland 1960-90.

    PubMed Central

    McKinney, A.; Sharp, L.; Macfarlane, G. J.; Muir, C. S.

    1995-01-01

    In Scotland over the last 31 years the incidence of gastric cancer has significantly declined by 0.6% per annum in males and 1.1% in females. In contrast, for oesophageal cancer, incidence rates have risen significantly by 3.0% and 2.0% per annum in males and females respectively. Increasing incidence of both adenocarcinomas and squamous carcinomas of the oesophagus in men and squamous and recently adenocarcinomas in women has been observed. This cannot be entirely accounted for by a growth in the proportion of histologically verified (HV) tumours over time. The incidence of adenocarcinoma of the stomach increased over the study period, most likely because of increasing proportions of HV tumours and improved diagnostic precision. Areas with high levels of deprivation in Scotland are strongly associated with high rates of oesophageal cancer in men, and of gastric cancer in both men and women. All these observations are discussed in the context of current knowledge of risk factors for these diseases. PMID:7841063

  8. Eradication Treatment of Helicobacter pylori Infection: Its Importance and Possible Relationship in Preventing the Development of Gastric Cancer

    PubMed Central

    Roesler, Bruna Maria; Costa, Sandra Cecília Botelho; Zeitune, José Murilo Robilotta

    2012-01-01

    Helicobacter pylori is the most important carcinogen for gastric adenocarcinoma. Bacterial virulence factors are essential players in modulating the immune response involved in the initiation of carcinogenesis in the stomach; host genetic factors contribute to the regulation of the inflammatory response and to the aggravation of mucosal damage. In terms of environmental factors, salt intake and smoking contribute to the development of lesions. Various therapeutic schemes are proposed to eradicate H. pylori infection, which could potentially prevent gastric cancer, offering the greatest benefit if performed before premalignant changes of the gastric mucosa have occurred. PMID:22778979

  9. Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma

    PubMed Central

    Lehenkari, Petri P.; Saarnio, Juha; Karttunen, Tuomo J.; Kauppila, Joonas H.

    2016-01-01

    Background Toll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett's esophagus, dysplasia and esophageal adenocarcinoma. Methods TLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99). Results We found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett's mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis. Conclusions TLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma. PMID:27008696

  10. Rebamipide inhibits gastric cancer growth by targeting survivin and Aurora-B

    SciTech Connect

    Tarnawski, A.; E-mail: andrzej.tarnawski@med.va.gov; Pai, R.; Chiou, S.-K.; Chai, J.; Chu, E.C.

    2005-08-19

    Rebamipide accelerates healing of gastric ulcers and gastritis but its actions on gastric cancer are not known. Survivin, an anti-apoptosis protein, is overexpressed in stem, progenitor, and cancer cells. In gastric cancer, increased and sustained survivin expression provides survival advantage and facilitates tumor progression and resistance to anti-cancer drugs. Aurora-B kinase is essential for chromosome alignment and mitosis progression but surprisingly its role in gastric cancer has not been explored. We examined in human gastric cancer AGS cells: (1) survivin expression, (2) localization of survivin and Aurora-B (3) cell proliferation, and (4) effects of specific survivin siRNA and/or rebamipide (free radical scavenging drug) on survivin and Aurora-B expression and cell proliferation. Survivin and Aurora-B are strongly expressed in human AGS gastric cancer cells and co-localize during mitosis. Survivin siRNA significantly reduces AGS cell viability. Rebamipide significantly downregulates in AGS cell survivin expression, its association with Aurora-B and cell proliferation. Rebamipide-induced downregulation of survivin is at the transcription level and does not involve ubiquitin-proteasome pathway.

  11. Epstein–Barr Virus in Gastro-Esophageal Adenocarcinomas – Single Center Experiences in the Context of Current Literature

    PubMed Central

    Genitsch, Vera; Novotny, Alexander; Seiler, Christian A.; Kröll, Dino; Walch, Axel; Langer, Rupert

    2015-01-01

    Epstein–Barr virus (EBV)-associated gastric carcinomas (GC) represent a distinct and well-recognized subtype of gastric cancer with a prevalence of around 10% of all GC. In contrast, EBV has not been reported to play a major role in esophageal adenocarcinomas (EAC) and adenocarcinomas of the gastro-esophageal junction (GEJ). We report our experiences on EBV in collections of gastro-esophageal adenocarcinomas from two surgical centers and discuss the current state of research in this field. Tumor samples from 465 primary resected gastro-esophageal adenocarcinomas (118 EAC, 73 GEJ, and 274 GC) were investigated. Presence of EBV was determined by EBV-encoded small RNAs (EBER) in situ hybridization. Results were correlated with pathologic parameters (UICC pTNM category, Her2 status, tumor grading) and survival. EBER positivity was observed in 14 cases. None of the EAC were positive for EBER. In contrast, we observed EBER positivity in 2/73 adenocarcinomas of the GEJ (2.7%) and 12/274 GC (4.4%). These were of intestinal type (seven cases) or unclassifiable (six cases), while only one case was of diffuse type according to the Lauren classification. No association between EBV and pT, pN, or tumor grading was found, neither was there a correlation with clinical outcome. None of the EBER positive cases were Her2 positive. In conclusion, EBV does not seem to play a role in the carcinogenesis of EAC. Moreover, adenocarcinomas of the GEJ show lower rates of EBV positivity compared to GC. Our data only partially correlate with previous reports from the literature. This highlights the need for further research on this distinct entity. Recent reports, however, have identified specific epigenetic and genetic alterations in EBV-associated GC, which might lead to a distinct treatment approach for this specific subtype of GC in the future. PMID:25859432

  12. Primary gastric tuberculosis mimicking gastric cancer

    PubMed Central

    Eray, İsmail Cem; Rencüzoğulları, Ahmet; Yalav, Orçun; Dalcı, Kubilay; Kakil, Erdem; Bağır, Emine; Parsak, Cem Kaan

    2015-01-01

    A 42-year-old female patient with no previous known diseases who had complaints of postprandial epigastric pain and weight loss and who could not be diagnosed by endoscopic biopsy, although gastric cancer was suspected radiologically and endoscopically, was diagnosed with primary gastric tuberculosis by laparotomy and frozen section. Following anti-tuberculosis treatment, a complete clinical, radiological, and endoscopic response was achieved. PMID:26504425

  13. Eosinophilic gastroenteritis associated with multiple gastric cancer.

    PubMed

    Otowa, Yasunori; Mitsutsuji, Masaaki; Urade, Takeshi; Chono, Teruhiro; Morimoto, Haruki; Yokoyama, Kunio; Hirata, Kenro; Kawamura, Shiro; Shimada, Etsuji; Fujita, Masayuki

    2012-06-01

    Eosinophilic gastroenteritis (EG) is an inflammation of the digestive tract that is characterized by eosinophilic infiltration. There are no specific symptoms, and are related to the layer in which eosinophilic infiltration is observed. A 69-year-old Japanese man presented to our hospital with a history of general malaise, diarrhea, and dysgeusia. Esophagogastroduodenoscopy showed reddish elevated lesions that were edematous all over the gastric mucosa. In addition, three tumors were also observed. The biopsies of the reddish elevated mucosa revealed eosinophilic infiltration and tubular adenocarcinoma from the tumors. Colonoscopy showed abnormal reddish elevated mucosa. The biopsies from the reddish elevated mucosa showed eosinophilic infiltration. From the abdominal contrast computed tomography scan, tumor stain was seen in the anterior wall of the gastric body. No ascites, intestinal wall thickening, or lymph node swelling were found. A slight elevation in the serum immunoglobulin E (IgE), 480 IU/ml, was found from the laboratory test results; other laboratory results were within normal limits including the number of peripheral eosinophils. No specific allergen was found from the multiple antigen simultaneous test and from the skin patch test. The parasitic immunodiagnosis was negative. He was diagnosed with EG associated with gastric cancer and underwent total gastrectomy, regional lymph node dissection with reconstruction by a Roux-en-Y method. He was prescribed prednisolone after the operation and showed a good clinical response. There are many case reports on EG, but none of them were associated with cancer. We encountered a case of EG associated with multiple gastric cancer; the patient underwent total gastrectomy.

  14. Wine and tobacco: risk factors for gastric cancer in France.

    PubMed

    Hoey, J; Montvernay, C; Lambert, R

    1981-06-01

    Cross-sectional studies in France have shown strong regional correlations between death rates from alcohol related diseases and death rates from gastric cancer. The present study involved 40 cases of newly diagnosed adenocarcinoma of the stomach and 168 control subjects with one of four other gastrointestinal diagnoses selected from the same hospital service during the same time period, 1978-1980. On the basis of a standard nutritional interview alcohol and particularly red wine were seen to be significant risk factors for this cancer (relative risks of 6.9 with 95% confidence limits (CL) of 3.3-14.3 for alcohol and 6.3 with CL 3.1-12.7 for wine). Smoking of one or more cigarettes per day was associated with a relative risk for gastric cancer of 4.8 with CL of 1.6-14.8. The presence of both risk factors was associated with a relative risk of 9.3 with 95% CL of 4.6-19.0. Possible confounding by age, smoking, and eating lettuce (a reported protective factor for gastric cancer in other studies) did not explain these results. The relative risks were consistently found and remained significant when each diagnostic group of control subjects was analyzed separately. These results suggest that alcohol, and particularly red wine, may be important risk factors for adenocarcinoma of the stomach in France. In addition, cigarette smoking, a risk factor in itself, when coupled with alcohol appears markedly to increase the risk.

  15. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

    PubMed Central

    Crabtree, Jean E.; Jeremy, Anthony H.T.; Duval, Cedric; Dixon, Michael F.; Danjo, Kazuma; Carr, Ian M.; Pritchard, D. Mark; Robinson, Philip A.

    2013-01-01

    Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR) and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H. pylori- induced gastric adenocarcinoma. PMID:25437333

  16. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  17. Gastric syphilis - Case report*

    PubMed Central

    Guimarães, Tais Ferreira; Novis, Camila Freitas Lobo; Bottino, Caroline Bertolini; D'Acri, Antonio Macedo; Lima, Ricardo Barbosa; Martins, Carlos José

    2016-01-01

    Gastric syphilis is an uncommon extracutaneous manifestation of syphilis, occurring in less than 1% of patients, presenting nonspecific clinical manifestations. In general, it occurs on secondary stage. The critical point is the recognition of the syphilitic gastric involvement, without which there may be incorrect diagnosis of malignancy of the digestive tract. In this report, a case of secondary syphilis with gastric involvement that had complete remission with benzathine penicillin will be described.

  18. [Gastric cancer in Taiwan].

    PubMed

    Wu, M S; Lin, J T; Lee, W J; Yu, S C; Wang, T H

    1994-09-01

    The study of gastric cancer is important in clinical medicine as well as in public health. Environmental factors play an important role in gastric carcinogenesis and thus primary prevention is feasible after improvement of these factors. The 5-year survival rate of resected early gastric cancer is over 90% and this provides an excellent paradigm for secondary prevention. Though its mortality rate has declined since 1970, gastric cancer remains common and carries a high mortality in Taiwan where about 2,000 patients die of gastric cancer annually. The age-adjusted mortality is 16.54 and 8.16/100,000 for male and female, ranking the third and fourth cancer death respectively. Epidemiologic data disclose a positive association between gastric cancer and some dietary factors in Taiwan. However, the role of Helicobacter pylori infection and hereditary susceptibility should be elucidated in the future. Endoscopy with biopsy is an excellent method of the diagnosis of gastric cancer. However, its invasiveness makes it impractical as a screening tool and thus the proportion of early gastric cancer to gastric cancer remains as low as 30% in most reports. The value of lymph node dissection remains controversial although surgery is one of the most effective methods of eradicating gastric cancer. Overall, the 5 year survival rate is 24.5% to 54%. Laser therapy is usually reserved for patients with high operative risk and specific types of gastric cancer. To improve the survival results, development of a simple and economic screening program based on the epidemiologic results and utilization of noninvasive examinations such as serologic markers to diagnose and treat gastric cancer at its earliest stage deserves further study.

  19. Application of Gold Nanorods for Photothermal Therapy in Ex Vivo Human Oesophagogastric Adenocarcinoma.

    PubMed

    Singh, Mohan; Harris-Birtill, David C C; Zhou, Yu; Gallina, Maria E; Cass, Anthony E G; Hanna, George B; Elson, Daniel S

    2016-03-01

    Gold nanoparticles are chemically fabricated and tuned to strongly absorb near infrared (NIR) light, enabling deep optical penetration and therapy within human tissues, where sufficient heating induces tumour necrosis. In our studies we aim to establish the optimal gold nanorod (GNR) concentration and laser power for inducing hyperthermic effects in tissues and test this photothermal effect on ex vivo human oesophagogastric adenocarcinoma. The ideal GNR concentration and NIR laser power that would elicit sufficient hyperthermia for tumour necrosis was pre-determined on porcine oesophageal tissues. Human ex vivo oesophageal and gastric adenocarcinoma tissues were incubated with GNR solutions and a GNR-free control solution with corresponding healthy tissues for comparison, then irradiated with NIR light for 10 minutes. Temperature rise was found to vary linearly with both the concentration of GNRs and the laser power. Human ex vivo oesophageal and gastric tissues consistently demonstrated a significant temperature rise when incubated in an optimally concentrated GNR solution (3 x 10(10) GNRs/ml) prior to NIR irradiation delivered at an optimal power (2 W/cm2). A mean temperature rise of 27 degrees C was observed in tissues incubated with GNRs, whereas only a modest 2 degrees C rise in tissues not exposed to any GNRs. This study evaluates the photothermal effects of GNRs on oesophagogastric tissue examines their application in the minimally invasive therapeutics of oesophageal and gastric adenocarcinomas. This could potentially be an effective method of clinically inducing irreversible oesophagogastric tumour photodestruction, with minimal collateral damage expected in (healthy) tissues free from GNRs. PMID:27280246

  20. Application of Gold Nanorods for Photothermal Therapy in Ex Vivo Human Oesophagogastric Adenocarcinoma.

    PubMed

    Singh, Mohan; Harris-Birtill, David C C; Zhou, Yu; Gallina, Maria E; Cass, Anthony E G; Hanna, George B; Elson, Daniel S

    2016-03-01

    Gold nanoparticles are chemically fabricated and tuned to strongly absorb near infrared (NIR) light, enabling deep optical penetration and therapy within human tissues, where sufficient heating induces tumour necrosis. In our studies we aim to establish the optimal gold nanorod (GNR) concentration and laser power for inducing hyperthermic effects in tissues and test this photothermal effect on ex vivo human oesophagogastric adenocarcinoma. The ideal GNR concentration and NIR laser power that would elicit sufficient hyperthermia for tumour necrosis was pre-determined on porcine oesophageal tissues. Human ex vivo oesophageal and gastric adenocarcinoma tissues were incubated with GNR solutions and a GNR-free control solution with corresponding healthy tissues for comparison, then irradiated with NIR light for 10 minutes. Temperature rise was found to vary linearly with both the concentration of GNRs and the laser power. Human ex vivo oesophageal and gastric tissues consistently demonstrated a significant temperature rise when incubated in an optimally concentrated GNR solution (3 x 10(10) GNRs/ml) prior to NIR irradiation delivered at an optimal power (2 W/cm2). A mean temperature rise of 27 degrees C was observed in tissues incubated with GNRs, whereas only a modest 2 degrees C rise in tissues not exposed to any GNRs. This study evaluates the photothermal effects of GNRs on oesophagogastric tissue examines their application in the minimally invasive therapeutics of oesophageal and gastric adenocarcinomas. This could potentially be an effective method of clinically inducing irreversible oesophagogastric tumour photodestruction, with minimal collateral damage expected in (healthy) tissues free from GNRs.

  1. What exists beyond cagA and vacA? Helicobacter pylori genes in gastric diseases.

    PubMed

    da Costa, Débora Menezes; Pereira, Eliane dos Santos; Rabenhorst, Silvia Helena Barem

    2015-10-01

    Helicobacter pylori (H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma. The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cagA and vacA genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cagA-negative. Several other virulence genes have been searched for, but these genes remain less well known that cagA and vacA. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and iceA based on the relevance shown in several studies in the literature.

  2. Perforated early gastric cancer: uncommon and easily missed a case report and review of literature.

    PubMed

    Lim, Raymond Hon Giat; Tay, Clifton Ming; Wong, Benjamin; Chong, Choon Seng; Kono, Koji; So, Jimmy Bok Yan; Shabbir, Asim

    2013-03-01

    Gastric carcinoma rarely presents as a perforation, but when it does, is perceived as advanced disease. The majority of such perforations are Stage III/IV disease. A T1 gastric carcinoma has never been reported to perforate spontaneously in English literature. We present a 56 year-old Chinese male who presented with a perforated gastric ulcer. Intra-operatively, there was no suspicion of malignancy. At operation, an open omental patch repair was performed. Post-operative endoscopy revealed a macroscopic Type 0~III tumour and from the ulcer edge biopsy was reported as adenocarcinoma. Subsequently, the patient underwent open subtotal gastrectomy and formal D2 lymphadenectomy. The final histopathology report confirms T1b N0 disease. The occurrence of a perforated early gastric cancer re-emphasises the need for vigilance, including intra-operative frozen section and/or biopsy, as well as routine post-operative endoscopy for all patients.

  3. Diagnosis and endoscopic treatment of esophago-bronchial fistula due to gastric heterotopy

    PubMed Central

    Katsanos, Konstantinos H; Christodoulou, Dimitrios K; Kamina, Sevasti; Maria, Kosmidou; Lambri, Evangelia; Theodorou, Stavroula; Tsampoulas, Konstantinos; Vasiliki, Mitsi; Tsianos, Epameinondas V

    2010-01-01

    Heterotopic gastric mucosa patches are congenital gastrointestinal abnormalities and have been reported to occur anywhere along the gastrointestinal tract from mouth to anus. Complications of heterotopic gastric mucosa include dysphagia, upper gastrointestinal bleeding, upper esophageal ring stricture, adenocarcinoma and fistula formation. In this case report we describe the diagnosis and treatment of the first case of esophago-bronchial fistula due to heterotopic gastric mucosa in mid esophagus. A 40-year old former professional soccer player was referred to our department for treatment of an esophago-bronchial fistula. Microscopic examination of the biopsies taken from the esophageal fistula revealed the presence of gastric heterotopic mucosa. We decided to do a non-surgical therapeutic endoscopic procedure. A sclerotherapy catheter was inserted through which 1 mL of ready to use synthetic surgical glue was applied in the fistula and it closed the fistula opening with excellent results. PMID:21160729

  4. Argininosuccinate synthetase 1 suppression and arginine restriction inhibit cell migration in gastric cancer cell lines.

    PubMed

    Shan, Yan-Shen; Hsu, Hui-Ping; Lai, Ming-Derg; Yen, Meng-Chi; Chen, Wei-Ching; Fang, Jung-Hua; Weng, Tzu-Yang; Chen, Yi-Ling

    2015-01-01

    Gastric cancer metastasis remains a major cause of cancer-related deaths. There is an urgent need to develop new therapeutic approaches targeting metastatic gastric cancer. Argininosuccinate synthetase 1 (ASS1) expression is increased in gastric cancer. We detected the protein expression of ASS1 in human gastric cancer cell lines (AGS, NCI-N87, and MKN45) and in murine gastric cancer cell lines (3I and 3IB2). We used vector-mediated short hairpin RNA (shRNA) expression to silence ASS1 expression in the MKN45 and 3IB2 cell lines, and analyzed the effects of this protein on cell migration and metastasis. We demonstrated that ASS1 silencing suppressed cell migration in the MKN45 and 3IB2 cell lines. ASS1 knockdown significantly reduced liver metastasis in mice after the intrasplenic implantation of 3IB2 cancer cell clones. To determine whether arginine restriction may represent a therapeutic approach to treat gastric cancer, the sensitivity of tumor cells to arginine depletion was determined in gastric cancer cells. Arginine depletion significantly inhibited cell migration in the gastric cancer cell line. The silencing of ASS1 expression in MKN45 and 3IB2 gastric cancer cells markedly decreased STAT3 protein expression. In conclusion, our results indicate that the ASS1 protein is required for cell migration in gastric cancer cell lines. PMID:25928182

  5. [The case of a solitary pulmonary tumor which could be diagnosed as early gastric cancer recurrence by detailed pathological examinations].

    PubMed

    Hayashi, Shigeya; Sato, Tsutomu; Yokose, Tomoyuki; Ito, Hiroyuki; Nakayama, Haruhiko; Segami, Kenki; Kawabe, Taichi; Aoyama, Toru; Makuuchi, Yousuke; Oshima, Takashi; Rino, Yasushi; Masuda, Munetaka; Ogata, Takashi; Cho, Haruhiko; Yoshikawa, Takaki

    2014-11-01

    We report the case of a solitary pulmonary tumor, which was diagnosed as recurrent early gastric cancer by detailed pathological examinations. A 59-year old man initially underwent total gastrectomy for gastric adenocarcinoma located at the esophago-gastric junction. A pathological examination indicated a papillary adenocarcinoma (pap ) that had invaded the submucosal layer (sm²), but had not metastasized to the regional lymph nodes (n0). The final diagnosis was P0H0M0T1bN0, Stage IA. Chest computed tomography (CT) 30 months after primary surgery indicated a solitary tumor with a diameter of 9 mm at S3 of the left lung. A positron emission tomography (PET)-CT scan showed an accumulation of ¹⁸F-fluordeoxy-glucose (FDG18) at the same location. Lung cancer was suspected and the patient was given a left upper lobectomy. The resected tumor was diagnosed as gastric cancer metastatic adenocarcinoma by permanent pathological examination. The tumors showed similar histology and immuno histochemical findings for CK7, CK20, TTF-1, SP-A, CDX-2, and HER2 . Early gastric cancer is an almost curable disease and recurrence is very rare. We report the details of this case and review the literature. PMID:25731547

  6. Correlation between Helicobacter pylori-associated gastric diseases and colorectal neoplasia

    PubMed Central

    Qing, Ying; Wang, Min; Lin, Ying-Min; Wu, Dong; Zhu, Jing-Yu; Gao, Lang; Liu, Yan-Yan; Yin, Teng-Fei

    2016-01-01

    AIM: To explore the correlation between Helicobacter pylori (H. pylori)-associated gastric diseases and colorectal neoplasia. METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenoscopy (EGD) along with histopathological measurement between March 2012 and March 2015 at Qi-Lu Hospital of Shandong University, who also had results of H. pylori detection. A total of 233 cases were selected. Demographic data, H. pylori infection status (including results of rapid urease tests and gastric mucosa pathological examinations) and histopathological examination results of gastric and colorectal mucosa were gathered and analyzed. The statistical analysis focused on the prevalence of colorectal neoplasms among patients with various histopathological categories of the stomach. ORs and their 95%CI were calculated to describe the strengths of the associations. RESULTS: The incidence rates of colorectal adenoma without high-grade intraepithelial neoplasia (HGIEN) (OR = 2.400, 95%CI: 0.969-5.941), adenoma with HGIEN (5.333, 1.025-27.758) and adenocarcinoma (1.455, 0.382-5.543) were all higher for patients with H. pylori-associated gastritis than for those in the control group. The incidence rate of colorectal adenoma with HGIEN (3.218, 0.767-13.509) was higher in patients with intestinal metaplasia than in the control group, while the incidence rates of adenoma without HGIEN (0.874, 0.414-1.845) and adenocarcinoma (0.376, 0.096-1.470) were lower in the intestinal metaplasia group than in the control group. The incidence rate of colorectal adenoma without HGIEN (3.111, 1.248-7.753) was significantly higher in the gastric intraepithelial neoplasia group than in the control group, while the rates of adenoma with HGIEN (1.481, 0.138-15.941) and adenocarcinoma (2.020, 0.561-7.272) were higher in the gastric intraepithelial neoplasia group. Incidence rates of colorectal adenoma without HGIEN (1.067, 0.264-4.314), adenoma with HGIEN (2.667, 0

  7. Pancreatic Adenocarcinoma Invading the Duodenum and Presenting as Idiopathic Gastroparesis with Nausea and Vomiting

    PubMed Central

    Cengia, Brent T.; Stuart, Paula S.

    2016-01-01

    A 65-year-old woman presented with a 5-month history of nausea, vomiting, and weight loss. Prior esophagogastrodudenoscopy showed retained food and delayed gastric emptying, but abdominal computed tomography was normal. The working diagnosis was idiopathic gastroparesis. Subsequently, an electrogastrogram test showed normal 3-cycle-per-minute activity, although it was suggestive of obstructive gastroparesis. Repeat esophagogastrodudenoscopy showed obstruction at the postbulbar duodenum. Repeat abdominal computed tomography revealed a 2.2 x 1.6-cm mass in the pancreaticoduodenal groove narrowing the descending duodenum and aspiration of the mass revealed adenocarcinoma. PMID:27807571

  8. Body iron status and gastric cancer risk in the EURGAST study.

    PubMed

    Fonseca-Nunes, Ana; Agudo, Antonio; Aranda, Núria; Arija, Victoria; Cross, Amanda J; Molina, Esther; Sanchez, Maria Jose; Bueno-de-Mesquita, H B As; Siersema, Peter; Weiderpass, Elisabete; Krogh, Vittorio; Mattiello, Amalia; Tumino, Rosario; Saieva, Calogero; Naccarati, Alessio; Ohlsson, Bodil; Sjöberg, Klas; Boutron-Ruault, Marie-Christine; Cadeau, Claire; Fagherazzi, Guy; Boeing, Heiner; Steffen, Annika; Kühn, Tilman; Katzke, Verena; Tjønneland, Anne; Olsen, Anja; Khaw, Kay-Tee; Wareham, Nick; Key, Tim; Lu, Yunxia; Riboli, Elio; Peeters, Petra H; Gavrila, Diana; Dorronsoro, Miren; Quirós, José Ramón; Barricarte, Aurelio; Jenab, Mazda; Zamora-Ros, Raúl; Freisling, Heinz; Trichopoulou, Antonia; Lagiou, Pagona; Bamia, Christina; Jakszyn, Paula

    2015-12-15

    Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2  = 0.80, 95% CI = 0.72-0.88; OR10%increment  = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 µg/dl  = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

  9. Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

    PubMed

    Jácome, Alexandre Andrade Dos Anjos; Lima, Enaldo Melo de; Kazzi, Ana Izabela; Chaves, Gabriela Freitas; Mendonça, Diego Cavalheiro de; Maciel, Marina Mara; Santos, José Sebastião Dos

    2016-04-01

    Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

  10. Spontaneous colonic adenocarcinoma in marmosets.

    PubMed

    Lushbaugh, C C; Humason, G L; Swartzendruber, D C; Richter, C B; Gengozian, N

    1978-01-01

    We find that colonic adenocarcinoma, which is an extremely rare neoplasm of all animals except man and carcinogen-treated rodents, occurs spontaneously in some marmosets. The cotton-topped Saguinus oedipus oedipus is particularly prone to develop it, but we have found it also at necropsy in Callimico goeldii (Goeldi's marmoset). Numerous metastases to regional lymph nodes develop. The cancers arise de novo in the mucosa and early invade the submucosa and lymphatic apparatus and paracolonic lymph nodes. These findings and the continuing occurrence of this cancer in our colony suggests that the marmoset may be the long-sought primate model for experimental intestinal carcinogenesis.

  11. Novel Therapeutics for Pancreatic Adenocarcinoma.

    PubMed

    Lowery, Maeve A; O'Reilly, Eileen M

    2015-08-01

    The last decade has seen significant developments in the use of combination systemic therapy for advanced pancreatic ductal adenocarcinoma (PDAC), with median survival approaching 1 year for select patients treated with FOLFIRINOX in the metastatic setting. However, it is sobering that these developments have been achieved with the use of traditional cytotoxics rather than from successes in the more modern fields of molecularly targeted therapies or immunotherapy. This article highlights several promising therapeutic approaches to PDAC currently under clinical evaluation, including immune therapies, molecularly targeted therapies, strategies for stromal depletion, and targeted therapy for genetically selected patients.

  12. Oncocytic adenocarcinoma of salivary glands.

    PubMed

    Goode, R K; Corio, R L

    1988-01-01

    Oncocytic adenocarcinoma of salivary gland origin is an extremely rare neoplasm. The diagnosis is established on the basis of oncocytic cellular features in conjunction with dysplastic change. These dysplastic changes may occur in benign oncocytomas or arise de novo. The tumor occurs most commonly in the parotid glands of persons over 60 years of age. Tumors that measure less than 2 cm at the initial surgical procedure appear to have a better prognosis than larger tumors. Aggressive surgical intervention at the initial presentation of the neoplasm, compared to simple enucleation, seems to offer a more favorable prognosis. Recurrence is an ominous feature. Metastasis, when it occurs, is widespread.

  13. Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer.

    PubMed

    He, Junyu; Zhu, Guangchao; Gao, Lu; Chen, Pan; Long, Yuehua; Liao, Shan; Yi, Hong; Yi, Wei; Pei, Zhen; Wu, Minghua; Li, Xiaoling; Xiang, Juanjuan; Peng, Shuping; Ma, Jian; Zhou, Ming; Xiong, Wei; Zeng, Zhaoyang; Xiang, Bo; Tang, Ke; Cao, Li; Li, Guiyuan; Zhou, Yanhong

    2015-11-01

    Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Fra-1 (FOSL1) plays important roles in oncogenesis in various malignancies. We investigated the expression of Fra-1 in gastric cancer (GC) tissues by qPCR, immunohistochemistry (IHC) and western blot technologies. The results showed that Fra-1 was overexpressed in gastric cancer tissues compared with the adjacent non‑cancerous tissues. To explore the possible mechanism of Fra-1 in GC, we elucidated the effect of Fra-1 in the apoptosis and cell cycle of gastric cancer cells, AGS, and found that a considerable decrease in apoptotic cells and increase of S phase rate were observed for AGS cells with Fra-1 overexpession. We identified and confirmed that Fra-1 affected the expression level of CTTN and EZR in vitro through LC-MS/MS analyses and western blot technology. Furthermore, we found that Fra-1 was correlated with dysregulation PI3K/Akt and p53 signaling pathway in gastric cancer tissues in vitro. Moreover, we found that Fra-1 overexpression affected the expression of PI3K, Akt, MDM2 and p53 in vivo. In summary, our results suggest that Fra-1 is upregulated in gastric cancer tissues and plays its function by affecting the PI3K/Akt and p53 signaling pathway in gastric cancer.

  14. 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

  15. hsa-miR-29c and hsa-miR-135b differential expression as potential biomarker of gastric carcinogenesis

    PubMed Central

    Vidal, Amanda Ferreira; Cruz, Aline MP; Magalhães, Leandro; Pereira, Adenilson L; Anaissi, Ana KM; Alves, Nélisson CF; Albuquerque, Paulo JBS; Burbano, Rommel MR; Demachki, Samia; Ribeiro-dos-Santos, Ândrea

    2016-01-01

    AIM: To investigate the expression profiles of hsa-miR-29c and hsa-miR-135b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-miR-29c and hsa-miR-135b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinal-type gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-miR-29c and hsa-miR-135b expression profiles in the grouped samples was evaluated by ANOVA and Student’s t-test tests. The results were adjusted for multiple testing by using Bonferroni’s correction. P values ≤ 0.05 were considered statistically significant. To evaluate hsa-miR-29c and hsa-miR-135b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-miR-29c and hsa-miR-135b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis. RESULTS: The expression levels of hsa-miR-29c were higher in normal gastric mucosal samples, and decreased progressively in non-atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal-type gastric adenocarcinoma samples. The expression of hsa-miR-29c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This microRNA (miRNA) has a good discriminatory accuracy between normal gastric samples and (1) intestinal-type gastric adenocarcinoma; and (2) intestinal metaplasia, and regulates the DMNT3A oncogene. hsa-miR-135b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples

  16. Duodenal Adenocarcinoma Metastatic to the Breast

    PubMed Central

    Yu, Haibo; Song, Hongliang; Jiang, Yi

    2016-01-01

    Abstract Duodenal adenocarcinoma, a very rare malignant gastrointestinal tumor, mainly metastasizes via the lymphatic system. Metastases from duodenal adenocarcinomas to the breast are very uncommon. A 31-year-old woman presented at our department with a left breast tumor. She had a past medical history of duodenal adenocarcinoma. Physical examination on admission confirmed a 2.5-cm-diameter tumor in the outer lower quadrant of the left breast. Computed tomography (CT) examination showed a soft lesion with tissue-like density and enlarged axillary lymph nodes. Local excision was performed to remove the breast lesion. The findings of cytologic, histologic, and immunohistochemistry examination indicated a breast metastasis from the previous duodenal adenocarcinoma. The patient was treated with palliative chemotherapy. Metastases from duodenal adenocarcinoma to the breast are rare. The diagnosis depends on medical history, imaging, and pathologic examination including immunohistochemistry. An accurate diagnosis is important to avoid unnecessary surgery. PMID:26986146

  17. Denervation suppresses gastric tumorigenesis

    PubMed Central

    Kodama, Yosuke; Muthupalani, Sureshkumar; Westphalen, Christoph B.; Andersen, Gøran T.; Flatberg, Arnar; Johannessen, Helene; Friedman, Richard A.; Renz, Bernhard W.; Sandvik, Arne K.; Beisvag, Vidar; Tomita, Hiroyuki; Hara, Akira; Quante, Michael; Li, Zhishan; Gershon, Michael D.; Kaneko, Kazuhiro; Fox, James G.; Wang, Timothy C.; Chen, Duan

    2015-01-01

    The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach. Vagotomy or botulinum toxin type A treatment also enhanced the therapeutic effects of systemic chemotherapy and prolonged survival. Denervation-induced suppression of tumorigenesis was associated with inhibition of Wnt signaling and suppression of stem cell expansion. In gastric organoid cultures, neurons stimulated growth in a Wnt-mediated fashion through cholinergic signaling. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic acetylcholine M3 receptor suppressed gastric tumorigenesis. In gastric cancer patients, tumor stage correlated with neural density and activated Wnt signaling, whereas vagotomy reduced the risk of gastric cancer. Together, our findings suggest that vagal innervation contributes to gastric tumorigenesis via M3 receptor–mediated Wnt signaling in the stem cells, and that denervation might represent a feasible strategy for the control of gastric cancer. PMID:25143365

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

    PubMed

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

    2015-05-14

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

  19. Protein Profiling Gastric Cancer and Neighboring Control Tissues Using High-Content Antibody Microarrays

    PubMed Central

    Sill, Martin; Schröder, Christoph; Shen, Ying; Marzoq, Aseel; Komel, Radovan; Hoheisel, Jörg D.; Nienhüser, Henrik; Schmidt, Thomas; Kastelic, Damjana

    2016-01-01

    In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much fewer molecules than the numbers usually identified in studies comparing tumor to healthy control tissues. Insulin-like growth factor-binding protein 7 (IGFBP7), S100 calcium binding protein A9 (S100A9), interleukin-10 (IL‐10) and mucin 6 (MUC6) exhibited the most profound variations. For an evaluation of the proteins’ capacity for discriminating gastric cancer, a Receiver Operating Characteristic curve analysis was performed, yielding an accuracy (area under the curve) value of 89.2% for distinguishing tumor from non-tumorous tissue. For confirmation, immunohistological analyses were done on tissue slices prepared from another cohort of patients with gastric cancer. The utility of the 17 marker proteins, and particularly the four molecules with the highest specificity for gastric adenocarcinoma, is discussed for them to act as candidates for diagnosis, even in serum, and targets for therapeutic approaches. PMID:27600085

  20. Treatment options in patients with metastatic gastric cancer: Current status and future perspectives

    PubMed Central

    Bilici, Ahmet

    2014-01-01

    Despite advances in the treatment of gastric cancer, it remains the world’s second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mainstay of treatment for these patients. However, no standard palliative chemotherapy regimen has been accepted for patients with metastatic gastric cancer. Palliative chemotherapy including fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival, and improves a high quality of life to a greater extent than best supportive care. The number of clinical investigations associated with targeted agents has recently increased. Agents targeting the epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 (HER2) have been widely tested. Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer. Trastuzumab in combination with chemotherapy was thus approved to be a new standard of care for patients with HER2-positive advanced esophagogastric adenocarcinoma. Thus, the evaluation of HER2 status in all patients with metastatic gastroesophageal adenocarcinoma should be considered. Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients. In this review, systemic chemotherapy and targeted therapies for metastatic gastric cancer in the first- and second-line setting are summarized in the light of recent advances. PMID:24744580

  1. Protein Profiling Gastric Cancer and Neighboring Control Tissues Using High-Content Antibody Microarrays.

    PubMed

    Sill, Martin; Schröder, Christoph; Shen, Ying; Marzoq, Aseel; Komel, Radovan; Hoheisel, Jörg D; Nienhüser, Henrik; Schmidt, Thomas; Kastelic, Damjana

    2016-01-01

    In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much fewer molecules than the numbers usually identified in studies comparing tumor to healthy control tissues. Insulin-like growth factor-binding protein 7 (IGFBP7), S100 calcium binding protein A9 (S100A9), interleukin-10 (IL-10) and mucin 6 (MUC6) exhibited the most profound variations. For an evaluation of the proteins' capacity for discriminating gastric cancer, a Receiver Operating Characteristic curve analysis was performed, yielding an accuracy (area under the curve) value of 89.2% for distinguishing tumor from non-tumorous tissue. For confirmation, immunohistological analyses were done on tissue slices prepared from another cohort of patients with gastric cancer. The utility of the 17 marker proteins, and particularly the four molecules with the highest specificity for gastric adenocarcinoma, is discussed for them to act as candidates for diagnosis, even in serum, and targets for therapeutic approaches. PMID:27600085

  2. Index-Based Dietary Patterns and Risk of Esophageal and Gastric Cancer in a Large Cohort Study

    PubMed Central

    Li, Wen-Qing; Park, Yikyung; Wu, Jennifer W.; Ren, Jian-Song; Goldstein, Alisa M.; Taylor, Philip R.; Hollenbeck, Albert R.; Freedman, Neal D.; Abnet, Christian C.

    2013-01-01

    Background & Aims Diet could affect risk for esophageal and gastric cancers, but associations have been inconsistent. The diet is complex, so studies of dietary patterns, rather than studies of individual foods, might be more likely to identify cancer risk factors. There is limited research on index-based dietary patterns and esophageal and gastric cancers. We prospectively evaluated associations between the Healthy Eating Index-2005 (HEI-2005) and alternate Mediterranean Diet (aMED) scores and risk of esophageal and gastric cancers. Methods We analyzed data from 494,968 participants in the National Institutes of Health (NIH)-AARP Diet and Health study, in which AARP members (51–70 y old) completed a self-administered baseline food frequency questionnaire between 1995 and 1996. Their answers were used to estimate scores for each index. Results During the follow-up period (1995–2006), participants developed 215 esophageal squamous cell carcinomas (ESCCs), 633 esophageal adenocarcinomas (EACs), 453 gastric cardia adenocarcinomas, and 501 gastric non-cardia adenocarcinomas. Higher scores from the HEI-2005 were associated with a reduced risk of ESCC (comparing the highest quintile with the lowest: hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.31–0.86; Ptrend=.001) and EAC (HR, 0.75; 95% CI, 0.57–0.98; Ptrend=.01). We observed an inverse association between ESCC, but not EAC, and higher aMED score (meaning a higher-quality diet). HEI-2005 and aMED scores were not significantly associated with gastric cardia or noncardia adenocarcinomas. Conclusions Using data collected from 1995 through 2006 from the NIH-AARP Diet and Health Study, HEI-2005 and aMED scores were inversely associated with risk for esophageal cancers—particularly ESCC. Adherence to dietary recommendations might help prevent esophageal cancers. PMID:23591281

  3. Advanced mucinous adenocarcinoma in pregnancy.

    PubMed

    Angioli, R; Yasin, S; Estape, R; Janicek, M; Adra, A; Sopo, C; Minhaj, M; Penalver, M

    1997-01-01

    The incidence of masses in pregnancy is estimated to occur in 1/81 to 1/2,500 pregnancies. The development of colorectal carcinoma during pregnancy is a more rare event, with less than 30 cases above the peritoneal reflection reported in the last 70 years. The differential diagnosis of mucinous adenocarcinoma of ovarian vs. gastrointestinal origin is often difficult. We report a pregnant patient affected by advanced colorectal cancer, who presented with an asymptomatic unilateral adnexal mass on ultrasound. A 28-year old woman was referred to our hospital after a routine ultrasound examination at 26 weeks gestation showing a right adnexal mass. At elective exploratory laparotomy, the patient was found to have metastatic mucinous adenocarcinoma. Diagnostic and treatment choices of such a cancer in a pregnant patient were explored. The final diagnosis of colorectal cancer was made only at the time of a subsequent emergency laparotomy. The goal of an obstetrician/gynecologist and other care givers of pregnant patients, is to achieve a healthy mother and child. Unfortunately, physicians may unwillingly sacrifice the health of the mother by denying or delaying her procedures or treatments simply because she is pregnant. It is especially important in the case of adnexal masses and their related pathology, due to the difficulty in detection and management of such cases during pregnancy, that doctors actively assume the responsibility of assuring that pregnant patients receive the proper care they need.

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

    PubMed

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

    2014-09-01

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

  5. Ramucirumab for gastric cancer.

    PubMed

    Shitara, Kohei; Ohtsu, Atsushi

    2015-02-01

    In recent years, various molecular target agents have been investigated for gastric cancer. VEGF is one of the most potent angiogenic factors and is a signaling molecule secreted by many solid tumors. High VEGF expression is one of the characteristic features of gastric carcinomas, thus targeting VEGF is considered a promising strategy for gastric cancer. Ramucirumab, an anti-VEGF receptor antibody, has proven to be effective for previously treated advanced gastric cancer. Details of ramucirumab, including two pivotal Phase III studies, will be discussed in this review. Ramucirumab, with or without chemotherapy, improved survival in gastric cancer after previous systemic chemotherapy, thus becoming the standard of care for this patient population. Optimal timing of ramucirumab use and adequate biomarkers for patient selection as well as mechanism of resistance should be explored in future research.

  6. [Intermediate gastric cancer].

    PubMed

    Fontán, A N; Marzano, C A; Martínez, M M; Palau, G; Rubio, H H

    1980-01-01

    Gastric Cancer comprises two basic types: Advanced Gastric Cancer (A.G.C.) and Early Gastric Cancer (E.G.C.). A.G.C. extends beyond the proper muscle layer with a 5 to 17%, five years survival rate after surgery. E.G.C. does not extend beyond the submucosa (with or without metastasis to regional lymph nodes) and has a 80 - 95% five years survival rate. Intermediate Gastric Cancer, PM G.C. (Gastric cancer of the proper muscle layer) does not surpass the proper muscle layer and offers a five years life expectance of near 60% after adequate surgical treatment, with peculiar features in radiology, endoscopy and evolutivity. We report a case of PM G.C., "depressed" and "protruded". The proper muscle layer was invaded by the depressed lesion". Both lesions were continguous.

  7. Study of gastric cancer samples using terahertz techniques

    NASA Astrophysics Data System (ADS)

    Wahaia, Faustino; Kasalynas, Irmantas; Seliuta, Dalius; Molis, Gediminas; Urbanowicz, Andrzej; Carvalho Silva, Catia D.; Carneiro, Fatima; Valusis, Gintaras; Granja, Pedro L.

    2014-08-01

    In the present work, samples of healthy and adenocarcinoma-affected human gastric tissue were analyzed using transmission time-domain THz spectroscopy (THz-TDS) and spectroscopic THz imaging at 201 and 590 GHz. The work shows that it is possible to distinguish between normal and cancerous regions in dried and paraffin-embedded samples. Plots of absorption coefficient α and refractive index n of normal and cancer affected tissues, as well as 2-D transmission THz images are presented and the conditions for discrimination between normal and affected tissues are discussed.

  8. Nucleic acid-sensing toll-like receptors 3, 7 and 8 in esophageal epithelium, barrett's esophagus, dysplasia and adenocarcinoma.

    PubMed

    Helminen, Olli; Huhta, Heikki; Lehenkari, Petri P; Saarnio, Juha; Karttunen, Tuomo J; Kauppila, Joonas H

    2016-05-01

    Toll-like receptors (TLRs) are immunological receptors recognizing various microbial and endogenous ligands, such as DNA, RNA, and other microbial and host components thus activating immunological responses. The expression of TLRs in esophageal adenocarcinoma is not well known. The aim of this study was to evaluate expression patterns of those TLRs that sense nucleic acids in Barrett's esophagus with and without dysplasia and in esophageal adenocarcinoma. TLRs 3, 7 and 8 were stained immunohistochemically and evaluated in a cohort of patients with esophageal adenocarcinoma or dysplasia. Specimens with normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were studied. We used immunofluorescence to confirm the subcellular localization of TLRs. We found abundant expression of TLR3, 7 and 8 in esophageal squamous epithelium, columnar metaplasia, dysplasia and adenocarcinoma. Cytoplasmic expression of TLR3, TLR7 or TLR8 did not associate to clinicopathological parameters or prognosis in esophageal cancer. High nuclear expression of TLR8, confirmed with immunofluorescence, in cancer cells was observed in tumors of high T-stage (p < 0.01) and in tumors with organ metastasis (p < 0.001). High nuclear TLR8 expression was associated with poor prognosis (p < 0.001). The expression of TLR3, TLR7 and TLR8 increased toward dysplasia and adenocarcinoma. We demonstrated nuclear localization of TLR8, which associates with metastasis and poor prognosis. TLR3 and TLR7 do not seem to have prognostic significance in esophageal adenocarcinoma. PMID:27467941

  9. Expression of e-cadherin, alpha-catenins and Beta-catenins in human gastric carcinomas - correlation with histology and tumor progression.

    PubMed

    Yasui, W; Kuniyasu, H; Akama, Y; Kitahara, K; Nagafuchi, A; Ishihara, S; Tsukita, S; Tahara, E

    1995-01-01

    The expression of cell-cell adhesion molecule, E-cadherin and its associated proteins, alpha- and beta-catenins in human gastric carcinomas was examined by Western blotting. All the seven gastric carcinoma cell lines expressed E-cadherin except KATOIII, which was derived from pleural effusion of a scirrhous type stomach cancer or Borrmann's type-4 carcinoma. The expression of alpha-catenin was not detected in HSC43 derived from scirrhous carcinoma, while HSC39 expressed abnormal beta-catenin caused by genetic alteration. In gastric carcinoma cases, the levels of E-cadherin and alpha-catenin were significantly lower in poorly differentiated adenocarcinomas and scirrhous carcinomas when compared to other types of gastric carcinomas. Deeply invasive carcinomas expressed E-cadherin and alpha-catenin at lower levels. However, the expression level of alpha-catenin was not necessarily consistent with that of E-cadherin. One of 10 gastric carcinomas examined showed complete deletion of alpha-catenin gene in Southern blotting. beta-catenin was expressed at lower level in poorly differentiated adenocarcinomas than in well-differentiated adenocarcinomas. These findings suggest that reduction in the expression of E-cadherin and its associated molecules, catenins, is involved in the development and infiltrative growth of scirrhous type gastric carcinomas. PMID:21597700

  10. AGS II

    SciTech Connect

    Palmer, R.B.

    1984-01-01

    Interest in rare K decays, neutrino oscillations and other fields have generated an increasing demand for running, and improved intensity and duty cycle, at the AGS. Current projects include acceleration of polarized protons and light ions (up to mass 32). Future plans are for a booster to increase intensity and allow heavy ions (up to mass 200), and a stretcher to give 100% duty cycle. A later upgrade could yield an average current of 32 ..mu.. amps. 6 figures, 2 tables.

  11. Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota

    PubMed Central

    Whary, Mark T.; Muthupalani, Sureshkumar; Ge, Zhongming; Feng, Yan; Lofgren, Jennifer; Shi, Hai Ning; Taylor, Nancy S.; Correa, Pelayo; Versalovic, James; Wang, Timothy C.; Fox, James G.

    2014-01-01

    Higher prevalence of helminth infections in H. pylori infected children was suggested to potentially lower the life-time risk for gastric adenocarcinoma. In rodent models, helminth co-infection does not reduce Helicobacter-induced inflammation but delays progression of pre-malignant gastric lesions. Because gastric cancer in INS-GAS mice is promoted by intestinal microflora, the impact of Heligmosomoides polygyrus co-infection on H. pylori-associated gastric lesions and microflora were evaluated. Male INS-GAS mice co-infected with H. pylori and H. polygyrus for 5 months were assessed for gastrointestinal lesions, inflammation-related mRNA expression, FoxP3+ cells, epithelial proliferation, and gastric colonization with H. pylori and Altered Schaedler Flora. Despite similar gastric inflammation and high levels of proinflammatory mRNA, helminth co-infection increased FoxP3+ cells in the corpus and reduced H. pylori-associated gastric atrophy (p<0.04), dysplasia (p<0.02) and prevented H. pylori-induced changes in the gastric flora (p<0.05). This is the first evidence of helminth infection reducing H. pylori-induced gastric lesions while inhibiting changes in gastric flora, consistent with prior observations that gastric colonization with enteric microbiota accelerated gastric lesions in INS-GAS mice. Identifying how helminths reduce gastric premalignant lesions and impact bacterial colonization of the H. pylori infected stomach could lead to new treatment strategies to inhibit progression from chronic gastritis to cancer in humans. PMID:24513446

  12. Small bowel diverticulosis in patient with early gastric cancer

    PubMed Central

    Kim, Pyeong Su; Jung, Eun-Joo

    2014-01-01

    Jejunal and ileal diverticula are rare in adults. Duodenal diverticula are five times more prevalent than jejunoileal diverticula. Most patients are asymptomatic. However, chronic symptoms including intermittent abdominal pain, flatulence, diarrhea and constipation are seen in 10%-30% of patients. Gastric cancer is the second most common cancer in South Korea and here we report a case of early gastric cancer with multiple duodenal and jejunal diverticula. A 67-year-old woman was admitted to Konkuk University Medical Center with chronic diarrhea and weight loss of 19 kg over 2 months. Following gastroduodenoscopy, we identified adenocarcinoma of the lower body of the stomach. On abdominopelvic computed tomography, diverticula of duodenum and jejunum were found. Patient underwent distal gastrectomy and gastroduodenostomy with lymphadenectomy. She was discharged on the tenth postoperative day without complications. PMID:25317417

  13. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs.

    PubMed

    Slot, A; Meerwaldt, J H; van Putten, W L; Treurniet-Donker, A D

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma (T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fractions in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial. PMID:2616813

  14. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs.

    PubMed

    Slot, A; Meerwaldt, J H; van Putten, W L; Treurniet-Donker, A D

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma (T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fractions in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial.

  15. Tests of gastric neuromuscular function.

    PubMed

    Parkman, Henry P; Jones, Michael P

    2009-05-01

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

  16. Simultaneous quadruple modal nonlinear optical imaging for gastric diseases diagnosis and characterization

    NASA Astrophysics Data System (ADS)

    Wang, Zi; Zheng, Wei; Lin, Jian; Huang, Zhiwei

    2015-03-01

    We report the development of a unique simultaneous quadruple-modal nonlinear optical microscopy (i.e., stimulated Raman scattering (SRS), second-harmonic generation (SHG), two-photon excitation fluorescence (TPEF), and third-harmonic generation (THG)) platform for characterization of the gastric diseases (i.e., gastritis, intestinal metaplasia (IM), intestinal type adenocarcinoma). SRS highlights the goblet cells found in IM. SHG images the distribution of collagen in lamina propria. Collagen is found to aggregate for intestinal type adenocarcinoma. TPEF reveals the cell morphology and can reflect the damage inside glands caused by the diseases. THG visualizes the nuclei with high spatial resolution, which facilitates the identification of neutrophils that are usually used as a feature of inflammation. This work shows that the co-registration of quadruple-modal images can be an effective means for diagnosis and characterization of gastric diseases at the cellular and molecular levels.

  17. Gastric Cancer Presenting as a Krukenberg Tumor at 22 Weeks' Gestation

    PubMed Central

    Gupta, Ashutosh; Attar, Bashar M; Demetria, Melchor

    2014-01-01

    Gastric cancer is rare during pregnancy, and often advanced upon presentation. A Krukenberg tumor presents a diagnostic and therapeutic challenge in the pregnant patient. We present a case of a 38-year-old woman at 22 weeks' gestation who presented with worsening epigastric pain, and was found to have a left pelvic mass on ultrasound, which was confirmed by magnetic resonance imaging. She went into active labor and delivered a viable infant via vaginal delivery. An exploratory laparotomy revealed a large mass originating from her left ovary and diffuse thickening of the lesser curvature of the stomach. Frozen section investigation revealed the presence of signet cell adenocarcinoma. Subsequent upper endoscopy showed linitis plastica, while biopsy confirmed the presence of adenocarcinoma. In conclusion, the occurrence of gastric cancer in pregnancy is rare despite extremely common symptoms. The management poses a challenge because of the need for early treatment, and the continuation of the pregnancy. PMID:25580361

  18. Resistin-Like Molecule-β Promotes Invasion and Migration of Gastric Carcinoma Cells

    PubMed Central

    Jiang, Rui; Zhao, Chunming; Wang, Xinyu; Wang, Shengxi; Sun, Xiaogang; Tian, Yang; Song, Wei

    2016-01-01

    Background Resistin-like molecule-β (RELMβ) is a novel secretory protein from intestinal goblet cells and participates in epithelial differentiation, tumor occurrence, and immune response. RELMβ is absent in normal gastric mucosa but is abundantly expressed in gastric carcinoma tissues, and is correlated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) is an important mechanism governing tumor cell invasion. This study thus investigated the modulation of RELMβ in gastric cancer metastasis and its correlation with EMT. Material/Methods We used RELMβ-low expression AGS cell line of gastric cancer and normal mucosa cell line GES1 as in vitro models, on which RELMβ0-expressing vector was transfected. The invasion and migration of cells were quantified by Transwell assay. EMT-related protein including E-cadherin, N-cadherin, Snail, and Vimentin were detected by Western blotting in transfected AGS cells. Results RELMβ transfection significantly potentiated invasion and migration abilities of AGS cells, whose RELMβ protein level was significantly elevated compared to those in untransfected AGS or GES1 cells. After RELMβ transfection, EMT-related proteins, including N-cadherin, Snail, and Vimentin levels, were elevated, but E-cadherin expression was depressed. Conclusions RELMβ-overexpression can facilitate invasion and migration of gastric carcinoma cells and it increases the expression of EMT-related proteins, such as N-cadherin, Snail, Vimentin, but decreases E-cadherin level, thus promoting the progression of EMT. PMID:27001185

  19. Interleukin 6 gene polymorphism -174 is associated with the diffuse type gastric carcinoma.

    PubMed

    Pohjanen, Vesa-Matti; Koivurova, Olli-Pekka; Mäkinen, Johanna M; Karhukorpi, Jari M; Joensuu, Tapio; Koistinen, Pentti O; Valtonen, Jarno M; Niemelä, Seppo E; Karttunen, Riitta A; Karttunen, Tuomo J

    2013-10-01

    The aim of this study was to assess the significance of the interleukin 6 gene polymorphism -174 in gastric cancer risk. The interleukin 6 -174 G/C (rs1800795) gene polymorphisms was analyzed in gastric cancer, peptic ulcer, and nonulcer dyspepsia patients and in healthy control subjects and the data were correlated with the histopathological features of the patients' biopsies. The interleukin 6 -174 GG and GC genotypes have been previously associated with high interleukin 6 serum levels. We discovered that the interleukin 6 -174 GG and GC genotypes are associated with an increased risk of the diffuse histologic subtype of gastric carcinomas (OR: 6.809, P = 0.034), but absent in the intestinal type carcinomas (OR: 1.109, P = 0.908). No significant associations with peptic ulcer, gastric atrophy, or intestinal metaplasia were seen. Our results demonstrate that the interleukin 6 -174 GG and GC genotypes increase the risk of the diffuse type gastric carcinoma, but not the intestinal type gastric carcinoma or its precursor conditions, including atrophy or intestinal metaplasia. Thus, interleukin 6 seems to be an important carcinogenetic factor in the diffuse type gastric adenocarcinoma and its carcinogenetic effect could be noninflammatory.

  20. Salivary gland tumours studied by means of the AgNOR technique.

    PubMed

    Morgan, D W; Crocker, J; Watts, A; Shenoi, P M

    1988-11-01

    Difficulty is sometimes encountered in distinguishing between pleomorphic adenoma, adenoid cystic carcinoma and adenocarcinoma, especially in small biopsies from salivary glands. The argyrophil (AgNOR) staining technique for nucleolar organizer regions (NORs) has been applied to a series of benign and malignant salivary gland tumours. We studied 35 salivary gland tumours, 13 benign and 22 malignant. In all specimens clearly defined silver-stained intranuclear AgNOR dots were visible. The differences between the numbers of AgNORs in the benign and malignant groups, notably pleomorphic adenomas, adenoid cystic carcinoma and adenocarcinoma, were highly significant. In view of this difference we propose that the AgNOR staining technique is of diagnostic help in distinguishing between these salivary gland tumours.

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

    PubMed

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

    2016-09-01

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

  2. Gastric conduit perforation.

    PubMed

    Patil, Nilesh; Kaushal, Arvind; Jain, Amit; Saluja, Sundeep Singh; Mishra, Pramod Kumar

    2014-08-16

    As patients with carcinoma of the esophagus live longer, complications associated with the use of a gastric conduit are increasing. Ulcers form in the gastric conduit in 6.6% to 19.4% of patients. There are a few reports of perforation of a gastric conduit in the English literature. Almost all of these were associated with serious complications. We report a patient who developed a tension pneumothorax consequent to spontaneous perforation of an ulcer in the gastric conduit 7 years after the index surgery in a patient with carcinoma of the gastroesophageal junction. He responded well to conservative management. Complications related to a gastric conduit can be because of multiple factors. Periodic endoscopic surveillance of gastric conduits should be considered as these are at a higher risk of ulcer formation than a normal stomach. Long term treatment with proton pump inhibitors may decrease complications. There are no guidelines for the treatment of a perforated gastric conduit ulcer and the management should be individualized.

  3. Laparoscopic removal of gastric band after laparoscopic gastric bypass and following placement of adjustable gastric band

    PubMed Central

    Lanaia, Andrea; Zizzo, Maurizio; Cartelli, Concetto M.; Fumagalli, Matteo; Bonilauri, Stefano

    2015-01-01

    Banded gastric bypass is a bariatric surgical intervention that has been regularly performed in many centers. According to some series, banded gastric bypass is safe and feasible. We describe the case of a 42-year-old woman undergoing laparoscopic gastric bypass in 2008. Subsequently, she underwent surgery in order to place adjustable gastric banding on previous bypass because of gastric pouch dilatation. Five months later, patient showed anorexia and signs of malnutrition. For this reason, she underwent laparoscopic removal of gastric banding. In our opinion, placing a device to restrict an already dilated gastric pouch must be avoided. PMID:26232597

  4. An Unusual Case of Gastric Cancer Presenting with Breast Metastasis with Pleomorphic Microcalcifications

    PubMed Central

    Ka, Solomon Yig Joon; Lo, Sherwin Shing Wai; Chu, Chi Yeung; Ma, Ming Wai

    2012-01-01

    Breast metastasis from gastric carcinoma is rare. We present a case of right breast mass with microcalcification in which the diagnosis of poorly differentiated adenocarcinoma from the stomach was made after a biopsy. Pleomorphic microcalcification was noted in the ill-defined breast mass, which is a rare feature in breast metastasis. Since breast metastasis usually signifies advanced metastatic disease, differentiating primary breast cancer from metastasis is important for appropriate treatment. PMID:23091550

  5. Relationship Between Interleukin-10 Gene C-819T Polymorphism and Gastric Cancer Risk: Insights From a Meta-Analysis.

    PubMed

    Cui, Xigang; Huang, Qingxian; Li, Xianglin; Liu, Fang; Wang, Dan; Yan, Dong; Wang, Bin; Yang, Chunhua; Mi, Jia; Tian, Geng

    2016-01-01

    BACKGROUND As a pleiotropic cytokine, interleukin-10 (IL-10) plays a regulatory role in carcinogenesis and tumor growth. The aim of this meta-analysis was to assess the susceptibility of the IL-10 gene C-819T polymorphism to gastric cancer. MATERIAL AND METHODS Study identification and data extraction were independently completed by 2 authors. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated and summarized. RESULTS In total, 11 articles including 1960 gastric cancer patients and 3705 controls were qualified. Overall analyses revealed a 13% reduced risk of gastric cancer conferred by the -819T allele relative to the -819C allele (OR=0.87; 95% CI: 0.77-0.97; P=0.016), without heterogeneity (I2=35.1%). In subgroup analyses, a significant difference was identified in East Asian populations (OR=0.85; 95% CI: 0.73-0.98; P=0.029, I2=43.6%), for gastric adenocarcinoma (OR=0.80; 95% CI: 0.66-0.96; P=0.017, I2=0.0%), and in population-based studies (OR=0.81; 95% CI: 0.70-0.93; P=0.003, I2=0.0%). The visual funnel plots and Egger's tests suggested no evidence of publication bias. CONCLUSIONS Extending previous findings, we demonstrate a protective role of the IL-10 gene -819T allele in susceptibility to gastric cancer, and this role was more evident for gastric adenocarcinoma. PMID:27516059

  6. Pattern-recognition receptors and gastric cancer.

    PubMed

    Castaño-Rodríguez, Natalia; Kaakoush, Nadeem O; Mitchell, Hazel M

    2014-01-01

    Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy.

  7. Pattern-Recognition Receptors and Gastric Cancer

    PubMed Central

    Castaño-Rodríguez, Natalia; Kaakoush, Nadeem O.; Mitchell, Hazel M.

    2014-01-01

    Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy

  8. Bursectomy in gastric cancer surgery: surgical technique and operative safety.

    PubMed

    Blouhos, Konstantinos; Boulas, Konstantinos A; Hatzigeorgiadis, Anestis

    2013-06-01

    Although there is little evidence that bursectomy has clinical benefit, its continuing practice imposes evaluation of bursectomy-related adverse effects, especially pancreatic fistula and intestinal obstruction. The aims of this study were to provide a detailed description of the technique of bursectomy as standardized by the authors and determine if extended surgery for gastric cancer with additional bursectomy can be performed safely in Western population. A total of 72 consecutive patients of median age 76.4 years and mean ASA score grade 2.1, who submitted to D2 or D2+ gastrectomy with additional bursectomy for gastric adenocarcinoma, were prospectively studied. Bursectomy was associated with a median additional operative time of 41 min and a median additional blood loss of 65 ml. The post-operative morbidity rate was 19.4 %. Among various adverse events, pancreatic fistula was observed in three patients (4.2 %) and intestinal obstruction was observed in eight patients (11.1 %) including two cases of delayed gastric emptying, one case of afferent loop syndrome, one case of early postoperative adhesions and four cases of prolonged postoperative ileus. The in-hospital mortality rate was 1.4 %. D2 or D2+ gastrectomy with additional bursectomy can be safely performed in Western patients. Although the incidence of pancreatic fistula that we reported was low, the incidence of bursectomy-related intestinal obstruction was high and should always be kept in mind when performing extended surgery for gastric cancer. PMID:23592040

  9. Microsatellite instability and loss of heterozygosity in gastric cancer

    SciTech Connect

    Schneider, B.G.; Pulitzer, D.R.; Moehlmann, R.D.

    1994-09-01

    In order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we evaluated loss of heterozygosity (LOH) in 78 gastric adenocarcinomas. A total of 46 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome, including several markers linked to known tumor suppressor genes (TP53, APC, DCC, RB1, and BRCA1). We detected elevated rates of LOH at D3S1478 on chromosome 3p21 (44%, or 22 of 50 cases), at D12S78 at 12q14q24.33 (39%), and 37% at D9S157 on 9p, three sites not previously known to be affected in gastric cancer. Another locus on chromosome 12q, D12S97, showed LOH in 40% of informative cases. LOH was detected on chromosome 17p near TP53 in 66% of informative cases (23 of 35). Microsatellite instability (MI) was observed in 22% of the cancers. Tumors varied greatly in percentage of sites exhibiting MI, from 0% to 77% of sites tested. These findings expand the description of the genetic lesions occurring in gastric cancer.

  10. Potential role of aquaporin 3 in gastric intestinal metaplasia

    PubMed Central

    Zhao, Haijian; Yang, Xiaojun; Zhou, Yangchun; Zhang, Weiming; Wang, Yao; Wen, Jianfei; Zhang, Zhihong; Shen, Lizong

    2015-01-01

    Gastric intestinal metaplasia (GIM) is a pre-cancerous condition and a pivotal step in the formation of gastric cancer (GC). Aquaporin 3 (AQP3) has been found to be expressed in goblet cells rather than mucus-secreting glands. To investigate the characteristics of GIM in non-cancerous tissues adjacent to GC, as well as the expression and role of AQP3 in GIM tissues, 16 patients diagnosed with gastric adenocarcinoma of intestinal type located in the lesser curve of the antrum were consecutively enrolled in this study. A new pathological technology called “gastric mucosal sausage roll” was introduced. GIM was determined according to the updated Sydney system, and AQP3 expression in goblet cells was determined by immunohistochemistry. GIM was found in all stomach specimens, and its incidence increased with progression to GC (P < 0.001). GIM prevalence displayed remarkable association with the distance to GC in the anterior gastric wall tissues (P = 0.016) and tissues toward the cardia (P = 0.014), such that GIM was more common in the areas closer to GC (P < 0.001). AQP3 was found to be expressed in 67.71% of parts with GIM, and AQP3 immunoreactivity was identified more frequently in severe GIM areas (P < 0.001). In short, the incidence and severity of GIM correlated with the distance from GC, and AQP3 was differentially expressed in goblet cells, with most AQP3-positive goblet cells presenting in severe GIM. Together, this study suggests that AQP3 may play an important role in gastric carcinogenesis from GIM. PMID:26506416

  11. [Alpha Fetoprotein-producing Lung Adenocarcinoma].

    PubMed

    Komori, Kazuyuki; Tabata, Toshiharu; Sato, Kimiaki; Katsumata, Hiroshi; Minowa, Muneo; Kondo, Takashi

    2015-11-01

    We report a case of alpha fetoprotein (AFP) -producing lung adenocarcinoma. A 53-year-old man was referred to our hospital due to right pneumothorax. Computed tomography showed right moderate pneumothorax, a solid tumor in the upper lobe (S3) and mediastinal lymph node swelling. The serum AFP level was as high as 223.0 ng/ml. Frozen examination revealed a low-differentiated adenocarcinoma. Based on the pathological and immunohistochemical findings, the tumor was diagnosed as AFP-producing lung adenocarcinoma.

  12. Gastric cancer detection in gastric ulcer disease.

    PubMed Central

    Mountford, R A; Brown, P; Salmon, P R; Alvarenga, C; Neumann, C S; Read, A E

    1980-01-01

    A retrospective study has been performed of all cases of gastric ulcer diagnosed or investigated within the Endoscopy Unit of the Department of Medicine, Bristol, over a three year period (1974-76). The average length of follow-up was two years. Two hundred and sixty five cases of gastric ulcer were studied of which 37 proved to be malignant (14%). Presenting complaints of anorexia, weight loss, nausea and/or vomiting, and multiple (greater than 3) symptoms, were commoner in the malignant ulcer group. Ulcer site and the presence of coexisting duodenal ulceration were largely unhelpful in deciding the status of an ulcer. Malignant ulcers tended to be large (greater than 1 cm diameter). Radiology was highly unreliable in distinguishing benign from malignant ulcers. Visual inspection at endoscopy was more reliable, but associated with a tendency to over-diagnose malignancy. False positive biopsies were uncommon (two cases). Three cases of clinically unsuspected superficial gastric carcinoma were revealed. Repeated endoscopy and biopsy of all gastric ulcers until they are completely healed is advised. Images Fig. 5 Fig. 6 PMID:7364322

  13. [Elevated gastric lesions].

    PubMed

    de Careaga, B; Villagómez, G; Pabón, J; Calderón, O; Elío, D; Pérez, J; Martínez, M; Patiño, F; Ponce, R; Lora, J

    1986-01-01

    Elevated gastric lesions, represent an important group among gastric pathology. To establish its incidence in our experience, we studied the endoscopic reports of two important hospitals in La Paz city: Instituto de Gastroenterología Boliviano Japonés and Hospital Obrero No. 1. In order to make a good endoscopic diagnosis among different elevated lesions we use some parameters like: location, shape, size, diameter, surface of the lesion and surrounding mucosa and characteristics of the falls. 10.472 endoscopic reports were reviewed, 497 elevated gastric lesions were found, 475 corresponded to mucosal lesions (352 benign lesions and 123 malignant lesions), 11 to submucosal and 11 extragastric lesions.

  14. Colorectal adenocarcinoma in Crohn's disease.

    PubMed Central

    Ribeiro, M B; Greenstein, A J; Sachar, D B; Barth, J; Balasubramanian, S; Harpaz, N; Heimann, T M; Aufses, A H

    1996-01-01

    OBJECTIVE: The authors' aim was to review the clinical features and estimate the long-term survival of patients with colorectal carcinoma complicating Crohn's disease. SUMMARY BACKGROUND DATA: Recent studies have demonstrated a significantly increased risk of colorectal carcinoma in patients with Crohns disease. METHODS: The authors reviewed retrospectively the medical records of 30 patients with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1989 in whom colorectal adenocarcinoma developed. All patients were operated on and follow-up was complete for all patients to 10 years after operation, to the time of death, or to the closing date of the study in December 1989. RESULTS: The 30 patients in the series had 33 colorectal adenocarcinomas; three patients (10%) presented with two synchronous cancers. The patients were relatively young (mean age, 53 years) and had long-standing Crohn's disease (duration >20 years in 87%). The 5-year actuarial survival was 44% for the overall series: 100% for stage A, 86% for stage B, 60% for stage C. All five patients with excluded bowel tumor died of large bowel cancer within 2.4 years; by contrast, the actuarial 5-year survival for patients with in-continuity tumors was 56%. CONCLUSIONS: The incidence, characteristics, and prognosis of colorectal carcinoma complicating Crohn's disease are similar to the features of cancer in ulcerative colitis, including young age, multiple neoplasms, long duration of disease, and greater than a 50% 5-year survival rate (without excluded loops). These observations suggest the advisability of surveillance programs for Crohn's disease of the colon similar to those for ulcerative colitis of comparable duration and extent. PMID:8597513

  15. A comparative study between the gastric mucosa of Chileans and other dwellers of the Pacific basin.

    PubMed

    Rubio, C A; Pisano, R; Llorens, P; Duarte, I

    1996-02-01

    A total of 3,289 sections of 120 gastrectomy specimens from Chile were reviewed. Intramucosal cysts were found in 61.7% of the specimens, ciliated metaplastic cells in 33.3%, large vacuolated cells in 20.8% and extensive intestinal metaplasia in 51.7%. The frequency of these non-neoplastic changes was significantly higher in specimens with early adenocarcinoma of intestinal type than in those with early adenocarcinoma of diffuse type or having a peptic ulcer. Similar results have been recorded in other inhabitants of the Pacific basin, but not inhabitants of the Atlantic basin. Interestingly, the gastric cancer incidence in the various populations studied in the Pacific basin is much higher than in those studied in the Atlantic basin. Environmental factors acting in Chile appear to have induced those non-neoplastic changes in the gastric mucosa. The question arises as to whether environmental factors (promoters?) acting in Chile (as well as in Japan, in Hawaii and in New Zealand) have favored the necessary non-neoplastic mucosal conditions required for the subsequent development of gastric adenocarcinoma (in particular of intestinal type.)

  16. Involvement of aquaporin-5 in differentiation of human gastric cancer cells.

    PubMed

    Watanabe, Tomoko; Fujii, Takuto; Oya, Takeshi; Horikawa, Naoki; Tabuchi, Yoshiaki; Takahashi, Yuji; Morii, Magotoshi; Takeguchi, Noriaki; Tsukada, Kazuhiro; Sakai, Hideki

    2009-03-01

    Litttle is known about the function of aquaporin (AQP) water channels in human gastric cancer. In the upper or middle part of human stomach, we found that expression level of AQP5 protein in intestinal type of adenocarcinoma was significantly higher than that in accompanying normal mucosa. AQP5 was localized in the apical membrane of the cancer cells. On the other hand, both AQP3 and AQP4 were not up-regulated in the adenocarcinoma. To elucidate the role of AQP5 in cancer cells, AQP5 was exogenously expressed in a cell line of poorly differentiated human gastric adenocarcinoma (MKN45). The AQP5 expression significantly increased the proportion of differentiated cells with a spindle shape, the activity of alkaline phosphatase, a marker for the intestinal epithelial cell type of cancer cells, and the expression level of laminin, an epithelial cell marker. Treatment of the MKN45 cells stably expressing AQP5 with HgCl(2), an inhibitor of aquaporins, significantly decreased the proportion of differentiated cells and the activity of alkaline phosphatase. Our results suggest that up-regulation of AQP5 may be involved in differentiation of human gastric cancer cells.

  17. Effects of IL-10 haplotype and atomic bomb radiation exposure on gastric cancer risk.

    PubMed

    Hayashi, Tomonori; Ito, Reiko; Cologne, John; Maki, Mayumi; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Hayashi, Ikue; Imai, Kazue; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Fujiwara, Saeko; Akahoshi, Masazumi; Nakachi, Kei

    2013-07-01

    Gastric cancer (GC) is one of the cancers that reveal increased risk of mortality and incidence in atomic bomb survivors. The incidence of gastric cancer in the Life Span Study cohort of the Radiation Effects Research Foundation (RERF) increased with radiation dose (gender-averaged excess relative risk per Gy = 0.28) and remains high more than 65 years after exposure. To assess a possible role of gene-environment interaction, we examined the dose response for gastric cancer incidence based on immunosuppression-related IL-10 genotype, in a cohort study with 200 cancer cases (93 intestinal, 96 diffuse and 11 other types) among 4,690 atomic bomb survivors participating in an immunological substudy. Using a single haplotype block composed of four haplotype-tagging SNPs (comprising the major haplotype allele IL-10-ATTA and the minor haplotype allele IL-10-GGCG, which are categorized by IL-10 polymorphisms at -819A>G and -592T>G, +1177T>C and +1589A>G), multiplicative and additive models for joint effects of radiation and this IL-10 haplotyping were examined. The IL-10 minor haplotype allele(s) was a risk factor for intestinal type gastric cancer but not for diffuse type gastric cancer. Radiation was not associated with intestinal type gastric cancer. In diffuse type gastric cancer, the haplotype-specific excess relative risk (ERR) for radiation was statistically significant only in the major homozygote category of IL-10 (ERR = 0.46/Gy, P = 0.037), whereas estimated ERR for radiation with the minor IL-10 homozygotes was close to 0 and nonsignificant. Thus, the minor IL-10 haplotype might act to reduce the radiation related risk of diffuse-type gastric cancer. The results suggest that this IL-10 haplotyping might be involved in development of radiation-associated gastric cancer of the diffuse type, and that IL-10 haplotypes may explain individual differences in the radiation-related risk of gastric cancer.

  18. [Helicobacter pylori and gastric cancer].

    PubMed

    León-Barúa, R; Recavarren-Arce, S; Berendson, R; Gilman, R H

    1995-01-01

    A review is done on the evidence in favor of a link between Helicobacter pylori infection and gastric cancer of the intestinal type. In countries at high risk of gastric cancer, like Perú, Hp infection begins early in life and is highly frequent and persistent. When Hp colonizes the gastric mucosa, it causes active chronic gastritis. Initially, the gastritis is of the superficial type. With time, and probably as a result of the concurrent action of nutritional, epidemiologic and immunologic modulating factors, chronic superficial gastritis may give rise to a progressive gastric pathology that leads to gastric premalignant lesions (chronic atrophic gastritis, intestinal metaplasia and dysplasia of the gastric mucosa) and increases the predisposition to gastric cancer. The principal modulating factors are described. The epidemiology of gastric premalignant lesions in Perú is also described. Finally, a discussion is done on the effect that eradication of Hp infection might have on the prevalence of gastric cancer.

  19. Hereditary Diffuse Gastric Cancer

    MedlinePlus

    ... with the syndrome is recommended. What are the estimated cancer risks associated with HDGC? Not everyone who ... the lifetime risk for diffuse gastric cancer is estimated to be 70% to 80% for men and ...

  20. Occupation and gastric cancer

    PubMed Central

    Raj, A; Mayberry, J; Podas, T

    2003-01-01

    Gastric cancer is a cause of significant morbidity and mortality. There are several risk factors, with occupation emerging as one of these. There is considerable evidence that occupations in coal and tin mining, metal processing, particularly steel and iron, and rubber manufacturing industries lead to an increased risk of gastric cancer. Other "dusty" occupations—for example, wood processing, or work in high temperature environments have also been implicated but the evidence is not strong. The mechanism of pathogenesis of gastric cancer is unclear and the identification of causative agents can be difficult. Dust is thought to be a contributor to the pathological process, but well known carcinogens such as N-nitroso compounds have been detected in some environments. Further research on responsible agents is necessary and screening for detection of precursor gastric cancer lesions at the workplace merits consideration. PMID:12782770

  1. Gastric Sleeve Surgery

    MedlinePlus

    ... or "sleeve" out of the rest. The new, banana-shaped stomach is much smaller than the original ... of your stomach, leaving you with a smaller banana-shaped stomach called the gastric sleeve. Because it's ...

  2. Role of the HLA-DQ locus in the development of chronic gastritis and gastric carcinoma in Mexican patients

    PubMed Central

    Herrera-Goepfert, Roberto; Yamamoto-Furusho, Jesús K; Oñate-Ocaña, Luis F; Camorlinga-Ponce, Margarita; Muñoz, Leopoldo; Ruiz-Morales, Jorge A; Vargas-Alarcón, Gilberto; Granados, Julio

    2006-01-01

    AIM: To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma. METHODS: Oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type gastric adenocarcinoma, and was then compared with 99 clinically healthy unrelated individuals. H pylori infection and CagA status were assessed in patients by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: We found a significant increased frequency of HLA-DQB1*0401 allele in H pylori-positive patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P = 1 × 10-7, odds ratio (OR) = 4.96; 95% confidence interval (95% CI), 3.87-6.35]. We also found a significant increased frequency of HLA-DQB1*0501 in patients with diffuse-type gastric carcinoma in comparison with healthy individuals (P = 1 × 10-6, OR = 13.07; 95% CI, 2.82-85.14). CONCLUSION: HLA-DQ locus may play a different role in the development of H pylori-related chronic gastritis and diffuse-type gastric adenocarcinoma in the Mexican Mestizo population. PMID:17203517

  3. Experimental study on Qizhu formula for modulating survivin, an inhibitor of apoptosis, in MGC-803 gastric cancer cells

    PubMed Central

    WEN, HAO; WANG, XIAOHUA; SHAN, ZHAOWEI

    2014-01-01

    The aim of this study was to investigate the mechanism of action of Qizhu formula, a Chinese medicinal empirical formula, in modulating the action of survivin, an inhibitor of apoptosis, in MGC-803 gastric cancer cells. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were applied to detect the effect of varying concentrations of Qizhu formula in the modulation of the expression of survivin in MGC-803 human gastric adenocarcinoma cells. The western blot analysis results demonstrated that Qizhu formula exerted no significant effects on the protein expression of the β-actin housekeeping gene, whereas it exerted a significant inhibitory effect on the protein expression of the apoptosis-related survivin gene at concentrations of 250 μg/ml and, particularly, 500 μg/ml. RT-PCR was used to detect the effect of Qizhu formula on survivin mRNA in MGC-803 human gastric adenocarcinoma cells. The ratio of survivin/β-actin in the 0.1% dimethylsulfoxide and the 125, 250 and 500 μg/ml groups of Qizhu formula was 0.4543, 0.4025, 0.2415 and 0.2235, respectively. Therefore, Qizhu formula exerted a distinct inhibitory effect on the mRNA expression of survivin in MGC-803 cells in a dose-dependent manner. In conclusion, Qizhu formula may modulate the apoptosis of MGC-803 human gastric adenocarcinoma cells, which is associated with the downregulation of survivin mRNA and protein expression. PMID:24772318

  4. Metastatic Colonic Adenocarcinoma in Breast: Report of Two Cases and Review of the Literature

    PubMed Central

    Kothadia, Jiten P.; Arju, Rezina; Kaminski, Monica; Ankireddypalli, Arvind; Duddempudi, Sushil; Chow, Jonathan; Giashuddin, Shah

    2015-01-01

    Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the suspicious areas identified on mammogram. Histopathology revealed neoplastic proliferation of atypical glandular components within benign breast parenchyma which were morphologically consistent with metastatic adenocarcinoma. By immunohistochemical staining, it was confirmed that the neoplastic components were immunoreactive to colonic markers and nonreactive to breast markers, thus further supporting the morphologic findings. It is extremely important to make this distinction between primary breast cancer and a metastatic process, in order to provide the most effective and appropriate treatment for the patient and to avoid any harmful or unnecessary surgical procedures. PMID:25883818

  5. CT of Gastric Emergencies.

    PubMed

    Guniganti, Preethi; Bradenham, Courtney H; Raptis, Constantine; Menias, Christine O; Mellnick, Vincent M

    2015-01-01

    Abdominal pain, nausea, and vomiting are common presenting symptoms among adult patients seeking care in the emergency department, and, with the increased use of computed tomography (CT) to image patients with these complaints, radiologists will more frequently encounter a variety of emergent gastric pathologic conditions on CT studies. Familiarity with the CT appearance of emergent gastric conditions is important, as the clinical presentation is often nonspecific and the radiologist may be the first to recognize gastric disease as the cause of a patient's symptoms. Although endoscopy and barium fluoroscopy remain important tools for evaluating patients with suspected gastric disease in the outpatient setting, compared with CT these modalities enable less comprehensive evaluation of patients with nonspecific complaints and are less readily available in the acute setting. Endoscopy is also more invasive than CT and has greater potential risks. Although the mucosal detail of CT is relatively poor compared with barium fluoroscopy or endoscopy, CT can be used with the appropriate imaging protocols to identify inflammatory conditions of the stomach ranging from gastritis to peptic ulcer disease. In addition, CT can readily demonstrate the various complications of gastric disease, including perforation, obstruction, and hemorrhage, which may direct further clinical, endoscopic, or surgical management. We will review the normal anatomy of the stomach and discuss emergent gastric disease with a focus on the usual clinical presentation, typical imaging appearance, and differentiating features, as well as potential imaging pitfalls.

  6. Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction.

    PubMed

    Phillips, B E; Tubbs, R R; Rice, T W; Rybicki, L A; Plesec, T; Rodriguez, C P; Videtic, G M; Saxton, J P; Ives, D I; Adelstein, D J

    2013-04-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated.

  7. Two-year follow-up period showing the natural history of a superficial esophageal adenocarcinoma arising in a long segment of Barrett's esophagus.

    PubMed

    Oguma, Junya; Ozawa, Soji; Kazuno, Akihito; Nitta, Miho; Ninomiya, Yamato; Tomita, Sakura

    2016-10-01

    A 55-year-old woman experienced gastrointestinal dysfunction caused by scleroderma. An initial endoscopy revealed an erosive lesion in a long segment of Barrett's esophagus, and a biopsy led to a diagnosis of ectopic gastric mucosa. Two years later, an irregular, elevated tumor developed at the same site. This tumor was suspected of having invaded the submucosal layer. A second biopsy led to a diagnosis of adenocarcinoma. The patient subsequently underwent a thoracoscopic esophagectomy. The resected specimen revealed an invasive tumor front that had invaded the deep layer of a duplicated muscularis mucosae. Intraepithelial neoplasia partially surrounded the tumor. This lesion was thought to have developed into an adenocarcinoma according to the orderly sequence of metaplasia, intraepithelial neoplasia and finally adenocarcinoma over a 2-year period. The present case suggests that erosive lesions in Barrett's esophagus should be strictly followed up by endoscopy, even if a biopsy does not reveal any neoplastic findings. PMID:27590624

  8. Frequent Overexpression of Aurora Kinase A in Upper Gastrointestinal Adenocarcinomas Correlates With Potent Antiapoptotic Functions

    PubMed Central

    Dar, Altaf A.; Zaika, Alexander; Piazuelo, Maria B.; Correa, Pelayo; Koyama, Tatsuki; Belkhiri, Abbes; Washington, Kay; Castells, Antoni; Pera, Manuel; El-Rifai, Wael

    2014-01-01

    BACKGROUND Upper gastrointestinal adenocarcinomas are a common cause of cancer-related deaths. In this study, the authors investigated the prevalence and biological significance of Aurora Kinase A (AURKA) overexpression in upper gastrointestinal adenocarcinomas. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining on tumor tissue microarrays (TMA) were used to study the expression of AURKA in upper gastrointestinal adenocarcinomas. To investigate the biological and signaling impact of AURKA, the authors used multiple in vitro assays that included 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), TUNEL (terminal deoxynucleotidyl transferase–mediated nick-end labeling), cytochrome C release, flow cytometry, luciferase reporter, and Western blot analysis. RESULTS Frequent overexpression of AURKA transcript in upper gastrointestinal adenocarcinomas was detected compared with normal samples (47%; P = .001). The immunohistochemical analysis of 130 tumors demonstrated moderate-to-strong immunostaining of AURKA in >50% of upper gastrointestinal adenocarcinomas. By using camptothecin as a drug-induced apoptosis in vitro model, the authors demonstrated that the expression of AURKA provided protection against apoptosis to gastrointestinal cancer cells (AGS and RKO) (P =.006) and RIE-1 primary intestinal epithelial cells (P =.001). The AURKA overexpression mediated an increase in phosphorylation of AKTSer473 with an increase in HDM2 level. The shRNA-knockdown of AKT in AURKA-overexpressing cells reversed this effect and showed a significant increase in the p53 protein level, indicating a possible nexus of AURKA/AKT/p53. Indeed, overexpression of AURKA led to a remarkable reduction in the transcription activity of p53, with subsequent reductions in transcript and protein levels of its downstream proapoptotic transcription targets (p21, BAX, NOXA, and PUMA). CONCLUSIONS Study results indicated that AURKA provides

  9. [A case of metastatic gastric cancer originating from transverse colon cancer].

    PubMed

    Nushijima, Youichirou; Nakano, Katsutoshi; Sugimoto, Keishi; Nakaguchi, Kazunori; Kan, Kazuomi; Maruyama, Hirohide; Doi, Sadayuki; Okamura, Shu; Murata, Kohei

    2014-11-01

    Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

  10. The isolation and properties of a non-pepsin proteinase from human gastric mucosa.

    PubMed Central

    Roberts, N B; Taylor, W H

    1978-01-01

    1. A non-pepsin proteinase, proteinase 2, was successfully isolated free from pepsinogen (by repetitive chromatography on DEAE- and CM-celluloses) from the gastric mucosa of a patient with a duodenal ulcer and the uninvaded mucosa of a patient with a gastric adenocarcinoma. 2. Proteinases 1a and 1b, found in gastric adenocarcinoma, were not found in the gastic mucosa of these patients. 3. Proteinase 2 was shown to have an asymmetrical broad pH-activity curve with a maximum over the pH range 3.0-3.7. 4. Proteolytic activity of proteinase 2 was inhibited by pepstatin; the concentration of pepstatin giving 50% inhibition is of the order of 3nm. 5. Inhibition of proteolytic activity by carbenoxolone and related triterpenoids indicated that at pH 4.0 proteinase 2 possesses structural characteristics relating it to the pepsins and at pH 7.4 to the pepsinogens. 6. The sites of cleavage of the B-chain of oxidized insulin for proteinase 2 at pH 1.7 and pH 3.5 were shown to be similar to those previously established for human pepsin 3 and for the cathepsin E of rabbit bone marrow. 7. The non-pepsin proteinase 2 (cathepsin) of human gastric mucosa has properties more similar to cathepsin E than to the cathepsins D. Images Fig. 2. Fig. 4. PMID:25649

  11. 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

  12. Improved Survival of a Patient with Gastric and Other Multiple Metastases from Ovarian Cancer by Multimodal Treatment: A Case Report

    PubMed Central

    Hwangbo, Seonmi; Kwon, Oh Kyoung; Chung, Ho Young

    2015-01-01

    Gastric metastasis from ovarian carcinoma is extremely rare and the prognosis for patients is poor. We report a case of multimodal treatment improving the survival time of a patient with gastric metastasis from ovarian cancer. A 73-year-old woman with known serous ovarian cancer was admitted to the hospital due to epigastric pain and dyspepsia. On esophagogastroduodenoscopy, a protruding mass was noted at the gastric antrum. She underwent distal gastrectomy with Billroth I anastomosis and lymph node dissection, including the para-aortic lymph nodes. The final pathology revealed gastric metastasis from ovarian serous adenocarcinoma. In this case, after cytoreductive surgery, chemotherapy was performed each time a recurrence was diagnosed, and remission was accomplished. She survived for 108 months after the first diagnosis of the metastatic tumor in the stomach. Multimodal treatment of metastatic lesions since the first diagnosis allowed the patient to survive longer than those in previous reports. PMID:26468421

  13. Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

    PubMed Central

    2013-01-01

    Background The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. Methods Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. Results 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. Conclusions CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post

  14. Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

    PubMed Central

    2011-01-01

    Background Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries. Methods Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers. Results Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways. Conclusions The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery. PMID:21781349

  15. Ramucirumab for metastatic gastric or gastroesophageal junction cancer: results and implications of the REGARD trial.

    PubMed

    Liguigli, Wanda; Tomasello, Gianluca; Toppo, Laura; Ratti, Margherita; Passalacqua, Rodolfo

    2014-01-01

    Gastric cancer is a highly aggressive disease. In metastatic setting, median overall survival, even with modern chemotherapy regimens, generally does not exceed 1 year and toxicity is a major concern. Angiogenesis plays a crucial role in cancer development and progression, and VEGF is one of the most important mediators of this process. Ramucirumab, an anti-VEGFR-2 antibody, has been recently evaluated in the large Phase III REGARD trial, demonstrating a significant survival benefit in second-line treatment of patients with advanced gastric or gastro-eosophageal junction adenocarcinoma. Unlike traditional chemotherapy, treatment with ramucirumab was associated with very few toxic effects. This article will review the main findings of the REGARD trial and discuss their potential impact on future treatment of metastatic gastric cancer.

  16. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

    PubMed Central

    Biondi, Alberto; Lirosi, Maria C; D’Ugo, Domenico; Fico, Valeria; Ricci, Riccardo; Santullo, Francesco; Rizzuto, Antonia; Cananzi, Ferdinando CM; Persiani, Roberto

    2015-01-01

    In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules. PMID:26690252

  17. General Information about Gastric Cancer

    MedlinePlus

    ... Research Gastric Cancer Treatment (PDQ®)–Patient Version General Information About Gastric Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  18. Phosphorylation of Focal Adhesion Kinase at Tyr397 in Gastric Carcinomas and its Clinical Significance

    PubMed Central

    Lai, I-Rue; Chu, Pei-Yu; Lin, Hsiao-Sheng; Liou, Jun-Yang; Jan, Yee-Jee; Lee, Jen-Chieh; Shen, Tang-Long

    2010-01-01

    Focal adhesion kinase (FAK) has been implicated in tumorigenesis in various cancers; however, it remains unclear how FAK participates in tumor malignancy in vivo. This study seeks to understand the role of FAK activation in gastric cancer progression. Using immunohistochemical staining and Western blotting, we found that pY397 FAK, an autophosphorylation site on FAK activation, was abundant in the cancerous tissues of 21 of 59 patients with gastric carcinomas. We attempted to correlate clinicopathological parameters, including histological types, TNM staging, and cancer recurrence, with the expression of FAK and pY397 FAK in cancerous tissues. Intriguingly, patients with higher levels of pY397 FAK displayed higher incidences of gastric cancer recurrence after surgery and poor 5-year recurrence-free survival. Furthermore, multivariate analyses showed that pY397 FAK was an independent predictor of gastric cancer recurrence. As a result, expression of pY397 FAK is a significant prognostic factor for the recurrence of gastric cancer. Additionally, in vitro studies showed that overexpression of Y397F, a dominant-negative mutant of FAK, in AGS human gastric carcinoma cells impaired cell migration, invasion, and proliferation compared with cells overexpressing wild-type FAK. Thus, activation of FAK through autophosphorylation at Tyr397 leads to the progression of gastric carcinomas by promoting cell migration, invasion, and proliferation. Collectively, our results have provided valuable insights for the development of novel diagnoses and therapeutic targets for gastric cancer treatments. PMID:20724588

  19. Absence of cyclin D2 expression is associated with promoter hypermethylation in gastric cancer.

    PubMed

    Yu, J; Leung, W K; Ebert, M P A; Leong, R W L; Tse, P C H; Chan, M W Y; Bai, A H C; To, K F; Malfertheiner, P; Sung, J J Y

    2003-05-19

    Expression of cyclin D2 is absent in 30-70% of gastric cancers. We investigated the role of promoter hypermethylation in the transcriptional silencing of cyclin D2 in five gastric cell lines and 47 primary gastric carcinomas. CpG island methylation status of the cyclin D2 gene was studied by methylation-specific polymerase chain reaction and bisulphite sequencing. RNA and protein expression was analysed by reverse transcription-PCR and Western blot, respectively. Dense methylation of cyclin D2 was detected in three cell lines (KATOIII, AGS and NCI-N87), which also lacked cyclin D2 mRNA and protein expression. Bisulphite DNA sequencing revealed that loss of cyclin D2 expression was closely associated with the density of methylation in the promoter region. Treatment with DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, restored the cyclin D2 expression level in methylated gastric cells. Among the 47 primary gastric cancers, cyclin D2 hypermethylation was detected in 23 (48.9%) cases. None of the 23 normal gastric biopsies from noncancer patients showed hypermethylation. Hypermethylation was associated with loss of mRNA (P&<0.001) and protein (P=0.006) expressions. Our study showed that cyclin D2 hypermethylation is associated with loss of cyclin D2 expression in a subset of gastric cancers, which may suggest an alternative gastric carcinogenesis pathway in the absence of cyclin D2 expression. PMID:12771922

  20. CDH1 mutations in gastric cancer patients from northern Brazil identified by Next- Generation Sequencing (NGS)

    PubMed Central

    El-Husny, Antonette; Raiol-Moraes, Milene; Amador, Marcos; Ribeiro-dos-Santos, André M.; Montagnini, André; Barbosa, Silvanira; Silva, Artur; Assumpção, Paulo; Ishak, Geraldo; Santos, Sidney; Pinto, Pablo; Cruz, Aline; Ribeiro-dos-Santos, Ândrea

    2016-01-01

    Abstract Gastric cancer is considered to be the fifth highest incident tumor worldwide and the third leading cause of cancer deaths. Developing regions report a higher number of sporadic cases, but there are only a few local studies related to hereditary cases of gastric cancer in Brazil to confirm this fact. CDH1 germline mutations have been described both in familial and sporadic cases, but there is only one recent molecular description of individuals from Brazil. In this study we performed Next Generation Sequencing (NGS) to assess CDH1 germline mutations in individuals who match the clinical criteria for Hereditary Diffuse Gastric Cancer (HDGC), or who exhibit very early diagnosis of gastric cancer. Among five probands we detected CDH1 germline mutations in two cases (40%). The mutation c.1023T > G was found in a HDGC family and the mutation c.1849G > A, which is nearly exclusive to African populations, was found in an early-onset case of gastric adenocarcinoma. The mutations described highlight the existence of gastric cancer cases caused by CDH1 germline mutations in northern Brazil, although such information is frequently ignored due to the existence of a large number of environmental factors locally. Our report represent the first CDH1 mutations in HDGC described from Brazil by an NGS platform. PMID:27192129

  1. CDH1 mutations in gastric cancer patients from northern Brazil identified by Next- Generation Sequencing (NGS).

    PubMed

    El-Husny, Antonette; Raiol-Moraes, Milene; Amador, Marcos; Ribeiro-Dos-Santos, André M; Montagnini, André; Barbosa, Silvanira; Silva, Artur; Assumpção, Paulo; Ishak, Geraldo; Santos, Sidney; Pinto, Pablo; Cruz, Aline; Ribeiro-Dos-Santos, Ândrea

    2016-05-13

    Gastric cancer is considered to be the fifth highest incident tumor worldwide and the third leading cause of cancer deaths. Developing regions report a higher number of sporadic cases, but there are only a few local studies related to hereditary cases of gastric cancer in Brazil to confirm this fact. CDH1 germline mutations have been described both in familial and sporadic cases, but there is only one recent molecular description of individuals from Brazil. In this study we performed Next Generation Sequencing (NGS) to assess CDH1 germline mutations in individuals who match the clinical criteria for Hereditary Diffuse Gastric Cancer (HDGC), or who exhibit very early diagnosis of gastric cancer. Among five probands we detected CDH1 germline mutations in two cases (40%). The mutation c.1023T > G was found in a HDGC family and the mutation c.1849G > A, which is nearly exclusive to African populations, was found in an early-onset case of gastric adenocarcinoma. The mutations described highlight the existence of gastric cancer cases caused by CDH1 germline mutations in northern Brazil, although such information is frequently ignored due to the existence of a large number of environmental factors locally. Our report represent the first CDH1 mutations in HDGC described from Brazil by an NGS platform. PMID:27192129

  2. CDH1 mutations in gastric cancer patients from northern Brazil identified by Next- Generation Sequencing (NGS).

    PubMed

    El-Husny, Antonette; Raiol-Moraes, Milene; Amador, Marcos; Ribeiro-Dos-Santos, André M; Montagnini, André; Barbosa, Silvanira; Silva, Artur; Assumpção, Paulo; Ishak, Geraldo; Santos, Sidney; Pinto, Pablo; Cruz, Aline; Ribeiro-Dos-Santos, Ândrea

    2016-05-13

    Gastric cancer is considered to be the fifth highest incident tumor worldwide and the third leading cause of cancer deaths. Developing regions report a higher number of sporadic cases, but there are only a few local studies related to hereditary cases of gastric cancer in Brazil to confirm this fact. CDH1 germline mutations have been described both in familial and sporadic cases, but there is only one recent molecular description of individuals from Brazil. In this study we performed Next Generation Sequencing (NGS) to assess CDH1 germline mutations in individuals who match the clinical criteria for Hereditary Diffuse Gastric Cancer (HDGC), or who exhibit very early diagnosis of gastric cancer. Among five probands we detected CDH1 germline mutations in two cases (40%). The mutation c.1023T > G was found in a HDGC family and the mutation c.1849G > A, which is nearly exclusive to African populations, was found in an early-onset case of gastric adenocarcinoma. The mutations described highlight the existence of gastric cancer cases caused by CDH1 germline mutations in northern Brazil, although such information is frequently ignored due to the existence of a large number of environmental factors locally. Our report represent the first CDH1 mutations in HDGC described from Brazil by an NGS platform.

  3. CDX-2 Expression in Primary Lung Adenocarcinoma.

    PubMed

    Cowan, Morgan L; Li, Qing K; Illei, Peter B

    2016-01-01

    Adenocarcinoma with enteric differentiation is a rare subtype of lung adenocarcinoma that is recognized as a variant type of primary adenocarcinoma in the 2015 World Health Organization classification of lung tumors. Published immunohistochemistry studies show variable staining pattern for CDX-2 ranging from positivity in 71% of the cases to no staining. As little is known about CDX-2 expression in lung adenocarcinomas lacking histologic features of enteric differentiation, our aim was to determine the rate of CDX-2 positivity in non-enteric-type lung adenocarcinomas. We performed immunohistochemistry for CDX-2, CK7, CK20, TTF-1, napsin A, and p40 using 4-μm sections of a previously constructed tissue microarray containing 93 primary lung adenocarcinomas that lack morphologic evidence of enteric differentiation. The cohort included 22 well, 54 moderately, and 17 poorly differentiated tumors (55 female, 38 male; age range: 42 to 86, median: 64.5). All 93 tumors were strongly CK7 positive, whereas variable CK20 staining was seen in 4 tumors (1 strong, 1 moderate, and 2 focal). Both TTF-1 and napsin A were positive in 81 of 93 (87%) tumors with only 6 of 93 (6.5%) tumors negative for both the markers. Eleven tumors were CDX-2 positive (5 strong, 3 moderate, and 3 weak), all of which were also TTF-1 and napsin A positive and p40 negative. One CDX-2-positive tumor showed focal CK20 staining. Mutation studies for EGFR/K-ras/ALK were performed in four CDX-2-positive tumors and detected a K-ras mutation in one of them. CDX-2 positivity can be seen in a subset (12%) of lung adenocarcinoma. These tumors are CK7, TTF-1, and napsin A positive and p40 negative. Focal CK20 staining is only seen in rare cases. CDX-2 positivity should not be used as the only criteria to exclude lung origin. PMID:26469326

  4. CDX-2 Expression in Primary Lung Adenocarcinoma.

    PubMed

    Cowan, Morgan L; Li, Qing K; Illei, Peter B

    2016-01-01

    Adenocarcinoma with enteric differentiation is a rare subtype of lung adenocarcinoma that is recognized as a variant type of primary adenocarcinoma in the 2015 World Health Organization classification of lung tumors. Published immunohistochemistry studies show variable staining pattern for CDX-2 ranging from positivity in 71% of the cases to no staining. As little is known about CDX-2 expression in lung adenocarcinomas lacking histologic features of enteric differentiation, our aim was to determine the rate of CDX-2 positivity in non-enteric-type lung adenocarcinomas. We performed immunohistochemistry for CDX-2, CK7, CK20, TTF-1, napsin A, and p40 using 4-μm sections of a previously constructed tissue microarray containing 93 primary lung adenocarcinomas that lack morphologic evidence of enteric differentiation. The cohort included 22 well, 54 moderately, and 17 poorly differentiated tumors (55 female, 38 male; age range: 42 to 86, median: 64.5). All 93 tumors were strongly CK7 positive, whereas variable CK20 staining was seen in 4 tumors (1 strong, 1 moderate, and 2 focal). Both TTF-1 and napsin A were positive in 81 of 93 (87%) tumors with only 6 of 93 (6.5%) tumors negative for both the markers. Eleven tumors were CDX-2 positive (5 strong, 3 moderate, and 3 weak), all of which were also TTF-1 and napsin A positive and p40 negative. One CDX-2-positive tumor showed focal CK20 staining. Mutation studies for EGFR/K-ras/ALK were performed in four CDX-2-positive tumors and detected a K-ras mutation in one of them. CDX-2 positivity can be seen in a subset (12%) of lung adenocarcinoma. These tumors are CK7, TTF-1, and napsin A positive and p40 negative. Focal CK20 staining is only seen in rare cases. CDX-2 positivity should not be used as the only criteria to exclude lung origin.

  5. The guggulsterone derivative GG-52 inhibits NF-κB signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice.

    PubMed

    Kim, Jung Mogg; Kim, Su Hyun; Ko, Su Hyuk; Jung, Jireh; Chun, Jaeyoung; Kim, Nayoung; Jung, Hyun Chae; Kim, Joo Sung

    2013-01-15

    Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.

  6. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report.

    PubMed

    Jiang, Meng-Jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-09-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.

  7. Laparoscopic transhiatal approach for resection of an adenocarcinoma in long-segment Barrett's esophagus.

    PubMed

    Shiozaki, Atsushi; Fujiwara, Hitoshi; Konishi, Hirotaka; Kinoshita, Osamu; Kosuga, Toshiyuki; Morimura, Ryo; Murayama, Yasutoshi; Komatsu, Shuhei; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Okamoto, Kazuma; Sakakura, Chouhei; Otsuji, Eigo

    2015-08-01

    Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long-segment BE (LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach (LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of the arch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 mL of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis. PMID:26269688

  8. Helicobacter pylori-negative gastric cancer: characteristics and endoscopic findings.

    PubMed

    Yamamoto, Yorimasa; Fujisaki, Junko; Omae, Masami; Hirasawa, Toshiaki; Igarashi, Masahiro

    2015-07-01

    Helicobacter pylori (H. pylori) leads to chronic gastritis and eventually causes gastric cancer. The prevalence of H. pylori infection is gradually decreasing with improvement of living conditions and eradication therapy. However, some reports have described cases of H. pylori-negative gastric cancers (HpNGC), and the prevalence was 0.42-5.4% of all gastric cancers. Diagnostic criteria of HpNGC vary among the different reports; thus, they have not yet been definitively established. We recommend negative findings in two or more methods that include endoscopic or pathological findings or serum pepsinogen test, and negative urease breath test or serum immunoglobulin G test and no eradication history the minimum criteria for diagnosis of HpNGC. The etiology of gastric cancers, excluding H. pylori infection, is known to be associated with several factors including lifestyle, viral infection, autoimmune disorder and germline mutations, but the main causal factor of HpNGC is still unclear. Regarding the characteristics of HpNGC, the undifferentiated type (UD-type) is more frequent than the differentiated type (D-type). The UD-type is mainly signet ring-cell carcinoma that presents as a discolored lesion in the lower or middle part of the stomach in relatively young patients. The gross type is flat or depressed. The D-type is mainly gastric adenocarcinoma of the fundic gland type that presents as a submucosal tumor-like or flat or depressed lesion in the middle and upper part of the stomach in relatively older patients. Early detection of HpNGC enables minimally invasive treatment which preserves the patient's quality of life. Endoscopists should fully understand the characteristics and endoscopic findings of HpNGC.

  9. Preparation, characterization, and photocatalytic activity of porous AgBr@Ag and AgBrI@Ag plasmonic photocatalysts

    NASA Astrophysics Data System (ADS)

    Yang, Fan; Tian, Baozhu; Zhang, Jinlong; Xiong, Tianqing; Wang, Tingting

    2014-02-01

    Porous AgBr@Ag and AgBrI@Ag plasmonic photocatalysts were synthesized by a multistep route, including a dealloying method to prepare porous Ag, a transformation from Ag to AgBr and AgBrI, and a photo-reduction process to form Ag nanoparticles on the surface of AgBr and AgBrI. It was found that the porous structure kept unchanged during Ag was transferred into AgBr, AgBrI, AgBr@Ag, and AgBrI@Ag. Both porous AgBr@Ag and porous AgBrI@Ag showed much higher visible-light photocatalytic activity than cubic AgBr@Ag for the degradation of methyl orange, which is because the interconnected pore channels not only provide more reactive sites but also favor the transportation of photo-generated electrons and holes. For AgBrI@Ag, AgBrI solid solution formed at the interface of AgBr and AgI, and the phase junction can effectively separate the photo-generated electrons and holes, favorable to the improvement of photocatalytic activity. The optimal I content for obtaining the highest activity is ∼10 at.%.

  10. [Tumor markers in gastric cancer].

    PubMed

    Ohkura, Hisanao

    2002-04-01

    There are two markers, pepsinogen isoenzymes and antibody against Helicobactor pyroli, for screening of high-risk group for gastric cancer. Most of markers are used in diagnosis, staging, monitoring and differentiating subgroups of gastric cancer. Markers in ascitic fluid are used for diagnosing peritoneal invasion of gastric cancer. PMID:11977555

  11. Role of human epidermal growth factor receptor 2 in gastric cancer: Biological and pharmacological aspects

    PubMed Central

    Jørgensen, Jan Trøst

    2014-01-01

    Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. The degree of HER2 overexpression and amplification varies with the location of the carcinoma, with higher expression in the gastroesophageal and proximal parts compared to the distal parts of the stomach. Further, HER2 overexpression and amplification also seems to be related to the Lauren histological classification, with higher levels found in the intestinal phenotype compared to the diffuse and mixed types. The prognostic properties of HER2 overexpression and amplification are still under debate, but a large number of studies seem to indicate that HER2 is a negative prognostic factor. The usefulness of HER2 targeted therapy in gastric cancer was demonstrated in the ToGA trial, where HER2-positive patients with advanced gastric and gastroesophageal junction adenocarcinoma were randomized to receive 5-FU/capecitabine and cisplatin, either alone or in combination with trastuzumab. A statically significant gain in overall survival was seen in patients who received the combined treatment of trastuzumab and chemotherapy. Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. As a consequence of the positive results of the ToGA trial, patients with advanced gastric or gastroesophageal junction adenocarcinoma are now routinely tested for HER2. The ToGA trial must be characterized as a landmark in the treatment of gastric cancer and it has paved the way for a number of new HER2 targeted compounds such as pertuzumab, ado-trastuzumab emtansine, lapatinib, afatinib, and dacomitinib, which are currently undergoing phase II and III clinical testing. Overall, this review will discuss the current status of HER2 in gastric and gastroesophageal junction cancer and the future direction in

  12. High-Throughput Sequencing of miRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers.

    PubMed

    Darnet, Sylvain; Moreira, Fabiano C; Hamoy, Igor G; Burbano, Rommel; Khayat, André; Cruz, Aline; Magalhães, Leandro; Silva, Artur; Santos, Sidney; Demachki, Samia; Assumpção, Monica; Assumpção, Paulo; Ribeiro-Dos-Santos, Ândrea

    2015-01-01

    Gastric cancer has a high incidence and mortality rate worldwide; however, the use of biomarkers for its clinical diagnosis remains limited. The microRNAs (miRNAs) are biomarkers with the potential to identify the risk and prognosis as well as therapeutic targets. We performed the ultradeep miRnomes sequencing of gastric adenocarcinoma and gastric antrum without tumor samples. We observed that a small set of those samples were responsible for approximately 80% of the total miRNAs expression, which might represent a miRNA tissue signature. Additionally, we identified seven miRNAs exhibiting significant differences, and, of these, hsa-miR-135b and hsa-miR-29c were able to discriminate antrum without tumor from gastric cancer regardless of the histological type. These findings were validated by quantitative real-time polymerase chain reaction. The results revealed that hsa-miR-135b and hsa-miR-29c are potential gastric adenocarcinoma occurrence biomarkers with the ability to identify individuals at a higher risk of developing this cancer, and could even be used as therapeutic targets to allow individualized clinical management. PMID:26157332

  13. High-Throughput Sequencing of miRNAs Reveals a Tissue Signature in Gastric Cancer and Suggests Novel Potential Biomarkers

    PubMed Central

    Darnet, Sylvain; Moreira, Fabiano C; Hamoy, Igor G; Burbano, Rommel; Khayat, André; Cruz, Aline; Magalhães, Leandro; Silva, Artur; Santos, Sidney; Demachki, Samia; Assumpção, Monica; Assumpção, Paulo; Ribeiro-dos-Santos, Ândrea

    2015-01-01

    Gastric cancer has a high incidence and mortality rate worldwide; however, the use of biomarkers for its clinical diagnosis remains limited. The microRNAs (miRNAs) are biomarkers with the potential to identify the risk and prognosis as well as therapeutic targets. We performed the ultradeep miRnomes sequencing of gastric adenocarcinoma and gastric antrum without tumor samples. We observed that a small set of those samples were responsible for approximately 80% of the total miRNAs expression, which might represent a miRNA tissue signature. Additionally, we identified seven miRNAs exhibiting significant differences, and, of these, hsa-miR-135b and hsa-miR-29c were able to discriminate antrum without tumor from gastric cancer regardless of the histological type. These findings were validated by quantitative real-time polymerase chain reaction. The results revealed that hsa-miR-135b and hsa-miR-29c are potential gastric adenocarcinoma occurrence biomarkers with the ability to identify individuals at a higher risk of developing this cancer, and could even be used as therapeutic targets to allow individualized clinical management. PMID:26157332

  14. [A Case of Unresectable Local Recurrence of Gastric Cancer Successfully Resected after Pre-Operative Chemotherapy with Trastuzumab].

    PubMed

    Okubo, Satoshi; Takahashi, Tsuyoshi; Miyazaki, Yasuhiro; Makino, Tomoki; Kurokawa, Yukinori; Yamazaki, Makoto; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2015-11-01

    A 69-year-old man was diagnosed with advanced gastric cancer and underwent total gastrectomy (tubular adenocarcinoma, tub2, pT3N0M0, stageⅡA). Eight months after the surgery, recurrence on the anastomosis was observed. Tumor invasion of the aortic artery was suspected, and the patient was considered inoperable. He was treated with S-1/CDDP plus trastuzumab therapy as a neoadjuvant chemotherapy regimen. After 4 courses of the chemotherapy, significant tumor reduction was observed, and the patient underwent anastomosis resection. Chemotherapy with trastuzumab appears to be an effective NAC treatment for HER2-positive, advanced gastric cancer. PMID:26805275

  15. Effect of gastric acid suppressants on human gastric motility

    PubMed Central

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

    1998-01-01

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

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

  16. A rare case of metastatic germ cell tumor to stomach and duodenum masquerading as signet ring cell adenocarcinoma

    PubMed Central

    Sundaram, Sridhar; Patil, Prachi; Mehta, Shaesta; Ramadwar, Mukta

    2016-01-01

    Adenocarcinomas are the most common cancers affecting stomach. However gastrointestinal stromal tumors (GIST), lymphomas and neuroendocrine tumors (NETs) can also affect the stomach. But stomach is relatively rare site of involvement by metastasis. In this case report a rare metastasis of germ cell tumor (GCT) into stomach is described which clinically and endoscopically masquerade as primary gastric cancers. But detailed clinical examination and vigilant histopathological reporting proves the origin of tumor distant from stomach and thereby change the whole approach of management. PMID:27668229

  17. A rare case of metastatic germ cell tumor to stomach and duodenum masquerading as signet ring cell adenocarcinoma.

    PubMed

    Mazumdar, Srijan; Sundaram, Sridhar; Patil, Prachi; Mehta, Shaesta; Ramadwar, Mukta

    2016-08-01

    Adenocarcinomas are the most common cancers affecting stomach. However gastrointestinal stromal tumors (GIST), lymphomas and neuroendocrine tumors (NETs) can also affect the stomach. But stomach is relatively rare site of involvement by metastasis. In this case report a rare metastasis of germ cell tumor (GCT) into stomach is described which clinically and endoscopically masquerade as primary gastric cancers. But detailed clinical examination and vigilant histopathological reporting proves the origin of tumor distant from stomach and thereby change the whole approach of management. PMID:27668229

  18. Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients?

    PubMed Central

    Huang, Lei; Xu, A-Man; Li, Tuan-Jie; Han, Wen-Xiu; Xu, Jing

    2014-01-01

    AIM: To investigate the necessity and correctness of acid suppression pre- and post-gastrectomy among gastric carcinoma (GC) patients. METHODS: From June 2011 to April 2013, 99 patients who were diagnosed with GC or adenocarcinoma of the gastroesophageal junction (type II or III) and needed surgical management were enrolled. They all underwent gastrectomy by the same operators [35 undergoing total gastrectomy (TG) plus Roux-en-Y reconstruction, 34 distal gastrectomy (DG) plus Billroth I reconstruction, and 30 proximal gastrectomy (PG) plus gastroesophagostomy]. We collected and analyzed their gastrointestinal juice and tissues from the pre-operational day to the 5th day post-operation, and 6 mo post-surgery. Gastric pH was detected with a precise acidity meter. Gastric juice contents including potassium, sodium and bicarbonate ions, urea nitrogen, direct and indirect bilirubin, and bile acid were detected using Automatic Biochemical Analyzer. Data regarding tumor size, histological type, tumor penetration and tumor-node-metastasis (TNM) stage were obtained from the pathological records. Reflux symptoms pre- and 6 mo post-gastrectomy were evaluated by reflux disease questionnaire (RDQ) and gastroesophageal reflux disease questionnaire (GERD-Q). SPSS 16.0 was applied to analyze the data. RESULTS: Before surgery, gastric pH was higher than the threshold of hypoacidity (4.25 ± 1.45 vs 3.5, P = 0.000), and significantly affected by age, tumor size and differentiation grade, and potassium and bicarbonate ions; advanced malignancies were accompanied with higher pH compared with early ones (4.49 ± 1.31 vs 3.66 ± 1.61, P = 0.008). After operation, gastric pH in all groups was of weak-acidity and significantly higher than that pre-gastrectomy; on days 3-5, comparisons of gastric pH were similar between the 3 groups. Six months later, gastric pH was comparable to that on days 3-5; older patients were accompanied with higher total bilirubin level, indicating more serious

  19. Multimodality management of resectable gastric cancer: A review.

    PubMed

    Shum, Helen; Rajdev, Lakshmi

    2014-10-15

    Adenocarcinoma of the stomach carries a poor prognosis and is the second most common cause of cancer death worldwide. It is recommended that surgical resection with a D1 or a modified D2 gastrectomy (with at least 15 lymph nodes removed for examination) be performed in the United States, though D2 lymphadenectomies should be performed at experienced centers. A D2 lymphadenectomy is the recommended procedure in Asia. Although surgical resection is considered the definitive treatment, rates of recurrences are high, necessitating the need for neoadjuvant or adjuvant therapy. This review article aims to outline and summarize some of the pivotal trials that have defined optimal treatment options for non-metastatic non-cardia gastric cancer. Some of the most notable trials include the INT-0116 trial, which established a benefit in concurrent chemoradiation and adjuvant chemotherapy. This was again confirmed in the ARTIST trial, especially in patients with nodal involvement. Later, the Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial provided evidence for the use of perioperative chemotherapy. Targeted agents such as ramucirumab and trastuzumab are also being investigated for use in locally advanced gastric cancers after demonstrating a benefit in the metastatic setting. Given the poor response rate of this difficult disease to various treatment modalities, numerous studies are currently ongoing in an attempt to define a more effective therapy, some of which are briefly introduced in this review as well.

  20. 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

  1. Effect of urokinase-type plasminogen activator system in gastric cancer with peritoneal metastasis

    PubMed Central

    DING, YOUCHENG; ZHANG, HUI; LU, AIGUO; ZHOU, ZHUQING; ZHONG, MINGAN; SHEN, DONGWEI; WANG, XUJING; ZHU, ZHENGGANG

    2016-01-01

    Peritoneal metastasis is a primary cause of mortality in patients with gastric cancer. Urokinase-type plasminogen activator (uPA) has been demonstrated to be associated with tumor cell metastasis through the degradation of the extracellular matrix. The present study aimed to investigate the mechanisms of the uPA system in gastric cancer with peritoneal metastasis. Expression of uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in four gastric cell lines (AGS, SGC7901, MKN45 and MKN28) was measured by semiquantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting. uPA activity was detected using a uPA activity kit. Peritoneal implantation models of rats were established by injecting four gastric cancer cell lines for the selection of the cancer cells with a high planting potential. Biological behaviors, including adhesion, migration and invasion, were determined using a methyl thiazolyl tetrazolium assay. Expression of the uPA system was observed to be highest in the SGC7901 cells among the four gastric cell lines. uPA activity was observed to be highest in the MKN45 cells and lowest in the AGS cells. Furthermore, peritoneal implantation analysis demonstrated that no peritoneal tumors were identified in the AGS cells, whilst the tumor masses observed in the SGC7901 and MKN45 cells were of different sizes. The survival times of the rats injected with the MKN28 and SGC7901 cells were longer than those of the rats injected with the MKN45 cells. Antibodies for uPA, uPAR and PAI-1 in the uPA system had the ability to inhibit the adhesion, migration and invasion of peritoneal metastasis in the gastric cancer cells. The results of the present study demonstrated that the uPA system was positively associated with peritoneal metastasis in gastric cancer. PMID:27313768

  2. 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

  3. Association of COX2 gene hypomethylation with intestinal type gastric cancer in samples of patients from northern Brazil.

    PubMed

    de Melo, Cynthia Farias Vieira; Gigek, Carolina Oliveira; da Silva, Juarez Nóbrega; Cardoso Smith, Marilia de Arruda; de Araújo, Rubistenia Miranda; Burbano, Rommel Rodríguez; Lima, Eleonidas Moura

    2014-02-01

    To verify the methylation status of THBS1, GPX3, and COX2 genes and to evaluate their association with Helicobacter pylori in gastric adenocarcinomas. Methylation-sensitive restriction enzyme PCR assay was performed in 16 diffuse type gastric cancer samples, 23 intestinal type, and 15 normal stomach tissue. The presence of H. pylori was performed by amplification of the fragment of the 16S rRNA. Statistical analyses were performed using Fisher's exact test. The hypermethylation of GPX3, THBS1, and COX2 occurred in 18 (n = 7), 5 (n = 2), and 36 % (n = 14) of gastric cancer samples, respectively, whereas in normal samples, it was found in 13, 7, and 67 %. The presence of H. pylori was detected in 67 % of gastric cancer samples and 67 % in normal gastric samples. The methylation of THBS1 and GPX3 was not significantly different between the types of tumors, normal sample, the presence of H. pylori, or clinicopathological variables studied (P > 0.05). However, the methylation status of the gene COX2 is significantly different between normal tissue and intestinal type gastric cancer (P = 0.02). Therefore, our results suggest that the methylation status of the gene COX2 is associated with the intestinal type of gastric cancer. PMID:24014049

  4. Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

    PubMed Central

    Chiurillo, Miguel Angel

    2015-01-01

    Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancer-related deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The aberrant activation of the Wnt/β-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/β-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/β-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors (mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput “omics” approaches will help in the search for Wnt pathway antagonist in the near future. PMID:25992323

  5. Expression of four CEA family antigens (CEA, NCA, BGP and CGM2) in normal and cancerous gastric epithelial cells: up-regulation of BGP and CGM2 in carcinomas.

    PubMed

    Kinugasa, T; Kuroki, M; Takeo, H; Matsuo, Y; Ohshima, K; Yamashita, Y; Shirakusa, T; Matsuoka, Y

    1998-03-30

    Four human carcinoembryonic antigen