Science.gov

Sample records for human gastric carcinoma

  1. Prognostic role of neuroendocrine cell differentiation in human gastric carcinoma

    PubMed Central

    Zhang, Tingting; Su, Dan; Mao, Zhiyuan; Guo, Xiaochuan; Wang, Lijie; Bai, Li

    2015-01-01

    The objective of the current study was to investigate the significance and biologic characteristic of neuroendocrine cell differentiation (NED) in gastric carcinoma by comparing the prognosis and clinicopathologic characteristics between patients with or without NED. Retrospective analyses of neuroendocrine markers, neuron specific enolase (NSE), chromogranin A (CgA), and synaptophysin (Syn) were performed in 174 human gastric carcinoma patients. NED association was found in 21.3% gastric carcinoma patients, with or without NED, and was correlated with tumor location, cancer emboli, infiltrative depth, TNM stage and distant metastasis (P < 0.05 in each case). The 1-year and 3-year survival rate of the patients who suffered from gastric carcinoma with NED were significantly lower than those without NED. The overall survival time of patients with NED was shorter than those with gastric carcinoma without NED, with a significant difference between the two types (P = 0.037). Cumulatively, gastric carcinoma patients with NED had shorter postoperative survival time and poorer prognosis. PMID:26221337

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

    PubMed

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

    2007-11-01

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

  3. Expression of interleukin-8 correlates with vascularity in human gastric carcinomas.

    PubMed Central

    Kitadai, Y.; Haruma, K.; Sumii, K.; Yamamoto, S.; Ue, T.; Yokozaki, H.; Yasui, W.; Ohmoto, Y.; Kajiyama, G.; Fidler, I. J.; Tahara, E.

    1998-01-01

    Interleukin (IL)-8 is a multifunctional cytokine that can stimulate the division of endothelial cells. We examined the expression of IL-8 mRNA using Northern blot analysis and in situ mRNA hybridization (ISH) and protein production using enzyme-linked immunosorbent assay and immunohistochemistry in 8 human gastric carcinoma cell lines and 39 gastric carcinomas and corresponding normal mucosa (34 surgical specimens and 5 biopsy specimens). Of the 8 human gastric carcinoma cell lines, 6 expressed 1.8-kb IL-8 mRNA and secreted various levels of IL-8 protein. The expression of IL-8 by TMK-1 cells was induced by exposure to IL-1 alpha, epidermal growth factor, and transforming growth factor-alpha, shown previously to be autocrine growth stimulators for human gastric carcinoma cells. In tumor tissues, most of the tumors (28 of 34 surgical specimens and 4 of 5 biopsy specimens) expressed IL-8 at higher levels than the corresponding normal mucosa. ISH and immunohistochemical analyses revealed that IL-8 mRNA and protein were localized in the cytoplasm of tumor cells. The number of blood vessels in the gastric carcinomas was determined by using antibodies against CD34. The level of IL-8 mRNA in the neoplasms strongly correlated with vascularization (Spearman correlation, r = 0.812; P = 0.001). The data suggest that IL-8 produced by tumor cells may regulate neovascularization and, hence, the growth and spread of human gastric carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9422527

  4. 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

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

    PubMed

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

    2013-11-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Chelidonine induces mitotic slippage and apoptotic-like death in SGC-7901 human gastric carcinoma cells.

    PubMed

    Qu, Zhongyuan; Zou, Xiang; Zhang, Xiujuan; Sheng, Jiejing; Wang, Yumeng; Wang, Jiaqi; Wang, Chao; Ji, Yubin

    2016-02-01

    mitotic slippage. In addition, apoptotic morphological changes in multinucleated cells were observed, the apoptosis rates increased gradually with administration of chelidonine in a time-dependent manner and the protein levels of caspase-3 increased significantly between 24 and 72 h. Thus, chelidonine induces mitotic slippage, and apoptotic-like death occurs in SGC-7901 cells undergoing mitotic catastrophe. Gastric cancer is a common malignancy, and ranks second in overall cancer-associated mortalities worldwide. The present study demonstrated that chelidonine induces M phase arrest and mitotic slippage of SGC-7901 human gastric carcinoma cells via downregulating the expression of BubR1, Cdk1 and cyclin B1 proteins. With the prolongation of chelidonine treatment, the giant cells with multiple micronuclei underwent mitotic slippage and were maintained in the G1 phase and did not survive. A number of multinucleated cells underwent apoptosis via a caspase-dependent signaling pathway. The current study proposes that chelidonine induces mitotic slippage and apoptotic-like death of SGC-7901 cells. PMID:26677104

  8. Xanthatin induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma MKN-45 cells.

    PubMed

    Zhang, Lei; Tao, Li; Ruan, Junshan; Li, Weidong; Wu, Yu; Yan, Linggeng; Zhang, Feng; Fan, Fangtian; Zheng, Shizhong; Wang, Aiyun; Lu, Yin

    2012-06-01

    Xanthatin, a natural bioactive compound of sesquiterpene lactones, was isolated and purified from air-dried aerial part of Xanthium sibiricum Patrin ex Widder. In the present study, we demonstrated the significant antiproliferative and proapoptotic effects of xanthatin on human gastric carcinoma MKN-45 cells. MTS assay showed that xanthatin produced obvious cytotoxicity in MKN-45 cells with IC50 values of 18.6, 9.3, and 3.9 µM for 12, 24, and 48 h, respectively. Results of flow cytometry analysis indicated that the antiproliferative activity induced by xanthatin might be executed via G2/M cell cycle arrest and proapoptosis in MKN-45 cells. Western blot analysis elucidated that: a) xanthatin downregulated expression of Chk1 and Chk2 and phosphorylation of CDC2, which are known as key G2/M transition regulators; b) xanthatin increased p53 activation, decreased the bcl-2/bax ratio and the levels of downstream procaspase-9 and procaspase-3, which are key regulators in the intrinsic apoptosis pathway; c) xanthatin blocked phosphorylation of NF-κB (p65 subunit) and of IκBα, which might contribute to its proapoptotic effects on MKN-45 cells. In conclusion, our results suggest that xanthatin may have therapeutic potential against human gastric carcinoma. PMID:22532019

  9. Gastric metastasis from salivary duct carcinoma mimicking primary gastric cancer

    PubMed Central

    Yamashita, Kanefumi; Takeno, Shinsuke; Nimura, Satoshi; Sugiyama, Yoshikazu; Sueta, Takayuki; Maki, Kenji; Kayashima, Yoshiyuki; Shiwaku, Hironari; Kato, Daisuke; Hashimoto, Tatsuya; Sasaki, Takamitsu; Yamashita, Yuichi

    2016-01-01

    Introduction We present a very rare case of gastric metastasis mimicking primary gastric cancer in a patient who had undergone surgery for salivary duct carcinoma. Presentation of case A 67-year-old man had been diagnosed as having right parotid cancer and had undergone a right parotidectomy and lymph node dissection. The histological diagnosis was salivary duct carcinoma. One year after the surgery, a positron emission tomography–computed tomography scan using fluorodeoxyglucose (FDG) revealed an abnormal uptake of FDG in the left cervical, mediastinal, paraaortic, and cardiac lymph nodes; stomach; and pancreas. On gastroduodenoscopy, there was a huge, easily bleeding ulcer mimicking primary gastric cancer at the upper body of the stomach. Biopsy revealed poorly differentiated adenocarcinoma. Therefore, we were unable to differentiate between the primary gastric cancer and the metastatic tumor using gastroduodenoscopy and biopsy. Because of the uncontrollable bleeding from the gastric cancer, we performed an emergency palliative total gastrectomy. On histological examination, the gastric lesion was found to be metastatic carcinoma originating from the salivary duct carcinoma. Discussion In the presented case, we could not diagnose the gastric metastasis originating from the salivary duct carcinoma even by endoscopic biopsy. This is because the histological appearance of salivary duct carcinoma is similar to that of high-grade adenocarcinoma, thus, resembling primary gastric cancer. Conclusion When we perform endoscopic examination of patients with malignant neoplasias, a possibility of metastatic gastric cancer should be taken into consideration. PMID:27085106

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

    PubMed

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

    2010-11-01

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

  11. Large-scale characterization of DNA methylation changes in human gastric carcinomas with and without metastasis

    PubMed Central

    Liu, Zhaojun; Zhang, Jun; Gao, Yanhong; Pei, Lirong; Zhou, Jing; Gu, Liankun; Zhang, Lianhai; Zhu, Budong; Hattori, Naoko; Ji, Jiafu; Yuasa, Yasuhito; Kim, Wooho; Ushijima, Toshikazu; Shi, Huidong; Deng, Dajun

    2014-01-01

    Purpose Metastasis is the leading cause of death for gastric carcinoma (GC). An epigenetic biomarker panel for predicting GC metastasis could have significant clinical impact on the care of GC patients. The main purpose of this study is to characterize the methylation differences between GCs with and without metastasis. Experimental Design Genome-wide DNA methylation profiles between 4 metastatic and 4 non-metastatic GCs and their surgical margins (SM) were analyzed using methylated-CpG island amplification with microarray. The methylation states of 73 candidate genes were further analyzed in GC patients in a discovery cohort (n=108) using DHPLC, bisulfite-sequencing, and MethyLight. The predictive values of potential metastasis-methylation biomarkers were validated in GC patient cohorts in China (n=330), Japan (n=129), and Korea (n=153). Results The GC genome showed significantly higher proportions of hypomethylation in the promoter and exon-1 regions, as well as increased hypermethylation of intragenic fragments when compared to SMs. Significant differential methylation was validated in the CGIs of 15 genes (Ps<0.05) and confirmed using bisulfite-sequencing. These genes included BMP3, BNIP3, CDKN2A, ECEL1, ELK1, GFRA1, HOXD10, KCNH1, PSMD10, PTPRT, SIGIRR, SRF, TBX5, TFPI2, and ZNF382. Methylation changes of GFRA1, SRF and ZNF382 resulted in up- or down-regulation of their transcription. Most importantly, the prevalence of GFRA1, SRF, and ZNF382 methylation alterations was consistently and coordinately associated with GC metastasis and the patients’ overall survival throughout discovery and validation cohorts in China, Japan and Korea. Conclusion Methylation changes of GFRA1, SRF, and ZNF382 may be a potential biomarker set for prediction of GC metastasis. PMID:25009298

  12. Patient-Derived Gastric Carcinoma Xenograft Mouse Models Faithfully Represent Human Tumor Molecular Diversity

    PubMed Central

    Fan, Shuqiong; Zhang, Meizhuo; Fu, Haihua; Liu, Yuanjie; Yin, Xiaolu; Chen, Hao; Xie, Liang; Zhang, Jingchuan; Gavine, Paul R.; Gu, Yi; Ni, Xingzhi; Su, Xinying

    2015-01-01

    Patient-derived cancer xenografts (PDCX) generally represent more reliable models of human disease in which to evaluate a potential drugs preclinical efficacy. However to date, only a few patient-derived gastric cancer xenograft (PDGCX) models have been reported. In this study, we aimed to establish additional PDGCX models and to evaluate whether these models accurately reflected the histological and genetic diversities of the corresponding patient tumors. By engrafting fresh patient gastric cancer (GC) tissues into immune-compromised mice (SCID and/or nude mice), thirty two PDGCX models were established. Histological features were assessed by a qualified pathologist based on H&E staining. Genomic comparison was performed for several biomarkers including ERBB1, ERBB2, ERBB3, FGFR2, MET and PTEN. These biomarkers were profiled to assess gene copy number by fluorescent in situ hybridization (FISH) and/or protein expression by immunohistochemistry (IHC). All 32 PDGCX models retained the histological features of the corresponding human tumors. Furthermore, among the 32 models, 78% (25/32) highly expressed ERBB1 (EGFR), 22% (7/32) were ERBB2 (HER2) positive, 78% (25/32) showed ERBB3 (HER3) high expression, 66% (21/32) lost PTEN expression, 3% (1/32) harbored FGFR2 amplification, 41% (13/32) were positive for MET expression and 16% (5/32) were MET gene amplified. Between the PDGCX models and their parental tumors, a high degree of similarity was observed for FGFR2 and MET gene amplification, and also for ERBB2 status (agreement rate = 94~100%; kappa value = 0.81~1). Protein expression of PTEN and MET also showed moderate agreement (agreement rate = 78%; kappa value = 0.46~0.56), while ERBB1 and ERBB3 expression showed slight agreement (agreement rate = 59~75%; kappa value = 0.18~0.19). ERBB2 positivity, FGFR2 or MET gene amplification was all maintained until passage 12 in mice. The stability of the molecular profiles observed across subsequent passages within the

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

    PubMed

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

    2016-05-01

    Lupeol, a dietary triterpene present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including cancer-preventive and anti-cancer effects in vitro and in vivo. Here, we investigated the anti-cancer efficacy and adjuvant chemotherapy action of lupeol in gastric cancer (GC) cells (SGC7901 and BGC823) and explored the underlying mechanisms. Cells were treated with lupeol and/or 5-fluorouracil (5-Fu) and subjected to cell viability, colony formation, apoptosis, western blot, semiquantitative RT-PCR, and xenograft tumorigenicity assay. Our results showed that lupeol and 5-Fu inhibited the proliferation of SGC7901 and BGC823 cells, and combination treatment with lupeol and 5-Fu resulted in a combination index < 1, indicating a synergistic effect. Co-treatment with lupeol and 5-Fu induced apoptosis through up-regulating the expressions of Bax and p53 and down-regulating the expressions of survivin and Bcl-2. Furthermore, co-treatment displayed more efficient inhibition of tumor weight and volume on BGC823 xenograft mouse model than single-agent treatment with 5-Fu or lupeol. Taken together, our findings highlight that lupeol sensitizes GC to 5-Fu treatment, and combination treatment with lupeol and 5-Fu would be a promising therapeutic strategy for human GC treatment. PMID:26892272

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

    PubMed Central

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

    2015-01-01

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

  15. Epstein-Barr virus in gastric carcinomas and gastric stump carcinomas: a late event in gastric carcinogenesis

    PubMed Central

    zur Hausen, A; van Rees, B P; van Beek, J; Craanen, M E; Bloemena, E; Offerhaus, G J A; Meijer, C J L M; van den Brule, A J C

    2004-01-01

    Background: To determine at what stage during gastric carcinogenesis Epstein-Barr virus (EBV) enters the gastric epithelial cells, the presence of EBV was investigated in two pathogenetically related but distinct forms of adenocarcinoma of the stomach—gastric carcinoma of the intact stomach (GCIS) and gastric stump carcinoma (GSC)—and their presumed precursor lesions. Patients and methods: Eleven patients with EBV positive GCIS and eight patients with EBV positive GSC, demonstrated by the highly sensitive EBV encoded RNA 1/2 (EBER1/2) RNA in situ hybridisation (RISH) technique, were studied. Paraffin wax embedded tissue available from preoperative gastric biopsies and tumour adjacent tissue from the resection specimens containing normal gastric mucosa, inflamed gastric mucosa, and preneoplastic lesions (intestinal metaplasia and dysplasia) was investigated by EBER1/2 RISH, in addition to EBV nuclear antigen 1 (EBNA-1) and latent membrane protein 1 (LMP-1) immunohistochemistry (IHC). Results: In both GCIS and GSC and their precursor lesions EBER1/2 transcripts were restricted to the carcinoma cells. In addition, positivity of EBNA-1 IHC was also restricted to the tumour cells. IHC for LMP-1 was negative in all cases tested. Conclusions: The absence of EBER1/2 transcripts in preneoplastic gastric lesions (intestinal metaplasia and dysplasia) and their presence in two distinct types of gastric carcinoma strongly suggest that EBV can only infect neoplastic gastric cells and thus is a late event in gastric carcinogenesis. PMID:15113855

  16. Enhanced exposure of phosphatidylserine in human gastric carcinoma cells overexpressing the half-size ABC transporter BCRP (ABCG2).

    PubMed Central

    Woehlecke, Holger; Pohl, Antje; Alder-Baerens, Nele; Lage, Hermann; Herrmann, Andreas

    2003-01-01

    Members of the ABC (ATP-binding cassette) transporter super-family are emerging to be involved in lipid transport. In the present study, we studied the organization of phospholipids in the plasma membrane of EPG85-257 human gastric carcinoma cells overexpressing BCRP (breast cancer resistance protein, ABCG-2), a half-size transporter belonging to the ABCG subfamily. A significantly increased plasma membrane association of the PS (phosphatidylserine)-binding probe FITC-Annexin V in comparison with control cells was observed. Treatment of BCRP -overexpressing cells with the inhibitor Tryprostatin A decreased FITC-Annexin V binding almost to the control level. This suggests an enhanced exposure of PS in BCRP -overexpressing cells, which is dependent on functional BCRP. A role of BCRP in the transverse distribution of lipids in the plasma membrane is supported by the increased outward transport of the lipid analogue C6- N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-PS in BCRP -overexpressing EPG85-257 cells and MCF-7 human breast cancer cells. As shown for BCRP -overexpressing EPG85-257 cells, enhanced outward redistribution of the lipid analogue is inhibited by Tryprostatin A as well as by reduction of BCRP expression on transfection with an anti- BCRP -ribozyme. We also observed an enhanced outward transport of C6- N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-phosphatidylcholine in BCRP -overexpressing EPG85-257 cells, suggesting that the influence of BCRP on transverse lipid organization is not highly specific. PMID:12946267

  17. Expression of sphingosine kinase gene in the interactions between human gastric carcinoma cell and vascular endothelial cell

    PubMed Central

    Ren, Juan; Dong, Lei; Xu, Cang-Bao; Pan, Bo-Rong

    2002-01-01

    AIM: To study the interactions between human gastric carcinoma cell (HGCC) and human vascular endothelial cell (HVEC), and if the expression of sphingosine kinase (SPK) gene was involved in these interactions. METHODS: The specific inhibitor to SPK, dimethyl sphingosine (DMS), was added acting on HGCC and HVEC, then the cell proliferation was measured by MTT. The conditioned mediums (CMs) of HGCC and HVEC were prepared. The CM of one kind of cell was added to the other kind of cell, and the cell proliferation was measured by MTT. After the action of CM, the cellular expression of SPK gene in mRNA level was detected with in situ hybridization (ISH). RESULTS: DMS could almost completely inhibit the proliferation of HGCC and HVEC. The growth inhibitory rates could amount to 97.21%, 83.42%, respectively (P < 0.01). The CM of HGCC could stimulate the growth of HVEC (2.70 ± 0.01, P < 0.01) while the CM of HVEC could inhibit the growth of HGCC (52.97% ± 0.01%, P < 0.01). There was no significant change in the mRNA level of SPK gene in one kind of cell after the action of the CM of the other kind of cell. CONCLUSION: SPK plays a key role in regulating the proliferation of HGCC and HVEC. There exist complicated interactions between HGCC and HVEC. HGCC can significantly stimulate the growth of HVEC while HVEC can significantly inhibit the growth of HGCC. The expression of SPK gene is not involved in the interactions. PMID:12174364

  18. The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions.

    PubMed Central

    Soman, N R; Correa, P; Ruiz, B A; Wogan, G N

    1991-01-01

    The TPR-MET oncogenic rearrangement was originally observed in an in vitro transformed human osteosarcoma cell line. Recently, we detected the expression of this rearrangement at very low levels in several cell lines derived from human tumors of nonhematopoietic origin using a highly sensitive method based on polymerase chain reaction amplification of the transcript. We report here the results of analysis of TPR-MET expression in cell lines derived from human gastric tumors and 22 biopsy samples of human gastric mucosa showing cancer or precursor lesions. The rearranged RNA was expressed in all four cell lines as well as in biopsy samples from 12 of the 22 patients. Overexpression of TPR-MET RNA in superficial gastritis lesions with hyperplasia of glandular neck cells suggests the possible involvement of this oncogene at an early stage of gastric tumorigenesis. Analysis of gastric biopsy samples for RAS gene mutations showed base substitutions occurring in the codon 12 region of Ki- and Ha-RAS genes in four cases, including two precursor lesions. Images PMID:2052572

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

    PubMed

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

    2015-04-01

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

  20. Epstein-Barr virus in gastric carcinoma.

    PubMed Central

    Tokunaga, M.; Land, C. E.; Uemura, Y.; Tokudome, T.; Tanaka, S.; Sato, E.

    1993-01-01

    Epstein-Barr virus (EBV) is known to be related to lymphoid tumors and some types of epithelial tumors, including lymphoepithelioma-like gastric carcinoma with marked lymphocytic stroma. In this study, prevalence of EBV involvement in gastric cancer, and characteristics of tumors with such involvement, were investigated by EBV-encoded RNA 1 in situ hybridization applied to paraffin sections, including the tumor and adjacent gastric tissue, from 999 gastric carcinomas observed in 970 consecutive cases from a large Japanese hospital. EBV involvement occurred in 6.9 percent of lesions, a significantly lower proportion than has been observed in a North American series. Involvement was significantly more frequent among males, in tumors in the upper part of the stomach, and in adenocarcinomas of the moderately differentiated tubular and poorly differentiated solid or medullary types. Almost all carcinomas with marked lymphoid stroma were EBV-positive. Positive lesions were characterized by the presence of uniform hybridized signals in almost all carcinoma cells and by their absence from adjacent non-neoplastic tissue. Images Figure 1 PMID:8238241

  1. HOXB5 induces invasion and migration through direct transcriptional up-regulation of β-catenin in human gastric carcinoma.

    PubMed

    Hong, Chang-Soo; Jeong, Oh; Piao, Zhengri; Guo, Chen; Jung, Mi-Ran; Choi, Chan; Park, Young-Kyu

    2015-12-15

    HOX (homeobox) genes encode a family of transcriptional regulators, which have an important role in morphogenesis and differentiation during embryonic development. Their deregulated expression is involved in the carcinogenesis of many human solid tumours. In the present study, we show that HOXB5 mRNA was significantly overexpressed in gastric cancer tissues compared with adjacent normal tissues. HOXB5-up-regulated cancer cells showed increased invasion and migration activity, but no change in proliferation activity, whereas HOXB5-down-regulated cells showed decreased invasion and migration activity. Up-regulation of HOXB5 resulted in up-regulation of β-catenin, whereas inhibition of HOXB5 expression by siRNA led to the down-regulation of β-catenin. Moreover, a significant correlation between HOXB5 and CTNNB1 (β-catenin) mRNA expression was detected in gastric cancer tissues. Furthermore, we found that HOXB5 binds directly to the CTNNB1 promoter region and activates the transcriptional expression of β-catenin, as well as its downstream target genes, encoding cyclin D1 and c-Myc, leading to an increase in the invasion and migration activity of human gastric cancer cells. Thus HOXB5 may be an important regulator of the Wnt/β-catenin signalling pathway, thereby contributing to gastric cancer progression and metastasis. PMID:26467157

  2. 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

  3. Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt pathway

    PubMed Central

    Yang, Zhi-Ping; Zhao, Yan; Huang, Fang; Chen, Jie; Yao, Ya-Hong; Li, Jun; Wu, Xiao-Nan

    2015-01-01

    AIM: To investigate the anti-tumor effects of equol in gastric cancer cells and the underlying molecular mechanisms. METHODS: MGC-803 cells were employed for in vitro experiments in this study. Cells were treated with control (vehicle, 0.1% DMSO) or equol under specified dose titration or time courses. Cell viability was examined by MTS assay, and the levels of Ki67 were determined by qPCR and immunofluorescent assay. Changes in cell cycle distribution and apoptosis rate were detected by flow cytometry. The mRNA expression of cyclin E1 and P21WAF1 was determined by qPCR. The protein levels of cell cycle regulators, PARP and Caspase-3 cleavage, and the phosphorylation of Akt were examined by Western blot. In addition, to characterize the role of elevated Akt activation in the anti-tumor effect exerted by equol, Ly294002, a PI3K/AKT pathway inhibitor, was used to pretreat MGC-803 cells. RESULTS: Equol (5, 10, 20, 40, or 80 μmol/L) inhibited viability of MGC-803 cells in a dose- and time-dependent manner after treatment for 24, 36, or 48 h (P < 0.05 for all). Equol also decreased the mRNA (P < 0.05 for 12 and 24 h treatment) and protein levels of Ki67. Equol treatment significantly induced G0/G1 cell cycle arrest (P < 0.05), with the percentages of G0/G1 cells of 32.23% ± 3.62%, 36.31% ± 0.24%, 45.58% ± 2.29%, and 65.10% ± 2.04% for equol (0, 10, 20, or 30 μmol/L) treatment, respectively, accompanied by a significant decrease of CDK2/4 (P < 0.05 for 24 and 48 h treatment) and Cyclin D1/Cyclin E1 (P < 0.05), and an increased level of P21WAF1 (P < 0.05). A marked increase of apoptosis was observed, with the percentages of apoptotic cells of 5.01% ± 0.91%, 14.57% ± 0.99%, 37.40% ± 0.58%, and 38.46% ± 2.01% for equol (0, 5, 10, or 20 μmol/L) treatment, respectively, accompanied by increased levels of cleaved PARP and caspase-3. In addition, we found that equol treatment increased P-Akt (Ser473 and Thr308) at 12 and 24 h compared to vehicle-treated control

  4. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    PubMed Central

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

    2016-01-01

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

  5. Inhibitory effect of vitamin K1 on growth and polyamine biosynthesis of human gastric and colon carcinoma cell lines.

    PubMed

    Linsalata, Michele; Orlando, Antonella; Tutino, Valeria; Notarnicola, Maria; D'Attoma, Benedetta; Russo, Francesco

    2015-08-01

    Gastric and colon cancers remain the leading cause of cancer mortality throughout the world. Since the gastrointestinal tract works in a constant link with the external environment, chemoprevention by dietary constituents could represent a possible approach to reduce cancer risk. Dietary vitamin K1 (VK1) has been shown to prevent the growth of many types of cancer cells. However, no data are available on possible different susceptibility to VK1 by gastric or colon neoplastic cell lines. Moreover, the exact mechanism of action of VK1 is still object of investigation, even if it has been reported that VK1 may induce cell cycle arrest and apoptosis. Therefore, molecules affecting cell growth such as the natural polyamines could be of interest in VK1 action. The aim of the present study was to investigate the effects of increasing concentrations of VK1 (from 10 to 200 µM) administered up to 72 h, on the cell proliferation and apoptosis of a gastric (HGC-27) and a colon (SW480) cancer cell line. Additionally, the polyamine biosynthesis and the MAPK pathway were also examined. VK1 treatments caused an inhibition of cell proliferation and an induction of apoptosis in both cell lines, with a concomitant significant decrease of the polyamine biosynthesis, increased phospho-ERK 1/2 expression was also observed. A different proliferative behavior and a different response to VK1 by gastric and colon cancer cells was evident, with colon cells showing a more pronounced susceptibility to VK1 action. VK1 is safe and without known toxicities in adult humans, consequently it could be effective in prevention and treatment of selected gastrointestinal neoplasms. Protocols based on the use of VK1, along with polyamine inhibitors and/or analogues, could represent a suitable alternative option for improving the efficacy of chemoprevention and treatment in future strategies for gastrointestinal cancer management. PMID:26043965

  6. CK2α phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients.

    PubMed

    Bae, Jun Sang; Park, See-Hyoung; Kim, Kyoung Min; Kwon, Keun Sang; Kim, Chan Young; Lee, Hun Ku; Park, Byung-Hyun; Park, Ho Sung; Lee, Ho; Moon, Woo Sung; Chung, Myoung Ja; Sylvester, Karl G; Jang, Kyu Yun

    2015-02-15

    CK2α has diverse effects on the tumorigenesis owing to its kinase activity, which phosphorylates various proteins involved in tumorigenesis. We, therefore, investigated the expression and role of CK2α in the phosphorylation of deleted in breast cancer 1 (DBC1) in gastric carcinomas. We used 187 gastric carcinomas and human gastric cancer cells to investigate the roles and relationship between CK2α and DBC1 in gastric carcinomas. Positive expression of CK2α and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2α expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2α was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2α was evidenced by co-immunoprecipitation of CK2α and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2α and DBC1 decreased proliferation and invasive activity of cancer cells. Decreased migration and invasive activity was associated with a downregulation of MMP2, MMP9 and the epithelial-mesenchymal transition. A mutation at the phosphorylation site of DBC1 also downregulated the signals related with the epithelial-mesenchymal transition. Our study demonstrated that CK2α is an independent prognostic indicator for gastric carcinoma patients and is involved in tumorigenesis by regulating the phosphorylation of DBC1. In addition, the blocking of CK2α and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2α-DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma. PMID:24962073

  7. Fine needle aspiration cytology of gastric carcinoma.

    PubMed Central

    Allen, D. C.; Irwin, S. T.

    1997-01-01

    Four patients between 58 and 81 years of age undergoing investigation and endoscopic biopsy for gastric carcinoma also were subjected to direct-vision fine needle aspiration cytology of their mucosal lesions which yielded malignant cells. The relevance of this technique is discussed regarding both intrinsic and extrinsic lesions of the gastrointestinal tract. Images Fig 1. (a) Fig 1. (b) Fig 2. (a) Fig 2. (b) PMID:9414941

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

    PubMed Central

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

    2016-01-01

    In clinical practice, cancer stage (or grade) and some biomarkers, such as carcinoembryonic antigen (CEA) and CA199, are widely used to predict the prognosis of gastric carcinoma patients. Due to the limited role of prognostic indicators for gastric carcinoma, this condition remains one of the most fatal human malignancies with a dismal prognosis. Nicotinamide N-methyltransferase (NNMT, EC.2.1.1.1), a metabolizing enzyme, is involved in the development and progression of various carcinomas. However, the prognostic and biological functions of NNMT in gastric carcinoma are not yet clear. In the present study, NNMT was found to be overexpressed at the mRNA and protein levels in gastric carcinoma tissues compared with adjacent tissues. Importantly, the survival analysis verified that NNMT expression is an independent prognostic factor for overall survival of gastric cancer patients. Moreover, NNMT expression was related to primary tumor size, lymph node metastasis, distant metastasis, and TNM (tumor, node, and metastasis) stage. We also demonstrated that knockdown of NNMT inhibits cellular proliferation, invasion and migration in vitro and in vivo. Overall, the results of this study suggest that NNMT is a promising prognostic predictor for gastric cancer patients and could be used as a new target for gastric cancer therapy. PMID:27152242

  9. [Synchronous or metachronous extragastric neoplasms associated with gastric neoplasia. Common pathogenesis of gastric intestinal and colonic carcinoma?].

    PubMed

    Planells Roig, M V; García Espinosa, R; Morcillo Ródenas, R; Rodero Rodero, D

    1990-12-01

    Coexistence of syncronous or metacronous extragastric carcinomas, particularly of the colon and small bowel may favour the hypothesis of a common origin with gastric carcinoma. Three cases of colonic carcinoma coexisting with early gastric cancer, are presented. The etiopathogenesis of intestinal-type gastric cancer and colonic cancer are discussed in the light of a possible common mechanism. PMID:2091707

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

    PubMed Central

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

    2016-01-01

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

  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. DBGC: A Database of Human Gastric Cancer.

    PubMed

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

    2015-01-01

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

  13. Gastric mixed adenoneuroendocrine carcinoma with a good prognosis.

    PubMed

    Fukuba, Nobuhiko; Yuki, Takafumi; Ishihara, Shunji; Sonoyama, Hiroki; Tada, Yasumasa; Kusunoki, Ryusaku; Oka, Akihiko; Oshima, Naoki; Moriyama, Ichiro; Kawashima, Kousaku; Kinoshita, Yoshikazu

    2014-01-01

    A flat, elevated lesion measuring 5 mm in diameter was found in the gastric body of an 80-year-old man. A biopsy showed moderately differentiated adenocarcinoma, and endoscopic ultrasonography revealed a hypoechoic mass located in the submucosa. Endoscopic submucosal dissection was subsequently performed, and a pathological examination revealed a tumor composed of adenocarcinoma and neuroendocrine carcinoma with submucosal infiltration. The pathological diagnosis was gastric mixed adenoneuroendocrine carcinoma (MANEC). An additional gastrectomy procedure was performed, and no recurrence was noted for at least three years. This case is interesting with respect to the carcinogenesis of endocrine cell carcinoma and MANEC. PMID:25400179

  14. Malignant Pericardial Tamponade in a Case of Signet Cell Gastric Carcinoma.

    PubMed

    Nambiar, Rakul; Prabhakaran, Sunil Prasobh; Pillai, Padmakumar Rajasekharan; Dalus, D

    2015-10-01

    We report a case of gastric signet cell carcinoma, presenting as cardiac tamponade, in a young male patient. The diagnosis of gastric signet cell carcinoma was confirmed by immunohistochemistry of the lymph node specimen in our patient. PMID:27608703

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

    PubMed

    Liu, Yanfang; Zhang, Xin; Zhang, Yujing; Hu, Zunqi; Yang, Dejun; Wang, Changming; Guo, Meng; Cai, Qingping

    2015-12-01

    Gastric cancer (GC) is the fourth most frequent malignant disease and the second leading cause of cancer mortality worldwide, but the molecular mechanisms underlying this clinically heterogeneous disease are complex and remain far from completely understood. Accumulating evidence suggests that abnormal microRNA (miRNA) expression is involved in tumorigenesis. However, their accurate expression pattern, function, and mechanism in GC remain unclear. Here, a heatmap analysis of the miRNomes was performed across TCGA datasets and the expression of miR-133 family was found to be consistently downregulated in GC. This result was confirmed in two GC cell lines and 20 pairs of primary GC tissues, and further study demonstrated that the downregulation of miR-133 was mainly mediated by histone modification within its promoter region. Importantly, restoration of miR-133b/a-3p expression could suppress GC cell proliferation and promote cell apoptosis by targeting anti-apoptotic molecules Mcl-1 and Bcl-xL. Consistent with in vitro results, reintroducing of miR-133b/a-3p expression significantly delayed tumor formation and reduced tumor size of GC cells in xenograft nude mice. And the inverse relationship between miR-133b/a-3p and its targets was verified in xenograft mice. Taken together, our findings suggest that miR-133b/a-3p acts as a tumor suppressor in GC by directly targeting Mcl-1 and Bcl-xL. Revealing novel mechanism for oncogene inhibition by miRNA-mediated pathways offers new avenues for GC treatment. PMID:26276722

  16. Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

    PubMed

    Geredeli, Caglayan; Dogru, Osman; Omeroglu, Ethem; Yilmaz, Farise; Cicekci, Faruk

    2015-05-01

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases. PMID:26266010

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

    PubMed

    Yamazaki, Mutsumi; Koutaka, Mitsuru; Une, Yumi

    2016-08-01

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

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

    PubMed Central

    YAMAZAKI, Mutsumi; KOUTAKA, Mitsuru; UNE, Yumi

    2016-01-01

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

  19. Aqueous extracts of Fructus Ligustri Lucide induce gastric carcinoma cell apoptosis and G2/M cycle arrest

    PubMed Central

    Zhang, Ru; Li, Ying-Xue; Wang, Li-Sheng; Song, Yang; Huang, Qing-Juan; Zhang, Ding-Guo

    2015-01-01

    Objective: Previous studies have shown that Fructus Ligustri Lucide (FLL) can be used to anti-cancer. However, the mechanism by which FLL mediate this effect is unclear. In the present study, aqueous extracts of FLL induced cell apoptosis in human gastric carcinoma cell was investigated. Methods: The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining and hoechst 33342 staining. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting. Results: Treatment of human gastric carcinoma cells with FLL induced cell death in a dose- and time-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that the proportion of the early and terminal phase of apoptosis cells had gained after FLL treatment as compared to untreated group. Moreover, human gastric carcinoma cells were exposed to the aqueous extracts of FLL for 48 h, which resulted in an accumulation of cells in G2/M phase. Apoptotic bodies were clearly observed in human gastric carcinoma that had been treated with FLL for 48 h and then stained with Hochest 33342. Treatment of gastric carcinoma cells with increasing doses of FLL and increasing durations significantly increased the protein expression of Bax and Caspase3, decreased the anti-apoptotic Bcl-2 level. The expression of CDC2 and cdc25C were downregulated upon FLL treatment in human gastric carcinoma. In contrast, p53 and p21 were obviously upregulated by FLL treatment in a concentration-dependent manner. Conclusions: These results confirmed that FLL could induce apoptosis in human gastric carcinoma, the underlying molecular mechanisms, at least partially, through activation p21/p53 and suppression CDC2/cdc25C signaling in vitro. PMID:26550140

  20. Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma

    PubMed Central

    2014-01-01

    Background To investigate on the expressions and the clinical significances of hepatocyte growth factor receptor (c-MET), phosphorylated c-MET (p-MET) and e2f-1 transcription factor in primary lesion of gastric adenocarcinoma (GC). Method Tissue samples from the primary lesion of GC in patients who accepted D2/D3 radical gastrectomy with R0/R1 resection were stained by immunohistochemistry of c-MET, p-MET, e2f-1 and Ki-67. The univariate and the multivariate analyses involving in clinicopathological parameters and prognostic factors were evaluated. Results The positivity rates for c-MET (66.12%, 80 cases/121 cases), p-MET (59.50%, 72 cases/121 cases), e2f-1 (38.84%, 47 cases/121 cases) and Ki-67 (72.73%, 88 cases/121 cases) in primary lesion of GC was significantly higher than that in non-cancerous tissue at 5 cm places far from the margin of primary lesion (P < 0.05, respectively). The deeper tumor invasion, the severer lymph node metastasis, the later stage of TNM and the higher expression of Ki-67 was respectively an independent risk factor for the higher expression of c-MET or p-MET, but the younger age and the shorter survival time was an independent risk factor for the higher expression of e2f-1 respectively. Survival analysis showed that the worse prognosis could be observed in the patients with the combination of both c-MET-positive and e2f-1-negative (P = 0.038) or both p-MET-positive and e2f-1-negative (P = 0.042). Cox analysis demonstrated that the severer lymphatic node metastasis and the higher positivity rate of c-MET, p-MET or e2f-1 were an independent prognosis factor respectively. The higher expression of e2f-1 was identified in patients with Stage I-II, which correlated with a shorter survival time. Survival analysis also revealed that the prognosis of patients with positive expression of e2f-1 at Stage I-II was significantly worse than that in patients with negative expression of e2f-1 (χ2 = 13.437, P = 0.001). However, in

  1. Gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation: case report and review of the literature.

    PubMed

    Pericleous, Marinos; Toumpanakis, Christos; Lumgair, Heather; Caplin, Martyn E; Morgan-Rowe, Luke; Clark, Ian; Luong, Tu Vinh

    2012-05-01

    Most gastric neuroendocrine tumours are well differentiated and considered as neuroendocrine neoplasms, whilst poorly differentiated lesions are considered as neuroendocrine carcinomas and account for only 6-16% of gastric neuroendocrine tumours. Gastric mixed adenoneuroendocrine carcinomas are rare malignancies usually composed of a neuroendocrine carcinoma and an adenocarcinoma with a variable grade of differentiation. Here, we report an unusual and rare gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation including a neuroendocrine carcinoma, an adenocarcinoma and a squamous cell carcinoma. A brief discussion of the histopathological features, biological behaviour and treatment of this rare tumour type is presented. PMID:22740822

  2. Gastric Mixed Adenoneuroendocrine Carcinoma with a Trilineage Cell Differentiation: Case Report and Review of the Literature

    PubMed Central

    Pericleous, Marinos; Toumpanakis, Christos; Lumgair, Heather; Caplin, Martyn E.; Morgan-Rowe, Luke; Clark, Ian; Luong, Tu Vinh

    2012-01-01

    Most gastric neuroendocrine tumours are well differentiated and considered as neuroendocrine neoplasms, whilst poorly differentiated lesions are considered as neuroendocrine carcinomas and account for only 6–16% of gastric neuroendocrine tumours. Gastric mixed adenoneuroendocrine carcinomas are rare malignancies usually composed of a neuroendocrine carcinoma and an adenocarcinoma with a variable grade of differentiation. Here, we report an unusual and rare gastric mixed adenoneuroendocrine carcinoma with a trilineage cell differentiation including a neuroendocrine carcinoma, an adenocarcinoma and a squamous cell carcinoma. A brief discussion of the histopathological features, biological behaviour and treatment of this rare tumour type is presented. PMID:22740822

  3. Exocrine and endocrine modulation in common gastric carcinoma.

    PubMed

    Canzonieri, Vincenzo; Colarossi, Cristina; Del Col, Laura; Perin, Tiziana; Talamini, Renato; Sigon, Roberto; Cannizzaro, Renato; Aiello, Eleonora; Buonadonna, Angela; Italia, Fabrizio; Massi, Daniela; Carbone, Antonino; Memeo, Lorenzo

    2012-05-01

    Diagnostic and prognostic implications of endocrine differentiation were evaluated in 103 common gastric adenocarcinomas and undifferentiated carcinomas. Maturely differentiated exocrine and endocrine phenotypes were evaluated by using gastric exocrine and endocrine markers along with intestinal exocrine and endocrine markers. Immunohistochemical analysis revealed that 66 tumors (64%) were positive for generic endocrine markers such as chromogranin A and/or synaptophysin. The 14 patients with more than 20% tumor cells positive for at least 1 endocrine marker experienced a poorer prognosis than patients with no (n = 37) or 1% to 20% (n = 52) positivity. The 16 carcinomas expressing the maturely differentiated exocrine gastric phenotype significantly correlated with poorer outcome compared with carcinomas with mature exocrine intestinal (n = 22) or mixed/gastrointestinal (n = 64) phenotypes. Among tumors expressing chromogranin A and/or synaptophysin, the maturely differentiated endocrine gastric phenotype (n = 26) was a negative prognostic factor compared with mature endocrine intestinal (n = 21) and mixed/gastrointestinal (n = 5) phenotypes. Endocrine differentiation and maturely exocrine/endocrine gastric phenotypes are associated with an unfavorable prognosis and may identify subsets of patients for tailored therapy. PMID:22523208

  4. MicroRNA-421 Gene Polymorphism in Gastric Carcinoma.

    PubMed

    Jin, Xin; Yu, Nong

    2016-01-01

    BACKGROUND As a common malignant tumor, gastric carcinoma requires early diagnosis to improve treatment efficacy. MicroRNA (miR) molecules have highly conserved nucleotide sequences and can negatively regulate target gene expression at the translational level. miR-421 has been suggested to be related with gastric cancer occurrence. The gene polymorphism of miR-421, however, has not been reported. This study thus investigated the G/C polymorphism of miR-421 and its role in progression and prognosis of gastric cancer. MATERIAL AND METHODS A total of 96 gastric cancer patients were recruited in this study and tumor samples were collected from surgical resection. Single-nucleotide polymorphism (SNP) of miR-421 was determined by DNA sequencing for analyzing the correlation between lymph node metastasis and miR-421 genotypes. Logistic regression analysis was used to determine the relationship between genotype and risk factors of gastric cancer. Kaplan-Meier survival analysis was also performed to compare GG and GC carriers. RESULTS Differential expression patterns existed between gastric cancer tissues and normal gastric mucosa. Logistic regression analysis showed GC and GG genotypes were risk factors for gastric cancer. Patients with lymph node metastasis had higher GG genotype frequency compared to those without metastasis. In survival analysis, GG carriers had shorter survival time than GC carriers. Furthermore, GG genotype was correlated with tumor prognosis (p<0.05). CONCLUSIONS G allele of miR-421 is a risk factor for gastric cancer. GG genotype is correlated with lymph node metastasis and prognosis, indicating it is a risk factor for gastric cancer. PMID:27133200

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

    SciTech Connect

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

    2014-06-13

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

  6. Epstein-Barr Virus Infection in Gastric Remnant Carcinoma and Recurrent Gastric Carcinoma in Qingdao of Northern China

    PubMed Central

    Liu, Shuzhen; Zhao, Zhenzhen; Han, Lu; Liu, Song; Luo, Bing

    2016-01-01

    Background Epstein-Barr virus (EBV) is associated with a subset of gastric carcinoma which was defined as EBV associated gastric carcinoma (EBVaGC). The proportion of EBVaGC in gastric remnant carcinoma (GRC) which occurs in the intact stomach five or more years after gastric surgery for benign disease is significantly higher than that in conventional gastric carcinoma (CGC). The infection of EBV in recurrent gastric carcinoma (RGC) with local anastomotic recurrence is poorly understood. Methods 53 cases of GRC and 58 cases of RGC were analyzed for the presence of EBV, and the variants of EBV Encoded RNAs (EBER), EBV Nuclear Antigen 1 (EBNA1) and Latent Membrane Protein 1 (LMP1) gene in both groups were investigated. Results Thirteen (24.5%) out of 53 GRC cases and 3 (5.2%) out of 58 RGC cases were identified as EBVaGCs. In 17 paired RGC cases, only one case was classified as EBVaGC in both times specimen. Another one case was identified as EBVaGC in the primary gastroectomy specimen while the recurrent gastric cancer was not. The third EBVaGC in RGC was identified while the primary gastric cancer was not EBVaGC. In GRC and RGC cases, type 1, type F, EB-6m, V-val subtype, del-LMP1 were predominant type or variants, accounting for 10(76.9%) and 2(66.7%), 13(100%) and 3(100%), 13(100%) and 3(100%), 9(69.2%) and 3(100%), 12(92.3%) and 3(100%), respectively. However, Type C was the predominant type in GRC accounting for 9(69.2%) cases while type D was the predominant one accounting for 2(66.7%) cases in RGC. Conclusions The prevalence of EBVaGc in GRC and RGC was significantly different. The distributions of these variants were similar to each other in the two groups which indicated that there were no more aggressive EBV variants in EBVaGC in GRC compared with that in RGC. PMID:26859565

  7. The JAK/STAT signaling cascade in gastric carcinoma (Review).

    PubMed

    Khanna, Puja; Chua, Pei Jou; Bay, Boon Huat; Baeg, Gyeong Hun

    2015-11-01

    Gastric carcinoma remains one of the most prevalent forms of cancer worldwide, despite the decline in incidence rates, increased awareness of the disease and advancement in treatment strategies. Helicobacter pylori infection, dietary factors, lifestyle influences and various genetic aberrations have been shown to contribute to the development and progression of gastric cancer. Recent studies on the genomic landscape of gastric adenocarcinoma have identified several key signaling molecules, including epidermal growth factor receptor family (ErbB) members, vascular endothelial growth factor receptor family (VEGFR) members and PI3K/Akt/mTOR pathway components, that have been implicated in the molecular pathogenesis of gastric cancers. However, clinical trials with compounds that target these molecules have failed to show a significant improvement in overall survival rates when supplemented with conventional therapies. Therefore, it is essential to identify effective prognostic and/or diagnostic biomarkers and develop molecular targeted therapies. The JAK/STAT cascade is a principal signal transduction pathway in cytokine and growth factor signaling, regulating various cellular processes such as cell proliferation, differentiation, migration and survival. Numerous in vivo and in vitro studies have shown that dysregulated JAK/STAT signaling is a driving force in the pathogenesis of various solid cancers as well as hematopoietic malignancies. Hence, a large number of preclinical and clinical studies of drugs targeting this pathway are currently underway. Notably, aberrant JAK/STAT signaling has also been implicated in gastric cancers. In this review, we focus on the ongoing research on the JAK/STAT cascade in gastric carcinoma and discuss the therapeutic potential of targeting JAK/STAT signaling for the treatment of gastric cancer. PMID:26398764

  8. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.

    PubMed

    Ding, Lin; El Zaatari, Mohamad; Merchant, Juanita L

    2016-01-01

    This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, "humanized" versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model. PMID:27573785

  9. Gastric metastasis of renal cell carcinoma 20 years after radical nephrectomy

    PubMed Central

    Akay, Ebru; Kala, Mehtap; Karaman, Hatice

    2016-01-01

    Renal cell carcinomas account for 2–3% of malignant neoplasms in adults. The lung, soft tissues and bone represent the most frequent sites of distant metastasis in renal cell carcinoma. Gastric metastasis is rare. Our case was a 72-year-old man with complaints of fatigue and loss of appetite. In history, he had unergone radical nephrectomy due to renal cell carcinoma in 1993. A polypoid lesion was observed in upper gastrointestinal endoscopy. Histopathology of gastric biopsy specimen was reported as renal cell carcinoma. In English literature, there are 50 cases diagnosed as gastric metastasis from renal cell carcinoma. To date, there are only 4 cases with extremely late gastric metastasis of renal cell carcinoma. Herein, we present a rare case which underwent radical nephrectomy due to renal cell carcinoma and found to have gastric metastasis at 20. year of his follow-up. PMID:27274897

  10. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma

    PubMed Central

    Zhang, Rong-Guang; Duan, Guang-Cai; Fan, Qing-Tang; Chen, Shuai-Yin

    2016-01-01

    Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review. PMID:26909232

  11. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma.

    PubMed

    Zhang, Rong-Guang; Duan, Guang-Cai; Fan, Qing-Tang; Chen, Shuai-Yin

    2016-02-15

    Gastric cancer (GC) is one of the most common carcinoma and the second leading cause of cancer-related deaths worldwide. Helicobacter pylori (H. pylori) infection causes a series of precancerous lesions like gastritis, atrophy, intestinal metaplasia and dysplasia, and is the strongest known risk factor for GC, as supported by epidemiological, preclinical and clinical studies. However, the mechanism of H. pylori developing gastric carcinoma has not been well defined. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progresses to GC. The outcomes of H. pylori infection are determined by bacterial virulence, genetic polymorphism of hosts as well as environmental factors. It is important to gain further understanding of the pathogenesis of H. pylori infection for developing more effective treatments for this common but deadly malignancy. The recent findings on the bacterial virulence factors, effects of H. pylori on epithelial cells, genetic polymorphism of both the bacterium and its host, and the environmental factors for GC are discussed with focus on the role of H. pylori in gastric carcinogenesis in this review. PMID:26909232

  12. 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

  13. A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

    ClinicalTrials.gov

    2014-04-21

    HER2 + Breast Cancer, HER2 + Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma; HER2 + Breast Cancer; HER2 + Gastric Cancer; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma

  14. A Case of Gastric Cancer with Neuroendocrine Carcinoma, Signet Ring Cell Carcinoma Components, and Intramural Metastases

    PubMed Central

    Aoyagi, Keishiro; Kizaki, Junya; Isobe, Taro; Akagi, Yoshito

    2016-01-01

    Patient: Male, 67 Final Diagnosis: Gastric cancer with neuroendocrine carcinoma Symptoms: — Medication: — Clinical Procedure: Total gastrectomy • splenectomy with D2 lymph node dissection Specialty: Surgery Objective: Rare co-existance of disease or pathology Background: Many neuroendocrine carcinomas exhibit medullary infiltration and expanded proliferation. Differentiated tubular adenocarcinoma is frequently seen in the superficial region in many neuroendocrine carcinoma cases. However, the present case showed non-medullary infiltration and signet ring cell carcinoma in the superficial region, with intramural metastases distributed throughout the whole of the stomach. Case Report: A 67-year-old man was referred to our institution for treatment of gastric cancer. Type IIc-like advanced gastric cancer was detected in the greater curvature of the middle body of the stomach. The patient underwent total gastrectomy, splenectomy with D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a large-cell endocrine carcinoma of the stomach. A solid growth of signet ring cells was seen in the mucosa and submucosa. Intramural metastases were observed in many other depressed lesions. Large-cell carcinoma invaded the submucosa, mainly in the intramural metastatic site. Metastasis to one lesser curvature lymph node was also seen on histological examination. The final diagnosis was a gastric cancer of type 0–IIc (T4a) [M] (with intramural metastases) at T4aN1H0P0M0 Stage IIIA. This patient has remained alive without recurrence for 72 months after surgery. Conclusions: We recommend close preoperative examination of neuroendocrine carcinoma, taking intramural metastases into consideration. PMID:27102318

  15. Immunohistochemical expression of tenascin in normal stomach tissue, gastric carcinomas and gastric carcinoma in lymph nodes.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kajiyama, K.; Haraguchi, Y.; Sasaki, O.; Sugimachi, K.

    1995-01-01

    The immunohistochemical expression of tenascin was examined in the normal adult mucosa of the stomach, primary tumours and lymph node metastases of gastric cancer patients. In normal gastric tissue tenascin was expressed in the muscularis mucosae, muscularis propria and vessel walls, however it was not expressed in either the mucosal connective tissue or the stromal tissue in the submucosal layer. In gastric cancer, tenascin was expressed in 35 of 85 primary tumours, and in 8 of 25 metastases in lymph nodes. Tenascin was located in the fibrous stroma surrounding foci of cancer. The expression of tenascin in the primary tumour did not correlate with the depth of invasion, lymph node metastasis or prognosis. Tenascin appears during the process of either malignant transformation or tumour progression in gastric cancer, and the positive expression of tenascin may be useful as a stromal marker for the early detection of gastric cancer. Images Figure 1 PMID:7541237

  16. [Treatment Strategy for Gastric Carcinoma with Lymphoid Stroma].

    PubMed

    Kobayashi, Ryosuke; Takiguchi, Nobuhiro; Nabeya, Yoshihiro; Ikeda, Atsushi; Souda, Hiroaki; Kainuma, Osamu; Tonooka, Toru; Imanishi, Shunsuke; Arimitsu, Hidehito; Chibana, Tomofumi; Ishige, Fumitaka; Sasaki, Kosuke; Yamamoto, Hiroshi

    2015-11-01

    Gastric carcinoma with lymphoid stroma (GCLS) is a histological type with severe lymphocytic infiltration. GCLS is very rare and few cases have been reported. We examined the clinical features, problems of preoperative diagnosis, and treatment of 14 cases (1.8%) that were diagnosed as GCLS out of 790 gastric cancers surgically resected in our hospital. The mean age was 69 years. Six, 8, and 0 cases were located in the upper, middle, and lower fields of the stomach, respectively, and 8, 1, 4, and 1 cases were macroscopically 0-Ⅱc, 0-Ⅰ, type 2, and type 3, respectively. The depth of invasion was M, SM1, SM2, MP, and SS in 0, 0, 9, 3, and 2 cases, respectively. There were 12 cases(86%)with infection by Epstein-Barr virus, and just 1 case with lymph node metastasis. All cases have had no evidence of recurrence. There were no cases that were diagnosed as GCLS before surgery. GCLS is recognized as having a more favorable prognosis compared with other types of gastric carcinoma, so an aggressive surgery might achieve good outcomes. However, preoperative diagnosis is very difficult and there is a compelling need for new techniques or criteria for diagnosis of GCLS. PMID:26805251

  17. Degranulation patterns of eosinophils in advanced gastric carcinoma: an electron microscopic study.

    PubMed

    Caruso, R A; Ieni, A; Fedele, F; Zuccalà, V; Riccardo, M; Parisi, E; Parisi, A

    2005-01-01

    Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and degranulation patterns of eosinophils in the tumor stroma. Seven cases of advanced gastric carcinomas were found to be massively infiltrated by eosinophils and studied by light and electron microscopy. Gastric carcinomas, despite having similar numbers of tissue eosinophils, exhibited markedly different degranulation patterns. In 2 cases, resting nondegranulating eosinophils were found. Piecemeal degranulation was the predominant mode of secretion from eosinophils localized within the tumor stroma in 4 cases. Eosinophil exocytosis and cytolysis were rarely observed. In 1 case, crystals morphologically similar to Charcot-Leyden crystals were observed at the extracellular level as well as in phagosomes of tissue macrophages, confirming active sequestrations of eosinophil Charcot-Leyden protein by macrophages in vivo. In the same case, eosinophils showed characteristic features of early and late apoptotic changes, such as condensed chromatin, focal dilatation of nuclear envelope, and preserved plasma membrane. Morphological association between apoptotic eosinophils and deposition of granules in the tumor stroma was found. Extracellular deposition of intact granules from apoptotic eosinophils was distinct from eosinophilic (necrotic) cytolysis, and has reported previously in experimental studies in vitro. To the knowledge of the authors, this case represents the first report of late apoptotic eosinophils that release their granules within the tumor stroma in a human gastric carcinoma. PMID:15931778

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

    PubMed

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

    2016-03-14

    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

  19. 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

  20. Gastric reflux is an independent risk factor for laryngopharyngeal carcinoma

    PubMed Central

    Langevin, Scott M.; Michaud, Dominique S.; Marsit, Carmen J.; Nelson, Heather H.; Birnbaum, Ariel E.; Eliot, Melissa; Christensen, Brock C.; McClean, Michael D.; Kelsey, Karl T.

    2013-01-01

    Background Gastric reflux can reach into the upper airway, inducing cellular damage in the epithelial lining. This condition is believed to be a risk factor for development of laryngopharyngeal squamous cell carcinoma (LPSCC), although the literature is conflicting. Methods To better clarify this relationship, we assessed the association of self-reported heartburn history and medication use among 631 LPSCC patients and 1234 control subjects (frequency-matched on age, gender and town of residence) enrolled as part of a population-based case-control study of head and neck squamous cell carcinoma in the greater Boston area. Results After adjusting for age, gender, race, smoking, alcohol consumption, HPV16 seropositivity, education and body mass index, subjects reporting a history of frequent heartburn and who were neither a heavy smoker nor heavy drinker had a significantly elevated risk of LPSCC (OR = 1.78, 95% CI: 1.00–3.16). Among those with a history of heartburn, there was an inverse association between antacid use and LPSCC relative to those never taking heartburn medication (OR = 0.59, 95% CI: 0.38–0.93) that remained consistent when analyzed by smoking/drinking status, HPV16 status, or by primary tumor site. Conclusions Our data show that gastric reflux is an independent risk factor for squamous cancers of the pharynx and larynx. Further studies are needed to clarify the possible chemopreventive role of antacid use for patients with gastric reflux. Impact Elucidation of additional risk factors for head and neck cancer can allow for risk stratification and inform surveillance of high-risk patients. PMID:23703970

  1. Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis

    PubMed Central

    Wang, Hai-Sheng; Nie, Xiaobo; Wu, Rui-Bing; Yuan, Hong-Wei; Ma, Yue-Hong; Liu, Xiu-Lan; Zhang, Jian-Yu; Deng, Xiu-Ling; Na, Qin; Jin, Hai-Yan; Bian, Yan-Chao; Gao, Yu-Min; Wang, Yan-Dong; Chen, Wei-Dong

    2016-01-01

    Aberrant activation of Wnt/β-catenin signaling pathways is closely involved in the occurrence and progression of several types of human malignancies. However, as a fundamental component in this cascade, Wnt3 has not been well understood for the expression level and pathogenic mechanism in gastric carcinogenesis. Here, this research was undertaken to elucidate the important role of Wnt3 in gastric cancer. Wnt3 expression in gastric carcinomas and their respective normal tissues was examined by immunoblotting and immunohistochemistry. In all cases, Wnt3 expression was significantly elevated in gastric carcinomas compared with normal tissues. Knocking down Wnt3 in MGC-803 gastric cancer cells by small interfering RNAs transfection led to an obvious decrease in both transcript and protein levels. Silence of Wnt3 expression in gastric cancer cells inhibited the expression of β-catenin and cyclin D1 genes in Wnt/β-catenin pathway, significantly blocked cellular proliferation, delayed cell cycle, suppressed cell invasion and metastasis, accompanied by a higher apoptosis rate. Together, we conclude that upregulation of Wnt3 plays a crucial role in gastric tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells, and Wnt3 might be a potential target for the treatment of gastric cancer. PMID:27390525

  2. miR-935 suppresses gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression.

    PubMed

    Yan, Chao; Yu, Jianchun; Kang, Weiming; Liu, Yuqin; Ma, Zhiqiang; Zhou, Li

    2016-01-29

    Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis. Expression of microRNAs (miRNAs) has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. The function of miR-935 has never been reported in cancer before. We found, using microRNA array, that expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. We also identified Notch1 as a direct target of miR-935. Knockdown of Notch1 reduced proliferation, migration/invasion of GSRCC cells, and overexpression Notch1's activated form (Notch intracellular domain) could rescue miR-935's tumor suppressive effect on GSRCC. Expression of miR-935 was lower in gastric carcinoma tissue than in paired normal tissue samples, and lower in GSRCC than in non-GSRCC. Our results demonstrate the inverse correlation between the expression of miR-935 and Notch1 in gastric tissues. We conclude that miR-935 inhibits gastric carcinoma cell proliferation, migration and invasion by targeting Notch1, suggesting potential applications of the miR-935-Notch1 pathway in gastric cancer clinical diagnosis and therapeutics, especially in gastric signet ring cell carcinoma. PMID:26742429

  3. Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas.

    PubMed

    Cho, Eun Yoon; Park, Kyeongmee; Do, Ingu; Cho, Junhun; Kim, Jiyun; Lee, Jeeyun; Kim, Seonwoo; Kim, Kyoung-Mee; Sohn, Tae Sung; Kang, Won Ki; Kim, Sung

    2013-05-01

    Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be

  4. Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

    PubMed Central

    Suzuki, Akira; Koide, Naohiko; Kitazawa, Masato; Mochizuka, Akiyoshi; Ota, Hiroyoshi; Miyagawa, Shinichi

    2012-01-01

    Alpha-fetoprotein-producing carcinoma (AFPC)/hepatoid adenocarcinoma (HAC) and neuroendocrine carcinoma (NEC) are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component. PMID:22482081

  5. Honey and Apoptosis in Human Gastric Mucosa

    PubMed Central

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

    2012-01-01

    Background: Gastric cancer is the fourth most common malignancy in the world. Honey is a complex mixture of special biological active constituents. Honey possesses antioxidant and antitumor properties. Nutritional studies have indicated that consumption of honey modulates the risk of developing gastric cancer. On the other hand, apoptosis has been reported to play a decisive role in precancerous changes. Our chief study was conducted to assess the relationship between consumption of honey and apoptosis in human gastric mucosa. Method: This cross-sectional study was conducted on 98 subjects over 18 years old, referred to two hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal endoscopy, 62 subjects were finally enrolled. Honey consumption was assessed by a Food Frequency Questionnaire (FFQ) and apoptosis was detected by TUNEL technique. We tested polynomial curve to find the best fit between honey consumption and apoptosis. Results: A positive relation between honey consumption and apoptosis was found (P=0.024). Our results indicated that the final and the best fit curve was: apoptosis = 1.714+1.648(honey amount) - 0.533(honey amount)2 +1.833×10-5(honey amount)7. Conclusion: Honey consumption had positive effects on gastric cancer by inducing apoptosis in gastric mucosa. PMID:24688918

  6. 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

  7. Breed predisposition to canine gastric carcinoma - a study based on the Norwegian canine cancer register

    PubMed Central

    2013-01-01

    Background Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The aim of the study was to retrospectively investigate the proportion and possible breed predisposition to canine gastric carcinoma using the Norwegian Canine Cancer Register for calculations of proportional morbidity ratios (PMRs) for the period 1998–2009. Results Histologically verified tumours recorded in the Norwegian Canine Cancer Register were studied (n = 19,715). A total of 31 (0.16%) cases of canine gastric carcinomas were identified. The median age of affected dogs was 10 years. The most commonly reported clinical signs were vomiting, anorexia, and weight loss. Males had significantly higher odds of gastric carcinoma than females (P = 0.02). The PMR with 95% confidence interval (CI) was calculated for each breed, and a breed predisposition was identified. Individuals of the breeds Tervuren (PMR 56.1), Bouvier des Flandres (PMR 36.5), Groenendael (PMR 34.5), Collie (PMR 26.1), Standard poodle (PMR 7.6), and Norwegian elkhound (PMR 6.1) had a significantly increased risk of developing gastric carcinoma. Discussion and conclusion The proportion of cases of gastric carcinoma recorded in the Norwegian Canine Cancer Register was found to be 0.16%, and a breed predisposition was identified. The breed predisposition observed in the current study indicates a genetic susceptibility to gastric carcinoma. PMID:23514604

  8. 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

  9. The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma

    PubMed Central

    Matsuoka, Tasuku; Yashiro, Masakazu

    2014-01-01

    The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key signaling pathways induced by various receptor-tyrosine kinases. Accumulating evidence shows that this pathway is an important promoter of cell growth, metabolism, survival, metastasis, and resistance to chemotherapy. Genetic alterations in the PI3K/Akt/mTOR pathway in gastric carcinoma have often been demonstrated. Many kinds of molecular targeting therapies are currently undergoing clinical testing in patients with solid tumors. However, with the exception of the ErbB2-targeting antibody, targeting agents, including PI3K/Akt/mTOR inhibitors, have not been approved for treatment of patients with gastric carcinoma. This review summarizes the current knowledge on PI3K/Akt/mTOR signaling in the pathogenesis of gastric carcinoma and the possible therapeutic targets for gastric carcinoma. Improved knowledge of the PI3K/Akt/mTOR pathway in gastric carcinoma will be useful in understanding the mechanisms of tumor development and for identifying ideal targets of anticancer therapy for gastric carcinoma. PMID:25003395

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

    PubMed Central

    Bimczok, Diane; Kao, John Y.; Zhang, Min; Cochrun, Steven; Mannon, Peter; Peter, Shajan; Wilcox, Charles M.; Mönkemüller, Klaus E.; Harris, Paul R.; Grams, Jayleen M.; Stahl, Richard D.; Smith, Phillip D.; Smythies, Lesley E.

    2014-01-01

    Despite the high prevalence of chronic gastritis caused by H. pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule, retinol, and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of retinol synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric DCs. Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation. PMID:25249167

  11. Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice

    PubMed Central

    Matsuoka, T; Adair, J E; Lih, F B; Hsi, L C; Rubino, M; Eling, T E; Tomer, K B; Yashiro, M; Hirakawa, K; Olden, K; Roberts, J D

    2010-01-01

    Background: Dietary (n-6)-polyunsaturated fatty acids influence cancer development, but the mechanisms have not been well characterised in gastric carcinoma. Methods: We used two in vivo models to investigate the effects of these common dietary components on tumour metastasis. In a model of experimental metastasis, immunocompromised mice were fed diets containing linoleic acid (LA) at 2% (LLA), 8% (HLA) or 12% (VHLA) by weight and inoculated intraperitoneally (i.p.) with human gastric carcinoma cells (OCUM-2MD3). To model spontaneous metastasis, OCUM-2MD3 tumours were grafted onto the stomach walls of mice fed with the different diets. In in vitro assays, we investigated invasion and ERK phosphorylation of OCUM-2MD3 cells in the presence or absence of LA. Finally, we tested whether a cyclooxygenase (COX) inhibitor, indomethacin, could block peritoneal metastasis in vivo. Results: Both the HLA and VHLA groups showed increased incidence of tumour nodules (LA: 53% HLA: 89% VHLA: 100% P<0.03); the VHLA group also displayed increased numbers of tumour nodules and higher total volume relative to LLA group in experimental metastasis model. Both liver invasion (78%) and metastasis to the peritoneal cavity (67%) were more frequent in VHLA group compared with the LLA group (22% and 11%, respectively; P<0.03) in spontaneous metastasis model. We also found that the invasive ability of these cells is greatly enhanced when exposed to LA in vitro. Linoleic acid also increased invasion of other scirrhous gastric carcinoma cells, OCUM-12, NUGC3 and MKN-45. Linoleic acid effect on OCUM-2MD3 cells seems to be dependent on phosphorylation of ERK. The data suggest that invasion and phosphorylation of ERK were dependent on COX. Indomethacin decreased the number of tumours and total tumour volume in both LLA and VHLA groups. Finally, COX-1, which is known to be an important enzyme in the generation of bioactive metabolites from dietary fatty acids, appears to be responsible for the

  12. Clinical significance of TIPE expression in gastric carcinoma

    PubMed Central

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

    2016-01-01

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

  13. Expression of NGF family and their receptors in gastric carcinoma: A cDNA microarray study

    PubMed Central

    Du, Jian-Jun; Dou, Ke-Feng; Peng, Shu-You; Qian, Bing-Zhi; Xiao, Hua-Sheng; Liu, Feng; Wang, Wei-Zhong; Guan, Wen-Xian; Gao, Zhi-Qing; Liu, Ying-Bin; Han, Ze-Guang

    2003-01-01

    AIM: To investigate the expression of NGF family and their receptors in gastric carcinoma and normal gastric mucosa, and to elucidate their effects on gastric carcinoma. METHODS: RNA of gastric cancer tissues and normal gastric tissues was respectively isolated and mRNA was purified. Probes of both mRNA reverse transcription product cDNAs labled with α-33P dATP were respectively hybridized with Atlas Array membrane where NGF and their family genes were spotted on. Hybridized signal images were scanned on phosphor screen with ImageQuant 5.1 software after hybridization. Normalized values on spots were analyzed with ArrayVersion 5.0 software. Differential expression of NGF family and their receptors mRNA was confirmed between hybridized Atlas Array membranes of gastric cancer tissues and normal gastric mucosa, then their effects on gastric carcinoma were investigated. RESULTS: Hybridization signal images on Atlas Array membrane appeared in a lower level of nonspecific hybridization. Both of NGF family and their receptors Trk family mRNA were expressed in gastric cancer and normal gastric mucosa. But adversely up-regulated expression in other tissues and organs. NGF, BDGF, NT-3, NT-4/5, NT-6 and TrkA, B and C were down-regulated simultaneously in gastric carcinoma in comparison with normal gastric mucosa. Degrees of down-regulation in NGF family were greater than those in their receptors Trk family. Down-regulation of NT-3 and BDGF was the most significant, and TrkC down-regulation level was the lowest in receptors Trk family. CONCLUSION: Down-regulated expression of NGF family and their receptors Trk family mRNA in gastric cancer is confirmed. NGF family and their receptors Trk family probably play a unique role in gastric cancer cell apoptosis by a novel Ras or Raf signal transduction pathway. Their synchronous effects are closely associated with occurrence and development of gastric carcinoma induced by reduction of signal transduction of programmed cell death

  14. Gastric Mixed Adenoneuroendocrine Carcinoma Occurring 50 Years after a Gastroenterostomy with Braun Anastomosis

    PubMed Central

    Nemoto, Hiroshi; Tate, Genshu; Yokomizo, Kazuaki; Umemoto, Takahiro; Matsubara, Taketo; Mizukami, Hiroki; Kigawa, Gaku; Matsumiya, Akihiko; Tanaka, Junichi

    2014-01-01

    A 75-year-old man was diagnosed with gastric cancer. Fifty years previously, he had undergone gastroenterostomy with a Braun enteroenterostomy. At present, a distal gastrectomy and small intestinal partial resection were performed. Intraoperatively, the tumor was localized to the previous stomal site. HE staining showed that the tumor comprised two elements: a tubular adenocarcinoma on the gastric side and a neuroendocrine carcinoma (NEC) on the jejunal side. The final pathologic diagnosis was mixed adenoneuroendocrine carcinoma based on an immunohistochemical analysis of endocrine markers and an elevated Ki-67 labeling index. The risk of later cancer development cancer recurrence near the gastrojejunostomy site is well known. Potentially, chronic enterogastric bile reflux may irritate the gastric mucosa and act as a promoter. Gastric NEC has a strong malignant potential. We suspect that, in the present case, the constant exposure to secondary bile may have induced a gastric mucosal adenocarcinoma, which finally differentiated into a NEC. PMID:24987352

  15. Oxidative-stress-related proteome changes in Helicobacter pylori-infected human gastric mucosa.

    PubMed Central

    Baek, Hye Yeon; Lim, Joo Weon; Kim, Hyeyoung; Kim, Jung Mogg; Kim, Joo Sung; Jung, Hyun Chae; Kim, Kyung Hwan

    2004-01-01

    Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration and gastric carcinoma. Proteomic analysis of the human gastric mucosa from the patients with erosive gastritis, peptic ulcer or gastric cancer, which were either infected or not with H. pylori, was used to determine the differentially expressed proteins by H. pylori in the human gastric mucosa in order to investigate the pathogenic mechanism of H. pylori -induced gastric diseases. Prior to the experiment, the expression of the main 18 proteins were identified in the gastric mucosa and used for a proteome map of the human gastric mucosa. Using two-dimensional electrophoresis of the protein isolated from the H. pylori -infected tissues, Coomassie Brilliant Blue staining and computerized analysis of the stained gel, the expression of eight proteins were altered in the H. pylori -infected tissues compared with the non-infected tissues. MS analysis (matrix-assisted laser desorption/ionization-time of flight MS) of the tryptic fragment and a data search allowed the the identification of the four increased proteins (78 kDa glucose-regulated protein precursor, endoplasmin precursor, aldehyde dehydrogenase 2 and L-lactate dehydrogenase B chain) and the four decreased proteins (intracellular chloride channel protein 1, glutathione S-transferase, heat-shock protein 60 and cytokeratin 8) caused by H. pylori infection in the gastric mucosa. These proteins are related to cell proliferation, carcinogenesis, cytoskeletal function and cellular defence mechanism. The common feature is that these proteins are related to oxidative-stress-mediated cell damage. In conclusion, the established gastric mucosal proteome map might be useful for detecting the disease-related protein changes. The H. pylori -induced alterations in protein expression demonstrate the involvement of oxidative stress in the pathogenesis of H. pylori -induced gastric diseases, including inflammation, ulceration and carcinogenesis

  16. Metabolomic studies of human gastric cancer: review.

    PubMed

    Jayavelu, Naresh Doni; Bar, Nadav S

    2014-07-01

    Metabolomics is a field of study in systems biology that involves the identification and quantification of metabolites present in a biological system. Analyzing metabolic differences between unperturbed and perturbed networks, such as cancerous and non-cancerous samples, can provide insight into underlying disease pathology, disease prognosis and diagnosis. Despite the large number of review articles concerning metabolomics and its application in cancer research, biomarker and drug discovery, these reviews do not focus on a specific type of cancer. Metabolomics may provide biomarkers useful for identification of early stage gastric cancer, potentially addressing an important clinical need. Here, we present a short review on metabolomics as a tool for biomarker discovery in human gastric cancer, with a primary focus on its use as a predictor of anticancer drug chemosensitivity, diagnosis, prognosis, and metastasis. PMID:25009381

  17. Neuroendocrine liver metastasis in gastric mixed adenoneuroendocrine carcinoma with trilineage cell differentiation: a case report.

    PubMed

    Zhang, Wenjin; Xiao, Weihua; Ma, Haifen; Sun, Mingfei; Chen, Hongtan; Zheng, Shusen

    2014-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) is a rare disease, which mostly occurs in the gastrointestinal tract and pancreas. Here we report a case of gastric MANEC with tri-lineage differentiation in which only the neuroendocrine component had metastasized to the liver. Liver and gastric masses were detected by abdominal computed tomography, and the preoperative relationship between liver and gastric masses was unknown. The histopathological analysis after operation confirmed the gastric mass to be MANEC, whereas the liver mass was actually the metastatic neuroendocrine component of the gastric MANEC. In the pathologic diagnosis, tri-lineage differentiation, including tubular adenocarcinoma, neuroendocrine carcinoma and squamous cell carcinoma was observed in the gastric MANEC tissues. The mitotic and Ki-67 labeling indexes of the resected tumor tissue were high, and thus, the tumor was classified as a grade G3 neuroendocrine carcinoma, which has a poor prognosis. Multiple low-density masses were found in the right lobe of the liver 2.5 months after operation. PMID:25337287

  18. Neuroendocrine liver metastasis in gastric mixed adenoneuroendocrine carcinoma with trilineage cell differentiation: a case report

    PubMed Central

    Zhang, Wenjin; Xiao, Weihua; Ma, Haifen; Sun, Mingfei; Chen, Hongtan; Zheng, Shusen

    2014-01-01

    Mixed adenoneuroendocrine carcinoma (MANEC) is a rare disease, which mostly occurs in the gastroin testinal tract and pancreas. Here we report a case of gastric MANEC with tri-lineage differentiation in which only the neuroendocrine component had metastasized to the liver. Liver and gastric masses were detected by abdominal computed tomography, and the preoperative relationship between liver and gastric masses was unknown. The histopathological analysis after operation confirmed the gastric mass to be MANEC, whereas the liver mass was actually the metastatic neuroendocrine component of the gastric MANEC. In the pathologic diagnosis, tri-lineage differentiation, including tubular adenocarcinoma, neuroendocrine carcinoma and squamous cell carcinoma was observed in the gastric MANEC tissues. The mitotic and Ki-67 labeling indexes of the resected tumor tissue were high, and thus, the tumor was classified as a grade G3 neuroendocrine carcinoma, which has a poor prognosis. Multiple low-density masses were found in the right lobe of the liver 2.5 months after operation. PMID:25337287

  19. Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma.

    PubMed Central

    Cravo, M; Pinto, R; Fidalgo, P; Chaves, P; Glória, L; Nobre-Leitão, C; Costa Mira, F

    1996-01-01

    BACKGROUND: Global DNA hypomethylation has been found in the premalignant stages of some neoplasms and has been implicated as an important factor for tumour progression. AIMS: The aim of this study was to evaluate whether DNA hypomethylation occurs during the process of gastric carcinogenesis. METHODS: Gastric specimens were obtained from 49 patients and histologically classified as: normal 10, superficial gastritis 14, chronic atrophic gastritis with intestinal metaplasia 15, and intestinal type of gastric carcinoma 10. Global DNA methylation was assessed by incubating DNA with (3H)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (3H) methyl groups reflects a lower degree of intrinsic methylation. RESULTS: A graduated increase in (3H) methyl group incorporation into DNA was found over the range extending from normal gastric mucosa, to superficial gastritis and to chronic atrophic gastritis (136,556 (24,085) v 235,725 (38,636) v 400,998 (26,747 dpm/micrograms/DNA respectively; p = 0.0002). No further increase was found in specimens from patients with carcinoma. No differences were found between extent of DNA methylation in neoplastic or non-neoplastic mucosa from patients with gastric carcinoma. Hypomethylation of DNA increased substantially with severe atrophy (p = 0.01) or with type III intestinal metaplasia (p = 0.15). CONCLUSIONS: Global DNA hypomethylation occurs in the early stages of gastric carcinogenesis, and it may be a novel biomarker of gastric neoplasia, useful in monitoring the response to chemopreventive agents. PMID:8949650

  20. Hydroxyflavanone inhibits gastric carcinoma MGC-803 cell proliferation

    PubMed Central

    Zhang, Haiyan; Zhan, Zhuo; Cui, Mingfu; Gao, Yongjian; Wang, Dayu; Feng, Ye

    2015-01-01

    Gastric carcinoma (GC) is the most common primary malignancy of the digestive tract, with increasing incidence in many countries. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess inhibition of HepG2 cell proliferation by 2’-hydroxyflavanone. The STAT3 pathway was performed. 2’-hydroxyflavanone reduced inhibitory effects on MGC-803 cell proliferation. 2’-hydroxyflavanone exhibited the highest inhibition rate. Treatment of MGC-803 cells with 400, 200, and 100 μg/ml 2’-hydroxyflavanone resulted in 88.9±0.7%, 81.2±0.5%, 68.4±0.5% decrease in cell viability, respectively, indicating an IC50 of 9.3 μg/ml. The 100 μg/ml 2’-hydroxyflavanone can significantly inhibit the STAT3 pathway activation. 2’-hydroxyflavanone inhibits MGC-803 cell proliferation by inhibiting STAT3 pathway activation. This extract is therefore a potential drug candidate for treatment of liver cancer. PMID:26629250

  1. Gastric Carcinomas in Young (Younger than 40 Years) Chinese Patients

    PubMed Central

    Zhou, Fan; Shi, Jiong; Fang, Cheng; Zou, Xiaoping; Huang, Qin

    2016-01-01

    Abstract Little is known about clinicopathological characteristics of gastric carcinoma (GC) in young (≤40 years) Chinese patients. We aimed in this study to analyze those features along with family history and prognostic factors after resection. We retrospectively reviewed all 4671 GC resections (surgical and endoscopic) performed at our center from 2004 to 2014 and identified 152 (3.2%) consecutive young patients. Patient demographics, clinical results, family history, and endoscopic-pathological findings were analyzed along with the older (>41 years) GC controls recruited in the same study period. Clinicopathological factors related to postresection outcomes were assessed statistically. The trend of GC resections in young patients was not changed over the study period. Compared to old GCs, the young GC cohort was predominant in women, positive family history, middle gastric location, the diffuse histology type, shorter duration of symptoms, and advanced stage (pIII+pIV, 53.3%). Radical resection was carried out in 90.1% (n = 137) with a better 5-year survival rate (70.3%) than palliative surgery (0%, n = 15). There was no significant difference in clinicopathological characteristics between familial GC (FGC, n = 38) and sporadic GC (SGC, n = 114) groups. Very young patients (≤ 30 years, n = 38) showed lower Helicobacter pylori (Hp) infection and significantly higher perineural invasion rates, compared to older (31–40 years) patients. Hp infection was more commonly seen in the Lauren's intestinal type and early pT stages (T1+T2). Independent prognostic factors for worse outcomes included higher serum CA 72–4, CA 125 levels, positive resection margin, and stage pIII–pIV tumors. The 5-year survival rate was significantly higher in patients with radical resection than those without. GCs in young Chinese patients were prevalent in women with advanced stages but showed no significant differences in clinicopathology between FGC and SGC

  2. Metastatic gastric signet-ring cell carcinoma: A rare cause of acute appendicitis

    PubMed Central

    Erçetin, Candaş; Dural, Ahmet Cem; Özdenkaya, Yaşar; Dural, Özlem; Dada, Huriye Gözde Muhafız; Yeğen, Gülçin; Kapran, Yersu; Erbil, Yeşim

    2016-01-01

    We report a 32-year-old patient who underwent laparoscopy with classical symptoms and signs of acute appendicitis. An inflamed, edematous and non-perforated appendix, also a large amount gelatinous ascites, omental and peritoneal implants were seen. Appendectomy was performed and multiple biopsies were taken from omentum and peritoneum for definitive diagnosis. Histopathologic diagnosis was a metastatic gastric signet-ring cell carcinoma (GSRCC) involving appendix and other specimens. A flat lesion involving corpus to antrum was diagnosed by gastroscopy and GSRCC was verified histopathologically in a tertiary centre and the case evaluated as stage IV gastric carcinoma. This case with no sign of gastric cancer was presented as an acute appendicitis. Metastatic carcinoma to the appendix, causing acute appendicitis is extremely rare in clinical practice and usually associated with high morbidity and mortality.

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

    PubMed Central

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

    2016-01-01

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

  4. Fever as a first manifestation of advanced gastric adenosquamous carcinoma: A case report

    PubMed Central

    Ajoodhea, Harsha; Zhang, Ren-Chao; Xu, Xiao-Wu; Jin, Wei-Wei; Chen, Ke; He, Yong-Tao; Mou, Yi-Ping

    2014-01-01

    Gastric adenosquamous carcinoma (ASC) is a rare type of gastric cancer. It is a mixed neoplasm, consisting of glandular cells and squamous cells. It is often diagnosed at an advanced stage, thus carrying a poor prognosis. We describe a case of a 73-year-old male, who presented with refractory fever and an intra-abdominal mass on imaging. He underwent a laparoscopic exploration followed by a successful totally laparoscopic total gastrectomy with D2 lymphadenectomy for gastric cancer. Postoperative pathology revealed primary gastric ASC (T4aN0M0). The patient received adjuvant radiotherapy and chemotherapy with S1 and is alive 20 mo after surgery without recurrence. This is the first case of advanced gastric ASC with fever as the initial presentation treated with totally laparoscopic total gastrectomy reported in the English literature. PMID:25110448

  5. Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China

    PubMed Central

    Pinto-Ribeiro, Ines; Ferreira, Rui M.; Batalha, Sellma; Hlaing, Thazin; Wong, Sio In; Carneiro, Fatima; Figueiredo, Ceu

    2016-01-01

    Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy. Infection with vacA s1, i1 and m1 strains increases the risk for progression of gastric premalignant lesions and for gastric carcinoma. However, in East Asian countries most of the H. pylori strains are vacA s1, regardless of the patients’ clinical status, and the significance of the vacA i1 and m1 genotypes for gastric carcinoma in this geographic area remains to be fully elucidated. The aim of the present study was to investigate this relationship in 290 patients from Macau, China. Using very sensitive and accurate genotyping methods, we detected infection with vacA i1 and with vacA m1 strains in, respectively, 85.2% and 52.6% of the patients that were infected with single genotypes. The prevalence of cagA-positive strains was 87.5%. No significant associations were observed between vacA genotypes or cagA and gastric carcinoma. It is worth noting that 37.5% of the infected patients had coexistence of H. pylori strains with different vacA genotypes. Additional studies directed to other H. pylori virulence factors should be performed to identify high risk patients in East Asia. PMID:27164143

  6. Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China.

    PubMed

    Pinto-Ribeiro, Ines; Ferreira, Rui M; Batalha, Sellma; Hlaing, Thazin; Wong, Sio In; Carneiro, Fatima; Figueiredo, Ceu

    2016-01-01

    Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy. Infection with vacA s1, i1 and m1 strains increases the risk for progression of gastric premalignant lesions and for gastric carcinoma. However, in East Asian countries most of the H. pylori strains are vacA s1, regardless of the patients' clinical status, and the significance of the vacA i1 and m1 genotypes for gastric carcinoma in this geographic area remains to be fully elucidated. The aim of the present study was to investigate this relationship in 290 patients from Macau, China. Using very sensitive and accurate genotyping methods, we detected infection with vacA i1 and with vacA m1 strains in, respectively, 85.2% and 52.6% of the patients that were infected with single genotypes. The prevalence of cagA-positive strains was 87.5%. No significant associations were observed between vacA genotypes or cagA and gastric carcinoma. It is worth noting that 37.5% of the infected patients had coexistence of H. pylori strains with different vacA genotypes. Additional studies directed to other H. pylori virulence factors should be performed to identify high risk patients in East Asia. PMID:27164143

  7. Level of circulated microRNA-421 in gastric carcinoma and related mechanisms

    PubMed Central

    Zhao, Guodong; Xu, Liang; Hui, Limei; Zhao, Jianjun

    2015-01-01

    As one of the most popular and deadly malignant tumors, gastric cancer still has difficulty in early-diagnosis. Recently the level of circulated DNA related with tumors can be used for diagnosis. MicroRNA-421 (miR-421) has been found to be up-regulated in tumor cells. Whether peripheral miR-421 can be used as a marker for diagnosis of gastric carcinoma, however, remains unclear. The expression level of miR-421 in both gastric cancer and normal people were firstly quantified. We then performed in vitro transfection of gastric carcinoma cell line to potentiate or silence miR-421 level. Cell apoptosis and apoptotic protein levels were quantified by flow cytometry and Western blotting, respectively. MiR-421 level in the peripheral blood of gastric cancer patients was significantly elevated. In gastric cancer cell line, the up-regulation of miR-421 significantly inhibited cell apoptosis. The silencing of miR-421 promoted cell apoptosis. Such anti-apoptotic role of miR-421 was accomplished by inhibiting caspase 3, up-regulating Bcl-2 and inhibiting Bax. MiR-421 was up-regulated in both tumor tissue and peripheral blood, and can modulate cell apoptosis. Circulated miR-421 can work as a serological marker for early diagnosis of gastric cancer. PMID:26823741

  8. Intramucosal gastric mixed adenoneuroendocrine carcinoma completely resected with endoscopic submucosal dissection.

    PubMed

    Yamasaki, Yasushi; Nasu, Junichiro; Miura, Kou; Kono, Yoshiyasu; Kanzaki, Hiromitsu; Hori, Keisuke; Tanaka, Takehiro; Kita, Masahide; Tsuzuki, Takao; Matsubara, Minoru; Kawano, Seiji; Kawahara, Yoshiro; Tabata, Masahiro; Okada, Hiroyuki; Yamamoto, Kazuhide

    2015-01-01

    Composite tumors in the stomach composed of adenocarcinoma and neuroendocrine carcinoma are rare. We herein report a case of intramucosal gastric mixed adenoneuroendocrine carcinoma (MANEC) that was treated with endoscopic submucosal dissection (ESD). A 77-year-old man who had previously received ESD for early gastric adenocarcinoma underwent esophagogastroduodenoscopy for screening, which showed a depressed lesion on the lesser curvature of the antrum. The tumor was removed en bloc via ESD and pathologically diagnosed as MANEC. The tumor was located within the mucosal layer, and no lymphovascular invasion was evident. Seven months after the ESD procedure, the patient is currently feeling well without recurrence or metastasis. PMID:25876572

  9. Gene expression profiling reveals sequential changes in gastric tubular adenoma and carcinoma in situ

    PubMed Central

    Lee, Chang-Hee; Bang, Seung-Hyun; Lee, Seung-Koo; Song, Kyu-Young; Lee, In-Chul

    2005-01-01

    AIM: To analyze the expression profiles of premalignant and/or preclinical lesions of gastric cancers. METHODS: We analyzed the expression profiles of normal gastric pit, tubular adenoma and carcinoma in situ using microdissected cells from routine gastric biopsies. For the DNA microarray analysis of formalin-fixed samples, we developed a simple and reproducible RNA extraction and linear amplification procedure applying two polymerase-binding sites. The amplification procedure took only 8 h and yielded comparable DNA microarray data between formalin-fixed tissues and unfixed controls. RESULTS: In comparison with normal pit, adenoma/carcinoma showed 504 up-regulated and 29 down-regulated genes at the expected false significance rate 0.15%. The differential expression between adenoma and carcinoma in situ was subtle: 50 and 22 genes were up-, and down-regulated in carcinomas at the expected false significance rate of 0.61%, respectively. Differentially expressed genes were grouped according to patterns of the sequential changes for the the ‘tendency analysis’ in the gastric mucosa-adenoma-carcinoma sequence. CONCLUSION: Groups of genes are shown to reflect the sequential expression changes in the early carcinogenic steps of stomach cancer. It is suggested that molecular carcinogenic pathways could be analyzed using routinely processed biopsies. PMID:15800983

  10. microRNA-25 Inhibits Cell Apoptosis of Human Gastric Adenocarcinoma Cell Line AGS via Regulating CCNE1 and MYC

    PubMed Central

    Zhang, Yong; Peng, Zheng; Zhao, Yunshan; Chen, Lin

    2016-01-01

    Background Gastric carcinoma is the second leading cause of cancer death. microRNAs play vital roles in regulating expression of related oncogenes. microRNA-25 (miR-25) has been found to be up-regulated in gastric carcinoma. However, its roles in affecting cell apoptosis of gastric carcinoma and the related mechanism remain elusive. This study aimed to uncover the influences of miR-25 on gastric carcinoma cell apoptosis and the possible functional mechanisms involved. Material/Methods Human gastric adenocarcinoma cell line AGS was used and transfected with lentivirus containing miR-25-specifc inhibitor sponge or expression vector to analyze the effects of miR-25. Results miR-25 had higher expression in AGS than in human gastric epithelial cell line GES-1 (P<0.01). Inhibition of miR-25 by its sponge in AGS cells resulted in suppressed cell viability (P<0.01) and promoted cell apoptosis (P<0.01), while overexpression of miR-25 abrogated these effects (P<0.01 and P<0.05), indicating that miR-25 can promote cell viability and inhibit cell apoptosis in AGS cells. Expression analysis of related factors by Western blot showed that inhibiting miR-25 led to the up-regulation of F-box and WD repeat domain-containing 7 (FBXW7, P<0.01) and the down-regulation of FBXW7 substrates, cyclin E1 (CCNE1, P<0.01), and v-myc avian myelocytomatosis viral oncogene homolog (MYC, P<0.001). Conclusions These results indicate that miR-25 has anti-apoptosis roles in AGS cells, possibly via inhibiting FBXW7 and thus promoting oncogenes, such as CCNE1 and MYC. This study provides basic evidence for using miR-25 as a possible therapeutic target in treating gastric carcinoma. PMID:27120728

  11. Rapidly growing gastric metastasis of Merkel cell carcinoma, an unusual cause of melena.

    PubMed

    Hulstaert, Eva; Smith, Vanessa; Mielants, Herman; Van Praet, Louis; De Kock, Joris; Lambrecht, Valérie; Rasschaert, Gertjan; Van Belle, Simon

    2016-08-01

    Merkel cell carcinoma (MCC) is an uncommon, highly aggressive neuroendocrine skin carcinoma that has a tendency for local recurrence and metastatic disease. We report a rare case of recurrent melena in a 77-year-old Caucasian male. Three years earlier, the patient had undergone a radical resection of a para-umbilical MCC. A repeat esophagogastroduodenoscopy proved necessary to identify rapidly proliferating gastric metastasis of MCC as the cause of bleeding. PMID:27075789

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

    PubMed

    Terragni, Rossella; Casadei Gardini, Andrea; Sabattini, Silvia; Bettini, Giuliano; Amadori, Dino; Talamonti, Chiara; Vignoli, Massimo; Capelli, Laura; Saunders, Jimmy H; Ricci, Marianna; Ricci, Marianna; Ulivi, Paola; Ulivi, Paola

    2014-01-01

    Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥ 1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer. PMID:24454858

  13. EGFR, HER-2 and KRAS in Canine Gastric Epithelial Tumors: A Potential Human Model?

    PubMed Central

    Bettini, Giuliano; Amadori, Dino; Talamonti, Chiara; Vignoli, Massimo; Capelli, Laura; Saunders, Jimmy H.; Ricci, Marianna; Ulivi, Paola

    2014-01-01

    Epidermal growth factor receptor (EGFR or HER-1) and its analog c-erbB-2 (HER-2) are protein tyrosine kinases correlated with prognosis and response to therapy in a variety of human cancers. KRAS mediates the transduction of signals between EGFR and the nucleus, and its mutation has been identified as a predictor of resistance to anti-EGFR drugs. In human oncology, the importance of the EGFR/HER-2/KRAS signalling pathway in gastric cancer is well established, and HER-2 testing is required before initiating therapy. Conversely, this pathway has never been investigated in canine gastric tumours. A total of 19 canine gastric epithelial neoplasms (5 adenomas and 14 carcinomas) were retrospectively evaluated for EGFR/HER-2 immunohistochemical expression and KRAS mutational status. Five (35.7%) carcinomas were classified as intestinal-type and 9 (64.3%) as diffuse-type. EGFR was overexpressed (≥1+) in 8 (42.1%) cases and HER-2 (3+) in 11 (57.9%) cases, regardless of tumour location or biological behaviour. The percentage of EGFR-positive tumours was significantly higher in the intestinal-type (80%) than in the diffuse-type (11.1%, p = 0.023). KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12 (G12R). EGFR and HER-2 may be promising prognostic and therapeutic targets in canine gastric epithelial neoplasms. The potential presence of KRAS mutation should be taken into account as a possible mechanism of drug resistance. Further studies are necessary to evaluate the role of dog as a model for human gastric cancer. PMID:24454858

  14. Clinical pathology of metastatic gastric carcinoma to the breast: A report of two cases and a review of literature

    PubMed Central

    TIAN, QIUHONG; ZENG, JINSHENG; TAO, XUEQIN; ZHANG, ZHANMIN; ZHOU, XIAODONG; WANG, YITING

    2016-01-01

    The breast is an unusual site for metastasis from a gastric carcinoma. The present study reports two cases of metastatic gastric carcinoma to the breast. The first patient, a 37-year-old woman, initially presented with gastric adenocarcinoma, prior to developing metastatic cancer to the breast 4 years later. The second female patient presented with a breast mass, and a modified radical mastectomy was performed; however, the subsequent pathological examination revealed the mass to be a metastatic signet ring cell carcinoma. An abdominal computed tomography scan revealed a diffuse gastric wall thickening that was consistent with gastric cancer. The findings suggest that immunohistochemistry is a useful tool to differentiate between primary breast tumors and gastrointestinal carcinomas that have metastasized to the breast. Additional studies are required in order to define the optimal treatment. PMID:27123067

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2007-01-01

    AIM: To distinguish subtypes of gastric signet ring cell (SRC) carcinoma by investigating the expression of gastric and intestinal phenotypic markers, and to study the significance of phenotypic classification in predicting tumor progression and outcome. METHODS: Immunohistochemistry was performed in 66 cases of SRC carcinoma with MUC2, VILLIN, CDX2, Li-cadherin antibodies as intestinal phenotype markers and MUC5AC, HGM, MUC6 antibodies as gastric phenotype markers, and the relationship was analyzed between the phenotypic expression pattern and clinicopathologic parameters, as well as the 3-year survival rate. RESULTS: Expression of intestinal phenotypic markers was positively associated with tumor size, wall invasion, vascular invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. Cases expressing one or more intestinal markers had a significant lower survival rate than cases expressing none of the intestinal markers. CONCLUSION: The SRC carcinomas expressing intestinal phenotype markers exhibited a high pro-liferative potential, bad biological behaviors and poor prognosis. Examination of phenotype expression may be useful in distinguishing histological type and in predicting the prognosis of gastric SRC carcinoma. PMID:17589897

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

    PubMed

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

    2010-03-01

    A metastatic gastric neuroendocrine carcinoma in a 2.5-year-old inland bearded dragon (Pogona vitticeps) with a chronic history of anorexia, weight loss, depression, and acute melena is described. Histologic examination of the gastric mass revealed a densely cellular tumor arranged in nests and occasional rosettes of hyperchromatic cells with oval to spindle-shaped nuclei and minimal cytoplasm; the tumor was supported by a moderate fibrovascular stroma. Similar cells invaded through the gastric mucosa, and there were multiple hepatic metastases. The neoplastic cells were weakly immunopositive for neuron-specific enolase and moderately positive for somatostatin but were negative for chromogranin AB and gastrin. Ultrastructural studies revealed scattered neurosecretory granules in the neoplastic cells, confirming the diagnosis of a neuroendocrine carcinoma. PMID:20224102

  18. Mutations of mitochondrial 12S rRNA in gastric carcinoma and their significance

    PubMed Central

    Han, Cheng-Bo; Ma, Jia-Ming; Xin, Yan; Mao, Xiao-Yun; Zhao, Yu-Jie; Wu, Dong-Ying; Zhang, Su-Min; Zhang, Yu-Kui

    2005-01-01

    AIM: To detect the variations of mitochondrial 12S rRNA in patients with gastric carcinoma, and to study their significance and the relationship between these variations and the genesis of gastric carcinoma. METHODS: PCR amplified mitochondrial 12S rRNA of 44 samples including 22 from gastric carcinoma tissues and 22 from adjacent normal tissues, was detected by direct DNA sequencing. Then laser capture microdissection technique (LCM) was used to separate the cancerous cells and dysplasia cells with specific mutations. Denaturing high performance liquid chromatography (DHPLC) plus allele-specific PCR (AS-PCR), nest-PCR and polyacrylamide gel electrophoresis (PAGE) were used to further evaluate this mutant property and quantitative difference of mutant type between cancerous and dysplasia cells. Finally, RNAdraw biosoft was used to analyze the RNA secondary structure of mutant-type 12S rRNA. RESULTS: Compared with Mitomap database, some new variations were found, among which np652 G insertion and np716 T-G transversion were found only in cancerous tissues. There was a statistic difference in the frequency of 12S rRNA variation between intestinal type (12/17, 70.59%) and diffusive type (5/17, 29.41%) of gastric carcinoma (P<0.05). DHPLC analysis showed that 12S rRNA np652 G insertion and np716 T-G transversion were heteroplasmic mutations. The frequency of 12S rRNA variation in cancerous cells was higher than that in dysplasia cells (P<0.01). 12S rRNA np652 G insertion showed obviously negative effects on the stability of 12S rRNA secondary structure, while others such as T-G transversion did not. CONCLUSION: The mutations of mitochondrial 12S rRNA may be associated with the occurrence of intestinal-type gastric carcinoma. Most variations exist both in gastric carcinomas and in normal tissues, and they might not be the characteristics of tumors. However, np652 G insertion and np716 T-G transversion may possess some molecular significance in gastric carcinogenesis

  19. Testicular metastasis from gastric carcinoma: A case report

    PubMed Central

    Li, Bo; Cai, Hui; Kang, Zheng-Chun; Wu, Hao; Hou, Jian-Guo; Ma, Li-Ye

    2015-01-01

    Gastric cancer (GC) is the most prevalent malignancy in the world, especially in China. GC has been postulated to spread via several different routes, including through hematogenous channels, lymphatic vessels, the seeding of peritoneal surfaces, direct extension through the gastric wall, and retrograde extension through the vas deferens or lymphatics. Testicular metastasis is rare. We show here a 53-year-old patient with GC who underwent a radical total gastrectomy approximately 22 mo ago after he presented with a sensation of heaviness and swelling of the right hemiscrotum. The diagnosis of metastatic adenocarcinoma was made after a right-side orchiectomy. We report the first case of testicular metastasis from gastric adenocarcinoma in mainland China and summarize the clinicopathologic features of the disease based on previously published papers. PMID:26074716

  20. Human Adrenocortical Carcinoma Cell Lines

    PubMed Central

    Wang, Tao; Rainey, William E.

    2011-01-01

    Summary The human adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgens. These steroids are produced from unique cell types located within the three distinct zones of the adrenal cortex. Disruption of adrenal steroid production results in a variety of diseases that can lead to hypertension, metabolic syndrome, infertility and androgen excess. The adrenal cortex is also a common site for the development of adenomas, and rarely the site for the development of carcinomas. The adenomas can lead to diseases associated with adrenal steroid excess, while the carcinomas are particularly aggressive and have a poor prognosis. In vitro cell culture models provide an important tool to examine molecular and cellular mechanisms controlling both the normal and pathologic function of the adrenal cortex. Herein we discuss the human adrenocortical cell lines and their use as model systems for adrenal studies. PMID:21924324

  1. Tumor-associated gastroparesis with esophageal carcinoma. Use of intravenous metoclopramide during radionuclide gastric emptying studies to predict clinical response

    SciTech Connect

    Choe, A.I.; Ziessman, H.A.; Fleischer, D.E.

    1989-07-01

    This case report describes a patient with esophageal carcinoma and tumor-associated gastroparesis. The radionuclide gastric emptying study diagnosed very delayed liquid and solid gastric emptying. Metoclopramide was administered intravenously during the study and was able to predict a good response to oral therapy.

  2. Lessons Learned From a Case of Gastric Cancer After Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Yang, Kun; Zhu, Hong; Chen, Chong-Cheng; Wen, Tian-Fu; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Guo, Dong-Jiao; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Abstract Nowadays, de novo malignancies have become an important cause of death after transplantation. According to the accumulation of cases with liver transplantation, the incidence of de novo gastric cancer is anticipated to increase among liver transplant recipients in the near future, especially in some East Asian countries where both liver diseases requiring liver transplantation and gastric cancer are major burdens. Unfortunately, there is limited information regarding the relationship between de novo gastric cancer and liver transplantation. Herein, we report a case of stage IIIc gastric cancer after liver transplantation for hepatocellular carcinoma, who was successfully treated by radical distal gastrectomy with D2 lymphadenectomy but died 15 months later due to tumor progression. Furthermore, we extract some lessons to learn from the case and review the literatures. The incidence of de novo gastric cancer following liver transplantations is increasing and higher than the general population. Doctors should be vigilant in early detection and control the risk factors causing de novo gastric cancer after liver transplantation. Curative gastrectomy with D2 lymphadenectomy is still the mainstay of treatment for such patients. Preoperative assessments, strict postoperative monitoring, and managements are mandatory. Limited chemotherapy could be given to the patients with high risk of recurrence. Close surveillance, early detection, and treatment of posttransplant cancers are extremely important and essential to improve the survival. PMID:26886605

  3. Implication of Reprimo and hMLH1 gene methylation in early diagnosis of gastric carcinoma

    PubMed Central

    Liu, Lianhua; Yang, Xiaofeng

    2015-01-01

    DNA methylation has been recently recognized as a novel tumor marker. This study investigated the methylation status of Reprimo and hMLH1 gene in both plasma and tissue samples from gastric cancer patients, in an attempt to investigate their diagnostic implications in gastric cancer. A total of 180 tissue and plasma samples (including 50 cases of gastric cancer, 50 dysplasia, 50 chronic atrophic gastritis with intestinal metaplasia and 30 normal controls) were collected for detecting DNA methylation status of Reprimo and hMLH1 genes using MSP method. Tissue protein expression levels were further tested by immunohistochemical (IHC) staining. The positive rate of DNA methylation rate was, in ascending sequence, gastritis tissue, dysplasia tissue and gastric carcinoma tissue. All those tissues had significantly elevated DNA methylation level compared to normal group (P < 0.05). Expression level of Reprimo and hMLH1 proteins were, however, decreased in pathological tissues compared to normal ones (P < 0.05). A significantly negative relationship existed between protein level and promoter region methylation level. The DNA methylation occurred in promoter regions of both Reprimo and hMLH1 genes depressed the protein expression, and may participate in the occurrence and progression and gastric cancer. The combined assay of serum Reprimo and hMLH1 DNA methylation levels thus had critical importance in the early diagnosis and gastric cancer. PMID:26823831

  4. Variations of gastric corpus microbiota are associated with early esophageal squamous cell carcinoma and squamous dysplasia

    PubMed Central

    Nasrollahzadeh, Dariush; Malekzadeh, Reza; Ploner, Alexander; Shakeri, Ramin; Sotoudeh, Masoud; Fahimi, Saman; Nasseri-Moghaddam, Siavosh; Kamangar, Farin; Abnet, Christian C.; Winckler, Björn; Islami, Farhad; Boffetta, Paolo; Brennan, Paul; Dawsey, Sanford M.; Ye, Weimin

    2015-01-01

    Observational studies revealed a relationship between changes in gastric mucosa and risk of esophageal squamous cell carcinoma (ESCC) which suggested a possible role for gastric microbiota in ESCC carcinogenesis. In this study we aimed to compare pattern of gastric corpus microbiota in ESCC with normal esophagus. Cases were included subjects with early ESCC (stage I–II) and esophageal squamous dysplasia (ESD) as the cancer precursor. Control groups included age and sex-matched subjects with mid-esophagus esophagitis (diseased-control), and histologically normal esophagus (healthy-control). DNA was extracted from snap-frozen gastric corpus tissues and 16S rRNA was sequenced on GS-FLX Titanium. After noise removal, an average of 3004 reads per sample was obtained from 93 subjects. We applied principal coordinate analysis to ordinate distances from beta diversity data. Pattern of gastric microbiota using Unifrac (p = 0.004) and weighted Unifrac distances (p = 0.018) statistically varied between cases and healthy controls. Sequences were aligned to SILVA database and Clostridiales and Erysipelotrichales orders were more abundant among cases after controling for multiple testing (p = 0.011). No such difference was observed between mid-esophagitis and healthy controls. This study is the first to show that composition of gastric corpus mucosal microbiota differs in early ESCC and ESD from healthy esophagus. PMID:25743945

  5. Comparison of Serum CA72-4 and CEA Levels in Patient with Endoscopically Suspected Gastric Carcinoma.

    PubMed

    Rehena, Z; Ghosh, C K; Afroz, F; Alam, M B; Ferdousi, S; Mahmuduzzaman, M; Sultana, T; Ahmed, A N

    2015-07-01

    Several serum tumour markers have been described for gastric cancer. Preoperative level of tumor marker helps to predict the diagnosis of gastric carcinoma. CA72-4 as a serum tumour marker for gastric cancer is evaluated, and compared its utility in this regard with that of carcinoembryonic antigen (CEA). Analysis of gastric carcinoma by serum levels of CEA and CA72-4 and their correlation with histopathology help the clinician to develop his management strategies for gastric carcinoma. A prospective observational study was carried out in the Department of Clinical Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU) in collaboration with Department of Surgery BSMMU, DMCH, Delta Hospital Limited, Dhaka, during the period of October 2010 to September 2011. Serum CA72-4 and CEA were analyzed in 71 endoscopically suspected patients for gastric carcinoma. Among them 58 cases were diagnosed as malignant gastric disease and 13 cases were nonmalignant gastric disease. Sensitivity of CA 72-4 and CEA were 48.3% and 31% respectively and specificity were 92.3% and 76.9% respectively. In poorly differentiated carcinoma, positivity for CA72-4 and CEA were 55.6% and 36.1% respectively. Because of the high positivity of CA72-4 in poorly differentiated carcinoma, CA72-4 is reliable tumour marker in advanced cases. As the sensitivity of CA72-4 was more than that of CEA in diagnosis of gastric cancer, CA72-4 can be used in conjunction with other diagnostic tests like endoscopy that would be more helpful for the patients. PMID:26329953

  6. 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

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

    Gastric carcinoma MKN45 cells stably transfected with the full-length ST3GAL4 gene were characterised by glycomic and sialoproteomic analysis. Complementary strategies were applied to assess the glycomic alterations induced by ST3GAL4 overexpression. The N- and O-glycome data were generated in two parallel structural analyzes, based on PGC-ESI-MS/MS. Data on glycan structure identification and relative abundance in ST3GAL4 overexpressing cells and respective mock control are presented. The sialoproteomic analysis based on titanium-dioxide enrichment of sialopeptides with subsequent LC-MS/MS identification was performed. This analysis identified 47 proteins with significantly increased sialylation. The data in this article is associated with the research article published in Biochim Biophys Acta “Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer” [1]. PMID:27077082

  9. Gastric carcinoma in China: Current status and future perspectives (Review)

    PubMed Central

    ZHU, XIAODONG; LI, JIN

    2010-01-01

    Gastric cancer is one of the most frequently occurring cancers in China, with an estimated 380,000 new cases each year, accounting for more than 40% of the worldwide annual cancer incidence. There is geographical clustering of the distribution of gastric cancer in China, with most of the high-risk areas being rural. D2 resection is the standard lymphadenectomy for curative resection in China, but more extensive lymphadenectomy is conducted for selected patients. Perioperative chemotherapy, postoperative chemotherapy or chemoradiotherapy can be combined with surgery. It remains uncertain which option is best, but if surgery is insufficient, adjuvant chemoradiotherapy is recommended. In the palliative setting, although there is no standard first-line chemotherapy, regimens based on taxane, oxaliplatin or capecitabine, or the epirubicin, cisplatin, 5-fluorouracil regimen and its modifications are the most common options selected by Chinese oncologists. Several studies to evaluate target therapy are ongoing, but it is too early to draw any conclusions. However, the development of target therapy is likely to become a milestone in the treatment of gastric cancer. PMID:22966316

  10. Chylothorax and lymphedema as the initial manifestations of gastric carcinoma: A case report and review of the literature

    PubMed Central

    WU, JIE; LV, LIANG; ZHOU, KUNYAN; HUO, JIRONG

    2016-01-01

    Chylothorax is the accumulation of lymph fluid in the pleura. Gastric carcinoma with chylothorax and lymphedema as the initial manifestations has rarely been reported, with only 14 cases reported to date. The mechanisms of gastric carcinoma generating chylothorax have not yet been determined. The current study reports the case of a 63-year-old woman presenting with chylothorax and lower extremity lymphedema, and reviews the existing literature. A chest radiograph performed on the present patient revealed large pleural effusion and chylothorax was diagnosed. Upper gastrointestinal endoscopy identified an irregular apophysis lesion and a biopsy confirmed poorly differentiated gastric adenocarcinoma. The patient was discharged at her request, and subsequently succumbed to the disease 4.5 months later. Based on the findings of the present study, as well as those of the literature, we proposed a novel form of gastric carcinoma infiltrating the body. Chylothorax and lymphedema may be a consequence of gastric carcinoma cells infiltrating the lymphatic circulatory system; therefore, the differential diagnosis of chylothorax and lymphedema of unknown cause should consider gastric carcinoma, regardless of gastrointestinal symptoms. PMID:27073560

  11. Ponicidin Induces Apoptosis via JAK2 and STAT3 Signaling Pathways in Gastric Carcinoma

    PubMed Central

    Liu, Yuan-Fei; Lu, Yun-Min; Qu, Guo-Qiang; Liu, Yuan; Chen, Wei-Xiong; Liao, Xiao-Hong; Kong, Wu-Ming

    2015-01-01

    Ponicidin has a variety of biological effects such as immunoregulatory and anti-inflammatory functions as well as anti-viral functions especially in the upper respiratory tract infection. This study was aimed to elucidate the antitumor effect of ponicidin in gastric carcinoma MKN28 cells and the possible molecular mechanism involved. Cell viability was measured by the Cell Count Kit-8 (CCK8). Cell apoptosis was assessed by flow cytometry as well as cell cycle and reactive oxygen species (ROS) analysis. Western blot analysis was used to detect the active form of caspase-3 as well as Bax and B-cell lymphoma-2 (Bcl-2) expressions after cells were treated with different concentrations of ponicidin. The results revealed that ponicidin could inhibit the growth of MKN28 cells significantly in both a time- and dose-dependent manner. The cell cycle was blocked and ROS generation was increased after the cells were treated with ponicidin. Bcl-2 expression was down-regulated remarkably while Bax expression and the active form of caspase-3 were increased after apoptosis occurred. We therefore conclude that ponicidin exhibited significant growth inhibition of gastric carcinoma cell line MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3). Ponicidin may serve as a potential therapeutic agent for gastric carcinoma. PMID:25588213

  12. Short and long-term outcomes after gastrectomy for gastric carcinoma in elderly patients

    PubMed Central

    Shu, Bo; Lei, Sanlin; Li, Fazhao; Hua, Songwen; Chen, Yong; Huo, Zhi

    2015-01-01

    As worldwide life expectancy rises, the number of candidates for surgical treatment of gastric carcinoma over 70 years will increase. This study aims to examine outcomes after gastric carcinoma in elderly patients. This study is a retrospective review of 697 patients undergoing gastrectomy with radical intent for gastric carcinoma during January 2007 to January 2013. A total of 534 patients were less than 70 years old (group A), and 163 patients 70 years or greater (group B). We analyzed the effect of age on short and long-term variables including overall survival and disease-free survival. Major morbidity was observed to occur in 19 patients of group A, and 15 of group B. Mortality, both 30-day and 90-day was observed in 1 and 3 of group A, and 3 and 6 of group B. Five-year overall survival and disease-free survival was 61% and 60% for group A, 50% and 43% for group B respectively. Gastrectomy should be carefully considered in patients 70 years old and can be justified with low mortality and acceptable long-term outcomes. PMID:26550297

  13. Primary Gastric Invasive Micropapillary Carcinoma: A Case Report.

    PubMed

    Vardar, Enver; Yardim, Bengü Günay; Vardar, Rukiye; Ölmez, Mustafa

    2015-01-01

    Invasive micropapillary carcinoma is a recently identified neoplasm. A 77-year-old-female was admitted to the hospital due to progressive loss of weight and nausea. Endoscopic biopsy of the antral/prepyloric located mass was diagnosed as moderately differentiated adenocarcinoma. Subtotal gastrectomy and regional lymph node resection were performed. The tumor was composed of moderately differentiated cells arranged in micropapillary structures with only a few poorly formed glandular foci in lamina propria. Immunohistochemically, neoplastic cells of micropapillary and focal conventional adenocarcinoma areas were diffusely positive for pancytokeratin, cytokeratin 7 and epithelial membrane antigen. In micropapillary areas, membranous and peripheral cytoplasmic positivity with epithelial membrane antigen in outside of the cell clusters called "inside-out polarity" pattern that is characteristic for invasive micropapillary carcinoma were seen. Invasive micropapillary carcinoma is very rare in the stomach in the English literature. PMID:26456969

  14. miRNA-223 inhibits epithelial-mesenchymal transition in gastric carcinoma cells via Sp1.

    PubMed

    Hu, Jing; Shan, Zhiyan; Hu, Kewei; Ren, Fengyun; Zhang, Wei; Han, Meiling; Li, Yuezhen; Feng, Kejian; Lei, Lei; Feng, Yukuan

    2016-07-01

    Sp1 plays critical roles in epithelial-mesenchymal transition (EMT) of certain cancer. However, few studies have indicated whether Sp1 is involved in the EMT of gastric cancer, and whether abnormal expression of Sp1 in gastric cancer EMT is regulated in a post-transcriptional manner, and the involvement of miRNAs in this regulation. In this study, we selected 20 cases of gastric cancers, their liver metastases and para-carcinoma tissues to examine the levels of Sp1 protein and mRNA by immunohistochemistry and fluorescent PCR, which showed that Sp1 was increased in gastric cancers and their metastases compared with adjacent tissues, but there was no difference in Sp1 mRNA between these three groups, suggesting changes in Sp1 may be attributed to inactivation of post-transcriptional regulation. We verified by a luciferase reporter system that miRNA-223 binds to 3'-UTR of Sp1 gene and inhibits its translation, in agreement with negative correlation between miRNA-223 and Sp1 protein levels in gastric cancer cells. By employing TGF-β1 to induce MGC-803, BGC-823 and SGC-7901, we successfully built cellular EMT model. Then, we overexpressed miRNA-223 in the model by using a lentiviral system, which diminished EMT indicators and suppressed proliferation and invasion ability, and induced apoptosis. Finally, we verified the specificity of the regulation pathway miRNA-223/Sp1/EMT. These findings suggest that low expression of miRNA-223 in gastric cancer cells is an important cause for EMT. miRNA-223 specifically regulates the EMT process of gastric cancer cells through its target gene Sp1. Overexpression of miRNA-223 in these cells inhibits EMT via the miRNA-223/Sp1/EMT pathway. PMID:27212195

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

    PubMed Central

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

    1998-01-01

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

  16. Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response

    PubMed Central

    Cho, Junhun; Kang, Myung-Soo

    2016-01-01

    Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC. PMID:27104020

  17. Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response.

    PubMed

    Cho, Junhun; Kang, Myung-Soo; Kim, Kyoung-Mee

    2016-03-01

    Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC. PMID:27104020

  18. Differences in gastric carcinoma microenvironment stratify according to EBV infection intensity: implications for possible immune adjuvant therapy.

    PubMed

    Strong, Michael J; Xu, Guorong; Coco, Joseph; Baribault, Carl; Vinay, Dass S; Lacey, Michelle R; Strong, Amy L; Lehman, Teresa A; Seddon, Michael B; Lin, Zhen; Concha, Monica; Baddoo, Melody; Ferris, Marybeth; Swan, Kenneth F; Sullivan, Deborah E; Burow, Matthew E; Taylor, Christopher M; Flemington, Erik K

    2013-01-01

    Epstein-Barr virus (EBV) is associated with roughly 10% of gastric carcinomas worldwide (EBVaGC). Although previous investigations provide a strong link between EBV and gastric carcinomas, these studies were performed using selected EBV gene probes. Using a cohort of gastric carcinoma RNA-seq data sets from The Cancer Genome Atlas (TCGA), we performed a quantitative and global assessment of EBV gene expression in gastric carcinomas and assessed EBV associated cellular pathway alterations. EBV transcripts were detected in 17% of samples but these samples varied significantly in EBV coverage depth. In four samples with the highest EBV coverage (hiEBVaGC - high EBV associated gastric carcinoma), transcripts from the BamHI A region comprised the majority of EBV reads. Expression of LMP2, and to a lesser extent, LMP1 were also observed as was evidence of abortive lytic replication. Analysis of cellular gene expression indicated significant immune cell infiltration and a predominant IFNG response in samples expressing high levels of EBV transcripts relative to samples expressing low or no EBV transcripts. Despite the apparent immune cell infiltration, high levels of the cytotoxic T-cell (CTL) and natural killer (NK) cell inhibitor, IDO1, was observed in the hiEBVaGCs samples suggesting an active tolerance inducing pathway in this subgroup. These results were confirmed in a separate cohort of 21 Vietnamese gastric carcinoma samples using qRT-PCR and on tissue samples using in situ hybridization and immunohistochemistry. Lastly, a panel of tumor suppressors and candidate oncogenes were expressed at lower levels in hiEBVaGC versus EBV-low and EBV-negative gastric cancers suggesting the direct regulation of tumor pathways by EBV. PMID:23671415

  19. 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

  20. Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer.

    PubMed

    Hu, Nan; Kadota, Mitsutaka; Liu, Huaitian; Abnet, Christian C; Su, Hua; Wu, Hailong; Freedman, Neal D; Yang, Howard H; Wang, Chaoyu; Yan, Chunhua; Wang, Lemin; Gere, Sheryl; Hutchinson, Amy; Song, Guohong; Wang, Yuan; Ding, Ti; Qiao, You-Lin; Koshiol, Jill; Dawsey, Sanford M; Giffen, Carol; Goldstein, Alisa M; Taylor, Philip R; Lee, Maxwell P

    2016-04-01

    Gastric cancer and esophageal cancer are the second and sixth leading causes of cancer-related death worldwide. Multiple genomic alterations underlying gastric cancer and esophageal squamous cell carcinoma (ESCC) have been identified, but the full spectrum of genomic structural variations and mutations have yet to be uncovered. Here, we report the results of whole-genome sequencing of 30 samples comprising tumor and blood from 15 patients, four of whom presented with ESCC, seven with gastric cardia adenocarcinoma (GCA), and four with gastric noncardia adenocarcinoma. Analyses revealed that an A>C mutation was common in GCA, and in addition to the preferential nucleotide sequence of A located 5 prime to the mutation as noted in previous studies, we found enrichment of T in the 5 prime base. The A>C mutations in GCA suggested that oxidation of guanine may be a potential mechanism underlying cancer mutagenesis. Furthermore, we identified genes with mutations in gastric cancer and ESCC, including well-known cancer genes, TP53, JAK3, BRCA2, FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including MACROD2, FHIT, and PARK2 that were often intragenic deletions. These structural alterations were validated using the The Cancer Genome Atlas dataset. Our studies provide new insights into understanding the genomic landscape, genome instability, and mutation profile underlying gastric cancer and ESCC development. Cancer Res; 76(7); 1714-23. ©2016 AACR. PMID:26857264

  1. Predictive value of CHFR and MLH1 methylation in human gastric cancer

    PubMed Central

    Li, Yazhuo; Yang, Yunsheng; Lu, Youyong; Herman, James G.; Brock, Malcolm V.; Zhao, Po; Guo, Mingzhou

    2016-01-01

    Background Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. Methods The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan–Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. Results The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3 % (35/102), 21.6 % (22/102), 12.7 % (13/102), 9.8 % (10/102), and 0 % (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95 % CI, 0.069–0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95 % CI, 1.064–8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). Conclusions CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a

  2. Distribution of Lgr5-positive cancer cells in intramucosal gastric signet-ring cell carcinoma.

    PubMed

    Nakajima, Tomoyuki; Uehara, Takeshi; Maruyama, Yasuhiro; Iwaya, Mai; Kobayashi, Yukihiro; Ota, Hiroyoshi

    2016-09-01

    Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a putative intestinal stem cell marker that is also expressed in various tumors. To analyze its pathological characteristics in mucosal gastric signet-ring cell carcinoma (SRCC), we investigated Lgr5 expression in 35 intramucosal gastric SRCC patients using RNAscope, a newly developed RNA in situ hybridization technique. Lgr5 expression in individual tumor cells was scored semi-quantitatively from 0 to 400. Ki67 was also examined by immunohistochemistry, with a linear arrangement of Ki67-expressing cells present in 20 of 35 cases. This area of Ki67-expressing cells was topographically divided into upper, middle, and lower regions. All cases with linear Ki67 expression patterns also had Lgr5-positive cells arranged in a linear fashion in the lower area-which was distinct from the area of high Ki67 expression. The rate of Ki67 positivity in Lgr5-positive cells was significantly lower than that of Lgr5-negative cells in areas of high Ki67 expression. In intramucosal SRCC, the low mitotic activity of Lgr5-positive cells suggests that they may represent cancer stem cells as seen in other types of stomach carcinomas. Intramucosal SRCC may therefore contain stem cells expressing Lgr5 in the lower area of the lamina propria, akin to normal gastric pyloric mucosa. PMID:27593551

  3. Synchronous Gastric Carcinoma and Nodal Malignant Lymphoma: A Rare Case Report and Literature Review.

    PubMed

    Xue, Li-Jun; Yang, Ji-Hong; Su, Quan-Sheng; Wang, Hai; Liu, Chang

    2010-01-01

    Synchronous double malignancies of gastric carcinoma (GC) and malignant lymphoma (ML) are rare and very difficult to treat. We report a case of synchronous GC and nodal ML, regarding which clinical and pathological features and treatment are discussed. A 68-year-old woman with a history of inguinal hernia was admitted for abdominal pain and high fever and subsequently underwent herniorrhaphy, but the fever remained. Computerized tomography showed a stomach mass and multiple enlarged lymph nodes in the abdominal cavity and inguinal regions. Gastric adenocarcinoma coexistent with advanced in situ follicular lymphoma was confirmed by endoscopy, biopsy of inguinal lymph nodes and bone marrow examination. Two chemotherapy regimens, R-CHOP (rituximab, cyclophosphamide, perarubicin, vincristine and prednisone) and systemic therapy (5-fluorouracil and calcium folinate) combined with regional perfusion (oxaliplatin and etoposide) through the left gastric artery were performed at intervals against ML and GC, respectively. Partial remission in both tumors was achieved after 4 courses of treatment, but the patient finally died of heart failure. Scrupulous biopsy of non-draining lymph nodes in patients with gastrointestinal carcinomas is supposed to improve the diagnostic rate of simultaneous nodal ML. The interval chemotherapy strategy with two independent regimens is beneficial for such patients, especially for those unable to tolerate major surgery. PMID:20740201

  4. HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily

    PubMed Central

    IENI, A.; BARRESI, V.; GIUFFRÈ, G.; CARUSO, R.A.; LANZAFAME, S.; VILLARI, L.; SALOMONE, E.; ROZ, E.; CABIBI, D.; FRANCO, V.; CERTO, G.; LABATE, A.; NAGAR, C.; MAGLIOLO, E.; BROGGI, B.; FAZZARI, C.; ITALIA, F.; TUCCARI, G.

    2013-01-01

    According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2-positive cases. Furthermore, the characteristics of histotype, grade, stage and Ki-67 expression were also analyzed. HER2 overexpression was encountered in 17.43% of all the gastric adenocarcinomas, which was consistent with the results that have been reported elsewhere in the literature. A progressive increase in HER2 overexpression was observed, from the poorly cohesive histotype to the tubular adenocarcinomas and gastric hepatoid adenocarcinomas. HER2 overexpression was significantly associated with a high grade, advanced stage and high Ki-67 labeling index. Further investigations performed jointly by pathologists and oncologists within the geographical area of the present study should confirm that the association of trastuzumab with chemotherapy results in an improvement of survival in patients with AGC. PMID:24260051

  5. [Aerophagia due to noninvasive mechanical ventilation: a first manifestation of silent gastric carcinoma].

    PubMed

    Mayoralas Alises, S; Gómez Mendieta, M A; Díaz Lobato, S

    2003-07-01

    Noninvasive mechanical ventilation (NIV) techniques have proven useful in treating patients with respiratory insufficiency of various etiologies. The problems most frequently associated with this ventilatory technique are the appearance of nasal and oropharyngeal dryness, pressure sores where the nasal mask touches the skin, ocular irritation due to air leakage and epistaxis. Aerophagia appears in up to half the patients with NIV and may lead to discontinuing treatment. Drugs that accelerate gastrointestinal transit, changes in the respirator settings or changing the ventilatory modality may help to ameliorate the problem. When the symptoms arising from abdominal distension due to NIV are intense and persistent, the coexistence of an underlying abdominal pathology must be ruled out. We report the cases of two patients with these characteristics in whom gastroscopy revealed gastric carcinoma. We think that patients with persistent symptoms of aerophagia that cannot be controlled by the usual measures should undergo endoscopic exploration to rule out silent gastric disease. PMID:12846962

  6. Widespread osteoblastic metastases and marked elevation of CA19-9 as a presentation of signet ring cell gastric carcinoma

    PubMed Central

    Romano, Asaf; Bejar, Jacob; Schiff, Elad; Dotan, Yaniv

    2016-01-01

    Widespread osteoblastic metastases, as well as marked elevations of CA19-9 and carcino-embryonic antigen (CEA), are the initial manifestations of gastric signet ring cell carcinoma. CT Imaging revealed diffuse sclerotic metastases in the axial skeleton. It was only following gastric biopsy that the primary site of metastatic bone tumor was identified. Recent studies suggest that early diagnosis of cancer origin, including tumor molecular profiling, may dictate specific therapy, improve prognosis and increase patient survival rates. PMID:27034800

  7. Tripe palm: a cutaneous manifestation of gastric carcinoma.

    PubMed

    Chakraborty, Partha Pratim; Datta, Saumik; Mandal, Sanjay Kumar; Kumar, Manoj

    2014-01-01

    Case 1: A 43-year-old farmer attended our clinic with increasing fatigability, nausea, loss of appetite, loss of weight, postprandial fullness along with thyroid-stimulating hormone value of 0.4 mIU/L and anaemia without any history of cough, chest pain, haemoptysis, osmotic symptoms, haematemesis or malena. The patient received albendazole and iron preparations before attending our clinic. Case 2: A 51-year-old woman, a known patient with type 2 diabetes for the past 8 years, on gliclazide and metformin (2 g), with unaltered liver function test and renal function test, presented with symptoms similar to case 1 of upper gastrointestinal features along with a history of weight loss (about 6 kg) over the past 3 months. Metformin was withdrawn by her primary care physician but her symptoms persisted. A velvety appearance with pigmentation on the palms of the hands was found in both cases. Endoscopy revealed an irregular mass in the stomach. Subsequently, both patients were diagnosed to have gastric adenocarcinoma. PMID:25323284

  8. Gastric atrophy and oesophageal squamous cell carcinoma: possible interaction with dental health and oral hygiene habit

    PubMed Central

    Nasrollahzadeh, D; Malekzadeh, R; Aghcheli, K; Sotoudeh, M; Merat, S; Islami, F; Kamangar, F; Abnet, C C; Shakeri, R; Pourshams, A; Semnani, S; Boffetta, P; Dawsey, S M; Ye, W

    2012-01-01

    Background: Gastric fundal atrophy has been hypothesised to increase the risk of oesophageal squamous cell carcinoma (OSCC), but studies have shown inconsistent results. Methods: We measured serum pepsinogen I (PGI) and pepsinogen II (PGII) among 293 incident cases and 524 matched neighbourhood controls in a high-risk area of Northern Iran. Conditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Results: After controlling for age, sex, residence area and other potential confounders, gastric atrophy (defined by a validated criterion, PGI <55 μg dl−1) was associated with a two-fold increased risk (OR=2.01, 95% CI: 1.18, 3.45) of OSCC in the absence of nonatrophic pangastritis (defined as PGII <11.8 μg dl−1). Stratification by PGII decreased the misclassification errors due to cancer-induced gastritis. Presence of both poor dental health, indicated by higher than median sum of decayed, missing, and filled teeth (DMFT score), and gastric atrophy further increased the risk of OSCC (OR=4.15, 95% CI: 2.04, 8.42) with relative excess risk due to interaction (RERI) of 1.47 (95% CI: −1.15, 4.1). Coexistence of poor oral hygiene habit with gastric atrophy elevated OSCC risk eight times (OR=8.65, 95% CI: 3.65, 20.46) and the additive interaction index was marginally statistically significant (RERI=4.34, 95% CI: −1.07, 9.76). Conclusion: Gastric atrophy is a risk factor for OSCC, and poor dental health and oral hygiene habit may act synergistically in increasing the risk. PMID:22814581

  9. Analysis of Endoscopic Electronic Image of Intramucosal Gastric Carcinoma Using a Software Program for Calculating Hemoglobin Index

    PubMed Central

    Kim, Gwang Ha; Kim, Kwang Baek; Lim, Eun Kyung; Choi, Seong Ho; Kim, Tae Oh; Heo, Jeong; Kang, Dae Hwan; Cho, Mong; Park, Do Youn

    2006-01-01

    Hemoglobin is the predominent pigment in the gastrointestinal mucosa, and the development of electronic endoscopy has made it possible to quantitatively measure the mucosal hemoglobin volume, by using a hemoglobin index (IHb). The aims of this study were to make a software program to calculate the IHb and then to investigate whether the mucosal IHb determined from the electronic endoscopic data is a useful marker for evaluating the color of intramucosal gastric carcinoma with regard to its value for discriminating between the histologic types. We made a software program for calculating the IHb in the endoscopic images. By using this program, the mean values of the IHb for the carcinoma (IHb-C) and those of the IHb for the surrounding non-cancerous mucosa (IHb-N) were calculated in 75 intestinal-type and 34 diffuse-type intramucosal gastric carcinomas. We then analyzed the ratio of the IHb-C to the IHb-N (C/N ratio). The C/N ratio in the intestinal-type carcinoma group was higher than that in the diffuse-type carcinoma group (p<0.001). In the diffuse-type carcinoma group, the C/N ratio in the body was lower than that in the antrum (p=0.022). The accuracy rate, sensitivity, specificity, and the positive and negative predictive values for the differential diagnosis of the diffuse-type carcinoma from the intestinal-type carcinoma were 94.5%, 94.1%, 94.7%, 88.9% and 97.3%, respectively. IHb is useful for making quantitative measurement of the endoscopic color in the intramucosal gastric carcinoma, and the C/N ratio by using the IHb would be helpful for distinguishing the diffuse-type carcinoma from the intestinal-type carcinoma. PMID:17179684

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

    PubMed

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

    2007-01-01

    Chitin digestion by humans has generally been questioned or denied. Only recently chitinases have been found in several human tissues and their role has been associated with defense against parasite infections and to some allergic conditions. In this pilot study we tested the gastric juices of 25 Italian subjects on the artificial substrates 4-methylumbelliferyl-beta-D-N,N',diacetylchitobiose or/and fluorescein isothiocyanate (FITC) chitin to demonstrate the presence of a chitinase activity. Since this chitinase activity was demonstrated at acidic pH, it is currently referred to acidic mammalian chitinase (AMCase). AMCase activity was present in gastric juices of twenty of 25 Italian patients in a range of activity from 0.21 to 36.27 nmol/ml/h and from 8,881 to 1,254,782 fluorescence emission (CPS), according to the used methods. In the remaining five of 25 gastric juices, AMCase activity was almost absent in both assay methods. An allosamidine inhibition test and the measurement at different pH values confirmed that this activity was characteristic of AMCase. The absence of activity in 20% of the gastric juices may be a consequence of virtual absence of chitinous food in the Western diet. PMID:17587796

  11. Mucus retention in heterotopic pancreas of the gastric antrum. A lesion mimicking mucinous carcinoma.

    PubMed

    Nopajaroonsri, C

    1994-09-01

    This report describes mucus retention developing in heterotopic pancreas of the gastric antrum. This unusual complication of heterotopic pancreas was seen in a 54-year-old black man who presented with postprandial nausea, vomiting, and weight loss. Gastroscopy revealed a 2-cm pyloric polyp, which was seen to intermittently obstruct the pylorus. Exploratory laparotomy confirmed an intramural mass in the antrum with serosal thickening and nodules. Frozen-section examination of the serosal nodule revealed a pool of mucus containing epithelial clusters and chronic inflammatory cells with no verifiable pancreatic tissue. These findings suggested the possibility of a mucinous carcinoma involving the serosa. Following gastrectomy, however, heterotopic pancreatic tissue was identified in the outer muscular propria extending to the mucosa of the antrum with no evidence of carcinoma. This heterotopic pancreatic tissue showed ductal obstruction and mucus retention. As a result, some ducts were ruptured and transformed into small nodules of mucus lakes with clusters of residual ductal epithelium. We therefore concluded that the mucous extravasation nodules on the antral serosa represented a benign lesion resulting from mucus retention in the heterotopic pancreas. In contrast to mucinous carcinoma, these benign mucous extravasation nodules were closely associated with the heterotopic pancreas, and showed significant inflammation and fibrosis but no overt epithelial anaplasia. The significance of the mucous extravasation nodule in the heterotopic pancreas is its potential confusion with mucinous carcinoma. PMID:8067516

  12. Clinicopathological Characteristics, Treatment, and Prognosis of 21 Patients with Primary Gastric Squamous Cell Carcinoma

    PubMed Central

    Xu, Feng; Cao, Yidan; Gu, Xingting; Wan, Yuming

    2016-01-01

    We performed a retrospective analysis of 21 patients with primary gastric squamous cell carcinoma (PGSCC) who were admitted to our hospital from October 2008 to October 2014. The median age was 67 years and male predominance was observed, the most common tumor locations were the upper third of the stomach, most of the clinical manifestations were identical to those of other types of gastric tumors, and the tumor cells had positive immunoreactivity for p63 and CK5/6. In terms of treatments, surgery (R0 resection) is the main treatment; the effect of other treatments is unclear. The median survival time for the surgery group and nonsurgery group was 46 and 4.5 months, respectively. Probably due to limited number of cases, no significant difference in median survival time was observed between the surgery alone group and the surgery plus adjuvant therapy group (46 versus 51 months, P = 0.310). A standard chemotherapy regimen for this disease has not yet been established; the choice of its chemotherapy regimens tends to follow the principle of the treatment of gastric adenocarcinoma or esophageal cancer. PGSCC generally had a poor prognosis, and early detection, early diagnosis, and early surgical treatment are beneficial to patients. PMID:27478431

  13. 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

  14. 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

  15. Helicobacter pylori infection and gastric carcinoma: Not all the strains and patients are alike

    PubMed Central

    Figura, Natale; Marano, Luigi; Moretti, Elena; Ponzetto, Antonio

    2016-01-01

    Gastric carcinoma (GC) develops in only 1%-3% of Helicobacter pylori (H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host’s factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C’-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta (IL-1β) group and tumour necrosis factor-alpha (TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability (MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes (such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development. PMID:26798436

  16. Mixed adeno(neuro)endocrine carcinoma arising from the ectopic gastric mucosa of the upper thoracic esophagus

    PubMed Central

    2013-01-01

    We report a case of mixed adenoendocrine carcinoma of the upper thoracic esophagus arising from ectopic gastric mucosa. A 64-year-old man who had been diagnosed with an esophageal tumor on the basis of esophagoscopy was referred to our hospital. Upper gastrointestinal endoscopy revealed the presence of ectopic gastric mucosa and an adjacent pedunculated lesion located on the posterior wall of the upper thoracic esophagus. Subtotal esophagectomy with three-field lymph node dissection was performed. A microscopic examination revealed that there was a partially intermingling component of neuroendocrine carcinoma adjacent to a tubular adenocarcinoma which was conterminous with the area of the ectopic gastric mucosa. Although the tubular adenocarcinoma was confined to the mucosa and submucosa, the neuroendocrine carcinoma had invaded the submucosaand there was vascular permeation. Each component accounted for 30% or more of the tumor, so the final histopathological diagnosis was mixed adenoendocrine carcinoma of the upper thoracic esophagus arising from ectopic gastric mucosa. Adjuvant chemotherapy was not performed, because the postoperative tumor stage was IA. The patient was well and had no evidence of recurrence 16 months after surgery. PMID:24139488

  17. Mixed gastric carcinoma with intestinal and cribriform patterns: a distinctive pathologic appearance associated with poor prognosis in advanced stages and a potential mimicker of metastatic breast carcinoma.

    PubMed

    Lino-Silva, Leonardo Saúl; Salcedo Hernández, Rosa Angélica; Molina-Frías, Ernesto

    2013-02-01

    Gastric adenocarcinoma is characterized by marked heterogeneity at cytological and architectural level and frequently shows overlap between microscopic patterns. This article describes a peculiar pattern of gastric adenocarcinoma, previously unreported, that combines intestinal type adenocarcinoma with areas of cribriform pattern that resembles both architectural and cytological in situ ductal carcinoma of the breast and to the best of the authors' knowledge, there are no earlier reports of this pattern in the stomach, which has been named "gastric carcinoma with cribriform component (CGA). The authors analyzed 12 cases of intestinal type adenocarcinoma with areas at least 20% of cribriform pattern (range from 20% to 90%) that was present in 9% of intestinal type gastric adenocarcinomas in their institution. There is slight predilection for male sex, and the median age of presentation is 55.8 years. The phenotype by immunohistochemistry is the same as with conventional (non-CGA) carcinomas. CGA shows more frequent lymphovascular invasion (P = .039), perineural invasion (P = .027) and resembles both in situ and invasive cribriform carcinoma of the breast. In clinical stage III the overall 3-year survival of CGA was worse than those with non-CGA component (38.6% vs 25%; 3-year survival, P = .010) and proves to be an independent adverse factor for overall survival in a multivariate analysis. Compared with conventional gastric carcinomas, CGA is deep infiltrating, has more nodal metastases, more lymphovascular and perineural invasion, and has decreased overall survival. Thus, proper recognition and report is important, even in small biopsies or small foci. PMID:22744963

  18. Expression of c-myc and PCNA in Epstein-Barr virus-associated gastric carcinoma

    PubMed Central

    ZHU, SHIGUANG; SUN, PING; ZHANG, YINGXIN; YAN, LIPING; LUO, BING

    2013-01-01

    The aim of this study was to detect the expression of proliferatng cell nuclear antigen (PCNA) and c-myc in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), as well as the expression of EBV-encoded proteins in EBVaGC and their effect on carcinogenesis and the development of gastric cancer. The PCNA and c-myc protein levels were assessed by immunohistochemistry in 13 EBVaGC and 45 EBVnGC specimens. The expression of related genes of EBV, including EB nuclear antigen (NA)-1 and EBNA2 genes, latent membrane protein 1 (LMP1) and early genes BARF1 and BHRF1 were tested by reverse transcription-polymerase chain reaction (RT-PCR) and southern blotting. The PCNA labeling index (LI) of EBVaGCs, EBVnGCs and the corresponding adjacent tissues of EBVaGCs were 49.3768±12.1832, 14.839±7.1847, 35.613±8.3831 and 24.2735±10.1332, respectively. The PCNA LI was significantly different between EBVaGC and EBVnGC of EBVaGC (t=4.686, P<0.01). The difference between EBVaGC and corresponding adjacent tissues of EBVaGC was also significant (t=8.805, P<0.01). The expression of c-myc protein was detected in 33 of 58 (55.39%) gastric carcinomas and in 21 of 58 (36.21%) adjacent tissues. There was a significant difference between the two groups (χ2=4.989, P<0.05). The expression of the c-myc protein was detected in 8 of 13 (61.54%) EBVaGCs and in 25 of 45 (55.56%) EBVnGCs. The difference between the two groups was not significant (χ2=0.147, P>0.05). EBNA1 mRNA was detected in all 13 EBVaGC cases, while EBNA2 and LMP1 mRNA was not detected in these cases. Of the 13 EBV-positive samples, 6 exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts. c-myc expression did not correlate with the presence of EBV in EBVaGC. EBV infection may induce PCNA expression. The lack of EBNA2 and LMP1 protein expression in EBVaGC suggests that EBNA2 and LMP1 do not correlate with cell apoptosis and c-myc expression. Early genes BARF1 and BHRF1

  19. Accumulation Mechanisms of CD4(+)CD25(+)FOXP3(+) Regulatory T Cells in EBV-associated Gastric Carcinoma.

    PubMed

    Zhang, Na-na; Chen, Jian-ning; Xiao, Lin; Tang, Fang; Zhang, Zhi-gang; Zhang, Yi-wang; Feng, Zhi-ying; Jiang, Ye; Shao, Chun-kui

    2015-01-01

    Approximately 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV) and are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are known to be accompanied by massive CD8(+) cytotoxic T cell (CTL) infiltration; however, adoptive cellular immunotherapy based on EBV-specific CD8(+) CTLs has been explored with limited success. Because regulatory T cells (Tregs) are regarded as a critical hurdle in anti-tumour immunity, we assessed the distribution of Tregs in 45 cases of EBVaGC and 45 cases of EBV-negative gastric carcinoma (EBVnGC) with matched clinicopathological parameters by immunohistochemistry. We showed that Tregs were significantly increased in EBVaGC compared to EBVnGC (15.92 ± 11.45/HPF vs. 8.45 ± 6.16/HPF, p = 0.001). In addition, we explored the accumulation mechanisms of Tregs in EBVaGC by using EBV (+) gastric carcinoma cell lines SNU719 and GT39 as ex vivo models. When peripheral blood mononuclear cells (PBMCs) were co-cultured with EBV (+) gastric carcinoma cell lines, the Treg frequency increased, and they underwent phenotypic and functional changes. The enhanced recruitment by CCL22 produced by EBVaGC cells, the decreased emigration due to CCR7 downregulation on the Treg surface, the higher proliferation rate, and the lower apoptosis rate of Tregs at tumour sites may promote the accumulation of Tregs in EBVaGC. PMID:26673957

  20. Increased risk of esophageal squamous cell carcinoma in patients with gastric atrophy: independent of the severity of atrophic changes.

    PubMed

    de Vries, Annemarie C; Capelle, Lisette G; Looman, Caspar W N; van Blankenstein, Mark; van Grieken, Nicole C T; Casparie, Mariël K; Meijer, Gerrit A; Kuipers, Ernst J

    2009-05-01

    An association between gastric atrophy and esophageal squamous cell carcinomas (ESCC) has been described. However, the mechanism of this association is unknown. In this study, we aimed to examine this relationship in a cohort of patients with varying grades of gastric atrophy to increase the understanding about the causality of the association. Patients diagnosed with gastric atrophy between 1991 and 2005 were identified in the Dutch nationwide histopathology registry (PALGA). The incidence of ESCC and, presumably unrelated, small cell lung carcinomas (SCLC) observed in these patients was compared with that in the general Dutch population. Relative risks (RRs) and 95% confidence intervals were calculated by a Poisson model. At baseline histological examination, 97,728 patients were diagnosed with gastric atrophy, of whom 23,278 with atrophic gastritis, 65,934 with intestinal metaplasia and 8,516 with dysplasia. During follow-up, 126 patients were diagnosed with ESCC and 263 with SCLC (overall rates 0.19, respectively 0.39/1,000 person-years at risk). Compared with the general Dutch population, patients with gastric atrophy ran a RR of developing ESCC of 2.2 [95% CI 1.8-2.6] and of SCLC of 1.8 [95% CI 1.6-2.1]. The risk of ESCC did not increase with increasing severity of gastric atrophy (p = 0.90). In conclusion, this study found an association between gastric atrophy and both ESCC and SCLC, but the risk of ESCC did not increase with the severity of gastric atrophy. Therefore, a causal relationship seems unlikely. Confounding factors, such as smoking, may explain both associations. PMID:19107937

  1. Analysis of microvascular density in early gastric carcinoma using magnifying endoscopy with narrow-band imaging

    PubMed Central

    Kawamura, Masashi; Naganuma, Hiroshi; Shibuya, Rie; Kikuchi, Tatsuya; Sakai, Yoshitaka; Nagasaki, Futoshi; Nomura, Eiki; Suzuki, Noriaki; Saito, Eri

    2016-01-01

    Background and study aims: Intramucosal vascular density differs between differentiated and undifferentiated type gastric carcinomas. This study aimed to evaluate the microvascular density characteristics of these two types of carcinoma using magnifying endoscopy with narrow-band imaging (ME-NBI). Patients and methods: In total, 42 differentiated and 10 undifferentiated types were evaluated. The microvessels observed using ME-NBI were extracted from stored still images and the microvascular density in the two carcinoma types was analyzed. Histological vascular density in resected specimens was also evaluated using CD34 immunostaining. Results: There were significant differences between the microvascular density in the differentiated and undifferentiated types of carcinoma (10.02 ± 4.72 % vs 4.02 ± 0.40 %; P < 0.001) using ME-NBI. Vascular density assessed histologically also differed significantly between differentiated and undifferentiated types in both the whole mucosal (5.81 ± 3.17 % vs 3.25 ± 1.21 %) and the superficial mucosal layers (0 – 100 μm) (6.38 ± 3.73 % vs 3.66 ± 1.46 %). However, the vascular density in the surrounding non-carcinomatous mucosa assessed using ME-NBI and histologically, was significantly lower in the differentiated than in the undifferentiated types (P < 0.001). There was good agreement between ME-NBI and histologically assessed microvascular density in both the whole (r = 0.740; P < 0.001) and superficial mucosal layers (r = 0.764; P < 0.001). White opaque substance (WOS) was seen in eight patients who had the differentiated type carcinoma. In almost all cases with WOS, the appearance of the carcinoma was discolored. Conclusions: There was a close relationship between ME-NBI assessed microvascular density and histologically assessed vascular density in the mucosal layer. Microvascular density differed significantly between the differentiated and undifferentiated

  2. Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma.

    PubMed Central

    Nakamura, M.; Katano, M.; Kuwahara, A.; Fujimoto, K.; Miyazaki, K.; Morisaki, T.; Mori, M.

    1998-01-01

    It has been generally accepted that transforming growth factor beta1 (TGF-beta1) has both negative and positive effects on tumour growth and progression. This study analysed the prognostic value of TGF-beta1 mRNA in advanced gastric carcinoma. A reverse transcriptase-polymerase chain reaction analysis (RT-PCR) was used for TGF-beta1 in endoscopic biopsy specimens from 42 advanced gastric carcinomas. Thirty specimens expressed TGF-beta1 mRNA while 12 specimens did not. The follow-up duration ranged from 4 to 37 months (mean 22.8 months). TGF-beta1-positive group demonstrated a shorter overall survival compared with the TGF-beta1 -negative group (P=0.0014). A significant correlation was also found in the 32 patients who underwent curative resection (P=0.0048). Significant correlations were found between TGF-beta1 mRNA expression and both stage (P=0.0015) and nodal involvement (P=0.0060). Multivariate analysis demonstrated that only TGF-beta1 mRNA expression (P=0.0306) was an independent prognostic factor. All of ten patients who underwent non-curative resection expressed TGF-beta1 mRNA. Expression of TGF-beta1 mRNA in gastric biopsy specimens may be an important preoperative prognostic variable for advanced gastric carcinoma. Images Figure 1 PMID:9823982

  3. HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif

    PubMed Central

    He, Changyu; Zhang, Baogui; Zhang, Jun; Liu, Bingya; Zeng, Naiyan; Zhu, Zhenggang

    2015-01-01

    HOXB9, a transcription factor, plays an important role in development. While HOXB9 has been implicated in tumorigenesis and metastasis, its mechanisms are variable and its role in gastric carcinoma (GC) remains unclear. In the present study, we demonstrated that the expression of HOXB9 decreased in gastric carcinoma and was associated with malignancy and metastasis. Re-expression of HOXB9 in gastric cell lines resulted in the suppression of cell proliferation, migration, and invasion, which was accompanied by the induction of mesenchymal-to-epithelial transition (MET). Comparative sequence analysis and examination of a HOXB9 structural model indicated that three sites might possibly be involved in MET regulation. The in vitro study of HOXB9 mutants showed that these were unable to inhibit MET induction. However, when overexpressing a HOXB9 mutant lacking the hexapeptide motif, a more potent MET induction and tumor suppression was observed compared to that of the wild-type, indicating that the presence of the hexapeptide motif reduced HOXB9 MET induction and tumor suppression activity. Therefore, the results of the present study suggested that HOXB9 is a tumor suppressor in gastric carcinoma, and its activity was controlled by different regulatory mechanisms such as the hexapeptide motif as a “brake” in this case. The results of these regulatory effects could lead to either oncogenic or tumor suppressive roles of HOXB9, depending on the context of the particular type of cancer involved. PMID:26536658

  4. Gastric large cell neuroendocrine carcinoma with venous tumor thrombus: the value of PET/CT and contrast-enhanced computed tomography.

    PubMed

    Song, Le; Jin, Zhu; Zhang, Weifang; Zhang, Yanyan

    2015-01-01

    Venous involvement is commonly detected microscopically on gastric neuroendocrine carcinomas (NECs), but related imaging studies have been rarely documented. We report a rare case of gastric large cell NEC with tumor thrombi in gastric and splenic veins, elevated serum alpha fetoprotein, and multiple hepatic nodules. In this case, (18)F-fluorodeoxyglucose positron emission tomography combined with contrast-enhanced computed tomography provided valuable information on tumor staging. PMID:25496669

  5. EBNA1 binding and epigenetic regulation of gastrokine tumor suppressor genes in gastric carcinoma cells

    PubMed Central

    2014-01-01

    Background Epstein-Barr Virus (EBV) latently infects ~10% of gastric carcinomas (GC). Epstein-Barr Nuclear Antigen 1 (EBNA1) is expressed in EBV-associated GC, and can bind host DNA, where it may impact cellular gene regulation. Here, we show that EBNA1 binds directly to DNA upstream of the divergently transcribed GC-specific tumor suppressor genes gastrokine 1 (GKN1) and gastrokine 2 (GKN2). Methods We use ChIP-Seq, ChIP-qPCR, and EMSA to demonstrate that EBNA1 binds directly to the GKN1 and GKN2 promoter locus. We generate AGS-EBV, and AGS-EBNA1 cell lines to study the effects of EBNA1 on GKN1 and GKN2 mRNA expression with or without 5′ azacytidine treatment. Results We show that gastrokine genes are transcriptionally silenced by DNA methylation. We also show that latent EBV infection further reduces GKN1 and GKN2 expression in AGS gastric carcinoma cells, and that siRNA depletion of EBNA1 partially alleviates this repression. However, ectopic expression of EBNA1 slightly increased GKN1 and GKN2 basal mRNA levels, but reduced their responsiveness to demethylating agent. Conclusions These findings demonstrate that EBNA1 binds to the divergent promoter of the GKN1 and GKN2 genes in GC cells, and suggest that EBNA1 contributes to the complex transcriptional and epigenetic deregulation of the GKN1 and GKN2 tumor suppressor genes in EBV positive GC. PMID:24460791

  6. Glutathione prevents ethanol induced gastric mucosal damage and depletion of sulfhydryl compounds in humans.

    PubMed Central

    Loguercio, C; Taranto, D; Beneduce, F; del Vecchio Blanco, C; de Vincentiis, A; Nardi, G; Romano, M

    1993-01-01

    Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione significantly decreased the extent of ethanol induced macroscopic injury to the mucosa of the gastric body and antrum. Glutathione's protective effect is associated with appreciable inhibition of ethanol induced depletion of gastric sulfhydryl compounds. This is the first report of protection against ethanol induced gastric mucosal damage by a sulfhydryl containing agent in humans. PMID:8432465

  7. α-fetoprotein-producing gastric carcinoma: A case report of a rare subtype and literature review

    PubMed Central

    SUN, NINGBO; SUN, QING; LIU, QUN; ZHANG, TIANXIAO; ZHU, QIANG; WANG, WEI; CAO, MING; ZANG, QI

    2016-01-01

    α-fetoprotein (AFP)-producing gastric carcinoma is a rare type of gastric cancer, and the characteristics have not yet been fully elucidated. The present study reports the case of a patient with this type of gastric cancer. A 66-year-old male was referred to the Department of Gastrointestinal Surgery, Qianfoshan Hospital, Shandong University (Jinan, China) with a 20-day history of retrosternal pain. A computed tomography (CT) scan revealed a thickening of the wall of the cardia and massive lymph node swelling in the region of the lesser curvature of the stomach. A laboratory investigation revealed that the serum AFP levels of the patient were elevated to 46.49 ng/ml (normal level, <12.00 ng/ml), and the serum carcinoembryonic antigen (CEA) levels were 382.22 ng/ml (normal range, <5.00 ng/ml). An endoscopy revealed an elevated tumor and AFP-producing gastric cancer was diagnosed. As the tumor was surgically unresectable, the patient received systemic adjuvant chemotherapy [consisting of 1 cycle of oxaliplatin (150 mg; day 1)-fluorouracil(1.0 g; days 2–6)-calcium folinate (0.3 g; days 2–6), 4 cycles of paclitaxel (80 mg; day 1 and 8, repeated day 21) and capecitabine (1,000 g/m2, twice daily; days 1–14, repeated day 21), and 2 cycles of oxaliplatin (130 mg/m2; day 1, repeated day 21) and S-1 (100 mg/d; day 1- day 14; repeated day 21)]. During the chemotherapy intermission, the patient experienced partial remission; the serum AFP levels remained between 44.5 and 32.7 ng/ml, and serum CEA levels decreased to a normal level. The CT scan revealed that the enlarged lymph nodes of the patient had decreased in size. During the preoperative examinations, an abdominal CT scan revealed no metastasis to the liver. A radical gastrectomy was performed on October 20, 2014. Additionally, the tumor did not demonstrate the diffusion of AFP. The histopathological examination revealed a poorly differentiated adenocarcinoma, with local and neuroendocrine differentiation and no

  8. The MSHA strain of Pseudomonas aeruginosa (PA-MSHA) inhibits gastric carcinoma progression by inducing M1 macrophage polarization.

    PubMed

    Wang, Changming; Hu, Zunqi; Zhu, Zhenxin; Zhang, Xin; Wei, Ziran; Zhang, Yu; Hu, Dali; Cai, Qingping

    2016-05-01

    Macrophages play crucial roles in promoting tumor development and progression. In the present study, we found that the mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) was efficient in inducing M1 macrophage polarization. PA-MSHA treatment increases expression of M1-related cytokines and promotes activation of murine peritoneal macrophages (MPM). Interestingly, PA-MSHA inhibits cell proliferation and migration and induces the apoptosis of gastric carcinoma cells. These effects of PA-MSHA on M1 polarization were associated with activation of NF-κB expression. Thus, inducing polarization of M1 by PA-MSHA may be one potential strategy for inhibiting gastric carcinoma progression in mice. PMID:26662800

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

    PubMed

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

    2015-11-01

    A man in his 40s was referred to our hospital with abdominal pain. A gastric submucosal tumor (SMT) was diagnosed nine years previously, but the patient was lost to follow-up. Upon our evaluation, the SMT had enlarged, as demonstrated by esophagogastroduodenoscopy and abdominal computed tomography. Endoscopic ultrasonography revealed a hypoechoic and isoechoic mosaic mass, which primarily occupied the third and fourth layers of the gastric wall. Aspiration cytodiagnosis was performed, the results of which led to a suspicion of adenocarcinoma arising from gastric ectopic pancreas. Next, we conducted segmental gastrectomy. Pathological examination showed adiponecrosis, a pancreatic stone, chronic inflammatory cell infiltration, and fibrosis. Thus, the patient was diagnosed with chronic pancreatitis occurring in a gastric aberrant pancreas. PMID:26537325

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. Detecting metastasis of gastric carcinoma using high-resolution micro-CT system: in vivo small animal study

    NASA Astrophysics Data System (ADS)

    Liu, Junting; Tian, Jie; Liang, Jimin; Li, Xiangsi; Yang, Xiang; Chen, Xiaofeng; Chen, Yi; Zhou, Yuanfang; Wang, Xiaorui

    2011-03-01

    Immunocytochemical and immunofluorescence staining are used for identifying the characteristics of metastasis in traditional ways. Micro-computed tomography (micro-CT) is a useful tool for monitoring and longitudinal imaging of tumor in small animal in vivo. In present study, we evaluated the feasibility of the detection for metastasis of gastric carcinoma by high-resolution micro-CT system with omnipaque accumulative enhancement method in the organs. Firstly, a high-resolution micro-CT ZKKS-MCT-sharp micro-CT was developed by our research group and Guangzhou Zhongke Kaisheng Medical Technology Co., Ltd. Secondly, several gastric carcinoma models were established through inoculating 2x106 BGC-823 gastric carcinoma cells subcutaneously. Thirdly, micro-CT scanning was performed after accumulative enhancement method of intraperitoneal injection of omnipaque contrast agent containing 360 mg iodine with a concentration of 350 mg I/ml. Finally, we obtained high-resolution anatomical information of the metastasis in vivo in a BALB/c NuNu nude mouse, the 3D tumor architecture is revealed in exquisite detail at about 35 μm spatial resolution. In addition, the accurate shape and volume of the micrometastasis as small as 0.78 mm3 can be calculated with our software. Overall, our data suggest that this imaging approach and system could be used to enhance the understanding of tumor proliferation, metastasis and could be the basis for evaluating anti-tumor therapies.

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

    PubMed

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

    2016-07-01

    Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment. Using a tissue chopper, fresh surgical tissue samples were cut in 400 μm slices and cultivated in 6-well plates for up to 6 days. The slices were processed for routine histopathology and immunohistochemistry. Cytokeratin stains (CK8, AE1/3) were applied for determining tumor cellularity, Ki-67 for proliferation, and cleaved caspase-3 staining for apoptosis. The slices were analyzed under naive conditions and following 2-4 days in vitro exposure to 5-FU and cisplatin. The slice culture technology allowed for a good preservation of tissue morphology and tumor cell integrity during the culture period. After chemotherapy exposure, a loss of tumor cellularity and an increase in apoptosis were observed. Drug sensitivity of the tumors could be assessed. Organotypic slice cultures of gastric and esophagogastric junction cancers were successfully established. Cytotoxic drug effects could be monitored. They may be used to examine mechanisms of drug resistance in human tissue and may provide a unique and powerful ex vivo platform for the prediction of treatment response. PMID:27073068

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

    PubMed Central

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

    2008-01-01

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

  15. Increased programmed death-ligand-1 expression in human gastric epithelial cells in Helicobacter pylori infection

    PubMed Central

    Wu, Y-Y; Lin, C-W; Cheng, K-S; Lin, C; Wang, Y-M; Lin, I-T; Chou, Y-H; Hsu, P-N

    2010-01-01

    B7-H1 [programmed death-ligand-1 (PD-L1)] is a B7-family member that binds to programmed death-1 (PD-1). Recently, deficiency of PD-L1 has been demonstrated to result in accelerated gastric epithelial cell damage in gastritis, and PD-L1 is suggested to play a critical role in regulating T cell homeostasis. Here, we aimed to gain more insight into gastric PD-L1 expression, regulation and function during Helicobacter pylori infection. PD-L1 expression in human gastric epithelial cells was analysed using Western blotting, quantitative polymerase chain reaction and fluorescence activated cell sorter analysis. Furthermore, co-culture experiments of human gastric epithelial cells with primary human T cells or Jurkat T cells were conducted. PD-L1 expression in primary human gastric epithelial cells was strongly enhanced by H. pylori infection and activated T cells, and augmented markedly by further stimulation with interferon-γ or tumour necrosis factor-α. Moreover, PD-L1 expression in gastric epithelial cells significantly induced apoptosis of T cells. Our results indicate that a novel bidirectional interaction between human gastric epithelial cells and lymphocytes modulates PD-L1 expression in human gastric epithelial cells, contributing to the unique immunological properties of the stomach. PMID:20646001

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

    PubMed Central

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

    2016-01-01

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

  17. The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type

    PubMed Central

    2010-01-01

    Background PIK3CA is one of the genes most frequently mutated in human cancers and it is a potential target for personalized therapy. The aim of this study was to assess the frequency and type of PIK3CA mutations in gastric carcinoma and compare them with their clinical pathological correlates. Methods We analysed 264 gastric cancers, including 39 with microsatellite instability (MSI), for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtained from microdissected cancer cells. Results The cases harbouring mutations were 42 (16%). All were heterozygous missense single base substitutions; the most common was H1047R (26/42; 62%) in exon 20 and the second was Q546K (4/42; 9.5%) in exon 9. All the mutated MSI cases (8/39) carried the H1047R mutation. No other association between PI3KCA mutations and their clinical pathological covariates was found. A metanalysis of the mutations occurring in the same regions presented in 27 publications showed that ratio between exon 20 and exon 9 prevalences was 0.6 (95% CI: 0.5 -0.8) for colon, 1.6 (95% CI: 1.1 -2.3) for breast, 2.7 (95% CI: 1.6 -4.9) for gastric and 4.1 (95% CI: 1.9 -10.3) for endometrial cancer. Conclusions The overall prevalence of PIK3CA mutations implies an important role for PIK3CA in gastric cancer. The lack of association with any clinical-pathological condition suggests that mutations in PIK3CA occur early in the development of cancer. The metanalysis showed that exon-selectivity is an important signature of cancer type reflecting different contexts in which tumours arise. PMID:20398348

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

    PubMed

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

    2016-01-01

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

  19. RRR-α-tocopheryl succinate induces apoptosis in human gastric cancer cells via the NF-κB signaling pathway.

    PubMed

    Sun, Yanpei; Zhao, Yan; Hou, Liying; Zhang, Xuguang; Zhang, Zhihong; Wu, Kun

    2014-09-01

    To investigate the effects of the nuclear factor (NF)-κB signaling pathway on the induction of apoptosis by vitamin E succinate (RRR-α-tocopheryl succinate; VES) in human gastric carcinoma cells. Human gastric carcinoma SGC-7901 cells were treated with temperate concentrations of VES and pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Cell viability and apoptosis were respectively estimated by methylthiazol tetrazolium (MTT) assay and the Annexin V‑FITC method. Western blot analysis was used to evaluate the protein expressions of NF-κBp65 and Bcl-2 family members Bcl-2, Bax and cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP). The DNA-binding activity of NF-κBp65 was measured by electrophoretic mobility shift assay (EMSA). Reverse transcription and polymerase chain reaction (RT-PCR) was implemented to evaluate the transcription of inhibitor of apoptosis (IAP) genes. Apoptosis assessment showed that VES induces apoptotic cell death in human gastric carcinoma cells. In the following experiments, PDTC (100 µM) was used in cell treatment 2 h before VES. The decreased ratio of the nuclear and cytosolic NF-κBp65 protein level was induced by VES and PDTC reinforced this trend. PDTC treatment significantly enhanced the decrease of NF-κB-DNA binding activity induced by VES in human gastric SGC-7901. The decrease in protein expression of Bcl-2 as well as the increase in the protein expression of Bax were induced by VES treatment. The cleavage of caspase-9, caspase-3 and PARP was induced. There was no effect on the gene transcription of c-IAP-1, c-IAP-2, and x-linked IAP (XIAP) compared with the control group, whereas mRNA levels of survivin and the neuronal apoptosis inhibitory protein (NAIP) markedly decreased. Notably, pretreatment with PDTC reinforced all the above VES-induced effects. In conclusion, VES-induced apoptosis in SGC-7901 cells is accompanied by the inhibition of the NF-κB signaling pathway, including

  20. [Giant gastric neuroendocrine cell carcinoma with extraluminal growth and direct invasion: a case report].

    PubMed

    Okawa, Takaomi; Nogami, Hiromi; Kadota, Eiji

    2015-11-01

    A 68-year-old man presented to our hospital requesting an operation for an anal prolapse. However, because of appetite loss and general malaise, we performed screening gastroscopy that revealed a huge ulcerative lesion in the greater curvature of the middle stomach. Biopsy showed a solid tumor with marked dyskaryosis that was positive for synaptophysin on immunohistochemical staining. Abdominal computed tomography revealed a tumor measuring larger than 20 cm in diameter in the greater curvature of the stomach and two hepatic metastases. A preoperative diagnosis of neuroendocrine cell carcinoma (NEC) was made and the patient underwent surgery. The lesion displayed extraluminal growth and directly infiltrated the ileum and colon. We therefore performed distal gastrectomy with combined resection of the gallbladder, ileum, transverse colon, and sigmoid colon. However, despite transcatheter arterial chemoembolization for the liver metastases, the patient died 1 year 2 months after the initial surgery. Gastric NECs are rare and have poor outcomes, being associated with rapid progression of lymph node and liver metastases. Moreover, they rarely show extraluminal growth or invasion to other organs. We present a report of this case along with a review of the literature. PMID:26537329

  1. Perioperative Allogenenic Blood Transfusion is Associated With Worse Clinical Outcome for Patients Undergoing Gastric Carcinoma Surgery

    PubMed Central

    Li, Lihong; Zhu, Dajian; Chen, Xiaowu; Huang, Yanfeng; Ouyang, Manzhao; Zhang, Weijie

    2015-01-01

    Abstract Whether perioperative allogenic blood transfusion (ABT) has adverse effect on patients with gastric carcinoma (GC) surgery or not, that is controversial. Our study evaluated the association between ABT and some clinical outcomes of GC surgery patients. Data of relevant studies were based on PubMed, EMBASE, and the Cochrane Library search. The relative risk (RR) of 5-year survival rates, tumor recurrence, and postoperative complications were performed; subgroup analyses included district, transfusion rates, age, participants, sex, and tumor stage. The study was approved by the ethics committee of the First People's Hospital of Shunde. In total, 9189 participants from 16 studies were included in the meta-analysis. The 5-year survival rate was decreased for the GC patients with ABT (RR = 0.74, 95% confidence interval [CI] = 0.69–0.79), the risk of tumor recurrence was significantly higher for ABT patients (RR = 1.82, 95% CI = 1.32–2.51), and postoperative complications increased in ABT patients (RR = 1.36, 95% CI = 1.02–1.81), respectively; in subgroup analyses, 5-year survival rates were not associated with the transfusion rates (χ2 = 0.37, P = 0.54). Transfusion for patients undergoing GC surgery, even low transfusion rates, would reduce the 5-year survival rates, and elevated the risk of tumor recurrence and postoperative complication. PMID:26426632

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

    PubMed Central

    Compare, Debora

    2015-01-01

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

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

    PubMed

    Oliveros-Bastidas, Alberto; Calcagno-Pissarelli, María Pía; Naya, Marlene; Ávila-Núñez, Jorge Luis; Alonso-Amelot, Miguel E

    2016-03-01

    Long term infection of Helicobacter pylori (Hp) virulent strains is a key factor in the genesis of human gastric cancer, and so are certain dietary proinflammatory and genotoxic compounds. Carcinogenic bracken fern (Pteridium spp.) is one of these. Toxins from this plant are consumed as bracken culinary preparations, through milk and meat of bracken-exposed livestock, and drain waters from bracken swards. Bracken toxin ptaquiloside (PtQ), a suspected human carcinogen, elicits complex responses in animals leading to death. PtQ and Hp might cooperate in gastric pathologies. This paper presents an hypothesis on PtQ-Hp association leading to the enhancement of carcinogenesis in the human gastric environment that might explain the high gastric cancer incidence and death rates among Hp-infected people living in bracken zones at two levels: (1) The macroscopic scale comprising the flow of PtQ in the human diet. (2) the microscopic scale encompassing (A) gastric luminal medium; (B) gastric mucus structure and mucin degradation elicited by Hp; (C) bacterial pH gradient modification of the gastric mucosa that favors PtQ survival and its penetration into epithelial tissue; (D) combined PtQ/Hp effects on gastric immune and inflammatory responses; (E) PtQ-Hp complementary activity at selected cell signaling cascades and genome disturbance. PMID:26632203

  4. Immunohistochemical study of DNA topoisomerase II in human gastric disorders.

    PubMed Central

    Yabuki, N.; Sasano, H.; Kato, K.; Ohara, S.; Toyota, T.; Nagura, H.; Miyaike, M.; Nozaki, N.; Kikuchi, A.

    1996-01-01

    Topoisomerase II (topo II) separates chromosomes at the end of mitosis and is also the target for various chemotherapeutic agents. Expression of this enzyme has been demonstrated to increase rapidly at the end of the S to G2/M phase and decrease after the completion of mitosis. We immunolocalized topo II in specimens of both normal and neoplastic human gastric mucosas to evaluate expression of this enzyme. Three different antibodies were used for the immunostaining of topo II (anti-topo II alpha isoform, anti-topo II beta isoform and anti-topo II alpha and -beta isoforms). There were no significant differences in topo II labeling index (LI) between frozen and paraffin-embedded tissue sections obtained from the same cases. Topo II LI was significantly correlated with Ki67 LI in all of the specimens examined. The area of cells positive for Topo II was much narrower than that of Ki67 in the normal gastric glands, and the pattern of Topo II immunolocalization in both adenomas and adenocarcinomas was also essentially the same as that of Ki67. The topo II LI values (positive cells/1000 cells) for normal gastric gland, adenoma, intestinal-type adenocarcinoma, and diffuse-type adenocarcinoma were 114.7 +/- 2.2, 266.7 +/- 18.8, 277.6 +/- 19.2, and 324.5 +/- 5.3, respectively. Significant differences in topo II LI and topo II/Ki67 index were observed between normal and neoplastic mucosas (P < 0.0001) and between adenomas or intestinal-type adenocarcinoma and diffuse-type adenocarcinoma (P < 0.001 and P < 0.01, respectively). Simultaneous measurement of topo II alpha and nuclear DNA content by two-parameter flow cytometry revealed that the Jurkat cell line established from acute lymphocytic leukemia cells expressed the enzyme in cells at other than S and G2/M phases of the cell cycle whereas topo-II alpha-positive cells were predominantly observed in S and G2/M phases of the cell cycle in the cells from normal lymph nodes. These findings suggest that dys-regulation or

  5. Gastric Carcinomas in Young (Younger than 40 Years) Chinese Patients: Clinicopathology, Family History, and Postresection Survival.

    PubMed

    Zhou, Fan; Shi, Jiong; Fang, Cheng; Zou, Xiaoping; Huang, Qin

    2016-03-01

    Little is known about clinicopathological characteristics of gastric carcinoma (GC) in young (≤40 years) Chinese patients. We aimed in this study to analyze those features along with family history and prognostic factors after resection. We retrospectively reviewed all 4671 GC resections (surgical and endoscopic) performed at our center from 2004 to 2014 and identified 152 (3.2%) consecutive young patients. Patient demographics, clinical results, family history, and endoscopic-pathological findings were analyzed along with the older (>41 years) GC controls recruited in the same study period. Clinicopathological factors related to postresection outcomes were assessed statistically. The trend of GC resections in young patients was not changed over the study period. Compared to old GCs, the young GC cohort was predominant in women, positive family history, middle gastric location, the diffuse histology type, shorter duration of symptoms, and advanced stage (pIII+pIV, 53.3%). Radical resection was carried out in 90.1% (n = 137) with a better 5-year survival rate (70.3%) than palliative surgery (0%, n = 15). There was no significant difference in clinicopathological characteristics between familial GC (FGC, n = 38) and sporadic GC (SGC, n = 114) groups. Very young patients (≤ 30 years, n = 38) showed lower Helicobacter pylori (Hp) infection and significantly higher perineural invasion rates, compared to older (31-40 years) patients. Hp infection was more commonly seen in the Lauren's intestinal type and early pT stages (T1+T2). Independent prognostic factors for worse outcomes included higher serum CA 72-4, CA 125 levels, positive resection margin, and stage pIII-pIV tumors. The 5-year survival rate was significantly higher in patients with radical resection than those without. GCs in young Chinese patients were prevalent in women with advanced stages but showed no significant differences in clinicopathology between FGC and SGC groups. High serum

  6. Gene cataloging and expression profiling in human gastric cancer cells by expressed sequence tags.

    PubMed

    Kim, Nam-Soon; Hahn, Yoonsoo; Oh, Jung-Hwa; Lee, Ju-Yeon; Oh, Kyung-Jin; Kim, Jeong-Min; Park, Hong-Seog; Kim, Sangsoo; Song, Kyu-Sang; Rho, Seung-Moo; Yoo, Hyang-Sook; Kim, Yong Sung

    2004-06-01

    To understand the molecular mechanism associated with gastric carcinogenesis, we identified genes expressed in gastric cancer cell lines and tissues. Of 97,609 high-quality ESTs sequenced from 36 cDNA libraries, 92,545 were coalesced into 10,418 human Unigene clusters (Build 151). The gene expression profile was produced by counting the cluster frequencies in each library. Although the profiles of highly expressed genes varied greatly from library to library, those genes related to cell structure formation, heat shock proteins, the glycolysis pathway, and the signaling pathway were highly represented in human gastric cancer cell lines and in primary tumors. Conversely, the genes encoding immunoglobulins, ribosomal proteins, and digestive proteins were down-regulated in gastric cancer cell lines and tissues compared to normal tissues. The transcription levels of some of these genes were confirmed by RT-PCR. We found that genes related to cell adhesion, apoptosis, and cytoskeleton formation were particularly up-regulated in the gastric cancer cell lines established from malignant ascites compared to those from primary tumors. This comprehensive molecular profiling of human gastric cancer should be useful for elucidating the genetic events associated with human gastric cancer. PMID:15177556

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

    NASA Astrophysics Data System (ADS)

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

    2006-09-01

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

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

    PubMed

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

    2016-09-01

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

  9. An antiproliferative gene FLNA regulates migration and invasion of gastric carcinoma cell in vitro and its clinical significance.

    PubMed

    Sun, G G; Sheng, S H; Jing, S W; Hu, W N

    2014-03-01

    This study aimed to analyze the expression and clinical significance of filamin A (FLNA) in gastric carcinoma and the biological effect in its cell line by FLNA overexpression. Immunohistochemistry and western blot were used to analyze FLNA protein expression in 47 cases of gastric cancer and 47 cases of normal tissues to study the relationship between FLNA expression and clinical factors. FLNA lentiviral vector and empty vector were respectively transfected into gastric cancer SGC-7901 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to detect the mRNA level and protein of FLNA. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and migration and invasion assays were also conducted to determine the influence of the upregulated expression of FLNA that might be found on SGC-7901 cell biological effect. Immunohistochemistry: The level of FLNA protein expression was found to be significantly lower in gastric cancer tissue than normal tissues (P < 0.05). Western blot: The relative amount of FLNA protein in gastric cancer tissue was found to be significantly lower than in normal tissues (P < 0.05). The level of FLNA protein expression was not correlated with gender, age, and tumor invasion (P > 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P < 0.05). Loss of FLNA expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function showed that SGC-7901 cell transfected FLNA had a lower survival fraction, significant decrease in migration and invasion, and lower matrix metallopeptidase 9 (MMP-9) protein expression compared with SGC-7901 cell untransfected FLNA (P < 0.05). FLNA expression decreased in gastric cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that FLNA may play

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

    PubMed Central

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

    2014-01-01

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

  11. 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).

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

    PubMed Central

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

    2015-01-01

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

  13. Potential prognostic, diagnostic and therapeutic markers for human gastric cancer

    PubMed Central

    Tsai, Ming-Ming; Wang, Chia-Siu; Tsai, Chung-Ying; Chi, Hsiang-Cheng; Tseng, Yi-Hsin; Lin, Kwang-Huei

    2014-01-01

    The high incidence of gastric cancer (GC) and its consequent mortality rate severely threaten human health. GC is frequently not diagnosed until a relatively advanced stage. Surgery is the only potentially curative treatment. Thus, early screening and diagnosis are critical for improving prognoses in patients with GC. Gastroscopy with biopsy is an appropriate method capable of aiding the diagnosis of specific early GC tumor types; however, the stress caused by this method together with it being excessively expensive makes it difficult to use it as a routine method for screening for GC on a population basis. The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of GC. Here, we review the serum-based tumor markers for GC and their clinical significance, focusing on discoveries from microarray/proteomics research. We also review tissue-based GC tumor markers and their clinical application, focusing on discoveries from immunohistochemical research. This review provides a brief description of various tumor markers for the purposes of diagnosis, prognosis and therapeutics, and we include markers already in clinical practice and various forthcoming biomarkers. PMID:25320517

  14. 18F-FDG PET/CT Role in Staging of Gastric Carcinomas: Comparison with Conventional Contrast Enhancement Computed Tomography

    PubMed Central

    Altini, Corinna; Niccoli Asabella, Artor; Di Palo, Alessandra; Fanelli, Margherita; Ferrari, Cristina; Moschetta, Marco; Rubini, Giuseppe

    2015-01-01

    Abstract The purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT). This retrospective study included 45 patients who underwent performed whole body CECT and 18F-FDG PET/CT before any treatment. We calculated CECT and 18F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of 18F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test. Sensitivity, specificity, accuracy, PPV and NPV of CECT, and 18F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and 18F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and 18F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. 18FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases. The 18F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with 18F-FDG PET/CT permits a more valid staging in these patients. PMID:25997066

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

    PubMed Central

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

    2013-01-01

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

  16. Roles of ZIC family genes in human gastric cancer.

    PubMed

    Ma, Gang; Dai, Weijie; Sang, Aiyu; Yang, Xiaozhong; Li, Qianjun

    2016-07-01

    The human zinc finger of the cerebellum (ZIC)family genes, comprised of 5 members, which are vertebrate homologues of the Drosophila odd-paired gene and encode zinc-finger transcription factors, have been shown to be involved in various diseases, including cancer. However, the roles of ZICs in human gastric cancer (GC) have not yet been fully elucidated. This study aimed to investigate the expression patterns of ZICs and determine their clinical significance in GC. The mRNA and protein expression levels of ZIC1-5 were detected by RT-qPCR and western blot analysis, respectively using 60 pairs of human GC and matched normal mucosa tissues. The expression pattern and subcellular localization of ZIC1 in 160 pairs of human GC and matched normal mucosa tissues were verified by immunohistochemistry. Moreover, the associations of ZIC1 expression with various clinicopathological characteristics and patient prognosis were evaluated. The mRNA and protein expression levels of ZIC1 were both found to be significantly decreased in the GC tissues compared to matched normal mucosa tissues (GC vs. normal, 2.15±0.69 vs. 4.28±0.95; P<0.001); however, ZIC2-5 expression exhibited no significant difference between the cancer and normal tissue samples. In addition, the downregulation of ZIC1 (ZIC1-low) was more frequently observed in the GC tissues with positive lymph node metastasis (P=0.006), an advanced TNM stage (P<0.001) and a great depth of invasion (P=0.01). Notably, a low ZIC1 expression was significantly associated with a poor disease-free and overall survival. Furthermore, multivariate analysis revealed that ZIC1 expression was an independent prognostic marker for patients with GC. In conclusion, among the human ZIC family genes, the dysregulation of ZIC1, but not of ZIC2, ZIC3, ZIC4 and ZIC5, may play a crucial role in the progression of GC. ZIC1 may thus serve as a novel molecular marker to predict the progression, survival and relapse of patients with GC. PMID

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients.

    PubMed

    Xu, Guifang; Zhang, Weijie; Lv, Ying; Zhang, Bin; Sun, Qi; Ling, Tingsheng; Zhang, Xiaoqi; Zhou, Zhihua; Wang, Lei; Huang, Qin; Zou, Xiaoping

    2016-07-01

    Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC. PMID:26423416

  2. Enhancement Patterns of Gastric Carcinoma on Contrast-Enhanced Ultrasonography: Relationship with Clinicopathological Features

    PubMed Central

    Wei, Fang; Huang, Pintong; Li, Shiyan; Chen, Jian; Zhang, Ying; Hong, Yurong; Wei, Shumei; Cosgrove, David

    2013-01-01

    The aim of this study was to assess the relationship between the enhancement patterns and clinicopathological features of gastric cancer using intravenous contrast-enhanced ultrasonography (CEUS). In this Ethics Committee-approved prospective study, five hundred fifty two patients with gastric cancer who gave informed consent were examined preoperatively with CEUS. The enhancement pattern of each tumor was analyzed visually. Gross and histopathological findings on the postoperative specimens were compared with the preoperative CEUS findings. The most common CEUS pattern in differentiated gastric cancer was homogeneous enhancement, whereas heterogeneous enhancement was the most common pattern in undifferentiated gastric cancer. The proportion of heterogeneous enhancement was significantly different between the two histological subtypes (Chi- square = 146.735, P<0.001). The sensitivity and specificity of early heterogeneous enhancement on CEUS in diagnosing undifferentiated gastric cancer were 78.84% and 72.59% respectively. Gastric cancers with heterogeneous enhancement were more often Borrmann III and IV macroscopic types than those with homogeneous enhancement (66.56% vs. 30.80%, P<0.001), more commonly T3 and T4 depth of invasion than those with homogeneous enhancement (71.52% vs. 59.60%, P<0.05), more often showed lymphatic invasion than those with homogeneous enhancement (84.44% vs. 76.40%, P<0.05), and were less likely to receive curative gastrectomy than those with homogeneous enhancement (74.83% vs. 86.40%, P<0.005). The intra- and inter-observer reproducibility were both almost perfect for assessing enhancement patterns, with Kappa values of 0.916 (P<0.001) for intra-observer and 0.842 (P<0.001) for inter-observer reproducibility. CEUS provided detailed information about tumor vascularity and contrast enhancement patterns in gastric cancer. CEUS is promising as a new and useful method to predict the histological type of gastric cancer. PMID:24039857

  3. 18F-FDG PET/CT of advanced gastric carcinoma and association of HER2 expression with standardized uptake value

    PubMed Central

    Kim, Jin Suk; Young Park, Shin

    2014-01-01

    Objective(s): Expression of HER2 in gastric carcinoma has direct prognostic and therapeutic implications in patient management. The aim of this study is to determine whether a relationship exists between standardized uptake value (SUV) and expression of HER2 in advanced gastric carcinoma. Methods: We analyzed the 18F-FDG PET/CT results of 109 patients that underwent gastrectomy for advanced gastric carcinoma. The 18F-FDG PET/CT imaging was requested at the initial staging before surgery. The examinations were evaluated semi-quantitatively, with calculation of maximum standardized uptake values (SUVmax). The clinicopathologic factors, including HER2 overexpression, were determined from tissue obtained from the primary tumor. Metabolic and clincopathologic parameters were correlated using a t-test, one way ANOVA and chi-square test. Results: Immunohistochemically, 26 patients (23.8%) showed HER2 overexpression. This overexpression was significantly associated with high SUV level (P=0.02). The SUV level was significantly correlated with tumor size (P=0.02) and differentiation (P<0.001), and Lauren histologic type (P=0.04). Multivariate analysis showed HER2 overexpression, large tumor size, and differentiation (P=0.022, P=0.002, P<0.001) were significantly correlated with the high level of SUV in advanced gastric carcinoma. No association was found between SUV and T stage and lymph node metastasis. A receiver-operating characteristic curve demonstrated a SUVmax of 3.5 to be the optimal cutoff for predicting HER2 overexpression (sensitivity; 76.9%, specificity; 60.2%). Conclusion: An association exists between high SUV and HER2 overexpression and 18F-FDG PET/CT could be a useful tool to predict the biological characteristics of gastric carcinoma.

  4. Inhibitory effects of dobutamine on human gastric adenocarcinoma

    PubMed Central

    Zheng, Hui-Xia; Wu, Li-Na; Xiao, Hong; Du, Qian; Liang, Jian-Fang

    2014-01-01

    AIM: To explore the inhibitory effects of dobutamine on gastric adenocarcinoma cells. METHODS: Dobutamine was used to treat gastric adenocarcinoma cells (SGC-7901) and cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of dobutamine combined with cisplatin on cell viability were also analyzed. Cell migration was studied using the wound healing assay, and cell proliferation was analyzed using the colony formation assay. A cell invasion assay was carried out using Transwell cell culture chambers. The cell cycle and cell apoptosis were analyzed by flow cytometry. Western blot and immunocytochemistry were performed to determine the expression of Yes-associated protein (YAP) in treated cells. RESULTS: Dobutamine significantly inhibited cell growth, migration, cell colony formation, and cell invasion into Matrigel. Dobutamine also arrested the cell cycle at G1/S phase, and increased the rate of apoptosis of gastric adenocarcinoma cells. The expression of YAP was detected mainly in the nucleus in the absence of dobutamine. However, reduced expression of phosphorylated YAP was mainly found in the cytosol following treatment with dobutamine. CONCLUSION: Dobutamine has significant inhibitory effects on gastric adenocarcinoma cells and may be used in neoadjuvant therapy not only for gastric cancer, but also for other tumors. PMID:25493021

  5. Living cells of probiotic Bifidobacterium bifidum YIT 10347 detected on gastric mucosa in humans.

    PubMed

    Shibahara-Sone, H; Gomi, A; Iino, T; Kano, M; Nonaka, C; Watanabe, O; Miyazaki, K; Ohkusa, T

    2016-06-01

    The probiotic strain Bifidobacterium bifidum YIT 10347 has been demonstrated to inhibit Helicobacter pylori activity, prevent injury to the gastric mucosa, and improve general gastric malaise symptoms in H. pylori positive patients. This study aimed to investigate the adhering activity and localisation of B. bifidum YIT 10347 to gastric cells and tissue in vitro, and in human in vivo to clarify the mechanism of its beneficial effects on the stomach. The in vitro study found the adhesion rate of B. bifidum YIT 10347 to human gastric epithelial cells was about 10 times higher than that of lactic acid bacteria and other bifidobacteria. In the human study, 5 H. pylori negative and 12 H. pylori positive subjects ingested milk fermented with B. bifidum YIT 10347. B. bifidum YIT 10347 cells were measured by RT-qPCR for in gastric biopsy samples. Living B. bifidum YIT 10347 cells were detected in the biopsy samples in H. pylori negative subjects (105 cells/g and 104 cells/g at 1 h and 2 h after ingestion, respectively) and H. pylori positive subjects (104 cells/g at 1 h after the ingestion). Moreover, immunostaining analysis of tissue sections found that B. bifidum YIT 10347 cells were located at the interstitial mucin layer of the stomach. These results suggest that cells of probiotic B. bifidum YIT 10347 adhered to the human gastric mucosa in a live state, and that the higher adhering activity of B. bifidum YIT 10347 to the gastric mucosa may be involved in its beneficial effects on the human stomach. PMID:26925600

  6. miR-486-5p expression pattern in esophageal squamous cell carcinoma, gastric cancer and its prognostic value

    PubMed Central

    Han, Chongxu; Fu, Deyuan; Zhou, Lin; Jin, Guangfu; Wang, Fuan; Wang, Daxin; Chen, Yong; Ma, Li; Zheng, Xucai; Han, Dongsheng

    2016-01-01

    Micro RNA (miR)-486-5p is often aberrantly expressed in human cancers. The aim of this study was to identify the prognostic value of miR-486-5p expression in digestive system cancers. Tissue microarrays were constructed with 680 samples including 185 esophageal squamous cell carcinomas (ESCCs), 90 gastric adenocarcinomas (GCs), and 60 digestive system cancer tissues from 10 ESCC, 10 GC, 10 colon, 10 rectum, 10 liver, 10 pancreatic cancer, and corresponding normal tissues. Twenty normal digestive system mucosa tissues from healthy volunteers were included as normal controls. In GC, miR-486-5p expression was decreased in 62.8% of cases (59/94), increased in 33.0% (31/94), and unchanged in 4.2% (4/94); in ESCC its expression was decreased in 66.2% (129/195), increased in 32.3% (63/195), and unchanged in 1.5% (3/195). Expression of miR-486-5p was decreased in 12, and increased in 8, of 20 cases of colon or rectum cancer; decreased in 6, and increased in 4, of 10 cases of liver cancer; and decreased in 8, and increased in 2, of 10 cases of pancreatic cancer. Multivariate and univariate regression analysis demonstrated that low/unchanged miR-486-5p predicted poor prognosis in ESCC (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.62–7.14; P < 0.001; HR, 3.88; 95% CI, 2.43–6.22; P < 0.001, respectively) and GC (HR, 2.46; 95% CI, 1.35–4.50; P = 0.003; HR, 2.55; 95% CI, 1.39–4.69; P = 0.002, respectively). MiR-486-5p might therefore be an independent tumor marker for evaluating prognosis in patients with ESCC or GC. PMID:26895105

  7. Microvessel density is a prognostic marker of human gastric cancer

    PubMed Central

    Zhao, Hong-Chuan; Qin, Rong; Chen, Xiao-Xin; Sheng, Xia; Wu, Ji-Feng; Wang, Dao-Bin; Chen, Gui-Hua

    2006-01-01

    AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis. METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohistochemical staining. To assess tumor angiogenesis, MVD was determined by immunohistochemical staining of endothelial protein factor VIII-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer. PMID:17171787

  8. Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma.

    PubMed

    Zhang, J; Huang, J Y; Chen, Y N; Yuan, F; Zhang, H; Yan, F H; Wang, M J; Wang, G; Su, M; Lu, G; Huang, Y; Dai, H; Ji, J; Zhang, J; Zhang, J N; Jiang, Y N; Chen, S J; Zhu, Z G; Yu, Y Y

    2015-01-01

    Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis. PMID:26330360

  9. Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma

    PubMed Central

    Zhang, J.; Huang, J. Y.; Chen, Y. N.; Yuan, F.; Zhang, H.; Yan, F. H.; Wang, M. J.; Wang, G.; Su, M.; Lu, G; Huang, Y.; Dai, H.; Ji, J.; Zhang, J.; Zhang, J. N.; Jiang, Y. N.; Chen, S. J.; Zhu, Z. G.; Yu, Y. Y.

    2015-01-01

    Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis. PMID:26330360

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

    PubMed

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

    2016-01-01

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

  11. Epstein-Barr virus-associated lymphoepithelioma-like early gastric carcinomas and endoscopic submucosal dissection: case series.

    PubMed

    Lee, Ji Young; Kim, Kyoung-Mee; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Jae Jun

    2014-02-01

    Epstein-Barr virus (EBV)-associated lymphoepithelioma-like gastric carcinoma (LELC) is characterized by a lower lymph node (LN) metastasis rate and a higher survival rate than other forms of gastric cancer. Although current prognosis for LELC is favorable, the most common approach is radical gastrectomy involving an extensive D2 lymph node dissection. Here, we report four cases of EBV-associated early LELC that were treated by an alternative approach, endoscopic submucosal dissection (ESD). The long-term outcome of this procedure is discussed. All patients were treated by ESD en bloc, and all ESD specimens showed tumor-free lateral resection margins. None of the lesions showed lymphovascular invasion. A pathological examination of ESD specimens revealed submucosal invasion of more than 500 μm in all four cases. One patient underwent additional radical surgery post-ESD; no residual tumor or LN metastasis was noted in the surgical specimen. The other three patients did not undergo additional surgery, either because of severe comorbidity or their refusal to undergo operation, but were subjected to medical follow-up. None of the ESD-treated patients reported local recurrence or distant metastases during the 27-32 mo of follow-up after ESD. PMID:24574813

  12. In Silico analysis of Gastric carcinoma Serial Analysis of Gene Expression libraries reveals different profiles associated with ethnicity

    PubMed Central

    Ossandon, Francisco J; Villarroel, Cynthia; Aguayo, Francisco; Santibanez, Eudocia; Oue, Naohide; Yasui, Wataru; Corvalan, Alejandro H

    2008-01-01

    Worldwide gastric carcinoma has marked geographical variations and worse outcome in patients from the West compared to the East. Although these differences has been explained by better diagnostic criteria, improved staging methods and more radical surgery, emerging evidence supports the concept that gene expression differences associated to ethnicity might contribute to this disparate outcome. Here, we collected datasets from 4 normal and 11 gastric carcinoma Serial Gene Expression Analysis (SAGE) libraries from two different ethnicities. All normal SAGE libraries as well as 7 tumor libraries were from the West and 4 tumor libraries were from the East. These datasets we compare by Correspondence Analysis and Support Tree analysis and specific differences in tags expression were identified by Significance Analysis for Microarray. Tags to gene assignments were performed by CGAP-SAGE Genie or TAGmapper. The analysis of global transcriptome shows a clear separation between normal and tumor libraries with 90 tags differentially expressed. A clear separation was also found between the West and the East tumor libraries with 54 tags differentially expressed. Tags to gene assignments identified 15 genes, 5 of them with significant higher expression in the West libraries in comparison to the East libraries. qRT-PCR in cell lines from west and east origin confirmed these differences. Interestingly, two of these genes have been associated to aggressiveness (COL1A1 and KLK10). In conclusion we found that in silico analysis of SAGE libraries from two different ethnicities reveal differences in gene expression profile. These expression differences might contribute to explain the disparate outcome between the West and the East. PMID:18302799

  13. MicroRNA‑21 expression is associated with the clinical features of patients with gastric carcinoma and affects the proliferation, invasion and migration of gastric cancer cells by regulating Noxa.

    PubMed

    Sun, Haibin; Wang, Panzhi; Zhang, Qiangnu; He, Xiaoyan; Zai, Guozhen; Wang, Xudong; Ma, Mei; Sun, Xiaoli

    2016-03-01

    The expression levels of microRNA‑21 (miR‑21) are increased in a number of types of solid tumors. However, the association between miR‑21 expression and clinical features of patients with gastric carcinoma, and gastric cancer proliferation, invasion and migration remains to be elucidated. The present study investigated the effect of miR‑21 on the clinical features, proliferation, invasion and migration of gastric cancer and the underlying mechanisms associated with Noxa. Reverse transcription quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the expression levels of miR‑21 and Noxa in samples of gastric cancer tissue and matched, adjacent, non‑tumor tissue. The association between miR‑21 expression and the clinical features of patients with gastric carcinoma, as well as the correlation between the mRNA and protein expression levels of miR‑21 and Noxa were analyzed. SGC‑7901 gastric cancer cells were cultured in vitro and transfected with an miR‑21 mimic. The effect of miR‑21 upregulation on proliferation and the cell cycle was determined using the MTT assay and flow cytometry. In addition, migration and invasion of SGC‑7901 cells were observed using the Transwell assay. The target gene of miR‑21 was identified using bioinformatics software and a dual luciferase reporting system. The effect of miR‑21 upregulation on Noxa expression levels in SGC‑7901 cells was also analyzed by RT‑qPCR and western blotting. Increased levels of miR‑21 expression and decreased levels of Noxa expression were observed in gastric cancer tissue samples when compared with the adjacent non‑tumor tissue samples. An increased miR‑21 expression level was identified as a risk factor for advanced stage gastric cancer, lymph node metastasis and larger primary tumors. Furthermore, the overexpression of miR‑21 inhibited Noxa expression levels in SGC‑7901 cells. Therefore, high levels of miR‑21 expression may induce gastric cancer

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

    PubMed Central

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

    2012-01-01

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

  15. [Biologic and molecular genetic properties of a transplantable human primary gastric cancer in nude mice].

    PubMed

    Chen, S S

    1989-05-01

    A human primary gastric cancer tissue (adenocarcinoma II-III) was transplanted into nude mice (SWISS/DF. nu/nu). It has been transferred for 8 generations at 56 sites in 28 nude mice with transplantable rate of 100%. The transplanted tumor is designated as transplantable human primary gastric cancer-1 in nude mice (THPGC-1). The growth of THPGC-1 is rather rapid and the size of transplanted tumor reaches 1 cm2, 4-5 weeks after transfer. The morphology and histochemistry of the original tumor were retained well in the initial and serial transplanted tumors. THPGC-1 could secret carcinoembryonic antigen (CEA). After intravenous or intraperitoneal injection of 131I-antiCEA monoclonal antibody into the THPGC-1 bearing nude mice, the radiolabeled antibody was concentrated and localized in the tumor as shown by gamma-camera analysis. Similar pattern of lactate dehydrogenase isoenzyme was observed both in primary gastric cancer tissue and THPGC-1 tissue. Chromosomal examination revealed that THPGC-1 was human aneuploid ones. Southern blot analysis showed that the pattern of repetitive DNA bands and the structures of 28s, rDNA, c-H-ras and c-myc genes in THPGC-1 were identical to the original primary gastric cancer DNA. The results suggest that THPGC-1 be a reliable model for the research of the molecular biology of cancer cells and experimental gastric cancer diagnosis and treatment. PMID:2693024

  16. [Uterine cervical carcinoma and human papillomaviruses].

    PubMed

    Sugase, M

    1992-06-01

    For many years it has been thought that a significant proportion of cervical cancer could be attributed to sexually transmitted agents, such as sperm, smegma, Treponema pallidum, Gonococcus and herpes simplexvirus type 2. Recent advances of molecular biology, however, have revealed that human papillomavirus (HPV) might be the most causative virus of the disease. Since HPV type 16 DNA was found in a patient with cervical cancer in 1983, many HPV types have been cloned from cervical cancers, also from premalignant lesions (intraepithelial neoplasias). In Japan, we have found 6 new types of HPV (HPV 58, 59, 61, 62, 64, 67) in the female genital tract so far. Especially, HPV 58, which was cloned from a patient with cervical squamous cell carcinoma and was already fully sequenced, is thought to be an important agent for the development of cervical cancer as well as HPV 16. Now we are investigating extensively to clarify the real relationship between genital HPV infection and cervical cancer. PMID:1327090

  17. Gastrin promotes the metastasis of gastric carcinoma through the β-catenin/TCF-4 pathway.

    PubMed

    Zhuang, Kun; Yan, Yuan; Zhang, Xin; Zhang, Jun; Zhang, Lingxia; Han, Kun

    2016-09-01

    Gastric cancer is the most common epithelial malignancy and the second leading cause of cancer-related death worldwide; metastasis is a crucial factor in the progression of gastric cancer. The present study applied gastrin-17 amide (G-17) in SGC7901 cells. The results showed that G-17 promoted the cell cycle by accelerating the G0/G1 phase and by increasing the cell proliferation rate by binding to the gastrin receptor. The migratory and invasive abilities of the SGC7901 cells were increased by G-17. The expression levels of matrix metalloproteinase (MMP)-7, MMP-9 and vascular endothelial growth factor (VEGF) were enhanced by G-17 as well. Moreover, G-17 caused the overexpression of β-catenin and TCF-4. G-17 also caused a preferential cytoplasmic and nuclear localization of β-catenin with a high TOP-FLASH activity. Finally, axin reduced the migratory and invasive abilities of the SGC7901 cells, and inhibited the expression of β-catenin, TCF-4, MMP-7, MMP-9 and VEGF; these effects were counteracted by adding G-17. In summary, the present study confirmed the proliferation and metastasis-promoting role of G-17 via binding to the gastrin receptor, and the β-catenin/TCF-4 pathway was found to be essential for mediating G-17-induced metastasis in gastric cancer. These results may provide a novel gene target for the treatment of gastric cancer. PMID:27430592

  18. A retrospective study on intensity-modulated radiation therapy combined with chemotherapy after D2 radical surgery for gastric carcinoma

    PubMed Central

    LUO, WENGUANG; ZHANG, HONGYAN; ZHAO, YUFEI; WANG, LIN; QI, LIJUN; RAN, JINGJING; LIU, LEI; WU, AIDONG

    2016-01-01

    In order to investigate the clinical value of different chemotherapies, the efficacy of intensity-modulated radiation therapy with concurrent chemotherapy following D2 radical surgery for gastric carcinoma was evaluated in this study. A total of 102 patients who underwent D2 radical surgery for gastric carcinoma followed by concurrent chemoradiotherapy (CRT) between January, 2008 and March, 2012, were selected. The 5/7 field intensity-modulated radiation therapy was used, with a planning target volume dose of 45 Gy in 25 fractions over 5 weeks. Among these patients, 45 were administered 400 mg/m2/day fluorouracil and 20 mg/m2/day tetrahydrofurfuryl alcohol through intravenous infusion 4 days before and 3 days after the radiotherapy (F-CRT group), while 57 patients received 825 mg/m2 capecitabine orally twice a day (C-CRT group). The 3-year overall and the disease-free survival rates were 75.5 and 70.5%, respectively. The overall 3-year survival rates of the F-CRT and C-CRT groups were 72.2 and 78.5% (P>0.05), respectively, and the 3-year disease-free survival rates were 67.7 and 72.8% (P>0.05), respectively. No significant differences were observed between the two groups. However, during the concurrent CRT, significant differences were found in the incidence of grade 1–2 haematological toxicity between the F-CRT and C-CRT groups (73.3 vs. 50.9%, respectively; χ2 =5.320, P=0.021). Significant differences were also found in the incidence of grade 1–2 gastrointestinal reactions between the two groups (77.8 vs. 57.9%, respectively; χ2=4.474, P=0.034). Therefore, intensity-modulated radiation therapy combined with concurrent chemotherapy following D2 radical surgery for gastric cancer was found to be safe and effective. In addition, radiotherapy was better tolerated and more likely to be completed using C-CRT rather than F-CRT. PMID:27123273

  19. Human papillomavirus-related carcinomas of the sinonasal tract.

    PubMed

    Bishop, Justin A; Guo, Theresa W; Smith, David F; Wang, Hao; Ogawa, Takenori; Pai, Sara I; Westra, William H

    2013-02-01

    High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (P<0.0001). The HPV-related carcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles

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

    NASA Astrophysics Data System (ADS)

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

    2008-02-01

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

  1. PEITC reverse multi-drug resistance of human gastric cancer SGC7901/DDP cell line.

    PubMed

    Tang, Tao; Song, Xin; Liu, Yu-Fen; Wang, Wen-Yue

    2014-04-01

    Gastric cancer is one of the leading causes of cancer death in the world and nearly all patients who respond initially to cisplatin later develop drug resistance, indicating multi-drug resistance is an essential aspect of the failure of treatment. Phenethyl isothiocyanate (PEITC) has been implicated in inhibiting metastasis of several types of human cancer. However, the effect and potential mechanism of PEITC reversed multi-drug resistance of human gastric cancer is not fully clear. We have identified the role of PEITC in multi-drug resistance reversal of human gastric cancer SGC7901/DDP cell line. PEITC inhibited cisplatin-resistant human SGC7901/DDP cell growth in a dose-dependent manner, causing increased apoptosis, ROS generation, glutathione depletion, accumulation of Rhodamine-123, decreased expression of P-glycoprotein and cell cycle arrest. mRNA and protein expression of the multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), survivin, and Mad2 was decreased, and phosphorylation of Akt and transcriptional activation of NF-κB were suppressed. PEITC may be useful as the therapeutic strategy for overcoming multi-drug resistance through suppressing the PI3K-Akt pathway in human gastric cancer. PMID:23956061

  2. Expression of E-cadherin and β-catenin in gastric carcinoma and its correlation with the clinicopathological features and patient survival

    PubMed Central

    Zhou, Yong-Ning; Xu, Cai-Pu; Han, Biao; Li, Min; Qiao, Liang; Fang, Dian-Chun; Yang, Jian-Min

    2002-01-01

    AIM: The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. We evaluated the expression pattern of E-cadherin and β-catenin in gastric carcinoma and dysplasia and analyzed their relationship with tumor clinicopathological features and patient survival. METHODS: Immunohistochemical staining of E-cadherin and β-catenin was performed from paraffin specimens of 163 gastric carcinomas, 44 gastric mucosal dysplasia, and 25 intestinal metaplasia, 28 atrophic gastritis and 12 healthy controls. RESULTS: Normal membrane staining was observed in intestinal metaplasia, atrophic gastritis and control biopsy specimens for E-cadherin and β-catenin. 36% and 16% of gastric dysplasia were stained abnormally for E-cadherin and β-catenin respectively. Abnormal expression of E-cadherin and β-catenin was demonstrated in 46% and 44% of gastric carcinoma respectively. Abnormal expression of E-cadherin and β- catenin occurred more significantly in Borrmann III/IV than in Borrmann I/II type (P < 0.005, respectively). A significantly higher proportion of signet-ring, mucinous and tubular adenocarcinomas were abnormally expressed for E-cadherin and β-catenin as compared with papillary adenocarcinomas (χ2 = 8.47, P < 0.005, and χ2 = 7.05, P < 0.01, respectively). Morever, abnormal E-cadherin and β-catenin staining occurred more frequently in diffuse than in intestinal type of tumor (χ2 = 18.18 and 17.79, P < 0.005, respectively). There was a significant correlation between abnormal β-catenin expression and positive lymph node metastasis. A survival advantage was noted in tumors retaining normal membranous expression of β-catenin, independent of type, grade, or stage of the disease (P < 0.0005). CONCLUSION: Abnormal expression of the E-cadherin-catenin complex occurs frequently in gatric carcinoma, closely related to

  3. A transgenic mouse model of metastatic carcinoma involving transdifferentiation of a gastric epithelial lineage progenitor to a neuroendocrine phenotype.

    PubMed

    Syder, Andrew J; Karam, Sherif M; Mills, Jason C; Ippolito, Joseph E; Ansari, Habib R; Farook, Vidya; Gordon, Jeffrey I

    2004-03-30

    Human neuroendocrine cancers (NECs) arise in various endoderm-derived epithelia, have diverse morphologic features, exhibit a wide range of growth phenotypes, and generally have obscure cellular origins and ill-defined molecular mediators of initiation and progression. We describe a transgenic mouse model of metastatic gastric cancer initiated by expressing simian virus 40 large tumor antigen (SV40 TAg), under control of regulatory elements from the mouse Atp4b gene, in the progenitors of acid-producing parietal cells. Parietal cells normally do not express endocrine or neural features, and Atp4b-Cre bitransgenic mice with a Cre reporter confirmed that the Atp4b regulatory elements are not active in gastric enteroendocrine cells. GeneChip analyses were performed on laser capture microdissected SV40 TAg-expressing cells in preinvasive foci and invasive tumors. Genes that distinguish invasive from preinvasive cells were then hierarchically clustered with DNA microarray datasets obtained from human lung and gastric cancers. The results, combined with immunohistochemical and electron microscopy studies of Apt4b-SV40 TAg stomachs, revealed that progression to invasion was associated with transdifferentiation of parietal cell progenitors to a neuroendocrine phenotype, and that invasive cells shared molecular features with NECs arising in the human pulmonary epithelium, including transcription factors that normally regulate differentiation of various endocrine lineages and maintain neural progenitors in an undifferentiated state. The 399 mouse genes identified as regulated during acquisition of an invasive phenotype and concomitant neuroendocrine transdifferentiation, plus their human orthologs associated with lung NECs, provide a foundation for molecular classification of NECs arising in other tissues and for genetic tests of the molecular mechanisms underlying NEC pathogenesis. PMID:15070742

  4. [A case of gastric adenosquamous carcinoma with peritoneal dissemination in which treatment with S-1 plus paclitaxel therapy resulted in improved long-term survival].

    PubMed

    Hirano, Masamitsu; Ozamoto, Yuki; Ichinose, Masumi; Togawa, Takeshi; Takao, Nobuyuki; Mizumoto, Akiyoshi; Tatsuno, Manami; Yamamoto, Yoshihiro; Yonemura, Yutaka

    2014-07-01

    Gastric adenosquamous carcinoma is a rare malignancy with a poor prognosis. We recently performed palliative gastrectomy for a gastric adenosquamous carcinoma with peritoneal dissemination and provided a course of systemic chemotherapy with S-1 plus paclitaxel(PTX)after the surgery. No serious adverse events were observed, and treatment with S-1 plus PTX was continued for 1 year before being switched to adjuvant chemotherapy with S-1 alone for another year. The tumor maker levels normalized within 2 months of the initial treatment, and the peritoneal dissemination could no longer be detected by abdominal computed tomography(CT). The patient remained in clinical remission and maintained long-term survival of over 8 years. PMID:25131877

  5. [Comparative genomic classification of human hepatocellular carcinoma].

    PubMed

    Kaposi-Novák, Pál

    2009-03-01

    Global transcriptome analysis has been successfully applied to characterize various human tumors, including hepatocellular carcinomas. This novel technology can facilitate early diagnosis, as well as prognostic and therapeutic diversification of cancer patients. To enhance access to the genomic information buried in archived pathology samples, we assessed RT-PCR amplification rates in paraffin-embedded tissues preserved in three different fixatives. Reliable amplification could be achieved from all paraffin-embedded specimens, when the amplicon size did not exceed 225 bp. A longer amplicon size resulted in rapid decrease of yield and reproducibility. In addition, formalin provided superior morphology and better reactivity with claudin-4 and -7 immunohistochemistry. Amplification of the initial sample is often required before transcriptome analysis of clinical specimens could be performed. We introduced a random nonamer primed T3 polymerase reaction into the conventional linear RNA amplification protocol. The modified T3T7 method generated a sense strand product ideal for synthesizing indirectly labeled cDNA templates. Microarray analysis of amplified frozen and laser-microdissected Myc and Myc/TGFalpha mouse liver tumors confirmed good reproducibility (r=0.9) of the reaction and conservation of original transcriptional patterns (r=0.78). Finally, we tested the utility of expression profiling for the classification of human HCC samples. By comparing expression data from HGF-treated c-Met conditional knock-out and control primary mouse hepatocytes, we identified 690 HGF/c-Met target genes. Functional analysis of the significant gene set implicated c-Met as key regulator of hepatocyte motility and oxidative homeostasis. Cross comparison of the c-Met-induced transcription signature with human HCC expression profiles revealed a group of tumors (27%) with potentially activated c-Met signaling (MET+). These tumors were characterized by higher vascular invasion rate

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-26

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

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

    PubMed

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

    2004-02-01

    Nowadays, the human immunodeficiency virus infection (HIV) is a chronic disease. In the frequent clinical situations with fever, lymph nodes and loss weight it is necessary to determine their etiology, for establishing a specific treatment. Gastrointestinal opportunistic infections or gastric lymphomatous or sarcomatous process, which can accumulate Ga67, may be present in the patient with acquired immunodeficiency syndrome. We report 2 cases with gastric uptake in which endoscopy and biopsy was obtained. In the first one, with previous treatment with omeprazol and almalgate for gastroesophagic reflux, endoscopy and biopsy were normal and in the second patient an Helicobacter pylori infection was diagnosed. We think that gastric uptake of Ga67 in HIV patients, must indicate to the clinician to rule out associated pathologies. PMID:14974895

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

    SciTech Connect

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

    2005-05-15

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

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

    PubMed Central

    2016-01-01

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

  11. Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells

    PubMed Central

    Das, Soumita; Sarkar, Arup; Ryan, Kieran A.; Fox, Sarah; Berger, Alice H.; Juncadella, Ignacio J.; Bimczok, Diane; Smythies, Lesley E.; Harris, Paul R.; Ravichandran, Kodi S.; Crowe, Sheila E.; Smith, Phillip D.; Ernst, Peter B.

    2014-01-01

    After Helicobacter pylori infection in humans, gastric epithelial cells (GECs) undergo apoptosis due to stimulation by the bacteria or inflammatory cytokines. In this study, we assessed the expression and function of brain angiogenesis inhibitor 1 (BAI1) in the engulfment of apoptotic GECs using human tissue and cells. After induction of apoptosis by H. pylori or camptothecin, there was a 5-fold increase in the binding of apoptotic GECs to THP-1 cells or peripheral blood monocyte-derived macrophages as assayed by confocal microscopy or conventional and imaging flow cytometry. Binding was impaired 95% by pretreating apoptotic cells with annexin V, underscoring the requirement for phosphatidylserine recognition. The phosphatidylserine receptor BAI1 was expressed in human gastric biopsy specimens and gastric phagocytes. To confirm the role of BAI1 in apoptotic cell clearance, the functional domain of BAI1 was used as a competitive inhibitor or BAI1 expression was inhibited by small interfering RNA. Both approaches decreased binding and engulfment >40%. Exposing THP-1 cells to apoptotic cells inhibited IL-6 production from 1340 to <364 pg/ml; however, this decrease was independent of phagocytosis. We conclude that recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti-inflammatory effects.—Das, S., Sarkar, A., Ryan, K. A., Fox, S., Berger, A. H., Juncadella, I. J., Bimczok, D., Smythies, L. E., Harris, P. R., Ravichandran, K. S., Crowe, S. E., Smith, P. D., Ernst, P. B. Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells. PMID:24509909

  12. 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

  13. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer.

    PubMed

    Kolin, David L; Sy, Keiyan; Rotondo, Fabio; Bassily, Mena N; Kovacs, Kalman; Brezden-Masley, Christine; Streutker, Catherine J; Yousef, George M

    2014-09-01

    The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer. PMID:25153389

  17. Reactivity to human papillomavirus type 16 L1 virus-like particles in sera from patients with genital cancer and patients with carcinomas at five different extragenital sites.

    PubMed

    Van Doornum, G J J; Korse, C M; Buning-Kager, J C G M; Bonfrer, J M G; Horenblas, S; Taal, B G; Dillner, J

    2003-04-01

    A retrospective seroepidemiologic study was performed to examine the association between human papillomaviruses (HPV) 16 infection and carcinomas of the oropharynx, the oesophagus, penis and vagina. Sera were selected from the serum bank from the Antoni van Leeuwenhoek Hospital (Netherlands Cancer Institute) and the Slotervaart Hospital in Amsterdam, the Netherlands. Presence of HPV 16 specific antibody was assessed using HPV 16 L1 capsids. Sera positive for HPV 16 capsid antibody were further tested for antibody against HPV 16 E7 peptides. Prevalence of antibody against HPV 16 L1 capsids among both the negative control group without cancer and the negative control group with gastric cancer was 18%, while seroprevalence among the control group of patients with HPV-associated cervical squamous cell carcinoma was 47% (P<0.001). Among the patients with penile squamous cell carcinoma seroprevalence was 38% (P<0.001), among patients with oropharyngeal carcinoma 33% (P=0.04) and among patients with oesophageal squamous cell carcinoma 14% (P=0.7). The serological evidence for association between HPV 16 infection and both oropharyngeal carcinoma and penile carcinoma was established. The conclusion that no association was found between the presence of antibody against HPV 16 L1 capsids and oesophageal squamous cell carcinoma was in accordance with results of other studies carried out in the Netherlands using HPV DNA technology. In the subjects with HPV 16 L1 capsid antibody, no association was found between the antibody against HPV 16 E7 and clinical outcome. PMID:12671710

  18. Expression of vascular endothelial growth factor C and chemokine receptor CCR7 in gastric carcinoma and their values in predicting lymph node metastasis

    PubMed Central

    Yan, Chao; Zhu, Zheng-Gang; Yu, Ying-Yan; Ji, Jun; Zhang, Yi; Ji, Yu-Bao; Yan, Min; Chen, Jun; Liu, Bing-Ya; Yin, Hao-Ran; Lin, Yan-Zhen

    2004-01-01

    AIM: To study the expression of vascular endothelial growth factor C (VEGF-C) and chemokine receptor CCR7 in gastric carcinoma and to investigate their associations with lymph node metastasis of gastric carcinoma and their values in predicting lymph node metastasis. METHODS: The expression of VEGF-C and CCR7 in gastric carcinoma tissues obtained from 118 patients who underwent curative gastrectomy was examined by immunohistochemistry. Among these patients, 39 patients underwent multi-slice spiral CT (MSCT) examination. RESULTS: VEGF-C and CCR7 were positively expressed in 52.5 and 53.4% of patients. VEGF-C expression was more frequently found in tumors with lymph node metastasis than those without it (P < 0.001). VEGF-C expression was also closely related to lymphatic invasion (P < 0.001), vascular invasion (P < 0.01), and TNM stage (P < 0.001). However, there was no significant correlation between VEGF-C expression and age at surgery, gender, tumor size, tumor location, Lauren classification, and depth of invasion. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P < 0.001) and was also associated with tumor size (P < 0.01), depth of invasion (P < 0.001), lymphatic invasion (P < 0.001), and TNM stage (P < 0.001). However, the presence of CCR7 had no correlation to age at surgery, gender, tumor location, Lauren classification, and vascular invasion. Among the 39 patients who underwent MSCT examination, only CCR7 expression was related to lymph node metastasis determined by MSCT (P < 0.05). In the current retrospective study, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of VEGF-C and CCR7 expression in the diagnosis of lymph node metastasis for patients with gastric carcinoma were 73.8%, 70.2%, 72.6%, 71.4% and 72.0%, and 82.0%, 77.2%, 79.4%, 80.0% and 79.7%, respectively. After subdivision according to the combination of

  19. Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib

    PubMed Central

    Hui, Kwai Fung; Yeung, Po Ling; Chiang, Alan K.S.

    2016-01-01

    Proteasome inhibitors and histone deacetylase (HDAC) inhibitors can synergistically induce apoptotic cell death in certain cancer cell types but their combinatorial effect on the induction of autophagy remains unknown. Here, we investigated the combinatorial effects of a proteasome inhibitor, bortezomib, and an HDAC inhibitor, romidepsin, on the induction of apoptotic and autophagic cell death in gastric carcinoma (GC) cells. Isobologram analysis showed that low nanomolar concentrations of bortezomib/romidepsin could synergistically induce killing of GC cells. The synergistic killing was due to the summative effect of caspase-dependent intrinsic apoptosis and caspase-independent autophagy. The autophagic cell death was dependent on the activation of MAPK family members (ERK1/2 and JNK), and generation of reactive oxygen species (ROS), but was independent of Epstein-Barr virus infection. In vivo, bortezomib/romidepsin also significantly induced apoptosis and autophagy in GC xenografts in nude mice. This is the first report demonstrating the potent effect of combination of HDAC and proteasome inhibitors on the induction of MAPK- and ROS-dependent autophagy in addition to caspase-dependent apoptosis in a cancer type. PMID:26683357

  20. Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib.

    PubMed

    Hui, Kwai Fung; Yeung, Po Ling; Chiang, Alan K S

    2016-01-26

    Proteasome inhibitors and histone deacetylase (HDAC) inhibitors can synergistically induce apoptotic cell death in certain cancer cell types but their combinatorial effect on the induction of autophagy remains unknown. Here, we investigated the combinatorial effects of a proteasome inhibitor, bortezomib, and an HDAC inhibitor, romidepsin, on the induction of apoptotic and autophagic cell death in gastric carcinoma (GC) cells. Isobologram analysis showed that low nanomolar concentrations of bortezomib/romidepsin could synergistically induce killing of GC cells. The synergistic killing was due to the summative effect of caspase-dependent intrinsic apoptosis and caspase-independent autophagy. The autophagic cell death was dependent on the activation of MAPK family members (ERK1/2 and JNK), and generation of reactive oxygen species (ROS), but was independent of Epstein-Barr virus infection. In vivo, bortezomib/romidepsin also significantly induced apoptosis and autophagy in GC xenografts in nude mice. This is the first report demonstrating the potent effect of combination of HDAC and proteasome inhibitors on the induction of MAPK- and ROS-dependent autophagy in addition to caspase-dependent apoptosis in a cancer type. PMID:26683357

  1. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids

    PubMed Central

    Batchelder, Cynthia A.; Martinez, Michele L.; Duru, Nadire; Meyers, Frederick J.; Tarantal, Alice F.

    2015-01-01

    Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease. PMID:26317980

  2. [A case of locoregional recurrence of gastric carcinoma that was treated using pancreaticoduodenectomy].

    PubMed

    Tokoro, Yukinari; Kametaka, Hisashi; Seike, Kazuhiro; Kamiya, Junichirou; Fukada, Takaomi; Makino, Hironobu; Koyama, Takashi

    2014-11-01

    A 71-year-old man underwent distal gastrectomy for gastric cancer in November 2011. The corresponding pathological diagnosis was of well differentiated adenocarcinoma, pT4a(SE), N1(2/15), H0, P0,M0, pStage IIIA. TS-1 was administered as an adjuvant therapy for one year from the second month after the operation. During the 16th month after the operation, we found an elevated tumor marker level and locoregional recurrence near the pancreas head and the abdominal wall upon computed tomography. We could not find any other suspected tumor recurrence using positron-emission tomography and computed tomography. We performed a pancreaticoduodenectomy and transverse colon merger resection in June 2013. Although the tumor marker was again found to be elevated during the second month after the metastasectomy, chemotherapy was continued because obstructive jaundice and gastrointestinal obstruction were prevented by the operation. PMID:25731508

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

    PubMed Central

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

    2016-01-01

    MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts as an indirect inhibitor of CRL by blocking cullin neddylation. Given that CRLs components are up-regulated, whereas neddylation modification is over-activated in a number of human cancers, MLN4924 was found to be effective in growth suppression of cancer cells. Whether MLN4924 is effective against gastric cancer cells, however, remains elusive. Here we showed that in gastric cancer cells, MLN4924 rapidly inhibited cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies in combination with siRNA knockdown-based rescue experiments revealed that MLN4924 induced the accumulation of a number of CRL substrates, including CDT1/ORC1, p21/p27, and PHLPP1 to trigger DNA damage response and induce growth arrest at the G2/M phase, to induce senescence, as well as autophagy, respectively. MLN4924 also significantly suppressed migration by transcriptionally activating E-cadherin and repressing MMP-9. Taken together, our study suggest that neddylation modification and CRL E3 ligase are attractive gastric cancer targets, and MLN4924 might be further developed as a potent therapeutic agent for the treatment of gastric cancer. PMID:27063292

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2016-01-01

    MLN4924 is a recently discovered small molecule inhibitor of NEDD8-Activating Enzyme (NAE). Because cullin RING ligase (CRL), the largest family of E3 ubiquitin ligase, requires cullin neddylation for its activity, MLN4924, therefore, acts as an indirect inhibitor of CRL by blocking cullin neddylation. Given that CRLs components are up-regulated, whereas neddylation modification is over-activated in a number of human cancers, MLN4924 was found to be effective in growth suppression of cancer cells. Whether MLN4924 is effective against gastric cancer cells, however, remains elusive. Here we showed that in gastric cancer cells, MLN4924 rapidly inhibited cullin 1 neddylation and remarkably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies in combination with siRNA knockdown-based rescue experiments revealed that MLN4924 induced the accumulation of a number of CRL substrates, including CDT1/ORC1, p21/p27, and PHLPP1 to trigger DNA damage response and induce growth arrest at the G2/M phase, to induce senescence, as well as autophagy, respectively. MLN4924 also significantly suppressed migration by transcriptionally activating E-cadherin and repressing MMP-9. Taken together, our study suggest that neddylation modification and CRL E3 ligase are attractive gastric cancer targets, and MLN4924 might be further developed as a potent therapeutic agent for the treatment of gastric cancer. PMID:27063292

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

    PubMed

    Meyer, J H; Elashoff, J; Porter-Fink, V; Dressman, J; Amidon, G L

    1988-06-01

    Microspheres of pancreatin should empty from the stomachs of patients with pancreatic insufficiency as fast as food. The present study was undertaken in 26 healthy subjects to identify the size of spheres that would empty from the stomach with food and to determine whether different meals alter this size. Spheres of predefined sizes were labeled with 113mIn or 99mTc. Using a gamma-camera, we studied the concurrent gastric emptying of spheres labeled with 113mIn and of chicken liver labeled with 99mTc in 100-g, 154-kcal or 420-g, 919-kcal meals, or the concurrent emptying of 1-mm vs. larger spheres. One-millimeter spheres emptied consistently (p less than 0.01, paired t-test) faster than 2.4- or 3.2-mm spheres when ingested together with either the 420- or 100-g meals. Thus, in the 1-3-mm range of diameters, sphere size was a more important determinant of sphere emptying than meal size. Statistical analyses indicated that spheres 1.4 +/- 0.3 mm in diameter with a density of 1 empty at the same rate as 99mTc-liver. Our data indicate some commercially marketed microspheres of pancreatin will empty too slowly to be effective in digestion of food. PMID:3360258

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

    SciTech Connect

    Meyer, J.H.; Elashoff, J.; Porter-Fink, V.; Dressman, J.; Amidon, G.L.

    1988-06-01

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

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

    PubMed

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

    2013-09-01

    The stomach is a target organ of the incretin hormone glucagon-like peptide-1 (GLP-1). However, the cellular expression and glandular distribution of its receptor (GLP-1R) in human gastric mucosa are not known. We determined the expression of GLP-1R in different regions of human stomach mucosa and its specific cellular association and distribution within gastric glands. Tissue samples from stomach body and antrum were obtained from 20 patients during routine esophagogastroduodenoscopy. mRNA encoding GLP-1R protein expression was evaluated by RT-PCR. Determination of cell types bearing GLP-1R, their localization, and their frequency in gastric glands in different gastric regions were estimated by immunohistochemical morphological analysis. Levels of GLP-1R mRNA were similar in body and antrum. GLP-1R immunoreactivity was found throughout the gastric mucosa in various types of glandular cells. The highest frequency of GLP-1R immunoreactive cells was found in the neck area of the principal glands in cells morphologically identified as parietal cells. GLP-1R immunostaining was also found on enteroendocrine-like cells in the pyloric glands. This study provides the first description of GLP-1R expression in human gastric glands and its specific cellular association. Our data suggest that GLP-1 may act directly on the gastric mucosa to modulate its complex functions. PMID:23803499

  9. The roles of tumor- and metastasis-promoting carcinoma-associated fibroblasts in human carcinomas.

    PubMed

    Mezawa, Yoshihiro; Orimo, Akira

    2016-09-01

    Carcinoma-associated fibroblasts (CAFs) constitute a substantial proportion of the non-neoplastic mesenchymal cell compartment in various human tumors. These fibroblasts are phenotypically converted from their progenitors via interactions with nearby cancer cells during the course of tumor progression. The resulting CAFs, in turn, support the growth and progression of carcinoma cells. These fibroblasts have a major influence on the hallmarks of carcinoma and promote tumor malignancy through the secretion of tumor-promoting growth factors, cytokines and exosomes, as well as through the remodeling of the extracellular matrix. Coevolution of CAFs and carcinoma cells during tumorigenesis is therefore essential for progression into fully malignant tumors. Recent studies have revealed the molecular mechanisms underlying CAF functions, especially in tumor invasion, metastasis and drug resistance and have highlighted the significant heterogeneity among these cells. In this review, we summarize the impacts of recently identified roles of tumor-promoting CAFs and discuss the therapeutic implications of targeting the heterotypic interactions of these fibroblasts with carcinoma cells. Graphical Abstract ᅟ. PMID:27506216

  10. The newly synthesized anticancer drug HUHS1015 is useful for treatment of human gastric cancer.

    PubMed

    Kaku, Yoshiko; Tsuchiya, Ayako; Kanno, Takeshi; Nakao, Shuhei; Shimizu, Tadashi; Tanaka, Akito; Nishizaki, Tomoyuki

    2015-03-01

    Naftopidil is clinically for treatment of benign prostate hyperplasia, and emerging evidence has pointed to its anticancer effect. To obtain the anticancer drug with the potential greater than that of naftopidil, we have newly synthesized the naftopidil analogue HUHS1015. The present study investigated the mechanism underlying HUHS1015-induced apoptosis of human gastric cancer cells and assessed the possibility for clinical use as an innovative anticancer drug. HUHS1015 reduced cell viability for MKN28 human well-differentiated gastric adenocarcinoma cell line and MKN45 human poorly differentiated gastric adenocarcinoma cell line in a concentration (0.3-100 μM)-dependent manner more effectively than cisplatin, a chemo-drug widely used. In the flow cytometry using propidium iodide (PI) and annexin V, HUHS1015 significantly increased the population of PI-positive and annexin V-negative cells, corresponding to primary necrosis and that of PI-positive and annexin V-positive cells, corresponding to late apoptosis/secondary necrosis, both in the two cell types. HUHS1015 significantly activated caspase-3, caspase-4, and caspase-8 in MKN45 cells, while no obvious caspase activation was found in MKN28 cells. HUHS1015 upregulated expression of the tumor necrosis factor α (TNFα) mRNA and protein in MKN45 cells, allowing activation of caspase-8 through TNF receptor and the effector caspase-3. HUHS1015 clearly inhibited tumor growth in mice inoculated with MKN45 cells, with the survival rate higher than that for the anticancer drugs cisplatin, paclitaxel, and irinotecan. The results of the present study show that HUHS1015 induces caspase-independent and caspase-dependent apoptosis of MKN28 and MKN45 human gastric cancer cells, respectively, and effectively suppresses MKN45 cell proliferation. PMID:25567349

  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. Rapid induction of senescence in human cervical carcinoma cells

    NASA Astrophysics Data System (ADS)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

    2000-09-01

    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

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

    PubMed Central

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

    2016-01-01

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

  14. A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma

    PubMed Central

    Nucera, Carmelo; Nehs, Matthew A.; Mekel, Michal; Zhang, Xuefeng; Hodin, Richard; Lawler, Jack; Nose, Vânia

    2009-01-01

    Background Orthotopic mouse models of human cancer represent an important in vivo tool for drug testing and validation. Most of the human thyroid carcinoma cell lines used in orthotopic or subcutaneous models are likely of melanoma and colon cancer. Here, we report and characterize a novel orthotopic model of human thyroid carcinoma using a unique thyroid cancer cell line. Methods We used the cell line 8505c, originated from a thyroid tumor histologically characterized by anaplastic carcinoma cell features. We injected 8505c cells engineered using a green fluorescent protein–positive lentiviral vector orthotopically into the thyroid of severe combined immunodeficient mice. Results Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins. Conclusions Here we describe a novel orthotopic thyroid carcinoma model using 8505c cells. This model can prove to be a reliable and useful tool to investigate in vivo biological mechanisms determining thyroid cancer aggressiveness, and to test novel therapeutics for the treatment of refractory or advanced thyroid cancers. PMID:19772429

  15. Human papillomavirus in vulvar and vaginal carcinoma cell lines.

    PubMed Central

    Hietanen, S.; Grénman, S.; Syrjänen, K.; Lappalainen, K.; Kauppinen, J.; Carey, T.; Syrjänen, S.

    1995-01-01

    A number of reports associate human papillomavirus (HPV) with cervical cancer and cancer cell lines derived from this tumour type. Considerably fewer reports have focused on the role of HPV in carcinomas from other sites of female anogenital squamous epithelia. In this study we have tested for the presence of HPV in eight low-passage vulvar carcinoma cell lines and one extensively passaged cell line, A431. One cell line from a primary vaginal carcinoma was included. The presence of the HPV was evaluated by the polymerase chain reaction (PCR), by Southern blot analysis and by two-dimensional gel electrophoresis. General primer-mediated PCR was applied by using primers from the L1 region, E1 region and HPV 16 E7 region. Southern blot hybridisation was performed under low-stringency conditions (Tm = -35 degrees C) using a whole genomic HPV 6/16/18 probe mixture and under high stringency conditions (Tm = -18 degrees C) with the whole genomic probes of HPV 16 and 33. HPV 16 E6-E7 mRNA was assessed by ribonuclease protection assay (RPA). HPV was found in only one vulvar carcinoma cell line, UM-SCV-6. The identified type, HPV 16, was integrated in the cell genome and could be amplified with all primers used. Also E6-E7 transcripts were found in these cells. Five original tumour biopsies were available from the HPV-negative cell lines for in situ hybridisation. All these were HPV negative with both the HPV 6/16/18 screening probe mixture under low stringency and the HPV 16 probe under high stringency. The results indicate that vulvar carcinoma cell lines contain HPV less frequently than cervical carcinoma cell lines and suggest that a significant proportion of vulvar carcinomas may evolve by an HPV-independent mechanism. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7599042

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

    PubMed Central

    Bennett, M; O'Connell, J; O'Sullivan, G; Roche, D; Brady, C; Kelly, J; Collins, J; Shanahan, F

    1999-01-01

    Background—Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. 
Aim—To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. 
Specimens—Thirty paraffin wax embedded human gastric adenocarcinomas. 
Methods—FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). 
Results—Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. 
Conclusions—Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer. 

 Keywords: Fas ligand; gastric cancer; immune escape; apoptosis; tumour; mRNA PMID:9895372

  17. Wernicke's encephalopathy in a patient with gastric carcinoma: a diagnosis not to miss

    PubMed Central

    Udyavara Kudru, Chandrashekar; Kaniyoor Nagiri, Shivashankara; Rao, Sandeep

    2014-01-01

    We describe a case of a patient who presented with a 20-day history of vomiting, generalised weakness and loss of appetite and a 2-day history of altered sensorium. On examination, he was grossly emaciated and there were no palpable lymph nodes. Central nervous system examination revealed nystagmus with bilateral lateral recti palsy and abdominal examination showed mild hepatomegaly. MRI of the brain showed bilateral and symmetrical hypertense signal changes in T2-weighted and fluid-attenuated inversion recovery sequences with diffusion restriction in the paramedian ventromedial thalamus. These findings were compatible with Wernicke's encephalopathy. He was started on thiamine supplementation with which neurological signs improved. An ultrasound of the abdomen showed mild hepatomegaly with multiple hyperechoic lesions and wall thickening of the pyloric antrum. Upper gastroduodenoscopy showed ulcerative lesions involving the antrum, pylorus and duodenum. Biopsy revealed moderately differentiated adenocarcinoma. The patient underwent palliative gastrojejunostomy and was clinically better at discharge. It is important to consider Wernicke encephalopathy in patients with gastric cancer who have acute neurological symptoms. PMID:24654252

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

    PubMed Central

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

    2015-01-01

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

  19. Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts

    PubMed Central

    Ge, Sai; Zhang, Qiyue; He, Qiong; Zou, Jianling; Liu, Xijuan; Li, Na; Tian, Tiantian; Zhu, Yan; Gao, Jing; Shen, Lin

    2016-01-01

    Famitinib (SHR1020), a novel multi-targeted tyrosine kinase inhibitor, has antitumor activity against several solid tumors via targeting vascular endothelial growth factor receptor 2, c-Kit and platelet-derived growth factor receptor β. The present study investigated famitinib's activity against human gastric cancer cells in vitro and in vivo. Cell viability and apoptosis were measured, and cell cycle analysis was performed following famitinib treatment using 3-(4,5-dimethylthiazol −2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and western blotting. Subsequently, cluster of differentiation 34 staining was used to evaluate microvessel density. BGC-823-derived xenografts in nude mice were established to assess drug efficacy in vivo. Famitinib inhibited cell proliferation by inducing cell cycle arrest at the G2/M phase and caused cell apoptosis in a dose-dependent manner in gastric cancer cell lines. In BGC-823 xenograft models, famitinib significantly slowed tumor growth in vivo via inhibition of angiogenesis. Compared with other chemotherapeutics such as 5-fluorouracil, cisplatin or paclitaxel alone, famitinib exhibited the greatest tumor suppression effect (>85% inhibition). The present study demonstrated for the first time that famitinib has efficacy against human gastric cancer in vitro and in vivo, which may lay the foundations for future clinical trials. PMID:27602110

  20. Exploratory study of oral mucosal colonization of human gastric Helicobacter pylori in mice

    PubMed Central

    Wan, Xueqin; Tang, Dongsheng; Zhang, Xiaohuan; Li, Hongming; Cui, Zhixin; Hu, Sijuan; Huang, Ming

    2014-01-01

    In this study, human gastric Helicobacter pylori (Hp) was closely attached to the pre-treated mouse buccal mucosa by using artificial oral film to induce the growth and colonization of Hp on the buccal mucosa in mice. Sixty BALB/c mice were divided into three groups, in which Hp biofilm colonization was detected in three mice in Hp film group (Hp mesh biofilm accumulation under an optical microscope; Hp accumulated colonization under an electron microscope). There were no Hp biofilms detected in Hp smear group or the control group with black film. In this study, human gastric Hp was first used to artificially induce the growth and colonization of Hp on the buccal mucosa in mice. The mouse model of oral infection with Hp was initially established, providing animal experimental evidences for oral conditions of growth and colonization of Hp on the buccal mucosa in mice, and providing a workable animal modeling method for further research of joint infection of Hp on the mouth and stomach, as well as the relationship between oral Hp and gastric Hp. PMID:24753744

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed

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

    2016-07-01

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

  4. Production of interleukin-10 by human bronchogenic carcinoma.

    PubMed Central

    Smith, D. R.; Kunkel, S. L.; Burdick, M. D.; Wilke, C. A.; Orringer, M. B.; Whyte, R. I.; Strieter, R. M.

    1994-01-01

    Interleukin-10 (IL-10) is a recently characterized cytokine with suppressive activity against various aspects of the cellular immune response. Our laboratory has previously demonstrated that another anti-inflammatory cytokine, IL-1 receptor antagonist (IRAP) is produced and secreted by human bronchogenic carcinomas. We speculated that tumor production of IRAP may mitigate host responses and confer increased tumor viability. In this study, we investigated the capacity of human bronchogenic tumors to produce IL-10 as another possible mechanism to attenuate host defenses. We found increased levels of antigenic IL-10 in tissue homogenates of human bronchogenic carcinomas compared with normal lung tissue (13.69 +/- 2.87 versus 5.84 +/- 0.84 ng/mg total protein). Immunohistochemical staining of tumors illustrate primary localization of antigenic IL-10 to individual tumor cells. Analysis of supernatants of several unstimulated human bronchogenic cell lines in vitro demonstrated the ability of tumor cells to constitutively produce IL-10. Functional studies of mononuclear cells, cultured in the presence of conditioned medium from a bronchogenic cell line, demonstrated their increased tumor necrosis factor and IL-6 production with the addition of neutralizing antibodies to IL-10. These findings demonstrate that human bronchogenic carcinomas elaborate functional IL-10, which may significantly impair immune effector cell function and enable the tumor to evade host defenses. Images Figure 1 Figure 2 PMID:8030748

  5. Latent Expression of the Epstein-Barr Virus (EBV)-Encoded Major Histocompatibility Complex Class I TAP Inhibitor, BNLF2a, in EBV-Positive Gastric Carcinomas

    PubMed Central

    Strong, Michael J.; Laskow, Thomas; Nakhoul, Hani; Blanchard, Eugene; Liu, Yaozhong; Wang, Xia; Baddoo, Melody; Lin, Zhen; Yin, Qinyan

    2015-01-01

    The Epstein-Barr virus (EBV) BNLF2a gene product provides immune evasion properties to infected cells through inhibition of transporter associated with antigen processing (TAP)-mediated transport of antigen peptides. Although BNLF2a is considered to be a lytic gene, we demonstrate that it is expressed in nearly half of the EBV-associated gastric carcinomas analyzed. Further, we show that BNLF2a expression is dissociated from lytic gene expression. BNLF2a is therefore expressed in this latency setting, potentially helping protect the infected tumor cells from immunosurveillance. PMID:26178981

  6. Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck.

    PubMed Central

    Easty, D. M.; Easty, G. C.; Carter, R. L.; Monaghan, P.; Butler, L. J.

    1981-01-01

    Ten cell lines of human squamous carcinomas of the tongue and larynx have been established from surgical specimens removed from 36 unselected patients, in order to provide systems for investigating the invasive and tissue-destructive capacity of squamous carcinomas of the head and neck. The morphology, ultrastructure and growth characteristics of the 10 lines are described. Detailed cytogenetic analysis of the first 4 lines indicates that each is karyotypically unique, with no evidence of cross-contamination. Nine of the 10 cell lines secrete immunoreactive beta human chorionic gonadotrophin (beta-hCG) in the culture medium. No correlation was demonstrated between the ability of the cell lines to secrete plasminogen activator and their capacity to grow in soft agar or as xenografts in immune-deficient mice. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:7195729

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2011-12-01

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

  9. Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells

    PubMed Central

    Shiozaki, Atsushi; Shimizu, Hiroki; Ichikawa, Daisuke; Konishi, Hirotaka; Komatsu, Shuhei; Kubota, Takeshi; Fujiwara, Hitoshi; Okamoto, Kazuma; Iitaka, Daisuke; Nakashima, Shingo; Nako, Yoshito; Liu, Mingyao; Otsuji, Eigo

    2014-01-01

    AIM: To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells. METHODS: Knockdown experiments were conducted with claudin 1 small interfering RNA (siRNA), and the effects on the cell cycle, apoptosis, migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells. The gene expression profiles of cells were analyzed by microarray and bioinformatics. RESULTS: The knockdown of claudin 1 significantly inhibited cell proliferation, migration and invasion, and increased apoptosis. Microarray analysis identified 245 genes whose expression levels were altered by the knockdown of claudin 1. Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway, which involved MMP7, TNF-SF10, TGFBR1, and CCL2. Furthermore, TNF- and nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1. TNF-α treatment increased claudin 1 expression and cell migration in MKN28 cells. Microarray analysis indicated that the depletion of claudin 1 inhibited 80% of the TNF-α-induced mRNA expression changes. Further, TNF-α did not enhance cell migration in the claudin 1 siRNA transfected cells. CONCLUSION: These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells. A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer. PMID:25548484

  10. Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

    PubMed Central

    Seitz, H K; Egerer, G; Simanowski, U A; Waldherr, R; Eckey, R; Agarwal, D P; Goedde, H W; von Wartburg, J P

    1993-01-01

    As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p < 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p < 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people. Images Figure

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  12. Deletion of Epstein-Barr virus latent membrane protein 1 gene in Japanese and Brazilian gastric carcinomas, metastatic lesions, and reactive lymphocytes.

    PubMed Central

    Hayashi, K.; Chen, W. G.; Chen, Y. Y.; Murakami, I.; Chen, H. L.; Ohara, N.; Nose, S.; Hamaya, K.; Matsui, S.; Bacchi, M. M.; Bacchi, C. E.; Chang, K. L.; Weiss, L. M.

    1998-01-01

    A 30-bp deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Information on this deletion in EBV-associated gastric carcinoma (EBVaGC) is limited. The association of gastric carcinoma (GC) with EBV was examined by EBV-encoded RNA (EBER) in situ hybridization in 510 patients from Japan and 80 patients from Brazil. We studied the prevalence of 30-bp LMP1 gene deletion in EBVaGC in Japan (29 cases) and Brazil (four cases) in comparison with the corresponding EBER1-positive metastatic lesions in lymph nodes (10 cases) and EBV-infected reactive lymphocytes from dissected nonmetastatic lymph nodes (22 cases), microdissected non-neoplastic gastric mucosa of EBVaGC (five cases), and EBV-nonassociated GC (25 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction products obtained after amplification with primers flanking the site of the deletion. We also performed EBV typing and LMP1 protein immunohistochemistry. EBV DNA was amplified by polymerase chain reaction in 30 of 33 EBVaGC cases, 8 of 10 metastatic carcinomas, 14 non-neoplastic tissues from 27 EBVaGC cases, and 12 of 25 non-EBV-associated GC cases with EBER1-positive lymphocytes. The 30-bp LMP1 gene deletion was observed in 23 of 26 (88.5%) cases of EBVaGC from Japan and two of four (50%) cases of Brazilian EBVaGC as compared with EBER1-positive reactive lymphocytes from 11 of 14 (78.6%) EBVaGC cases and 9 of 12 (75%) cases of non-EBV-associated GC. The variant type (the 30-bp deletion variant or nondeleted wild type) of LMP1 gene was the same among reactive lymphocytes, primary and secondary lesions of EBVaGC in all cases for which all three tissue types were studied (six of six). There was no correlation between the presence of the 30-bp deletion with depth of cancer invasion or presence of metastasis. Type A was detected in all available EBV

  13. Telomerase Activity in Human Ovarian Carcinoma

    NASA Astrophysics Data System (ADS)

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

    1994-04-01

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

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

    SciTech Connect

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

    1989-05-12

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

  15. Genetic Variants in Epidermal Growth Factor Receptor Pathway Genes and Risk of Esophageal Squamous Cell Carcinoma and Gastric Cancer in a Chinese Population

    PubMed Central

    Li, Wen-Qing; Hu, Nan; Wang, Zhaoming; Yu, Kai; Su, Hua; Wang, Lemin; Wang, Chaoyu; Chanock, Stephen J.; Burdett, Laurie; Ding, Ti; Qiao, You-Lin; Fan, Jin-Hu; Wang, Yuan; Xu, Yi; Giffen, Carol; Xiong, Xiaoqin; Murphy, Gwen; Tucker, Margaret A.; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.; Goldstein, Alisa M.; Taylor, Philip R.

    2013-01-01

    The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10−3). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms. PMID:23874846

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

    SciTech Connect

    Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

    1983-08-01

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

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

    PubMed

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

    2016-05-01

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

  18. MiRNA Expression Profile for the Human Gastric Antrum Region Using Ultra-Deep Sequencing

    PubMed Central

    Hamoy, Igor G.; Darnet, Sylvain; Burbano, Rommel; Khayat, André; Gonçalves, André Nicolau; Alencar, Dayse O.; Cruz, Aline; Magalhães, Leandro; Araújo Jr., Wilson; Silva, Artur; Santos, Sidney; Demachki, Samia; Assumpção, Paulo; Ribeiro-dos-Santos, Ândrea

    2014-01-01

    Background MicroRNAs are small non-coding nucleotide sequences that regulate gene expression. These structures are fundamental to several biological processes, including cell proliferation, development, differentiation and apoptosis. Identifying the expression profile of microRNAs in healthy human gastric antrum mucosa may help elucidate the miRNA regulatory mechanisms of the human stomach. Methodology/Principal Findings A small RNA library of stomach antrum tissue was sequenced using high-throughput SOLiD sequencing technology. The total read count for the gastric mucosa antrum region was greater than 618,000. After filtering and aligning using with MirBase, 148 mature miRNAs were identified in the gastric antrum tissue, totaling 3,181 quality reads; 63.5% (2,021) of the reads were concentrated in the eight most highly expressed miRNAs (hsa-mir-145, hsa-mir-29a, hsa-mir-29c, hsa-mir-21, hsa-mir-451a, hsa-mir-192, hsa-mir-191 and hsa-mir-148a). RT-PCR validated the expression profiles of seven of these highly expressed miRNAs and confirmed the sequencing results obtained using the SOLiD platform. Conclusions/Significance In comparison with other tissues, the antrum’s expression profile was unique with respect to the most highly expressed miRNAs, suggesting that this expression profile is specific to stomach antrum tissue. The current study provides a starting point for a more comprehensive understanding of the role of miRNAs in the regulation of the molecular processes of the human stomach. PMID:24647245

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Ziebarth, D; Schramm, T; Töppel, A

    1989-01-01

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

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

    PubMed

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

    2003-11-01

    X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP family that exerts antiapoptotic effects by interfering with the activities of caspases. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. To explore the candidacy of XAF1, Smac/DIABLO, and HtrA2 as a tumor suppressor in gastric tumorigenesis, we investigated the expression and mutation status of the genes in 123 gastric tissues and 15 cancer cell lines. Whereas Smac/DIABLO and HtrA2 transcripts were normally expressed in all cancer specimens we examined, XAF1 transcript was not expressed or present at extremely low levels in 40% (6 of 15) of cancer cell lines and in 23% (20 of 87) of primary carcinomas. Abnormal reduction of XAF1 expression showed a strong correlation with stage and grade of tumors, and a tumor-specific down-regulation of XAF1 was observed in 45% (9 of 20) of matched sets. Unlike XAF1, XIAP expression exhibited no detectable alteration in cancers. Whereas loss of heterozygosity within the XAF1 region or somatic mutations of the gene was not detected, expression of XAF1 transcript was reactivated in all nonexpressor cell lines after 5-aza-2-deoxycytidine treatment. The 5' upstream region of the XAF1 gene encompasses no gastric cell-rich region that rigorously satisfies the formal criteria for CpG islands. However, bisulfite DNA sequencing analysis for 34 CpG sites in the promoter region revealed a strong association between hypermethylation and gene silencing. Moreover, transcriptional silencing of XAF1 was tightly associated with hypermethylation of seven CpGs located in the 5' proximal region (nucleotides -23 to -234). Additionally, loss or abnormal reduction of XAF1 expression was found to inversely correlate with p53 mutations, suggesting that epigenetic inactivation of XAF1 and mutational alteration of p53 might be mutually exclusive

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

    PubMed Central

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

    2016-01-01

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

  3. Ghrelin immunohistochemistry of gastric adenocarcinoma and mucoepidermoid carcinoma of salivary gland.

    PubMed

    Aydin, S; Ozercan, I H; Dagli, F; Aydin, S; Dogru, O; Celebi, S; Akin, O; Guzel, S P

    2005-01-01

    Ghrelin (G-HH) synthesized in several tissues including salivary and stomach glands stimulates appetite in humans by modulating neuropeptide Y neurons in the hypothalamic arcuate nucleus. Loss of appetite is one of the most important symptoms of stomach cancer. We conducted a study using immunohistochemistry to determine whether salivary glands and stomach cancer tissues produce ghrelin. We determined that negative ghrelin immunohistochemistry discriminates tumors from normal tissues and may therefore further our understanding of the clinically important problem of reduced food intake and anorexia in cancer patients. Radioimmunoassay analyses confirmed that cancer cells do not produce a G-HH peptide, whereas normal cells yield this peptide. PMID:16298902

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

    PubMed

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

    2012-09-01

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

  5. Detection of gastrin mRNA in fresh human colonic carcinomas by reverse transcription-polymerase chain reaction.

    PubMed

    Monges, G; Biagini, P; Cantaloube, J F; Chicheportiche, C; Frances, V; Brandini, D; Parc, P; Seitz, J F; Giovannini, M; Sauvan, R

    1993-10-01

    To investigate the hypothesis that gastrin might be synthesized by tumour tissues in cancer of the colon, samples from six human colon tumours, one hepatic metastasis, four normal colonic mucosal samples and two antral and one fundic gastric mucosal samples from nine patients were analysed to determine whether gastrin mRNA was present. RNA was extracted from surgical specimens by ultracentrifugation on a CsCl cushion, purified using the guanidinium thiocyanate method, reverse-transcribed and amplified by polymerase chain reaction. Gastrin mRNA was detected in each colonic carcinoma sample (including the hepatic metastasis), while no such signal was observed in normal colon biopsies. Positive and negative controls (gastric antrum and fundus respectively) gave the expected results. In each of the positive samples, the chemiluminescent revelation of amplified products after Southern blotting corresponded to gastrin mRNA without the intron. These findings demonstrate the ability of primary and metastatic human colonic tumours to produce gastrin mRNA. Since malignant cell lines have been reported to produce gastrin peptide, and since gastrin receptors were present in some cases, our results support the idea that gastrin may be involved in an autocrine mechanism. PMID:7507679

  6. Luteolin Induces Apoptosis by Up-regulating miR-34a in Human Gastric Cancer Cells.

    PubMed

    Wu, Hao; Huang, Min; Liu, Yatian; Shu, Yongqian; Liu, Ping

    2015-12-01

    Luteolin (39, 49, 5, 7-tetrahydroxyflavone) is a natural flavonoid that exists in several types of vegetables, fruits, and medicinal herbs that inhibits tumorigenesis in different types of cancer. In this study, we demonstrate luteolin-mediated regulation of cell apoptosis in a gastric cancer cell line through inhibition of the apoptosis regulatory protein Bcl-2. MTT and flow cytometric analysis indicate that luteolin inhibits cell proliferation and induces apoptosis in gastric cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that miR-34a expression is downregulated in the majority of human primary gastric cancer tissues (8/12, 66.7%), compared with adjacent, pair-matched non-tumor tissues. Target analysis indicated that micro RNA (miR)-34a directly regulates Bcl-2, and miR-34a overexpression decreased Bcl-2 protein level in gastric cancer cells. We also found that luteolin upregulates miR-34a expression and downregulates Bcl-2 expression. Furthermore, anti-miR-34a oligonucleotides (AMO) partly reverse luteolin-induced Bcl-2 downregulation in gastric cancer cells. Based on these results, we can draw the conclusion that luteolin partly decreases Bcl-2 expression through upregulating miR-34a expression. This study shows for the first time that the miR-34a pathway plays an important role in luteolin-induced apoptosis in gastric cancer cells. PMID:24988056

  7. Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit.

    PubMed

    Geyer, Philipp Emanuel; Maak, Matthias; Nitsche, Ulrich; Perl, Markus; Novotny, Alexander; Slotta-Huspenina, Julia; Dransart, Estelle; Holtorf, Anne; Johannes, Ludger; Janssen, Klaus-Peter

    2016-05-01

    The B-subunit of the bacterial Shiga toxin (STxB), which is nontoxic and has low immunogenicity, can be used for tumor targeting of breast, colon, and pancreatic cancer. Here, we tested whether human gastric cancers, which are among the most aggressive tumor entities, express the cellular receptor of Shiga toxin, the glycosphingolipid globotriaosylceramide (Gb3/CD77). The majority of cases showed an extensive staining for Gb3 (36/50 cases, 72%), as evidenced on tissue sections of surgically resected specimen. Gb3 expression was detected independent of type (diffuse/intestinal), and was negatively correlated to increasing tumor-node-metastasis stages (P = 0.0385), as well as with markers for senescence. Gb3 expression in nondiseased gastric mucosa was restricted to chief and parietal cells at the bottom of the gastric glands, and was not elevated in endoscopic samples of gastritis (n = 10). Gb3 expression in established cell lines of gastric carcinoma was heterogeneous, with 6 of 10 lines being positive, evidenced by flow cytometry. STxB was taken up rapidly by live Gb3-positive gastric cancer cells, following the intracellular retrograde transport route, avoiding lysosomes and rapidly reaching the Golgi apparatus and the endoplasmic reticulum. Treatment of the Gb3-expressing gastric carcinoma cell line St3051 with STxB coupled to SN38, the active metabolite of the topoisomerase type I inhibitor irinotecan, resulted in >100-fold increased cytotoxicity, as compared with irinotecan alone. No cytotoxicity was observed on gastric cancer cell lines lacking Gb3 expression, demonstrating receptor specificity of the STxB-SN38 compound. Thus, STxB is a highly specific transport vehicle for cytotoxic agents in gastric carcinoma. Mol Cancer Ther; 15(5); 1008-17. ©2016 AACR. PMID:26826119

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

    PubMed Central

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

    2016-01-01

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

  9. Human chorionic gonadotropin measurements in parathyroid carcinoma

    PubMed Central

    Rubin, Mishaela R; Bilezikian, John P; Birken, Steven; Silverberg, Shonni J

    2010-01-01

    Objective Preoperatively, it is difficult to differentiate between parathyroid cancer (PtCa) and severe primary hyperparathyroidism (PHPT) due to a benign tumor. Human chorionic gonadotropin (hCG) is a tumor marker in trophoblastic and nontrophoblastic cancers and hyperglycosylated hCG is increased in hCG-secreting malignancies. We investigated whether hCG can distinguish PtCa cancer from benign disease and add prognostic information. Design Observational study. Methods Measurement of urinary hCG (total and malignant isoforms) and serum malignant hCG in 8 subjects with PtCa and in 18 subjects with PHPT (measurement of urine in ten and serum in eight). Results Total urinary hCG was normal in the benign PHPT control subjects (range: 0–17 fmol/mg Cr; nl < 50). In the PtCa subjects, three had normal total urinary hCG levels and survived complication free for at least 2 years; three had persistently elevated total urinary hCG levels (range: 217–1986 fmol/mg Cr) and sustained hip fracture (n = 3) and died (n = 2) within 3 and 6 months respectively; two had a rise in total urinary hCG and had hip fracture (n = 1) and died (n = 2) within 4 and 10 months respectively. Elevated urinary hCG was of the malignant hyperglycosylated isoform. Serum malignant hyperglycosylated hCG values in all of the cancer patients exceeded the maximal serum malignant hCG level of the PHPT subjects with benign disease (3.77 pmol/l). Conclusion hCG, especially itshyperglycosylated isoform, might add diagnostic and prognostic information in PtCa. Further studies would help to elucidate the role of hCG as a potential tumor marker in this disease. PMID:18625691

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

    PubMed Central

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

    2016-01-01

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

  11. Differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts.

    PubMed Central

    Yashiro, M.; Chung, Y. S.; Kubo, T.; Hato, F.; Sowa, M.

    1996-01-01

    Scirrhous gastric cancer cells proliferate rapidly with fibrosis, when the cancer cells invade into the submucosa of the stomach. To investigate the mechanisms responsible for the rapid proliferation, the growth interaction between gastric cancer cells and fibroblasts was examined. Human gastric cancer cell lines established from scirrhous carcinoma or well-differentiated adenocarcinoma were used. Human fibroblast cell lines were obtained from various organs. The growth interaction between gastric cancer cells and fibroblasts was examined by calculating the number of cancer cells or by measuring [3H]thymidine incorporation of cancer cells. Gastric fibroblasts specifically stimulated the growth of scirrhous gastric cancer cells, but not that of well-differentiated adenocarcinoma cells. The growth factor(s) produced from gastric fibroblasts were then partially purified and characterised. The growth-promoting factor(s) had apparent molecular weights of 10000 dalton and was sensitive both to heat and proteinase treatment. No inhibition for the factor(s) was achieved with defined anti-growth factor antibodies. In this study, differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts were shown. Rapid proliferation of scirrhous gastric carcinoma should be partly controlled by orthotopic fibroblasts. The growth factor(s) from gastric fibroblasts, which was distinct from various defined growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), transforming growth factor-alpha (TGF-alpha), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-beta 1) may play an important role in the progression of scirrhous gastric cancer cells. PMID:8855981

  12. Cytomegalovirus Replicates in Differentiated but not in Undifferentiated Human Embryonal Carcinoma Cells

    NASA Astrophysics Data System (ADS)

    Gonczol, Eva; Andrews, Peter W.; Plotkin, Stanley A.

    1984-04-01

    To study the mode of action of human cytomegalovirus, an important teratogenic agent in human populations, the susceptibility of a pluripotent human embryonal carcinoma cell line to the virus was investigated. Viral antigens were not expressed nor was infectious virus produced by human embryonal carcinoma cells after infection, although the virus was able to penetrate these cells. In contrast, retinoic acid-induced differentiated derivatives of embryonal carcinoma cells were permissive for antigen expression and infectious virus production. Replication of human cytomegalovirus in human teratocarcinoma cells may therefore depend on cellular functions associated with differentiation.

  13. LGR4 and LGR6 are differentially expressed and of putative tumor biological significance in gastric carcinoma.

    PubMed

    Steffen, Jan Simon; Simon, Eva; Warneke, Viktoria; Balschun, Katharina; Ebert, Matthias; Röcken, Christoph

    2012-10-01

    Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide. We investigated the differential expression and putative tumor biological significance of five G-protein-coupled receptors (GPCRs) in GC, i.e., LGR4, LGR6, GPR34, GPR160, and GPR171. Based on our previous microarray analyses, we identified five candidate genes in human GC samples. Real-time RT-PCR was carried out to validate their expression in malignant and non-malignant tissues on an independent collective comprising 32 GC patients with and without lymph node metastases. Selected protein targets LGR4 and LGR6 were further validated on paraffin-embedded sections of ten intestinal and ten poorly cohesive (diffuse)-type GCs and their corresponding non-malignant tissue using immunohistochemistry. Additionally, the putative tumor biological significance of LGR4 and LGR6 was studied using tissue microarrays obtained from a cohort of 481 GC patients. On transcriptional level, GPR34, GPR160, and GPR171 were not differentially expressed in GC compared with non-neoplastic mucosa. LGR4 and LGR6 were up-regulated on transcriptional (real-time RT-PCR) and translational (immunohistochemistry) levels in GC. Furthermore, in tissue microarray analysis, LGR6 expression was significantly associated with local tumor growth (T-category; p = 0.04) and correlated with patient survival. LGR4 expression was significantly correlated with nodal spread (N-category; p = 0.025). Our systematic analysis indicates that LGR4 and LGR6 may play a role in GC biology. Future studies will have to demonstrate whether these are also putative diagnostic, prognostic, and/or therapeutic targets for GC. PMID:22855134

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

    PubMed

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

    2016-01-01

    Hydrogen sulfide (H2S), the third gasotransmitter, is endogenously generated by certain H2S synthesizing enzymes, including cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) from L-cysteine in the mammalian body. Several studies have shown that endogenous and exogenous H2S affects the proliferation of cancer cells, although the effects of H2S appear to vary with cell type, being either promotive or suppressive. In the present study, we determined whether endogenously formed H2S regulates proliferation in human gastric cancer AGS cells. CSE, but not CBS, was expressed in AGS cells. CSE inhibitors, DL-propargylglycine (PPG) and β-cyano-L-alanine (BCA), significantly suppressed the proliferation of AGS cells in a concentration-dependent manner. CSE inhibitors did not increase lactate dehydrogenase (LDH) release in the same concentration range. The inhibitory effects of PPG and BCA on cell proliferation were reversed by repetitive application of NaHS, a donor of H2S. Interestingly, nuclear condensation and fragmentation were detected in AGS cells treated with PPG or BCA. These results suggest that endogenous H2S produced by CSE may contribute to the proliferation of gastric cancer AGS cells, most probably through anti-apoptotic actions. PMID:27150157

  15. Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori.

    PubMed

    Watanabe, Tatsuro; Takahashi, Atsushi; Suzuki, Kaori; Kurusu-Kanno, Miki; Yamaguchi, Kensei; Fujiki, Hirota; Suganuma, Masami

    2014-05-15

    Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. Tipα acts as a homodimer with 38-kDa protein, whereas del-Tipα is an inactive monomer. H. pylori isolated from gastric cancer patients secreted large amounts of Tipα, which are incorporated into gastric cancer cells by directly binding to nucleolin on the cell surface, which is a receptor of Tipα. The binding complex induces expression of TNF-α and chemokine genes, and activates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). To understand the mechanisms of Tipα in tumor progression, we looked at numerous effects of Tipα on human gastric cancer cell lines. Induction of cell migration and elongation was found to be mediated through the binding to surface nucleolin, which was inhibited by the nucleolin-targeted siRNAs. Tipα induced formation of filopodia in MKN-1 cells, suggesting invasive morphological changes. Tipα enhanced the phosphorylation of 11 cancer-related proteins in serine, threonine and tyrosine, indicating activation of MEK-ERK signal cascade. Although the downregulation of E-cadherin was not shown in MKN-1 cells, Tipα induced the expression of vimentin, a significant marker of the epithelial-mesenchymal transition (EMT). It is of great importance to note that Tipα reduced the Young's modulus of MKN-1 cells determined by atomic force microscopy: This shows lower cell stiffness and increased cell motility. The morphological changes induced in human gastric cancer cells by Tipα are significant phenotypes of EMT. This is the first report that Tipα is a new inducer of EMT, probably associated with tumor progression in human gastric carcinogenesis. PMID:24249671

  16. Human Papilloma Virus and Squamous Cell Carcinoma of the Anus

    PubMed Central

    Gami, Bhavna; Kubba, Faris; Ziprin, Paul

    2014-01-01

    The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus. PMID:25288893

  17. HER2, MET and FGFR2 oncogenic driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma

    PubMed Central

    Liu, Y J; Shen, D; Yin, X; Gavine, P; Zhang, T; Su, X; Zhan, P; Xu, Y; Lv, J; Qian, J; Liu, C; Sun, Y; Qian, Z; Zhang, J; Gu, Y; Ni, X

    2014-01-01

    Background: Gastric cancer (GC) is a leading cause of cancer deaths worldwide. Since the approval of trastuzumab, targeted therapies are emerging as promising treatment options for the disease. This study aimed to explore the molecular segmentation of several known therapeutics targets, human epidermal growth factor receptor 2 (HER2), MET and fibroblast growth factor receptor 2 (FGFR2), within GC using clinically approved or investigational kits and scoring criteria. Knowledge of how these markers are segmented in the same cohort of GC patients could improve future clinical trial designs. Methods: Using immunohistochemistry (IHC) and FISH methods, overexpression and amplification of HER2, FGFR2 and MET were profiled in a cohort of Chinese GC samples. The correlations between anti-tumour sensitivity and the molecular segments of HER2, MET and FGFR2 alterations were further tested in a panel of GC cell lines and the patient-derived GC xenograft (PDGCX) model using the targeted inhibitors. Results: Of 172 GC patients, positivity for HER2, MET and FGFR2 alternations was found in 23 (13.4%), 21 (12.2%) and 9 (5.2%) patients, respectively. Positivity for MET was found in 3 of 23 HER2-positive GC patients. Co-positivity for FGFR2 and MET was found in 1 GC patient, and amplification of the two genes was found in different tumour cells. Our study in a panel of GC cell lines showed that in most cell lines, amplification or high expression of a particular molecular marker was mutually exclusive and in vitro sensitivity to the targeted agents lapatinib, PD173074 and crizotinib was only observed in cell lines with the corresponding high expression of the drugs' target protein. SGC031, an MET-positive PDGCX mouse model, responded to crizotinib but not to lapatinib or PD173074. Conclusions: Human epidermal growth factor receptor 2, MET and FGFR2 oncogenic driver alterations (gene amplification and overexpression) occur in three largely distinct molecular segments in GC. A

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Perrella, Sharon L; Hepworth, Anna R; Gridneva, Zoya; Simmer, Karen N; Hartmann, Peter E; Geddes, Donna T

    2015-07-01

    We evaluated the effects of fortification and composition on gastric emptying and curding in un/fortified pairs of mother's own milk (MOM, n = 17) and pasteurized donor human milk (PDHM, n = 15) in preterm infants. Retained meal proportions (%) and curding were determined from sonography. Immediate and subsequent postprandial % were higher for PDHM (23%, P = 0.026; 15%, P = 0.006) and fortified meals (31.5%; 8.8%, both P < 0.001), whereas higher casein, whey, and lactose concentrations were associated with lower immediate postprandial % (all P < 0.006). Curding did not affect emptying. Influences of fortification, pasteurization, and differing breast milk compositions are small and unlikely implicated in preterm feeding intolerance. PMID:25729886

  1. MicroRNA-190 regulates FOXP2 genes in human gastric cancer

    PubMed Central

    Jia, Wen-Zhuo; Yu, Tao; An, Qi; Yang, Hua; Zhang, Zhu; Liu, Xiao; Xiao, Gang

    2016-01-01

    Objective To investigate how microRNA-190 (miR-190) regulates FOXP2 genes in gastric cancer (GC) cell line SGC7901. Methods We identified that miR-190 could target FOXP2 genes by using dual luciferase enzyme assay. Precursor fragment transfection of miR-190 was performed with GC cell line SGC7901 and human gastric mucosal cell line GES-1. miR-190 expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and FOXP2 protein expression was measured by Western blotting. Results FOXP2-3′-untranslated region (UTR) in miR-190 transfection group was significantly decreased as compared with other groups. There were no significant differences in fluorescence signals of FOXP2mut-3′-UTR in each group. Therefore, it was assumed that miR-190 can target FOXP2 genes. Through RT-PCR verification, it was observed that the expression level of miR-190 was significantly higher in GC cell line SGC7901 than in human gastric mucosa cell line GES-1 after transfection with miR-190 mimics. The expression level of miR-190 was significantly higher in GES-1 cells than in SGC7901 cells after transfection with miR-190 inhibitors. Western blotting results showed the expression level of FOXP2 was significantly lower in GC cell line SGC7901 than in GES-1 cells. Compared with blank, mimics control, and inhibitors control groups, the miR-190 mimics group showed significantly enhanced proliferation, migration, and invasion abilities, while miR-190 inhibitors group showed decreased abilities toward proliferation, migration, and invasion (P<0.05). The transcription level of miR-190 and the expression level of FOXP2 in tumor tissues and adjacent normal tissues in GC patients were verified to be consistent with those of cell line experiments. Conclusion Upregulation of miR-190 can lead to downregulation of FOXP2 protein expression. miR-190 may serve as a potential target for GC diagnosis. PMID:27382302

  2. Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies.

    PubMed Central

    Moll, R.; Löwe, A.; Laufer, J.; Franke, W. W.

    1992-01-01

    The authors have recently identified a new cytokeratin (CK) polypeptide, CK 20, whose expression is almost entirely confined to the gastric and intestinal epithelium, urothelium, and Merkel cells. Seven monoclonal antibodies (MAbs) specific for CK 20 were raised and characterized by applying immunoblotting and immunocytochemical screening. All of them reacted on frozen tissue sections. A further MAb, IT-Ks20.8, recognized CK 20 in sections of formalin-fixed, paraffin-embedded tissue samples. A total of 711 cases of primary and metastatic cancer, mostly carcinomas, were analyzed immunohistochemically for CK-20 expression, using CK-20 specific guinea-pig antibodies and MAbs. The expression spectrum of CK 20 in carcinomas resembled that seen in the corresponding normal epithelia of origin. CK-20 positivity was seen in the vast majority of adenocarcinomas of the colon (89/93 cases), mucinous ovarian tumors, transitional-cell and Merkel-cell carcinomas and frequently also in adenocarcinomas of the stomach, bile system, and pancreas. Most squamous cell carcinomas in general and most adenocarcinomas from other sites (breast, lung, endometrium), nonmucinous tumors of the ovary, and small-cell lung carcinomas were essentially or completely negative. The authors propose to use CK 20 as a diagnostic marker valuable in distinguishing different types of carcinomas, notably when presenting as metastases. Images Figure 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1371204

  3. The role of K+ conductances in regulating membrane excitability in human gastric corpus smooth muscle

    PubMed Central

    Lee, Ji Yeon; Ko, Eun-ju; Ahn, Ki Duck; Kim, Sung

    2015-01-01

    Changes in resting membrane potential (RMP) regulate membrane excitability. K+ conductance(s) are one of the main factors in regulating RMP. The functional role of K+ conductances has not been studied the in human gastric corpus smooth muscles (HGCS). To examine the role of K+ channels in regulation of RMP in HGCS we employed microelectrode recordings, patch-clamp, and molecular approaches. Tetraethylammonium and charybdotoxin did not affect the RMP, suggesting that BK channels are not involved in regulating RMP. Apamin, a selective small conductance Ca2+-activated K+ channel (SK) blocker, did not show a significant effect on the membrane excitability. 4-Aminopyridine, a Kv channel blocker, caused depolarization and increased the duration of slow wave potentials. 4-Aminopyridine also inhibited a delayed rectifying K+ current in isolated smooth muscle cells. End-product RT-PCR gel detected Kv1.2 and Kv1.5 in human gastric corpus muscles. Glibenclamide, an ATP-sensitive K+ channel (KATP) blocker, did not induce depolarization, but nicorandil, a KATP opener, hyperpolarized HGCS, suggesting that KATP are expressed but not basally activated. Kir6.2 transcript, a pore-forming subunit of KATP was expressed in HGCS. A low concentration of Ba2+, a Kir blocker, induced strong depolarization. Interestingly, Ba2+-sensitive currents were minimally expressed in isolated smooth muscle cells under whole-cell patch configuration. KCNJ2 (Kir2.1) transcript was expressed in HGCS. Unique K+ conductances regulate the RMP in HGCS. Delayed and inwardly rectifying K+ channels are the main candidates in regulating membrane excitability in HGCS. With the development of cell dispersion techniques of interstitial cells, the cell-specific functional significance will require further analysis. PMID:25591864

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

    SciTech Connect

    Suzuki, Kanayo; Sakaguchi, Minoru; Tanaka, Satoshi; Yoshimoto, Tadashi; Takaoka, Masanori

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  5. Apoptosis induction by glycoprotein isolated from Laminaria japonica is associated with down-regulation of telomerase activity and prostaglandin E2 synthesis in AGS human gastric cancer cells.

    PubMed

    Han, Min Ho; Kim, Gi Young; Moon, Sung-Kwon; Kim, Wun-Jae; Nam, Taek-Jeong; Choi, Yung Hyun

    2011-02-01

    Glycoprotein isolated from Laminaria japonica (LJGP) is known to exhibit significant cytotoxic activity against human cancer cells; however, the mechanisms of its cytoxicity are poorly understood. In this study, we investigated further possible mechanisms by which LJGP exerts its anti-cancer action in cultured human gastric carcinoma AGS cells. LJGP treatment of AGS cells resulted in inhibition of growth and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay, fluorescence microscopy, and flow cytometry analysis. The increase in apoptosis was associated with up-regulation of pro-apoptotic Bax expression, down-regulation of anti-apoptotic Bcl-2 and IAP family members, and activation of caspase-3 and -9. LJGP treatment markedly down-regulated the activity of telomerase and expression of human telomerase reverse transcriptase, a main determinant of telomerase enzymatic activity, with inhibition of Sp1 and c-Myc expression in a concentration-dependent manner. Furthermore, LJGP treatment also caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. These results provide important new insights into the possible molecular mechanisms of the anti-cancer activity of LJGP. PMID:21132266

  6. Annexin A6 protein is downregulated in human hepatocellular carcinoma.

    PubMed

    Meier, Elisabeth M; Rein-Fischboeck, Lisa; Pohl, Rebekka; Wanninger, Josef; Hoy, Andrew J; Grewal, Thomas; Eisinger, Kristina; Krautbauer, Sabrina; Liebisch, Gerhard; Weiss, Thomas S; Buechler, Christa

    2016-07-01

    Annexin A6 (AnxA6) is a lipid-binding protein highly expressed in the liver, regulating cholesterol homeostasis and signaling pathways with a role in liver physiology. Here, we analyzed whether hepatic AnxA6 levels are affected by pathological conditions that are associated with liver dysfunction and liver injury. AnxA6 levels in the fatty liver of mice fed a high-fat diet, in ob/ob and db/db animals and in human fatty liver are comparable to controls. Similarly, AnxA6 levels appear unaffected in murine nonalcoholic steatohepatitis and human liver fibrosis. Accordingly, adiponectin, lysophosphatidylcholine, palmitate, and TGFbeta, all of which have a role in liver injury, do not affect AnxA6 expression in human hepatocytes. Likewise, adiponectin and IL8 do not alter AnxA6 levels in primary human hepatic stellate cells. However, in hepatic tumors of 18 patients, AnxA6 protein levels are substantially reduced compared to nontumorous tissues. AnxA6 mRNA is even increased in the tumors suggesting that posttranscriptional mechanisms are involved herein. Lipidomic analysis shows trends toward elevated cholesteryl ester and sphingomyelin in the tumor samples, yet the ratio of tumor to nontumorous AnxA6 does not correlate with these lipids. The current study shows that AnxA6 is specifically reduced in human hepatocellular carcinoma suggesting a role of this protein in hepatocarcinogenesis. PMID:27334756

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

    SciTech Connect

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

    1985-11-01

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

  8. Human Papilloma Virus and Oropharyngeal Carcinoma - Lessons from History.

    PubMed

    Vlantis, Alexander Chris

    2016-03-01

    The human papilloma virus (HPV) is a common virus that infects epithelium in 10% of the world's population. While most sexually active people become infected, the majority with a healthy natural immunity control their infection. When the infection becomes persistent in cervical mucosa for instance, it is associated with nearly all cervical cancers. Fortunately cervical cancer screening is both sensitive and specific and when accessed has led to significant reductions of this disease. Despite this, cervical cancer still remains one of the leading causes of death from cancer. Oropharyngeal mucosa is becoming persistently infected with HPV in an increasing number of people leading to a potential epidemic of oropharyngeal carcinoma. While only 10% of new oropharyngeal infections persist, those in elderly men who smoke are more likely to do so. Some centres report more than 70% of oropharyngeal cancers are associated with HPV infection, which is different to cancers caused by alcohol and tobacco. Other centres report only a 20% association. Education against high-risk sexual behaviour has been met with limited success. Screening for oropharyngeal HPV infection has been disappointing with a pickup rate of only 40%. Some hope lies in detecting viral DNA in both the saliva and plasma. A HPV vaccine has been available since 2006 but is not yet routinely given to both sexes in many countries. Its effect on the incidence of HPV-positive oropharyngeal carcinomas is currently unknown. Vigilance by dental and medical colleagues in the meantime is essential. PMID:26981602

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

    PubMed

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

    2016-08-01

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

  10. Recent developments and innovations in gastric cancer.

    PubMed

    Mihmanli, Mehmet; Ilhan, Enver; Idiz, Ufuk Oguz; Alemdar, Ali; Demir, Uygar

    2016-05-01

    Gastric cancer has an important place in the worldwide incidence of cancer and cancer-related deaths. It can metastasize to the lymph nodes in the early stages, and lymph node metastasis is an important prognostic factor. Surgery is a very important part of gastric cancer treatment. A D2 lymphadenectomy is the standard surgical treatment for cT1N+ and T2-T4 cancers, which are potentially curable. Recently, the TNM classification system was reorganized, and the margins for gastrectomy and lymphadenectomy were revised. Endoscopic, laparoscopic and robotic treatments of gastric cancer have progressed rapidly with development of surgical instruments and techniques, especially in Eastern countries. Different endoscopic resection techniques have been identified, and these can be divided into two main categories: endoscopic mucosal resection and endoscopic submucosal dissection. Minimally invasive surgery has been reported to be safe and effective for early gastric cancer, and it can be successfully applied to advanced gastric cancer with increasing experience. Cytoreductive surgery and hyperthermıc intraperıtoneal chemotherapy were developed as a combined treatment modality from the results of experimental and clinical studies. Also, hyperthermia increases the antitumor activity and penetration of chemotherapeutics. Trastuzumab which is a monoclonal antibody interacts with human epidermal growth factor (HER) 2 and is related to gastric carcinoma. The anti-tumor mechanism of trastuzumab is not clearly known, but mechanisms such as interruption of the HER2-mediated cell signaling pathways and cell cycle progression have been reported previously. H. pylori is involved in 90% of all gastric malignancies and Japanese guidelines strongly recommend that all H. pylori infections should be eradicated regardless of the associated disease. In this review, we present innovations discussed in recent studies. PMID:27158199

  11. Recent developments and innovations in gastric cancer

    PubMed Central

    Mihmanli, Mehmet; Ilhan, Enver; Idiz, Ufuk Oguz; Alemdar, Ali; Demir, Uygar

    2016-01-01

    Gastric cancer has an important place in the worldwide incidence of cancer and cancer-related deaths. It can metastasize to the lymph nodes in the early stages, and lymph node metastasis is an important prognostic factor. Surgery is a very important part of gastric cancer treatment. A D2 lymphadenectomy is the standard surgical treatment for cT1N+ and T2-T4 cancers, which are potentially curable. Recently, the TNM classification system was reorganized, and the margins for gastrectomy and lymphadenectomy were revised. Endoscopic, laparoscopic and robotic treatments of gastric cancer have progressed rapidly with development of surgical instruments and techniques, especially in Eastern countries. Different endoscopic resection techniques have been identified, and these can be divided into two main categories: endoscopic mucosal resection and endoscopic submucosal dissection. Minimally invasive surgery has been reported to be safe and effective for early gastric cancer, and it can be successfully applied to advanced gastric cancer with increasing experience. Cytoreductive surgery and hyperthermıc intraperıtoneal chemotherapy were developed as a combined treatment modality from the results of experimental and clinical studies. Also, hyperthermia increases the antitumor activity and penetration of chemotherapeutics. Trastuzumab which is a monoclonal antibody interacts with human epidermal growth factor (HER) 2 and is related to gastric carcinoma. The anti-tumor mechanism of trastuzumab is not clearly known, but mechanisms such as interruption of the HER2-mediated cell signaling pathways and cell cycle progression have been reported previously. H. pylori is involved in 90% of all gastric malignancies and Japanese guidelines strongly recommend that all H. pylori infections should be eradicated regardless of the associated disease. In this review, we present innovations discussed in recent studies. PMID:27158199

  12. Preparation of humanized ovarian carcinoma anti-idiotypic minibody.

    PubMed

    Chang, Xiaohong; Cui, Heng; Feng, Jie; Li, Yi; Liu, Bei; Cao, Shanjin; Cheng, Yexia; Qian, Henian

    2003-04-01

    Murine anti-idiotypic monoclonal antibody (MAb) 6B11 mimicking the tumor-associated antigen OC166-9 is used as a vaccine for the induction of an anti-tumoral immunity in experiments of in vitro and in vivo animal model with ovarian carcinoma. In this article, we have humanized 6B11 anti-idiotypic minibody using overlap polymerase chain reaction (PCR) and DNA recombinant technique, prokaryotic expression vector was produced by genetic fusion of 6B11V(L)-V(H) to human IgG1 hinge and CH3 region. Transformed E. coli BL21(DE3) were propagated and induced by isopropyl-beta D-thiogalactopyranoside (IPTG). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein band with molecular weight of 50kD appeared as the expected size after transformation. Molecular weight of 100 kDa may be examined by electrophoresis in nondenaturing systems. The fusion protein was analyzed with enzyme-linked immunosorbant assay (ELISA), inhibition ELISA tests and Western blot, respectively. The humanized anti-idiotype minibody showed capacity of bivalent binding to ovarian cancer MAb COC166-9 and goat anti-human immunoglobulin IgG1. It is useful reagents for clinical use. PMID:12831536

  13. Human papillomavirus tumor infection in esophageal squamous cell carcinoma

    PubMed Central

    Ludmir, Ethan B.; Stephens, Sarah J.; Palta, Manisha; Willett, Christopher G.

    2015-01-01

    The association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) has been recognized for over three decades. Recently, multiple meta-analyses have drawn upon existing literature to assess the strength of the HPV-ESCC linkage. Here, we review these analyses and attempt to provide a clinically-relevant overview of HPV infection in ESCC. HPV-ESCC detection rates are highly variable across studies. Geographic location likely accounts for a majority of the variation in HPV prevalence, with high-incidence regions including Asia reporting significantly higher HPV-ESCC infection rates compared with low-incidence regions such as Europe, North America, and Oceania. Based on our examination of existing data, the current literature does not support the notion that HPV is a prominent carcinogen in ESCC. We conclude that there is no basis to change the current clinical approach to ESCC patients with respect to tumor HPV status. PMID:26029456

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

    PubMed Central

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

    2016-01-01

    Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets. PMID:27322246

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

    SciTech Connect

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  16. Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells.

    PubMed

    Gao, Shiyong; Tan, Huixin; Zhu, Nan; Gao, Haiyu; Lv, Chunyu; Gang, Jian; Ji, Yubin

    2016-06-01

    Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC50) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells. PMID:27082253

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

    PubMed

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

    2016-01-01

    Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients' survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets. PMID:27322246

  18. Radiation and taxol effects on synchronized human cervical carcinoma cells

    SciTech Connect

    Geard, C.R.; Jones, J.M. )

    1994-06-15

    The purpose was to evaluate the effectiveness of the plant derived chemotherapeutic agent taxol alone and in combination with ionizing radiation on synchronous and asynchronous human cervical carcinoma cells and to define the mechanistic basis for this cytotoxic response. Asynchronous and synchronous cells (obtained by modified mitotic shake-off) derived from carcinomas of the human uterine cervix were treated with a range of concentrations of taxol (0, 1.0, 2.5, 5.0, 10.0, and 20.0 nM) for either 8, 24, or 48 h. Synchronized cell cycling was evaluated by counting mitotic indices and by uptake of bromodeoxyuridine (BrdUrd). Cells were irradiated ([sup 137]Cs [gamma] rays at 1.12 Gy/min) alone and after taxol treatment and plating efficiencies and radiosensitivity determined. Taxol treatment resulted in a dose time dependent loss of colony forming ability with 10 nM for 24 h producing about 10% cell survival. Irradiating taxol treated cells resulted in a strictly additive response in contrast to previous supra-additive results with astrocytoma and melanoma cells. Mitotically synchronized cells rapidly moved into G[sub 1] phase with a second mitotic peak at 28 h (total cycle time). Taxol treatment resulted in a continued accumulation of mitoses, and a failure and/or delay of entry of a fraction of cells into S phase after a G[sub 1] phase of at least 10 h. That is, taxol effects cell cycling at a stage other than G[sub 2]/M. Irradiating (3 Gy) synchronized cells showed a 10-fold variation in sensitivity, with mitosis as the most sensitive phase with taxol alone resulting in some cytotoxicity and combined effects additive or less than additive. This may explain the failure to obtain taxol radiosensitization with these cells and it may indicate that taxol has a multiplicity of actions with differences in effectiveness likely between cells of different origins. 24 refs., 5 figs.

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

    PubMed

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

    2016-09-01

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

  20. Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane

    PubMed Central

    Saghravanian, Nasrollah; Ghazi, Narges; Meshkat, Zahra; Mohtasham, Nooshin

    2015-01-01

    Objectives Squamous cell carcinoma (SCC) is the most common oral malignancy, and verrucous carcinoma (VC) is a less invasive type of SCC. Leukoplakia (LP) is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV) has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high-risk subtypes (HPV HR) has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions. Methods One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs) and 18 normal mucosa samples (as a control group) were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction. Results The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%), we observed the presence of HPV HR (types 16 and 18). All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230). Additionally, 15 (13.1%) SCCs showed HPV positivity, but this was not significant (p=0.830). The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11). A statistically significant association was not observed between HPV and SCC or VC in the oral cavity. Conclusion More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions. PMID:26674929

  1. O-6-methylguanine-DNA Methyltransferase Inhibits Gastric Carcinoma Cell Migration and Invasion by Downregulation of Matrix Metalloproteinase 2.

    PubMed

    Li, Chenglong; Deng, Li; Shen, Hugang; Meng, Qingyou; Qian, Aimin; Sang, Hongfei; Xia, Jiazeng; Li, Xiaoqiang

    2016-01-01

    MGMT plays a key role in many kinds of cancers. However, the molecular mechanisms of MGMT involvement in gastric cancer (GC) are poorly elucidated. Here, we investigated the role of MGMT in GC cell migration, invasion and metastatic potential. Our data showed that MGMT expression was negatively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by downregulation of matrix metalloproteinase 2 (MMP2). Loss of MGMT expression induced increases in GC cell metastasis and invasion potential in vitro and in vivo. These effects were reversed by inhibition of MGMT and MMP2. MGMT overexpression downregulated MMP2 protein levels, whereas this effect was counteracted by MGMT siRNA. In summary, MGMT is involved in gastric carcinogenesis via downregulation of MMP2. The MGMT/MMP2 pathway plays an essential role in GC metastasis and may be a potential therapeutic target for GC treatment. PMID:27291049

  2. Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells

    SciTech Connect

    Yasuda, Hiroshi . E-mail: hiroshi-yasuda@showa-university-fujigaoka.gr.jp; Hirata, Shuko; Inoue, Kazuaki; Mashima, Hirosato; Ohnishi, Hirohide; Yoshiba, Makoto

    2007-03-02

    Bile acids, which have been implicated in gastrointestinal-tract cell carcinogenesis, share properties with tumor promoters in that both affect signal transduction pathways responsible for cell proliferation and apoptosis. In the present study, we demonstrate that EGFR-ERK1/2 is activated following treatment of AGS human gastric carcinoma cells with bile acids. EGFR phosphoactivation is ligand-dependent, since treatment of cells with HB-EGF antisera or CM197 (a selective inhibitor of HB-EGF) markedly inhibits deoxycholate (DC)-promoted activation. Membrane-type bile acid receptor (M-BAR)/TGR5 is a recently identified G-protein-coupled receptor (GPCR). In AGS cells, siRNAs that target M-BAR suppress DC-induced phosphorylation of EGFR. Furthermore, introduction of siRNAs targeting ADAM17 transcripts resulted in suppression of DC-induced activation of EGFR and ERK1/2. These results suggest that in AGS cells, DC transactivates EGFR through M-BAR- and ADAM/HB-EGF-dependent mechanisms.

  3. The significance of Brf1 overexpression in human hepatocellular carcinoma

    PubMed Central

    Shi, Ganggang; Huang, Yi; Zhang, Yanmei; Levy, Daniel; Zhong, Shuping

    2016-01-01

    Brf1 (TFIIB-related factor 1) plays a crucial role in cell transformation and tumorigenesis. However, the significance of Brf1 expression in human HCC (hepatocellular carcinoma) cases remains to be addressed. In this study, biopsies of human HCC, liver tumor samples of mice and cell lines of normal and tumor liver were utilized to determine the alteration of Brf1 expression using cytological and molecular biological approaches. Brf1 expression is increased in human HCC cases, which is correlated with shorter survival times. Levels of Brf1 and Pol III (RNA polymerase III-dependent) gene transcription in HCC patients with alcohol consumption are higher than the cases of non-HCC with or without alcohol intake. Induction of Brf1 and Pol III genes by ethanol in hepatoma cells is higher than in non-tumor cells. Ethanol increases the rate of cell transformation. Repression of Brf1 inhibits alcohol-promoted cell transformation. Alcohol consumption enhances Brf1 expression to promote cell transformation. These studies demonstrate that Brf1 is a new biomarker of HCC. PMID:26701855

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

    PubMed Central

    Öztürk, Bahadır; Durak, Zahide Esra; Büber, Süleyman; Kocaoğlu, Ender Hilmi

    2016-01-01

    Aim. To investigate the effects of static magnetic field (SMF) on oxidant and antioxidant parameters of the cancerous and noncancerous human gastric tissues. Materials and Methods. Gastric tissues obtained from patients with gastric cancer were used in the study. SMF was created by using two static magnets. Before and after treatment with SMF, oxidant and antioxidant parameters were measured in the tissue samples. Results. In the cancerous tissue, superoxide dismutase (SOD) activity was found higher and malondialdehyde (MDA) level was found lower as compared with noncancerous tissue. SMF affects oxidant/antioxidant parameters differently in the cancerous and noncancerous tissues. In this regard, SMF causes increase in SOD activity and decrease in MDA level in the noncancerous tissue. However, it decreases SOD and glutathione peroxidase (GSH-Px) activities and increases MDA level and catalase (CAT) activity in the cancerous tissue. There were no differences between nitric oxide (NO) and nitric oxide synthase (NOS) parameters in or among the cancerous and noncancerous tissues. Conclusions. SMF accelerates peroxidation reactions possibly by suppressing SOD and GSH-Px enzymes in the cancerous gastric tissue. This event caused by SMF might play part in the death of cancer cells, which may be a good supportive vehicle for the cancer therapy. PMID:27313958

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

    PubMed

    Öztürk, Bahadır; Durak, Zahide Esra; Büber, Süleyman; Kocaoğlu, Ender Hilmi

    2016-01-01

    Aim. To investigate the effects of static magnetic field (SMF) on oxidant and antioxidant parameters of the cancerous and noncancerous human gastric tissues. Materials and Methods. Gastric tissues obtained from patients with gastric cancer were used in the study. SMF was created by using two static magnets. Before and after treatment with SMF, oxidant and antioxidant parameters were measured in the tissue samples. Results. In the cancerous tissue, superoxide dismutase (SOD) activity was found higher and malondialdehyde (MDA) level was found lower as compared with noncancerous tissue. SMF affects oxidant/antioxidant parameters differently in the cancerous and noncancerous tissues. In this regard, SMF causes increase in SOD activity and decrease in MDA level in the noncancerous tissue. However, it decreases SOD and glutathione peroxidase (GSH-Px) activities and increases MDA level and catalase (CAT) activity in the cancerous tissue. There were no differences between nitric oxide (NO) and nitric oxide synthase (NOS) parameters in or among the cancerous and noncancerous tissues. Conclusions. SMF accelerates peroxidation reactions possibly by suppressing SOD and GSH-Px enzymes in the cancerous gastric tissue. This event caused by SMF might play part in the death of cancer cells, which may be a good supportive vehicle for the cancer therapy. PMID:27313958

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

    SciTech Connect

    Mojaverian, P.; Ferguson, R.K.; Vlasses, P.H.; Rocci, M.L. Jr.; Oren, A.; Fix, J.A.; Caldwell, L.J.; Gardner, C.

    1985-08-01

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

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

    PubMed Central

    Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

    2015-01-01

    Liver cancer is one of the world’s most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury. PMID:26576090

  8. The effect of aloe emodin-encapsulated nanoliposome-mediated r-caspase-3 gene transfection and photodynamic therapy on human gastric cancer cells.

    PubMed

    Li, Kai-Ting; Duan, Qin-Qin; Chen, Qing; He, Juan-Wen; Tian, Si; Lin, Hai-Dan; Gao, Qing; Bai, Ding-Qun

    2016-02-01

    Gastric carcinoma (GC) has high incidence and mortality rates in China. Surgery and chemotherapy are the main treatments. Photodynamic therapy (PDT) has become a new treatment modality, appearing in recent experimental studies and clinical trials in various tumors. This study explores the combined effect of gene transfection with PDT on GC cells using aloe emodin (AE)-encapsulated nanoliposomes, which acted as gene carrier as well as one photosensitizer (PS). AE-encapsulated nanoliposomes (nano-AE) were prepared by reverse evaporation method. Electron microscopy and nano-ZS90 analyzer were used to detect its morphology, size, and wavelength. Western blot was used to detect the expression of the caspase-3 after transfection. MTT assay and flow cytometry were employed to determine the cytotoxic and apoptotic rates, respectively. Hoechst 33342 staining was adopted to detect the morphological changes in death gastric cancer cells. Cellular reactive oxygen species (ROS) contents were measured by DCFH-DA staining. Outcomes demonstrated that the nano-AE has good properties as gene delivery carriers as well as a PS. The group in which the recombinant plasmid of r-caspase-3 was transfected had higher protein expression of the caspase-3 than controls, meanwhile the proliferation rates of the transfected cells were inhibited by the nano-AE-mediated PDT in an energy-dependent manner. In addition, in the transfected cells, the death rate increased to 77.3% as assessed 12 h after PDT (6.4 J/cm(2) ). Hochest 33342 staining also revealed that the death rate increased significantly in the transfected group compared with other groups. Compared to control groups, the production of ROS in nano-AE PDT group had quadrupled in SGC-7901 cells as early as 1 h after PDT, while it is similar to the group of nano-AE transfection and PDT. Nano-AE-mediated r-caspase-3 gene transfection coupled with PDT could inhibit the proliferation rate and increase the apoptotic rate remarkably in human

  9. Chromosome band 16q24 is frequently deleted in human gastric cancer.

    PubMed

    Mori, Y; Matsunaga, M; Abe, T; Fukushige, S; Miura, K; Sunamura, M; Shiiba, K; Sato, M; Nukiwa, T; Horii, A

    1999-05-01

    We have analysed the loss of heterozygosity (LOH) on chromosome bands 16q22-q24 in 24 primary gastric cancer tissues and found three regions of frequent allelic loss (16q22, 16q24.1-q24.3 and 16q24.3). The region for the most frequent allelic loss (63%) was in 16q24.1-q24.3. LOH of this region had no relationship with histological subtype, but a significant association between LOH and microscopic lymphangial invasion was observed. Although not significant, vascular and gastric wall invasions are also associated with LOH. The region includes the locus for the H-cadherin gene. Therefore we examined the genetic and epigenetic alterations of this gene. Markedly reduced expression was observed in gastric cancer cell lines compared with that of normal gastric mucosa. However, no mutation was found in this gene in any of the gastric cancer tissues or the gastric cancer cell lines. Furthermore, we analysed the methylation status of the 5'-flanking region of the gene, but no significant association was found. We suggest that some other tumour suppressor gene(s) in 16q24.1-q24.3 may be responsible for gastric carcinogenesis. PMID:10408866

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

    PubMed

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng; Cao, Zhifei

    2015-09-01

    Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L., and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. PMID:25982451

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

    SciTech Connect

    Liu, Wenming; Meng, Mei; Zhang, Bin; Du, Longsheng; Pan, Yanyan; Yang, Ping; Gu, Zhenlun; Zhou, Quansheng Cao, Zhifei

    2015-09-01

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

  12. Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT-YB1-MDR1 Signaling Pathway.

    PubMed

    Mo, Dongliang; Fang, Hongbo; Niu, Kaifeng; Liu, Jing; Wu, Meng; Li, Shiyou; Zhu, Tienian; Aleskandarany, Mohammed A; Arora, Arvind; Lobo, Dileep N; Madhusudan, Srinivasan; Balajee, Adayabalam S; Chi, Zhenfen; Zhao, Yongliang

    2016-05-15

    Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic and chemotherapeutic significance of RECQL4 in human gastric cancer, which has yet to be determined. We observed significant increases in RECQL4 mRNA or protein in >70% of three independent sets of human gastric cancer specimens examined, relative to normal gastric tissues. Strikingly, high RECQL4 expression in primary tumors correlated well with poor survival and gastric cancer lines with high RECQL4 expression displayed increased resistance to cisplatin treatment. Mechanistic investigations revealed a novel role for RECQL4 in transcriptional regulation of the multidrug resistance gene MDR1, through a physical interaction with the transcription factor YB1. Notably, ectopic expression of RECQL4 in cisplatin-sensitive gastric cancer cells with low endogenous RECQL4 was sufficient to render them resistant to cisplatin, in a manner associated with YB1 elevation and MDR1 activation. Conversely, RECQL4 silencing in cisplatin-resistant gastric cancer cells with high endogenous RECQL4 suppressed YB1 phosphorylation, reduced MDR1 expression, and resensitized cells to cisplatin. In establishing RECQL4 as a critical mediator of cisplatin resistance in gastric cancer cells, our findings provide a therapeutic rationale to target RECQL4 or the downstream AKT-YB1-MDR1 axis to improve gastric cancer treatment. Cancer Res; 76(10); 3057-66. ©2016 AACR. PMID:27013200

  13. Gastric carcinoma distal to the cardia: a review of the epidemiological pathology of the precusors to a preventable cancer.

    PubMed

    Stemmermann, Grant N; Fenoglio-Preiser, Cecilia

    2002-12-01

    A distinctive gastritis precedes the development of cancer distal to the cardia. Helicobacter pylori infection and the use of pickled foods as substitutes for fresh fruits and vegetables constitute the most important environmental factors that generate this gastritis. This review describes the anatomical changes that characterise the step-by-step evolution of a process that begins in childhood and culminates in invasive cancer in middle and old age. Progression of the gastritis can be followed by measuring the host antibody response to the H. pylori infection and by serum assays that indicate loss of parietal cell mass. Cancer of the distal stomach will disappear if adequate, sanitary housing and year-round fresh vegetables are made available to all economic levels of society. Programmes that offer these reforms must be sustained over several generations, since the anatomical changes that precede gastric cancer are probably not reversible and begin early in life. In the absence of these reforms, death from gastric cancer may be prevented if patients with asymptomatic, early cancers are identified. High H. pylori antibody levels and serum pepsinogen assays may be used to identify persons with the extensive gastritis that favours the presence of such early cancers. PMID:12555987

  14. Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?

    PubMed Central

    Singh, Shikha Satendra; Yap, Wei Ney; Arfuso, Frank; Kar, Shreya; Wang, Chao; Cai, Wanpei; Dharmarajan, Arunasalam M; Sethi, Gautam; Kumar, Alan Prem

    2015-01-01

    Frequent activation of phosphatidylinositol-3 kinases (PI3K)/Akt/mTOR signaling pathway in gastric cancer (GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3CA gene or loss of function of PTEN, a tumor suppressor protein, to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis, hence, there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development, further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein, we review the common dysregulation of PI3K/Akt/mTOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/mTOR pathway inhibition. PMID:26604635

  15. Epirubicin-based compared with docetaxel-based chemotherapy for advanced gastric carcinoma: A systematic review and meta-analysis.

    PubMed

    Petrioli, Roberto; Roviello, Giandomenico; Zanotti, Laura; Roviello, Franco; Polom, Karol; Bottini, Alberto; Marano, Luigi; Francini, Edoardo; Marrelli, Daniele; Generali, Daniele

    2016-06-01

    Docetaxel or Epirubicin-based regimens are both approved for the treatment of metastatic gastric cancer. We perform a systemic review with metanalysis to evaluate the efficacy and toxicities of docetaxel-based chemotherapy compared with epirubicin-containing regimens. A metaanalysis of randomized studies in accordance with the preference guidelines for reported items in systematic reviews and meta-analyses is performed in which the databases of PubMed, the Cochrane Library, and the ASCO University Meeting were searched for relevant publications. The primary outcome was efficacy, the secondary toxicities. A total of 553 cases were included in the meta-analysis; 278 received epirubicin-based treatment and 313 received docetaxel. The pooled risk ratio to achieve an objective response and a disease control rate were 1.08 (95% CI 0.85-1.37; P=0.52) and 0.90 (95% CI 0.75-1.08; P=0.27) respectively. EPI arm showed a decrease in the risk of neutropenia, anemia, fatigue, asthenia and diarrhea, paraesthesia; docetaxel arm showed a decrease in the risk of leucopenia, thrombocytopenia, anorexia, nausea, nausea-vomiting, stomatitis and neutropenic fever. The results of our study suggest a similar activity of docetaxel and epirubicin-based chemotherapeutic regimens in metastatic gastric cancer. Other parameters as, comorbidity, concomitant diseases and prior therapies should be taken into account to address the clinician's choice in selecting the best therapeutical approach for any single patient. PMID:27083592

  16. Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells.

    PubMed

    Xu, Mei-Ying; Lee, Dong Hwa; Joo, Eun Ji; Son, Kun Ho; Kim, Yeong Shik

    2013-09-01

    In this study, we investigated the anticancer mechanism of akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides in human gastric cancer cell lines. It was shown that AS-induced cell death is caused by autophagy and apoptosis in AGS cells. The apoptosis-inducing effect of AS was characterized by annexin V/propidium (PI) staining, increase of sub-G1 phase and caspase-3 activation, while the autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF1) decreased AS-induced cell death and caspase-3 activation, but caspase-3 inhibitor Ac-DEVD-CHO did not affect LC3-II accumulation or AS-induced cell viability, suggesting that AS induces autophagic cell death and autophagy contributes to caspase-3-dependent apoptosis. Furthermore, AS activated p38/c-Jun N-terminal kinase (JNK), which could be inhibited by BaF1, and caspase-3 activation was attenuated by both SB202190 and SP600125, indicating that AS-induced autophagy promotes mitogen-activated protein kinases (MAPKs)-mediated apoptosis. Taken together, these results demonstrate that AS induces autophagic and apoptotic cell death and autophagy plays the main role in akebia saponin PA-induced cell death. PMID:23850994

  17. Identification of Serum Biomarkers for Gastric Cancer Diagnosis Using a Human Proteome Microarray.

    PubMed

    Yang, Lina; Wang, Jingfang; Li, Jianfang; Zhang, Hainan; Guo, Shujuan; Yan, Min; Zhu, Zhenggang; Lan, Bin; Ding, Youcheng; Xu, Ming; Li, Wei; Gu, Xiaonian; Qi, Chong; Zhu, Heng; Shao, Zhifeng; Liu, Bingya; Tao, Sheng-Ce

    2016-02-01

    We aimed to globally discover serum biomarkers for diagnosis of gastric cancer (GC). GC serum autoantibodies were discovered and validated using serum samples from independent patient cohorts encompassing 1,401 participants divided into three groups, i.e. healthy, GC patients, and GC-related disease group. To discover biomarkers for GC, the human proteome microarray was first applied to screen specific autoantibodies in a total of 87 serum samples from GC patients and healthy controls. Potential biomarkers were identified via a statistical analysis protocol. Targeted protein microarrays with only the potential biomarkers were constructed and used to validate the candidate biomarkers using 914 samples. To provide further validation, the abundance of autoantibodies specific to the biomarker candidates was analyzed using enzyme-linked immunosorbent assays. Receiver operating characteristic curves were generated to evaluate the diagnostic accuracy of the serum biomarkers. Finally, the efficacy of prognosis efficacy of the final four biomarkers was evaluated by analyzing the clinical records. The final panel of biomarkers consisting of COPS2, CTSF, NT5E, and TERF1 provides high diagnostic power, with 95% sensitivity and 92% specificity to differentiate GC patients from healthy individuals. Prognosis analysis showed that the panel could also serve as independent predictors of the overall GC patient survival. The panel of four serum biomarkers (COPS2, CTSF, NT5E, and TERF1) could serve as a noninvasive diagnostic index for GC, and the combination of them could potentially be used as a predictor of the overall GC survival rate. PMID:26598640

  18. A rare case of verrucous carcinoma of penis in an human immunodeficiency virus- infected patient

    PubMed Central

    Noronha, Tonita Mariola; Girisha, Banavasi S.; Bhat, Shubha P.; Christy, Carol M.; Handattu, Sripathi; Fernandes, Michelle S.

    2015-01-01

    Cancer is a significant cause of morbidity and mortality in human immunodeficiency virus-infected subjects. Verrucous carcinoma is a peculiarly slow evolving, but relentlessly expanding variant of epidermoid carcinoma that is extremely reluctant to metastasize. A 60-year-old unmarried male patient presented with urethral discharge of 3 weeks duration. Dorsal slit of the prepuce revealed an ulceroproliferative growth measuring 3 cm × 3 cm arising from prepuce and involving glans. Biopsy from the growth in the prepuce showed histopathological features of verrucous carcinoma. Partial amputation of the penis was done. Human papillomavirus DNA by polymerase chain reaction was negative. The patient was started on antiretroviral therapy. PMID:26692616

  19. Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells.

    PubMed

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

    2014-01-01

    Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer. PMID:24911042

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

    PubMed

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

    2015-11-01

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

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

    PubMed Central

    Somarajan, S; Muszynski, ND; Obioha, C; Richards, WO; Bradshaw, LA

    2012-01-01

    We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes, and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in MGG and in mucosal electrodes (r =0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes. PMID:22735166

  2. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    SciTech Connect

    Wu Xiaofeng; Fan Jia; E-mail: jiafan99@yahoo.com; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-04-20

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment.

  3. A Proteomic Study of Human Merkel Cell Carcinoma

    PubMed Central

    Shao, Qiang; Byrum, Stephanie D.; Moreland, Linley E.; Mackintosh, Samuel G.; Kannan, Aarthi; Lin, Zhenyu; Morgan, Michael; Stack, Brendan C.; Cornelius, Lynn A.; Tackett, Alan J.; Gao, Ling

    2014-01-01

    Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin. The incidence has been quadrupled with a 5-year mortality rate of 46%, presently there is no cure for metastatic disease. Despite the contribution of Merkel cell polyomavirus, the molecular events of MCC carcinogenesis are poorly defined. To better understand MCC carcinogensis, we have performed the first quantitative proteomic comparison of formalin-fixed, paraffin-embedded (FFPE) MCC tissues using another neuroendocrine tumor (carcinoid tumor of the lung) as controls. Bioinformatic analysis of the proteomic data has revealed that MCCs carry distinct protein expression patterns. Further analysis of significantly over-expressed proteins suggested the involvement of MAPK, PI3K/Akt/mTOR, wnt, and apoptosis signaling pathways. Our previous study and that from others have shown mTOR activation in MCCs. Therefore, we have focused on two downstream molecules of the mTOR pathway, lactate dehydrogenase B (LDHB) and heterogeneous ribonucleoprotein F (hnRNPF). We confirm over-expression of LDHB and hnRNPF in two primary human MCC cell lines, 16 fresh tumors, and in the majority of 80 tissue microarray samples. Moreover, mTOR inhibition suppresses LDHB and hnRNPF expression in MCC cells. The results of the current study provide insight into MCC carcinogenesis and provide rationale for mTOR inhibition in pre-clinical studies. PMID:25284964

  4. A Proteomic Study of Human Merkel Cell Carcinoma.

    PubMed

    Shao, Qiang; Byrum, Stephanie D; Moreland, Linley E; Mackintosh, Samuel G; Kannan, Aarthi; Lin, Zhenyu; Morgan, Michael; Stack, Brendan C; Cornelius, Lynn A; Tackett, Alan J; Gao, Ling

    2013-11-25

    Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin. The incidence has been quadrupled with a 5-year mortality rate of 46%, presently there is no cure for metastatic disease. Despite the contribution of Merkel cell polyomavirus, the molecular events of MCC carcinogenesis are poorly defined. To better understand MCC carcinogensis, we have performed the first quantitative proteomic comparison of formalin-fixed, paraffin-embedded (FFPE) MCC tissues using another neuroendocrine tumor (carcinoid tumor of the lung) as controls. Bioinformatic analysis of the proteomic data has revealed that MCCs carry distinct protein expression patterns. Further analysis of significantly over-expressed proteins suggested the involvement of MAPK, PI3K/Akt/mTOR, wnt, and apoptosis signaling pathways. Our previous study and that from others have shown mTOR activation in MCCs. Therefore, we have focused on two downstream molecules of the mTOR pathway, lactate dehydrogenase B (LDHB) and heterogeneous ribonucleoprotein F (hnRNPF). We confirm over-expression of LDHB and hnRNPF in two primary human MCC cell lines, 16 fresh tumors, and in the majority of 80 tissue microarray samples. Moreover, mTOR inhibition suppresses LDHB and hnRNPF expression in MCC cells. The results of the current study provide insight into MCC carcinogenesis and provide rationale for mTOR inhibition in pre-clinical studies. PMID:25284964

  5. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas.

    PubMed

    Nault, Jean-Charles; Datta, Shalini; Imbeaud, Sandrine; Franconi, Andrea; Mallet, Maxime; Couchy, Gabrielle; Letouzé, Eric; Pilati, Camilla; Verret, Benjamin; Blanc, Jean-Frédéric; Balabaud, Charles; Calderaro, Julien; Laurent, Alexis; Letexier, Mélanie; Bioulac-Sage, Paulette; Calvo, Fabien; Zucman-Rossi, Jessica

    2015-10-01

    Hepatocellular carcinomas (HCCs) are liver tumors related to various etiologies, including alcohol intake and infection with hepatitis B (HBV) or C (HCV) virus. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We found clonal integration of adeno-associated virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase reverse transcriptase; one case), CCNE1 (cyclin E1; three cases), TNFSF10 (tumor necrosis factor superfamily member 10; two cases) and KMT2B (lysine-specific methyltransferase 2B; one case), leading to overexpression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 of 11 cases) and without known risk factors (6 of 11 cases), suggesting a pathogenic role for AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC. PMID:26301494

  6. 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

  7. MicroRNA-106a functions as an oncogene in human gastric cancer and contributes to proliferation and metastasis in vitro and in vivo.

    PubMed

    Zhu, Meng; Zhang, Ning; He, Shuixiang; Yan, Ruirui; Zhang, Jun

    2016-06-01

    Mounting evidences has shown that miRNAs are involved in the development and progression of gastric cancer acts as tumor suppressor genes or oncogenes. In our previous studies, we have found that the up-regulation of miR-106a occurs frequently in human gastric cancer tissues compared with that of normal tissues. Here, we investigate the role of the ectopic expressed miR-106a in the progression and metastasis of gastric cancer in vitro and in vivo. FFPE samples have the priority to be included and qRT-PCR was used to detect the miR-106a expression. Human gastric cancer cells and immortalized gastric epithelial cell were selected and the miR-106a mimic and inhibitor were transfected. Cell growth was determined by MTT method. The flow cytometric analysis for cell apoptosis and transwell assays for evaluating the cell migration and invasion were conducted. Luciferase assay and western blot confirmed the direct binding site of miR-106a and its target. BALB/c nude mice were randomly divided to explore the implantation of gastric cancer cells transfected with miR-106a antagomir. Abnormal over-expression of miR-106a significantly promoted gastric cancer cell proliferation, metastasis, inhibited the cell apoptosis. Functional experiment ascertained that miR-106a interacted with FAS and mediated caspase3 pathway. Knockdown of miR-106a leaded to the attenuation of gastric cancer implantation capacity in vivo. Moreover, expression of TIMP2 was inversely associated with miR-106a in nodule tissues. Apoptotic body was also seen under electron microscope accompanied by silencing of miR-106a. Together, this data indicated that miR-106a may act as an oncogene and contribute to gastric cancer development. PMID:27142596

  8. Galectin-1 mediates TGF-β-induced transformation from normal fibroblasts into carcinoma-associated fibroblasts and promotes tumor progression in gastric cancer

    PubMed Central

    Zheng, Lingyan; Xu, Cong; Guan, Zhonghai; Su, Xingyun; Xu, Zhenzhen; Cao, Jiang; Teng, Lisong

    2016-01-01

    Rcinoma-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment. Cancer cells can induce the transformation from normal fibroblasts (NFs) into CAFs, reciprocally, CAFs promote tumor invasion and proliferation. TGF-β has been the mostly accepted factor to fuel NFs transformation into CAFs. Galectin-1 (Gal1) is highly upregulated in CAFs of multiple human cancers, and overexpression of Gal1 in CAFs promotes tumor progression. The effect of Gal1 on TGF-β-induced CAFs activation has not yet been established in gastric cancer (GC). In this study, we show that Gal1 expression in stroma is positively related to TGF-β in epithelial cells by retrospective analysis of GC patient samples. Meanwhile, conditioned media (CMs) from gastric cancer cells induce expression of both Gal1 and the CAFs marker alpha smooth muscle actin (α-SMA) in NFs via TGF-β secretion. Knockdown of Gal1 prevents TGF-β-induced the conversion of NFs to CAFs. CMs from fibroblasts overexpressing Gal1 inhibits cancer cells apoptosis, promotes migration and invasion in vitro. Thus, Gal1 is significantly involved in the development of tumor-promoting microenvironment by enhancing TGF-β signaling in a positive feedback loop. Targeting Gal1 in tumor stroma should be considered as a potential therapeutic target for GC. PMID:27186290

  9. Effect of sodium bicarbonate on aspirin-induced damage and potential difference changes in human gastric mucosa

    PubMed Central

    Bowen, Bruce K; Krause, William J; Ivey, Kevin J

    1977-01-01

    Two aspirin tablets in 100 ml fluid will produce microscopical damage to the human stomach. A study was performed to determine whether a small amount of sodium bicarbonate (equivalent to one-third of a teaspoonful of baking soda) could protect against this damage. Sequential gastric biopsy specimens were taken from 15 healthy subjects before, during, and after intragastric instillation of one of the following isotonic solutions: saline; sodium bicarbonate; 600 mg aspirin suspended in sodium bicarbonate; and aspirin suspended in saline. On a separate day the same solutions were instilled, but gastric transmucosal potential differences were monitored. Light microscopy and scanning electron microscopy of the biopsy specimens showed occasional mucous degranulation of mucosal surface cells, but no cell damage during instillation of sodium bicarbonate. Light microscopy studies 10 minutes after aspirin in saline showed damage in 20% of surface cells, with focal areas of cellular disruption and microscopic erosions, but only 3·4% of cells were damaged after aspirin in bicarbonate and there were no erosions. Electron microscopy showed a damaged honeycombed appearance of surface epithelium after aspirin in saline and a normal cobblestone appearance after aspirin in bicarbonate. Aspirin dissolved in bicarbonate failed to induce the usual fall in potential difference. These findings indicate that sodium bicarbonate in amounts equivalent to one-third of a teaspoonful of baking soda protects the gastric mucosa against aspirin-induced damage and prevents the usual fall in potential difference after aspirin. ImagesFIG 2FIG 3FIG 4 PMID:922417

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2014-01-01

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

  12. 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

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

    PubMed Central

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

    2016-01-01

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

  14. Prognostic value of decreased expression of RBM4 in human gastric cancer

    PubMed Central

    Yong, Hongmei; Zhu, Huijun; Zhang, Shu; Zhao, Wei; Wang, Wei; Chen, Chen; Ding, Guipeng; Zhu, Lun; Zhu, Ziyuan; Liu, Huaidong; Zhang, Yongjie; Wen, Jinbo; Kang, Xing; Zhu, Jin; Feng, Zhenqing; Liu, Baorui

    2016-01-01

    RNA-binding motif 4 (RBM4) is a multifunctional protein that participates in regulating alternative splicing and mRNA translation. Its reduced expression has been associated with poor overall survival in lung cancer, breast cancer and ovarian cancer. We assessed RBM4 protein expression levels with immunohistochemistry in tissue microarrays containing malignant gastric cancer tissues and benign tissues from 813 patients. We also examined the expression levels of RBM4 mRNA in twenty-five paired gastric cancer samples and adjacent noncancerous tissues. Both RBM4 protein and mRNA expression levels were significantly lower in gastric cancer tissues compared with the adjacent noncancerous tissues. There was a significant association between reduced RBM4 protein expression and differentiation (P < 0.001), lymph node metastasis (P = 0.026), TNM state (P = 0.014) and distant metastasis (P = 0.036). Patients with reduced RBM4 expression (P < 0.001, CI = 0.315–0.710) and TNM stage III and IV (P < 0.001, CI = 4.757–11.166) had a poor overall survival. These findings suggest that RBM4 is a new biomarker in gastric cancer, as the reduced expression of this protein is correlated with poor differentiation, lymph node status and distant metastasis. Further, lower RBM4 expression is an independent prognostic marker for gastric cancer. PMID:27324405

  15. Targeted Glycoproteomic Identification of Biomarkers for Human Breast Carcinoma

    PubMed Central

    Abbott, Karen L.; Aoki, Kazuhiro; Lim, Jae-Min; Porterfield, Mindy; Johnson, Rachelle; O’Regan, Ruth M.; Wells, Lance; Tiemeyer, Michael; Pierce, Michael

    2016-01-01

    Glycosylation is a dynamic post-translational modification that changes during the development and progression of various malignancies. During the oncogenesis of breast carcinoma, the glycosyltransferase known as N-acetylglucosaminyltransferase Va (GnT-Va) transcript levels and activity are increased due to activated oncogenic signaling pathways. Elevated GnT-V levels leads to increased β(1,6)-branched N-linked glycan structures on glycoproteins that can be measured using a specific carbohydrate binding protein or lectin known as L-PHA. L-PHA does not bind to nondiseased breast epithelial cells, but during the progression to invasive carcinoma, cells show a progressive increase in L-PHA binding. We have developed a procedure for intact protein L-PHA-affinity enrichment, followed by nanospray ionization mass spectrometry (NSI-MS/MS), to identify potential biomarkers for breast carcinoma. We identified L-PHA reactive glycoproteins from matched normal (nondiseased) and malignant tissue isolated from patients with invasive ductal breast carcinoma. Comparison analysis of the data identified 34 proteins that were enriched by L-PHA fractionation in tumor relative to normal tissue for at least 2 cases of ductal invasive breast carcinoma. Of these 34 L-PHA tumor enriched proteins, 12 are common to all 4 matched cases analyzed. These results indicate that lectin enrichment strategies targeting a particular glycan change associated with malignancy can be an effective method of identifying potential biomarkers for breast carcinoma. PMID:18271524

  16. NHE1 activity contributes to migration and is necessary for proliferation of human gastric myofibroblasts.

    PubMed

    Czepán, Mátyás; Rakonczay, Zoltán; Varró, Andrea; Steele, Islay; Dimaline, Rod; Lertkowit, Nantaporn; Lonovics, János; Schnúr, Andrea; Biczó, György; Geisz, Andrea; Lázár, György; Simonka, Zsolt; Venglovecz, Viktória; Wittmann, Tibor; Hegyi, Péter

    2012-03-01

    Myofibroblasts play central roles in wound healing, deposition of the extracellular matrix and epithelial function. Their functions depend on migration and proliferation within the subepithelial matrix, which results in accelerated cellular metabolism. Upregulated metabolic pathways generate protons which need to be excreted to maintain intracellular pH (pH(i)). We isolated human gastric myofibroblasts (HGMs) from surgical specimens of five patients. Then we characterized, for the first time, the expression and functional activities of the Na(+)/H(+) exchanger (NHE) isoforms 1, 2 and 3, and the functional activities of the Na(+)/HCO(3)(-) cotransporter (NBC) and the anion exchanger (AE) in cultured HGMs using microfluorimetry, immunocytochemistry, reverse transcription polymerase chain reaction and immunoblot analysis. We showed that NHE1-3, NBC and AE activities are present in HGMs and that NHE1 is the most active of the NHEs. In scratch wound assays we also demonstrated (using the selective NHE inhibitor HOE-642) that carbachol and insulin like growth factor II (IGF-II) partly stimulate migration of HGMs in a NHE1-dependent manner. EdU incorporation assays revealed that IGF-II induces proliferation of HGMs which is inhibited by HOE-642. The results indicate that NHE1 is necessary for IGF-II-induced proliferation response of HGMs. Overall, we have characterized the pH(i) regulatory mechanisms of HGMs. In addition, we demonstrated that NHE1 activity contributes to both IGF-II- and carbachol-stimulated migration and that it is obligatory for IGF-II-induced proliferation of HGMs. PMID:22138972

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

    SciTech Connect

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

    2008-03-07

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

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

    PubMed

    Ortakci, F; Sert, S

    2012-12-01

    The objective of this study was to determine the effect of encapsulation on survival of probiotic Lactobacillus acidophilus ATCC 4356 (ATCC 4356) in yogurt and during artificial gastric digestion. Strain ATCC 4356 was added to yogurt either encapsulated in calcium alginate or in free form (unencapsulated) at levels of 8.26 and 9.47 log cfu/g, respectively, and the influence of alginate capsules (1.5 to 2.5mm) on the sensorial characteristics of yogurts was investigated. The ATCC 4356 strain was introduced into an artificial gastric solution consisting of 0.08 N HCl (pH 1.5) containing 0.2% NaCl or into artificial bile juice consisting of 1.2% bile salts in de Man, Rogosa, and Sharpe broth to determine the stability of the probiotic bacteria. When incubated for 2h in artificial gastric juice, the free ATCC 4356 did not survive (reduction of >7 log cfu/g). We observed, however, greater survival of encapsulated ATCC 4356, with a reduction of only 3 log cfu/g. Incubation in artificial bile juice (6 h) did not significantly affect the viability of free or encapsulated ATCC 4356. Moreover, statistically significant reductions (~1 log cfu/g) of both free and encapsulated ATCC 4356 were observed during 4-wk refrigerated storage of yogurts. The addition of probiotic cultures in free or alginate-encapsulated form did not significantly affect appearance/color or flavor/odor of the yogurts. However, significant deficiencies were found in body/texture of yogurts containing encapsulated ATCC 4356. We concluded that incorporation of free and encapsulated probiotic bacteria did not substantially change the overall sensory properties of yogurts, and encapsulation in alginate using the extrusion method greatly enhanced the survival of probiotic bacteria against an artificial human gastric digestive system. PMID:23021757

  19. A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer

    ClinicalTrials.gov

    2015-06-10

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  20. Automated quantification of aligned collagen for human breast carcinoma prognosis

    PubMed Central

    Bredfeldt, Jeremy S.; Liu, Yuming; Conklin, Matthew W.; Keely, Patricia J.; Mackie, Thomas R.; Eliceiri, Kevin W.

    2014-01-01

    Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS) are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries. PMID:25250186

  1. 3,3'-Diindolylmethane induces anti-human gastric cancer cells by the miR-30e-ATG5 modulating autophagy.

    PubMed

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

    2016-09-01

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

  2. Sweat gland carcinoma in a human immunodeficiency virus-infected patient.

    PubMed

    Toi, M; Kauffman, L; Peterson, L; Golitz, L; Myers, A

    1995-02-01

    Eccrine (sweat gland) carcinoma is a rare form of skin cancer that may be locally destructive. It is known to recur after resection and can metastasize to regional or distant lymph nodes. There have been two reported cases in association with patients immunocompromised as the result of organ transplantation (I. Penn: Prog Allergy. 37: 259, 1986). We report here the first case of sweat gland carcinoma in a patient infected with the human immunodeficiency virus. PMID:7539911

  3. Treatment of gastric cancer

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    NIE, CHAO; ZHOU, JIE; QIN, XIAOKANG; SHI, XIANMING; ZENG, QINGQI; LIU, JIA; YAN, SHIHAI; ZHANG, LEI

    2016-01-01

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

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

    PubMed Central

    Jiang, Zheng; Liu, Yao; Wang, Chuan

    2016-01-01

    Background Although elevated expression of NanogP8 has been detected in many human tumor tissues, its role in gastric tumorigenesis remains unclear. Therefore, this study aimed to investigate the function and regulatory mechanism of NanogP8 in gastric cancer. Methods In this study, NanogP8 cDNA was amplified by real time polymerase chain reaction from the human gastric cancer cell line SGC-7901. The shRNA for RNA interference was established. The NanogP8, pAkt, Akt, pERK, ERK, p-mTOR, and mTOR proteins were detected by using the Western blot assay. Cell viability was evaluated by using the CCK-8 assay. Cell migration and invasion were also examined by using the transwell assay. Results The results indicated that the NanogP8 overexpression promoted proliferation and migration of SGC-7901 cell line, whereas its ablation exerted opposite effects. Interestingly, NanogP8 activated Akt, a key mediator of survival signals, and without affecting total Akt protein level. The NanogP8-increased gastric cell proliferation was downregulated by Akt inhibition. Our results further showed that increasing NanogP8 expression in human gastric cancer cells promoted cell proliferation by activating the AKT/mTOR pathway and further maintained gastric cell survival. Conclusion Our findings extend the knowledge regarding the oncogenic functions and proved that the NanogP8 regulates cell proliferation and migration by Akt/mTOR signaling pathway in human gastric cancer SGC-7901cell line. PMID:27563247

  6. Characterization of a novel human papillomavirus DNA in the cervical carcinoma cell line ME180.

    PubMed Central

    Reuter, S; Delius, H; Kahn, T; Hofmann, B; zur Hausen, H; Schwarz, E

    1991-01-01

    The human cervical carcinoma cell line ME180 was examined for human papillomavirus (HPV) DNA and RNA. The integrated DNA of a presumably new HPV type showing a relationship closer to HPV39 than to HPV18 was cloned and sequenced. HPV sequences from the E6-E7-E1 region are expressed as poly(A)+ RNAs. Images PMID:1716694

  7. Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

    PubMed Central

    Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2015-01-01

    Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients. PMID:26497995

  8. Differentiation of immature DCs into endothelial-like cells in human esophageal carcinoma tissue homogenates.

    PubMed

    Lu, Jing; Bai, Ruihua; Qin, Zhenzhu; Zhang, Yanyan; Zhang, Xiaoyan; Jiang, Yanan; Yang, Hongyan; Huang, Youtian; Li, Gang; Zhao, Mingyao; Dong, Ziming

    2013-08-01

    We previously reported endothelial-like differentiation (ELD) of immature dendritic cells (iDCs) in the microenvironment derived from EC9706 human esophageal squamous cell carcinoma conditioned medium (CM). However, the CM is far different from the esophageal carcinoma tissue of patients. In addition, the potential role of peri-esophageal carcinoma in the ELD of iDCs is also unknown. In the present study, we showed that the tumor microenvironment derived from esophageal carcinoma homogenate promoted iDCs to differentiate from the DC pathway toward endothelial cells, while the peri-esophageal carcinoma homogenate did not have this function. During the course of ELD, ERK signaling pathway and CREB were activated. Blocking MEK, both the phosphorylation of ERK and CREB, and the ELD of iDCs were inhibited. These data suggest that esophageal carcinoma tissue, not peri-esophageal carcinoma tissue, can drive iDCs to differentiate into endothelial-like cells, instead of differentiation into mature DCs, thereby losing the ability of antigen presentation. PMID:23708958

  9. GASTRIC MOTOR DISTURBANCES IN PATIENTS WITH IDIOPATHIC RAPID GASTRIC EMPTYING

    PubMed Central

    Bharucha, Adil E.; Manduca, Armando; Lake, David S.; Fidler, Jeff; Edwards, Phillip; Grimm, Roger C.; Zinsmeister, Alan R.; Riederer, Stephen J.

    2011-01-01

    Background and Aims The mechanisms of “idiopathic” rapid gastric emptying, which is associated with functional dyspepsia and functional diarrhea, are not understood. Our hypotheses were that increased gastric motility and reduced postprandial gastric accommodation contribute to rapid gastric emptying. Methods Fasting and postprandial (300kCal nutrient meal) gastric volumes were measured by magnetic resonance imaging (MRI) in 20 healthy people and 17 with functional dyspepsia; 7 had normal and 10 had rapid gastric emptying. In 17 healthy people and patients, contractility was analyzed by spectral analysis of a time-series of gastric cross-sectional areas. Logistic regression models analyzed whether contractile parameters, fasting volume, and postprandial volume change could discriminate between health and patients with normal or rapid gastric emptying. Results While upper gastrointestinal symptoms were comparable, patients with rapid emptying had a higher (p = 0.002) body mass index (BMI) than normal gastric emptying. MRI visualized propagating contractions at ~ 3 cpm in healthy people and patients. Compared to controls (0.16 ± 0.02, Mean ± SEM), the amplitude of gastric contractions in the entire stomach was higher (OR 4.1, 95% CI 1.2–14.0) in patients with rapid (0.24 ± 0.03) but not normal gastric emptying (0.10 ± 0.03). Similar differences were observed in the distal stomach. However, the propagation velocity, fasting gastric volume, and the postprandial volume change were not significantly different between patients and controls. Conclusions MRI provides a noninvasive and refined assessment of gastric volumes and contractility in humans. Increased gastric contractility may contribute to rapid gastric emptying in functional dyspepsia. PMID:21470342

  10. An assessment of human gastric fluid composition as a function of PPI usage

    PubMed Central

    Foltz, Emily; Azad, Sassan; Everett, Mary Lou; Holzknecht, Zoie E.; Sanders, Nathan L.; Thompson, J. Will; Dubois, Laura G.; Parker, William; Keshavjee, Shaf; Palmer, Scott M.; Davis, R. Duane; Lin, Shu S.

    2015-01-01

    Abstract The standard of care for chronic gastro‐esophageal reflux disease (GERD), which affects up to 40% of the population, is the use of drugs such as proton pump inhibitors (PPIs) that block the production of stomach acid. Despite widespread use, the effects of PPIs on gastric fluid remain poorly characterized. In this study, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Various enzymatic and immunoassays as well as mass spectrometry were utilized to analyze the concentrations of bile, gastricsin, trypsin, and pepsin in the gastric fluid. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. In general, the concentrations of all analytes evaluated varied over several orders of magnitude, covering a minimum of a 2000‐fold range (gastricsin) and a maximum of a 1 × 106 –fold range (trypsin). Furthermore, the concentrations of various analytes were poorly correlated with one another in the samples. For example, trypsin and bile concentrations showed a significant (P < 0.0001) but not strong correlation (r = 0.54). Finally, direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid. These results further delineate the profound effects that PPI usage has on the physiology of the stomach. PMID:25626870

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

    PubMed Central

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

    2004-01-01

    Helicobacter pylori infects over half the world's population and is a leading cause of peptic ulcer and gastric cancer. H. pylori infection results in chronic inflammation of the gastric mucosa, and progression of chronic inflammation leads to glandular atrophy and intestinal metaplasia. However, how this chronic inflammation is induced or maintained is not well known. Here, we show that chronic inflammation caused by H. pylori infection is highly correlated with de novo synthesis of peripheral lymph node addressin (PNAd) presented on high-endothelial venule (HEV)-like vessels. The number of HEV-like vessels dramatically increases as chronic inflammation progresses. We found that the PNAd is bound by L-selectin·IgM chimeric protein, and decorated by NCC-ST-439 antibody, which is suggested to recognize both nonsulfated and 6-sulfated sialyl Lewis X on core 2 branched O-glycans, and MECA-79 antibody, which reacts with 6-sulfo N-acetyllactosamine on extended core 1 O-glycans. These results indicate that PNAd on HEV-like vessels present in the gastric mucosa subsequent to H. pylori infection is similar to those on HEVs present in the secondary lymphoid organs, which are essential for lymphocyte circulation. Moreover, eradication of H. pylori is associated with the disappearance of HEV-like vessels in the gastric mucosa. By contrast, very few PNAd were found in the gastric mucosa of patients with chemical gastritis caused by nonsteroidal antiinflammatory drugs. These results strongly suggest that PNAd in HEV-like vessels plays a critical role in lymphocyte recruitment during chronic inflammation induced by H. pylori infection. PMID:15591109

  12. Modulation of microRNAs by ionizing radiation in human gastric cancer.

    PubMed

    He, Jinpeng; Hua, Junrui; Ding, Nan; Xu, Shuai; Sun, Rui; Zhou, Guangming; Xie, Xiaodong; Wang, Jufang

    2014-08-01

    Gastric cancer is one of the most common cancers in China. Although surgery is the primary therapeutic method, radiotherapy has become an integral part, particularly in the early and intermediate stages of gastric cancer. microRNAs (miRNAs) are involved in the regulation of diverse cellular processes in response to intrinsic and extrinsic stress. A change in miRNA expression profile has been identified in various types of tumor cells in response to radiation; however, there is no relevant information concerning gastric cancer. In the present study, we investigated the miRNA profiles of two clinical gastric cancer samples exposed to X‑rays using miRNA microarray. We found that 16 miRNAs were downregulated and 2 miRNAs were upregulated significantly in both irradiated samples when compared with the unirradiated samples. Decreases in the levels of miR‑300 and miR‑642 expression were confirmed by qRT‑PCR in more clinical samples and in cultured cell lines. We predicted the targets of the two miRNAs with TargetScan and classified all the candidate targets with Gene Ontology, which indicated that both miR‑300 and miR‑642 potentially regulate cellular radiation response by modulating apoptosis, cell cycle regulation and DNA damage and repair pathway-related genes. Cell cycle assay and immunofluorescence assay demonstrated that miR‑300 regulates radiation‑induced G2 cell cycle arrest and DNA damage repair. In conclusion, our findings indicate that ionizing radiation modulates the miRNA expression profile, and the changes in several specific miRNAs such as miR‑300 have the potential to be used in the treatment, diagnosis and prognosis of gastric cancer. PMID:24919435

  13. Properties of a potassium channel in cultured human gastric cells (HGT-1) possessing specific omeprazole binding sites.

    PubMed Central

    Sandle, G I; Fraser, G; Fogg, K; Warhurst, G

    1993-01-01

    The HGT-1 human gastric cell line is similar to acid secreting parietal cells in that it possesses H2 receptors, histamine sensitive adenyl cyclase, and Cl- channels, which are activated by histamine by a cyclic adenosine monophosphate (cAMP) dependent mechanism. To discover if HGT-1 cells have additional properties found in parietal cells, [3H]omeprazole and patch clamp recording techniques were used to evaluate specific omeprazole binding sites and K+ channels in the plasma membrane. HGT-1 cells exhibited [3H]omeprazole binding in the non-stimulated state, which increased 100% in the presence of 1 mM histamine. High conductance (about 155 pS) K+ channels were active spontaneously in 17% of cell attached or excised inside out patches in non-stimulated subconfluent HGT-1 cells. In inside out patches, channel activity increased fivefold during depolarisation, ion substitution experiments confirmed that the channels were highly selective for K+, and channel activity was almost abolished by removal of Ca2+ or addition of 5 mM Ba2+. In quiescent cell attached patches, 0.1 mM dibutyryl cAMP failed to activate K+ channels. In contrast, 6.7 microM A23187 (a Ca2+ ionophore) increased intracellular Ca2+ concentration from mean (SEM) 14 (3) nM to 248 (30) nM and activated K+ channels in 21% of patches. It is concluded that the plasma membrane of HGT-1 cells possesses (a) specific 3H-omeprazole binding sites, which may reflect the omeprazole sensitive H+,K(+)-ATPase present in gastric parietal cells; and (b) Ca(2+)-activated K+ channels, which may be located in the basolateral membrane of human gastric parietal cells and play a part in acid secretion triggered by Ca(2+)-mediated secretory agonists. PMID:8244097

  14. Nobiletin Induces Protective Autophagy Accompanied by ER-Stress Mediated Apoptosis in Human Gastric Cancer SNU-16 Cells.

    PubMed

    Moon, Jeong Yong; Cho, Somi Kim

    2016-01-01

    Nobiletin, a major component of citrus fruits, is a polymethoxyflavone derivative that exhibits anticancer activity against several forms of cancer, including SNU-16 human gastric cancer cells. To explore the nobiletin-induced cell death mechanism, we examined the changes in protein expression caused by nobiletin in human gastric cancer SNU-16 cells by means of two-dimensional gel electrophoresis (2-DGE), followed by peptide mass fingerprinting (PMF) analysis. Seventeen of 20 selected protein spots were successfully identified, including nine upregulated and eight downregulated proteins. In nobiletin-treated SNU-16 cells the glucose-regulated protein 78 kDa (GRP78) mRNA level was induced most significantly among six proteins related to cell survival and death. Western blot analysis was used to confirm the expression of GRP78 protein. We detected increases in the levels of the ER-stress related proteins inositol requiring enzyme 1 alpha (IRE1-α), activating transcription factor 4 (ATF-4), and C/EBP homology protein (CHOP), as well as GRP78, in response to nobiletin in SNU-16 cells. Furthermore, the ER stress-mediated apoptotic protein caspase-4 was proteolytically activated by nobiletin. Pretreatment with chloroquine, an autophagy inhibitor, strongly augmented apoptosis in SNU-16 cells, as evidenced by decreased cell viability, an increased number of sub-G1 phase cells and increased levels of cleaved PARP. Our results suggest that nobiletin-induced apoptosis in SNU-16 cells is mediated by pathways involving intracellular ER stress-mediated protective autophagy. Thus, the combination of nobiletin and an autophagy inhibitor could be a promising treatment for gastric cancer patients. PMID:27428937

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

    SciTech Connect

    Schlosser, Paul M. Sasso, Alan F.

    2014-10-15

    Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. - Highlights: • Hexavalent chromium (Cr-VI) reduction in gastric juices is a key detoxifying step. • pH-dependent Cr-VI reduction rates are explained using known chemical speciation. • Reduction in rodents appears to involve multiple pools of electron donors. • Reduction appears to continue after 60 min, although more slowly than initial rates.

  16. 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

  17. Nanosecond laser pulse induced stress waves enhanced magnetofection of human carcinoma cells in vitro

    NASA Astrophysics Data System (ADS)

    Durdík, Š.; Babincová, M.; Bergemann, C.; Babinec, P.

    2012-09-01

    We have developed a novel platform for efficient gene delivery into cells using magnetic force for pre-concentration of gene-magnetic nanoparticle complex on the surface of cells with subsequent nanosecond laser pulse for generation of stress waves in transfection chamber which is able to permeabilize cell membrane for the facilitated delivery of gene into the cell interior. Combination of these two physical factors increased the efficiency of three different human carcinoma cells transfection with plasmid coding green fluorescence protein from 43% to 67%, from 35% to 54%, and from 23% to 39%, for HeLa (cervical carcinoma), MCF-7 (breast carcinoma), and UCI-107 (ovarian carcinoma) cells, respectively, as compared with using only magnetofection. Proposed fast, simple, and efficient method may have far reaching applications for cancer gene therapy.

  18. Human papillomavirus-related squamous cell carcinoma of the anal canal with papillary features

    PubMed Central

    Leon, Marino E; Shamekh, Rania; Coppola, Domenico

    2015-01-01

    Human papillomavirus (HPV) related squamous cell carcinoma (SCC) involving the anal canal is a well-known carcinoma associated with high-risk types of HPV. HPV-related SCC with papillary morphology (papillary SCC) has been described in the oropharynx. We describe, for the first time, a case of anal HPV-related squamous carcinoma with papillary morphology. The tumor arose from the anal mucosa. The biopsies revealed a superficially invasive SCC with prominent papillary features and associated in situ carcinoma. The tumor cells were positive for p16 and were also positive for high-risk types of HPV using chromogenic in situ hybridization. The findings are consistent with a HPV-related SCC of the anal canal with papillary features. This tumor shows histologic features similar to a papillary HPV-related SCC of the oropharynx. Additional studies are needed to characterize these lesions. PMID:25717259

  19. Cellular inhibitor of apoptosis protein 1 (cIAP1) stability contributes to YM155 resistance in human gastric cancer cells.

    PubMed

    Jung, Soo-A; Park, Yong-Man; Hong, Seung-Woo; Moon, Jai-Hee; Shin, Jae-Sik; Lee, Ha-Reum; Ha, Seung-Hee; Lee, Dae-Hee; Kim, Jeong Hee; Kim, Seung-Mi; Kim, Jeong Eun; Kim, Kyu-pyo; Hong, Yong Sang; Choi, Eun Kyung; Lee, Jung Shin; Jin, Dong-Hoon; Kim, TaeWon

    2015-04-17

    YM155, which blocks the expression of survivin, a member of the inhibitor of apoptosis (IAP) family, induces cell death in a variety of cancer types, including prostate, bladder, breast, leukemia, and non-small lung cancer. However, the mechanism underlying gastric cancer susceptibility and resistance to YM155 is yet to be specified. Here, we demonstrate that cIAP1 stability dictates resistance to YM155 in human gastric cancer cells. Treatment of human gastric cancer cells with YM155 differentially induced cell death dependent on the stability of cIAP1 as well as survivin. Transfection with cIAP1 expression plasmids decreased cell sensitivity to YM155, whereas knockdown of endogenous cIAP1 using RNA interference enhanced sensitivity to YM155. In addition, double knockdown of survivin and cIAP1 significantly induced cell death in the YM155-resistant cell line, MKN45. We also showed that YM155 induced autoubiquitination and proteasome-dependent degradation of cIAP1. Surprisingly, survivin affected the stability of cIAP1 through binding, contributing to cell sensitivity to YM155. Thus, our findings reveal that YM155 sensitizes human gastric cancer cells to apoptotic cell death by degrading cIAP1, and furthermore, cIAP1 in gastric cancer cells may act as a PD marker for YM155 treatment. PMID:25635055

  20. Alpha-fetoprotein-producing hepatoid gastric adenocarcinoma in a child presenting with spontaneous gastric perforation.

    PubMed

    Emir, Suna; Karakurt, Neslihan; Karakuş, Esra; Şenel, Emrah; Kırsaçlıoğlu, Ceyda; Demir, Hacı Ahmet; Orhan, Diclehan

    2014-01-01

    Gastric adenocarcinoma is a rare entity in the pediatric population. Gastric hepatoid adenocarcinoma with elevated serum alpha-fetoprotein (AFP) is seen extremely rarely in children. A 12-year-old boy was admitted to the hospital with complaint of abdominal pain. X-ray revealed free air density below the diaphragm. Emergent laparotomy showed perforated stomach. Four weeks after the operation, he was readmitted with severe gastrointestinal obstruction symptoms. He underwent an explorative laparotomy, which revealed intestinal edema and diffuse small solid nodules covering the peritoneum. Serum AFP level was mildly elevated. Endoscopic evaluation of the upper gastrointestinal tract was performed, and a gastric mass was detected. All pathological findings were compatible with gastric carcinoma showing hepatoid differentiation. We report an unusual case of AFP-producing hepatoid gastric adenocarcinoma presenting with gastric perforation. This is, to the best of our knowledge, the first reported case of AFP- producing hepatoid gastric adenocarcinoma presenting with gastric perforation in a child. PMID:24827954

  1. RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions.

    PubMed

    Broad, John; Takahashi, Nobuyuki; Tajimi, Masaomi; Sudo, Masaki; Góralczyk, Adam; Parampalli, Umesh; Mannur, Kesava; Yamamoto, Toshinori; Sanger, Gareth J

    2016-02-01

    The aim was to characterise RQ-00201894, a novel non-macrolide motilin agonist, using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. A reporter gene assay assessed motilin receptor function. Selectivity of action was determined using a panel of different receptors, ion channels, transporters and enzymes. Cholinergically-mediated muscle contractions were evoked by electrical field stimulation (EFS) of human gastric antrum. The results showed that RQ-00201894, motilin and erythromycin acted as full motilin receptor agonists (EC50: 0.20, 0.11, 69 nM, respectively). In this function, RQ-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (EC50 19 nM) and greater selectivity over all other receptors/mechanisms tested. In human stomach RQ-00201894 0.1-30 μM concentration-dependently increased EFS-evoked contractions (up to 1209%; pEC50 6.0). At 0.1-10 μM this activity was usually prolonged. At higher concentrations (3-30 μM) RQ-00201894 also caused a short-lasting muscle contraction, temporally disconnected from the increase in EFS-evoked contractions. RQ-00201894 10 μM did not consistently affect submaximal contractions evoked by carbachol. In conclusion, RQ-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach, an activity thought to correlate with an ability to increase gastric emptying. PMID:26685754

  2. Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway.

    PubMed

    Wang, Lan; Ouyang, Fei; Liu, Xiaobo; Wu, Shu; Wu, Hong-Mei; Xu, Yuandong; Wang, Bin; Zhu, Jinrong; Xu, Xuehu; Zhang, Liang

    2016-01-26

    CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer. PMID:26565812

  3. Overexpressed CISD2 has prognostic value in human gastric cancer and promotes gastric cancer cell proliferation and tumorigenesis via AKT signaling pathway

    PubMed Central

    Wang, Lan; Ouyang, Fei; Liu, Xiaobo; Wu, Shu; Wu, Hong-mei; Xu, Yuandong; Wang, Bin; Zhu, Jinrong; Xu, Xuehu; Zhang, Liang

    2016-01-01

    CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer. PMID:26565812

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer. PMID:27507203

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

    PubMed

    Schlosser, Paul M; Sasso, Alan F

    2014-10-15

    Chronic oral exposure to hexavalent chromium (Cr-VI) in drinking water has been shown to induce tumors in the mouse gastrointestinal (GI) tract and rat oral cavity. The same is not true for trivalent chromium (Cr-III). Thus reduction of Cr-VI to Cr-III in gastric juices is considered a protective mechanism, and it has been suggested that the difference between the rate of reduction among mice, rats, and humans could explain or predict differences in sensitivity to Cr-VI. We evaluated previously published models of gastric reduction and believe that they do not fully describe the data on reduction as a function of Cr-VI concentration, time, and (in humans) pH. The previous models are parsimonious in assuming only a single reducing agent in rodents and describing pH-dependence using a simple function. We present a revised model that assumes three pools of reducing agents in rats and mice with pH-dependence based on known speciation chemistry. While the revised model uses more fitted parameters than the original model, they are adequately identifiable given the available data, and the fit of the revised model to the full range of data is shown to be significantly improved. Hence the revised model should provide better predictions of Cr-VI reduction when integrated into a corresponding PBPK model. PMID:25151221

  7. Helicobacter pylori-infected MSCs acquire a pro-inflammatory phenotype and induce human gastric cancer migration by promoting EMT in gastric cancer cells

    PubMed Central

    ZHANG, QIANG; DING, JUAN; LIU, JINJUN; WANG, WEI; ZHANG, FENG; WANG, JUNHE; LI, YUYUN

    2016-01-01

    Accumulating clinical and experimental evidence has suggested that Helicobacter pylori (H. pylori) infection-associated gastric cancer (GC) is associated with high rates of mortality and serious health effects. The majority of patients succumb to H. pylori infection-associated GC due to metastasis. Mesenchymal stem cells (MSCs), which have multipotent differentiation potential, may be recruited into the tumor-associated stroma. MSCs are crucial components of the H. pylori infection-associated GC microenvironment, and may be critical for GC cell migration. In this study, an MSCs/H. pylori co-culture model was designed, and the effect of H. pylori-infected MSCs on the migration of GC cells was evaluated using a Transwell migration assay. H. pylori-infected MSC cytokine expression was evaluated using Luminex/ELISA. The expression of epithelial-mesenchymal transition (EMT) markers in the GC cells treated with supernatants from H. pylori-infected MSCs were detected by western blot analysis. The results demonstrated that the interaction between MSCs and H. pylori may induce GC cell migration, through secretion of a combination of cytokines that promote EMT in GC cells. The expression of phosphorylated forms of nuclear factor-κB (NF-κB) was observed to be increased in MSCs by H. pylori. Inhibition of NF-κB activation by pyrrolidine dithiocarbamate blocked the effects of H. pylori-infected MSCs on SGC-7901 human stomach adenocarcinoma cell migration. Overall, the results of the present study suggest that H. pylori-infected MSCs acquire a pro-inflammatory phenotype through secretion of a combination of multiple cytokines, a number of which are NF-κB-dependent. These cytokines enhance H. pylori infection-associated GC cell migration by promoting EMT in GC cells. The results of the present study provide novel evidence for the modulatory effect of MSCs in the tumor microenvironment and provide insight into the significance of stromal cell involvement in GC progression

  8. Correlation between DNA methyltransferases expression and Epstein-Barr virus, JC polyomavirus and Helicobacter pylori infections in gastric carcinomas.

    PubMed

    Ksiaa, F; Ziadi, S; Gacem, R B; Dhiab, M B; Trimeche, M

    2014-01-01

    It' is accepted that aberrant expression of DNA methyltransferases (DNMTs) is responsible for hypermethylation in genes. However, there are limited data related to factors inducing aberrant expression of DNMTs. A total of 43 surgically resected gastrc carcinomas (GC) samples were analysed. Using immunohistochemistry assay we have determined expression level of DNMT1 and 3b. The presence of H.pylori was evaluated by histology, whereas JC polyomavirus (JCV) and Epstein-Barr virus (EBV) detection were carried out by PCR and in situ hybridization techniques, respectively. High expression of DNMT1 and 3b were detected in 46.5% and 53.5% of GC cases, respectively. Co-expression of DNMT1 and 3b were found in 37.2% of cases. Using different techniques, H. pylori, JCV and EBV were detected in 55.8%, 32.6% and 9%, respectively. Moreover, in 37% of cases, we noted the presence of JCV and/or EBV infections. H.pylori co-infection was found in 64.3% (9/14) of JCV positive cases and in 50% of EBV positive GC, without a reliable significant relationship. Correlation analyses have showed a marked increase in DNMT1 expression in EBV associated GC (P= 0.02). Also, co-expression of DNMT1 and 3b was significantly associated with EBV infection in GC (P=0.05). Similarly, JCV associated GC mostly displayed DNMT1 positive status, but the difference did not reach the significant threshold. Nevertheless, infection with JCV and/or EBV was significantly correlated with increased expression of DNMT1 in GC (P= 0.05). Our study suggests that EBV and JCV infections in GC correlated with deregulation of DNA methyltransferases. PMID:25341997

  9. Cloning and analysis of human gastric mucin cDNA reveals two types of conserved cysteine-rich domains.

    PubMed Central

    Klomp, L W; Van Rens, L; Strous, G J

    1995-01-01

    Human gastric mucin was isolated by successive CsCl-gradient ultracentrifugation in the presence of guanidinium hydrochloride to prevent degradation of the polypeptide moieties of the molecules. The amino acid sequence of a tryptic fragment of this molecule was identical to that of a tryptic fragment of tracheobronchial mucin. An oligonucleotide based on this sequence hybridized specifically to human stomach mRNA and was subsequently used to screen a human stomach lambda ZAPII cDNA library. The largest of 10 positive clones encoded 850 amino acid residues, including the tryptic fragment, with high amounts of threonine, serine and proline residues. Interestingly, cysteine accounted for almost 8% of the amino acid residues. The 3' part of the sequence was very similar but not identical to the 3' region of human tracheobronchial cDNA. No tandem repeated sequences were present and the deduced polypeptide sequence contained two potential N-linked glycosylation sites. Four cysteine-rich clusters were detected, one of which was apparently homologous to the D-domains present in other mucins and in von Willebrand factor. The arrangement of the cysteines in three other cysteine-rich clusters was conserved in the human gastric mucin cDNA in a similar fashion as in two domains in the MUC2 gene product. The cysteine-rich domains were separated by short stretches of non-repetitive amino acid residues with a very high content of threonine and serine residues. These data suggest that the encoded polypeptide of this clone may be involved in disulphide-bond-mediated oligomerization of the mucin, and provide new insights into the molecular organization of mammalian apomucins. Images Figure 1 PMID:8948439

  10. 4-Methoxycinnamaldehyde inhibited human respiratory syncytial virus in a human larynx carcinoma cell line.

    PubMed

    Wang, Kuo Chih; Chang, Jung San; Chiang, Lien Chai; Lin, Chun Ching

    2009-09-01

    4-Methoxycinnamaldehyde, an active constituent of Agastache rugosa, was examined for its cytoprotective activity against RSV by XTT method in human larynx carcinoma cell line. 4-Methoxycinnamaldehyde could effectively inhibit cytopathic effect of RSV (p<0.0001) with an estimated IC(50) of 0.055microg/ml and a selectivity index (SI) of 898.2. 4-Methoxycinnamaldehyde (0.03microg/ml) could inhibit viral entrance by interfering viral attachment (IC(50) of 0.06microg/ml; p<0.0001) and internalization (IC(50) of 0.01microg/ml; p<0.0001). 4-Methoxycinnamaldehyde significantly increased the basal production of IFN (p=0.0015), but not the virus-induced IFN production. Therefore, its cytoprotective activity against RSV was not mediated by interferon. In conclusion, 4-methoxycinnamaldehyde might be helpful to manage the disease induced by RSV infection. PMID:19303275

  11. Gastric Emptying After Pickle-Juice Ingestion in Rested, Euhydrated Humans

    PubMed Central

    Miller, Kevin C.; Mack, Gary W.; Knight, Kenneth L.

    2010-01-01

    Abstract Context: Small volumes of pickle juice (PJ) relieve muscle cramps within 85 seconds of ingestion without significantly affecting plasma variables. This effect may be neurologic rather than metabolic. Understanding PJ's gastric emptying would help to strengthen this theory. Objective: To compare gastric emptying and plasma variables after PJ and deionized water (DIW) ingestion. Design: Crossover study. Setting: Laboratory. Patients or Other Participants: Ten men (age  =  25.4 ± 0.7 years, height  =  177.1 ± 1.6 cm, mass  =  78.1 ± 3.6 kg). Intervention(s): Rested, euhydrated, and eunatremic participants ingested 7 mL·kg−1 body mass of PJ or DIW on separate days. Main Outcome Measure(s): Gastric volume was measured at 0, 5, 10, 20, and 30 minutes postingestion (using the phenol red dilution technique). Percentage changes in plasma volume and plasma sodium concentration were measured preingestion (−45 minutes) and at 5, 10, 20, and 30 minutes postingestion. Results: Initial gastric volume was 624.5 ± 27.4 mL for PJ and 659.5 ± 43.8 mL for DIW (P > .05). Both fluids began to empty within the first 5 minutes (volume emptied: PJ  =  219.2 ± 39.1 mL, DIW  =  305.0 ± 40.5 mL, P < .05). Participants who ingested PJ did not empty further after the first 5 minutes (P > .05), whereas in those who ingested DIW, gastric volume decreased to 111.6 ± 39.9 mL by 30 minutes (P < .05). The DIW group emptied faster than the PJ group between 20 and 30 minutes postingestion (P < .05). Within 5 minutes of PJ ingestion, plasma volume decreased 4.8% ± 1.6%, whereas plasma sodium concentration increased 1.6 ± 0.5 mmol·L−1 (P < .05). Similar changes occurred after DIW ingestion. Calculated plasma sodium content was unchanged for both fluids (P > .05). Conclusions: The initial decrease in gastric volume with both fluids is likely attributable to gastric distension. Failure of the PJ group to empty afterward is likely due to PJ

  12. Antitumor effects of L6, an IgG2a antibody that reacts with most human carcinomas.

    PubMed Central

    Hellström, I; Beaumier, P L; Hellström, K E

    1986-01-01

    Mouse monoclonal antibody L6 (IgG2a subtype) recognizes a ganglioside antigen expressed at the surface of cells from human non-small-cell lung carcinomas, breast carcinomas, and colon carcinomas. We now show that this antibody can lyse L6 antigen-positive human tumor cells in the presence of Leu-11b-positive human lymphocytes (i.e., mediate antibody-dependent cellular cytotoxicity) or human serum (mediate complement-dependent cytotoxicity) and that it can inhibit the outgrowth of an L6 antigen-positive human tumor transplanted onto nude mice. PMID:3462743

  13. [Research on Early Diagnosis of Gastric Cancer by the Surface Enhanced Raman Spectroscopy of Human Hemoglobin].

    PubMed

    Wang, Wei; Pan, Zhi-feng; Tang, Wei-yue; Li, Yun-tao; Fan, Chun-zhen

    2015-12-01

    Early diagnosis have great positive effect on the treatment of gastric cancer patients. Raman spectroscopy can provide a useful monitor for hemoglobin dynamics. Besides, Raman spectroscopy has notable advantages in the fields of abnormal hemoglobin diagnosis, hemoglobin oxygen saturation deter mination and blood methemoglobin analysis. In this paper, novel silver colloid was synthesized by microwave heated method. The surface enhanced Raman spectrums of hemoglobin from 11 normal persons and 20 gastric cancer patients are measured and analyzed in order to obtain spectrums which are high repeatability and characteristic peaks protruding. By analyzing the assignations of the SERS bands, it found that the content of asparagine, tyrosine and phenylalanine in the hemoglobin are significantly lower than healthy people. Discussing the structure of hemoglobin, when hemoglobin combines with oxygen, Fe²⁺ is in a low spin state, ionic radius shrinks and moves 0. 075 nm and fall into the pore in the middle of the heme porphyrin ring plane. This spatial variation affects F8His connected with the iron, will narrow the gap between the globin in the two strands of the helix, as a result, HC2 tyrosine pushed out of the void. Using this mechanism, the absorption peak of 1 560 cm⁻¹ confirmed that the tyrosine content in patients with gastric cancer was lower than that of normal people. Principal component analysis(PCA) is employed to get a three-dimensional scatter plot of PC scores for the health and cancer groups, and it can be learned that they are distributed in separate areas. By using the method of discriminate analysis, it is found that the diagnostic algorithm separates the two groups with sensitivity of 90.0% and diagnostic specificity of 90.9%, the overall diagnostic accuracy was 90.3%. The results from this exploratory study demonstrate that, SERS detection of oxyhemoglobin combined with multivariate analysis would be an effective method for early diagnosis of gastric

  14. Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway

    PubMed Central

    Kong, Gui-Mei; Tao, Wen-Hua; Diao, Ya-Li; Fang, Peng-Hua; Wang, Ji-Jun; Bo, Ping; Qian, Feng

    2016-01-01

    8695.7 ± 449.1 U/g). The expression of the Cyt C, Endo G, and AIF proteins in SGC-7901 cells was significantly higher than those in the control (P < 0.05), while the expression of the Smac/Diablo protein was significantly lower than the control group after melittin exposure (P < 0.01). Ac-DEVD-CHO did not, however, have any effect on the expression of caspase-8 and FAS in the SGC-7901 cells. CONCLUSION: Melittin can induce apoptosis of human gastric cancer (GC) cells through the mitochondria pathways, and it may be a potent agent in the treatment of human GC. PMID:27003995

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

    SciTech Connect

    Kim, Jihye; Kim, Cherlhyun; Kim, Tae Sung; Bang, Sa Ik; Yang, Young; Park, Hyunjeong; Cho, Daeho . E-mail: cdhkor@sookmyung.ac.kr

    2006-06-16

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

  16. Parallel gastric emptying of nonhydrolyzable fat and water after a solid-liquid meal in humans

    SciTech Connect

    Cortot, A.; Phillips, S.F.; Malagelada, J.R.

    1982-05-01

    Our aim was to examine the control of gastric emptying of the oil phase of a mixed solid and liquid meal. Previous studies had shown that liquid dietary fats normally leave the stomach at a slower rate than does water. We wished to determine whether the slower emptying of fats was due to the physical characteristics of food (lower density and greater viscosity than water), to retardation by duodenal feedback mechanisms, or whether both factors contributed. Thus, we quantified the emptying rates of water and sucrose polyester (a nonabsorbable analog of dietary fat) ingested by healthy volunteers as a mixed solid and liquid meal. Gastric emptying was quantified by an intubation-perfusion method incorporating an occlusive jejunal balloon to facilitate recovery. Four phase-specific, nonabsorbable markers were used. (14C(Sucrose octaoleate and polyethylene glycol were incorporated in the meal and traced the lipid and water phases, respectively; (3H)glycerol triether and phenolsulfonphthalein were used as duodenal recovery markers. Sucrose polyester (substituting for dietary fat) was emptied very rapidly, and at about the same rate as was water, in contrast to natural fat, which empties very slowly. Emptying of water was rapid and comparable to that observed after mixed meals containing natural fat. These results imply that gastric emptying of the oil phase is controlled by receptors sensitive to the hydrolytic products of fat digestion and that the slow emptying of dietary fat is not simply due to its lower density.

  17. Effects of ophiopogonin B on the proliferation and apoptosis of SGC-7901 human gastric cancer cells

    PubMed Central

    ZHANG, WEIYUE; ZHANG, QIAOYAN; JIANG, YIPING; LI, FENG; XIN, HAILIANG

    2016-01-01

    Ophiopogonin B (OP-B) is a bioactive component of Radix Ophiopogon japonicus, which is often used in traditional Chinese medicine to treat cancer. The present study aimed to investigate the antitumor activity of OP-B in gastric cancer. Cell Counting kit-8, flow cytometry with Annexin V-fluorescein isothiocyanate, Hoechst staining, mitochondrial membrane potential (MMP) detection, and reactive oxygen species (ROS) assay were used to detect the biological function of SGC-7901 gastric cancer cells. The results demonstrated that high concentrations of OP-B (5, 10 and 20 μmol/l) exerted potent antiproliferative effects on SGC-7901 cells in a dose-dependent manner. Furthermore, apoptotic rates were increased and cell morphology was altered following treatment with OP-B. In addition, OP-B-induced apoptosis of SGC-7901 cells was associated with loss of MMP and increased ROS generation. Western blotting indicated that treatment with OP-B increased the protein expression levels of caspase-3 and B-cell lymphoma 2 (Bcl-2)-associated X protein, whereas the expression levels of Bcl-2 and the phosphorylation levels of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases 1/2 were decreased. These results suggest that OP-B may be considered a potential inhibitor of gastric cancer progression, and may be used as an alternative compound for its treatment. PMID:27121658

  18. [Human papilloma viruses: other risk factor of head and neck carcinoma].

    PubMed

    Woto-Gaye, G; M'Farrej, M K; Doh, K; Thiam, I; Touré, S; Diop, R; Dial, C

    2016-08-01

    Head and neck carcinoma (HNC) occupy the sixth place as the most frequent type of cancer worldwide. Next to alcohol and tobacco intoxication, other risk factors (RF) are suspected, including the human papilloma viruses (HPVs). The aim of this study was to highlight the prevalence of HPVs and histo-epidemiological characteristics of HNC HPV+ in Senegal. This is a prospective, multicenter preliminary study of 18 months (January 1, 2012-June 30, 2014). The cases of HNC histologically confirmed in Senegal were then sent to the bio-pathology department of the Curie Institute in Paris to search HPVs. In the 90 included cases, the PCR technique was successful in 54 cases (60%). HPVs were found in seven cases, that is, a prevalence of 13%. HPVs were associated with 5 cases of hypopharyngeal carcinoma and 2 cases of carcinoma of the oral cavity. Patients with HNC HPV+ had a median age of 42 years against 49 years for HPV-patients. Three patients (42.8%) with HPV+ carcinomas were smokers. Of the 47 HPV-patients, 40 patients (87.1%) had alcohol intoxication and/or smoking. The concept of oral sex was refuted by all our patients. Squamous cell carcinoma was the only histological type found. HPV+ cell carcinoma showed no specific histological appearance. HPVs are another certain RF of HNC in Senegal. The major therapeutic and prognostic impact of HPVinduced cancers requires the systematic search of the viruses by the PCR technique. PMID:27325173

  19. Establishment of two new cell lines derived from human breast carcinomas with HER-2/neu amplification.

    PubMed Central

    Meltzer, P.; Leibovitz, A.; Dalton, W.; Villar, H.; Kute, T.; Davis, J.; Nagle, R.; Trent, J.

    1991-01-01

    Two human cell lines (UACC-812 and 893), both containing significant amplification of the HER-2/neu gene, were established from biopsy specimens of breast carcinomas. One patient had Stage II breast carcinoma; the other had metastatic disease. Characterisation of these lines has revealed that both are highly aneuploid containing multiple clonal chromosome alterations, have doubling times near 100 h, and are oestrogen and progesterone receptor negative. Electron microscopy demonstrates that both lines contain numerous microvilli, cytoplasmic filaments, multivesicular bodies, and desmosomes. Immunoblot analysis for P-glycoprotein using the monoclonal antibody C219 was negative for both patient cell lines. These relatively rare cell lines may represent a useful model to investigate human breast carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1674877

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

    PubMed

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

    2015-01-01

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

  1. 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

  2. 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

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

    PubMed Central

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

    2014-01-01

    Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy. PMID:25115854

  4. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    PubMed Central

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  5. Neoadjuvant Chemotherapy Followed by Surgery versus Surgery Alone for Gastric Carcinoma: Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Gao, Shuang; Han, Wen-Xiu; Wei, Zhi-Jian

    2014-01-01

    Background The effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC. Methods We systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed. Results A total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65–1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20–3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment. Conclusions NAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with

  6. Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia

    PubMed Central

    Asano, Teita; Aida, Shuji; Suemasu, Shintaro; Tahara, Kayoko; Tanaka, Ken-ichiro; Mizushima, Tohru

    2015-01-01

    Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here. PMID:26620883

  7. Apoptosis initiation of β-ionone in SGC-7901 gastric carcinoma cancer cells via a PI3K-AKT pathway.

    PubMed

    Liu, Qian; Dong, Hong-Wei; Sun, Wen-Guang; Liu, Ming; Ibla, Juan C; Liu, Lian-Xin; Parry, John W; Han, Xiao-Hui; Li, Ming-Song; Liu, Jia-Ren

    2013-03-01

    β-ionone has been shown to hold potent anti-proliferative and apoptosis induction properties in vitro and in vivo. To investigate the effects of β-ionone on apoptosis initiation and its possible mechanisms of action, we qualified cell apoptosis, proteins related to apoptosis and a phosphatidylinositol 3-kinase (PI3K)-AKT pathway in human gastric adenocarcinoma cancer SGC-7901 cells. The results demonstrated that β-ionone-induced apoptosis in a dose-dependent manner in SGC-7901 cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. β-ionone was also shown to induce the expression of cleaved-caspase-3 and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. The significantly decreased levels of p-PI3K and p-AKT expression were observed in SGC-7901 cells after β-ionone treatments in a time- and dose-dependent manner (P < 0.01). Thus, the apoptosis induction in SGC-7901 cells by β-ionone may be regulated through a PI3K-AKT pathway. These results demonstrate a potential mechanism by which β-ionone to induce apoptosis initiation in SGC-7901 cells. PMID:23100158

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  9. Dietary fibers affect viscosity of solutions and simulated human gastric and small intestinal digesta.

    PubMed

    Dikeman, Cheryl L; Murphy, Michael R; Fahey, George C

    2006-04-01

    Two experiments were conducted to determine the viscosities of both soluble and insoluble dietary fibers. In Expt. 1, corn bran, defatted rice bran, guar gum, gum xanthan, oat bran, psyllium, soy hulls, stabilized rice bran, wheat bran, wood cellulose, and 2 methylcellulose controls (Ticacel 42, Ticacel 43) were hydrated in water overnight at 0.5, 1, 1.5, or 2% concentrations. In Expt. 2, guar gum, oat bran, psyllium, rice bran, wheat bran, and wood cellulose were subjected to a 2-stage in vitro gastric and small intestinal digestion simulation model. Viscosity was measured every 2 and 3 h during gastric and small intestinal simulation, respectively. Viscosities in both experiments were measured at multiple shear rates. Viscosities of all fiber solutions were concentration- and shear rate-dependent. Rice brans, soy hulls, and wood cellulose had the lowest viscosities, whereas guar gum, psyllium, and xanthan gum had the highest viscosities, regardless of concentration. During gastric simulation, viscosity was higher (P < 0.05) at 4 h than at 0 h for guar gum, psyllium, rice bran, and wheat bran. During small intestinal simulation, viscosities were higher (P < 0.05) between 3 and 9 h compared with 18 h for guar gum, oat bran, and rice bran. Guar gum, psyllium, and oat bran exhibited viscous characteristics throughout small intestinal simulation, indicating potential for these fibers to elicit blood glucose and lipid attenuation. Wheat and rice brans and wood cellulose did not exhibit viscous characteristics throughout small intestinal digestion; thus, they may be beneficial for laxation. PMID:16549450

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

    PubMed

    Muhammad, Jibran S; Zaidi, Syed F; Zhou, Yue; Sakurai, Hiroaki; Sugiyama, Toshiro

    2016-04-01

    Persistent Helicobacter pylori (H. pylori) infection in hostile gastric mucosa can result in gastric diseases. Helicobacter pylori induces to express antimicrobial peptides from gastric epithelial cells, especially human β-defensin 3 (hBD3), as an innate immune response, and this expression of hBD3 is mediated by epidermal growth factor receptor (EGFR) activation. In this study, we found that phosphorylation of a serine residue of EGFR via transforming growth factor β-activated kinase-1 (TAK1), and subsequent p38α activation is essential for H. pylori-induced hBD3 release from gastric epithelial cells. We showed that this pathway was dependent on H. pylori type IV secretion system and was independent of H. pylori-derived CagA or peptidoglycan. H. pylori infection induced phosphorylation of serine residue of EGFR, and this phosphorylation was followed by internalization of EGFR; consequently, hBD3 was released at an early phase of the infection. In the presence of TAK1 or p38α inhibitors, synthesis of hBD3 was completely inhibited. Similar results were observed in EGFR-, TAK1- or p38α-knockdown cells. However, NOD1 knockdown in gastric epithelial cells did not inhibit hBD3 induction. Our study has firstly demonstrated that this novel EGFR activating pathway functioned to induce hBD3 at an early phase of H. pylori infection. PMID:26733497

  11. 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.

  12. Circadian Rhythm Genes CLOCK and PER3 Polymorphisms and Morning Gastric Motility in Humans

    PubMed Central

    Yamaguchi, Mitsue; Kotani, Kazuhiko; Tsuzaki, Kokoro; Takagi, Ayaka; Motokubota, Naoko; Komai, Naho; Sakane, Naoki; Moritani, Toshio; Nagai, Narumi

    2015-01-01

    Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut. PMID:25775462

  13. Downregulated MicroRNA-133a in Gastric Juice as a Clinicopathological Biomarker for Gastric Cancer Screening.

    PubMed

    Shao, Juan; Fang, Peng-Hua; He, Biao; Guo, Li-Li; Shi, Ming-Yi; Zhu, Yan; Bo, Ping; Zhen-Wen, Zhen-Wen

    2016-01-01

    Circulatory miR-133a is a marker shared by several types of cancer. In this study we evaluated the feasibility of using miR-133a levels in gastric juice to screen for gastric cancer. A total of 204 samples of gastric juice and mucosa from gastric cancer, atrophic gastritis, gastric ulcer, superficial gastritis and healthy cases were collected by gastroscopy. The results showed that miR-133a levels in gastric juice and carcinoma tissues of patients with gastric cancer were significantly downregulated and positively correlated. Moreover, miR-133a in gastric juice has high operability, high reliability, high sensitivity, high specificity and relative stability, fit for clinical diagnosis of gastric cancer. PMID:27268657

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

    PubMed Central

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

    2016-01-01

    Helicobacter pylori infects ~50% of the world population, causing chronic gastritis and other forms of cellular damage. The present study assessed the influence of H. pylori on the mRNA expression levels of nuclear factor-κB1 (NFKB1), p38α and tumor necrosis factor-α (TNF-α) in human gastric mucosa in a southern Brazilian population. Human gastric tissue was collected by upper endoscopy and H. pylori diagnosis was performed using a rapid urease test and histological analysis. Total RNA was extracted and purified for subsequent cDNA synthesis and analysis by quantitative polymerase chain reaction (qPCR). The gastric tissue samples were divided into four groups as follows: Normal, inactive chronic gastritis, active chronic gastritis and intestinal metaplasia. The SDHA gene was classified as the most stable when compared with ACTB, GAPDH, B2M and HPRT1 genes, and was therefore selected as the reference gene for qPCR data normalization. TNF-α mRNA expression was significantly higher in samples that were positive for H. pylori and with active chronic gastritis. However, no difference was detected in the mRNA expression levels of NFKB1 and p38α between the groups. The present study concluded that the presence of H. pylori is associated with TNF-α upregulation in human gastric mucosa, but had no effect on NFKB1 and p38α mRNA expression levels. PMID:27284322

  15. Expression of Cyclooxygenase-2 in Human Transitional Cell Carcinoma of the Urinary Bladder

    PubMed Central

    Ristimäki, Ari; Nieminen, Outi; Saukkonen, Kirsi; Hotakainen, Kristina; Nordling, Stig; Haglund, Caj

    2001-01-01

    Recent studies suggest that expression of cyclooxygenase-2 (Cox-2) is elevated in transitional cell carcinoma (TCC) of the urinary bladder and that inhibition of Cox-2 activity suppresses bladder cancer in experimental animal models. We have investigated the expression of Cox-2 protein in human TCCs (n = 85), in in situ carcinomas (Tis) of the urinary bladder (n = 17), and in nonneoplastic urinary bladder samples (n = 16) using immunohistochemistry. Cox-2 immunoreactivity was detected in 66% (67 of 102) of the carcinomas, whereas only 25% (4 of 16) of the nonneoplastic samples were positive (P < 0.005). Cox-2 immunoreactivity localized to neoplastic cells in the carcinoma samples. The rate of positivity was the same in invasive (T1–3; 70%, n = 40) and in noninvasive (Tis and Ta; 65%, n = 62) carcinomas, but noninvasive tumors had a higher frequency (32%) of homogenous pattern of staining (>90% of the tumor cells positive) than the invasive carcinomas (10%) (P < 0.05). However, several invasive TCCs exhibited the strongest intensity of Cox-2 staining in the invading cells, whereas other parts of the tumor were virtually negative. Finally, strong Cox-2 positivity was also found in nonneoplastic ulcerations (2 of 2) and in inflammatory pseudotumors (2 of 2), in which the immunoreactivity localized to the nonepithelial cells. Taken together, our data suggest that Cox-2 is highly expressed in noninvasive bladder carcinomas, whereas the highest expression of invasive tumors associated with the invading cells, and that Cox-2 may also have a pathophysiological role in nonneoplastic conditions of the urinary bladder, such as ulcerations and inflammatory pseudotumors. PMID:11238034

  16. [Solubilization, purification and molecular characterization of H2 histamine receptor from human tumoral gastric cells HGT-1].

    PubMed

    Reyl-Desmars, F; Cherifi, Y; Le Romancer, M; Pigeon, C; Le Roux, S; Lewin, M J

    1991-01-01

    This communication reports the solubilization, the purification and the molecular characterization of the H2-histamine receptor from the cell line HGT-1 derived from a human gastric cancer. The receptor has been solubilized by Triton X100 and purified by gel filtration onto Sephacryl, affinity-chromatography (Sepharose-famotidine) and high performance liquid chromatography (HPLC). The purified receptor specifically bound the H2 selective ligand 3H-methyltiotidine with a kD of 160 nM (vs 50 nM for the intact HGT-1 cell) and a maximal binding capacity of 14,000 pmol/mg protein which represents a 12,170-fold enrichment and a degree of purity of 98%. It is a glycoprotein of 70 kDa molecular mass containing N-acetylglucosamine residues. PMID:1904297

  17. Human papillomavirus and oropharyngeal squamous cell carcinoma: what the clinician should know.

    PubMed

    Genden, Eric M; Sambur, Ian M; de Almeida, John R; Posner, Marshall; Rinaldo, Alessandra; Rodrigo, Juan P; Strojan, Primož; Takes, Robert P; Ferlito, Alfio

    2013-02-01

    The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising in contrast to the decreasing incidence of carcinomas arising in other subsites of the head and neck. The human papillomavirus (HPV) infection has played an increasing role in these epidemiological changes and as the etiology for a significant fraction of head and neck squamous cell carcinomas, OPSCC in particular. Most importantly, many retrospective studies have shown that the prognosis differs significantly between patients with HPV-associated tumors and non-HPV associated tumors. Thus, questions arise on the choices of treatment for patients based on HPV status and the consequences of therapy. Given the recognized relevance of HPV status in OPSCC, many new questions concerning the biology, treatment, and prevention of HPV infection arise. This review is intended to highlight some of the major issues and frequently asked questions relevant for the clinician dealing with patients with OPSCC. PMID:22752642

  18. Human Papilloma Virus in Oral Squamous Cell Carcinoma - The Enigma Unravelled.

    PubMed

    Khot, Komal P; Deshmane, Swati; Choudhari, Sheetal

    2016-03-01

    Squamous cell carcinoma of the head and neck (HNSCC) has long been regarded as a disease entity having a remarkable incidence worldwide and a fairly onerous prognosis; thus encouraging further research on factors that might modify disease outcome. Squamous cell carcinomas encompass at least 90% of all oral malignancies. Several factors like tobacco and tobacco-related products, alcohol, genetic predisposition and hormonal factors are suspected as possible causative factors. Human papilloma virus (HPV), the causal agent of cervical cancer also appears to be involved in the aetiology of oral and oropharyngeal cancer. HPVpositive squamous cell carcinoma (SCC) seems to differ from HPV-negative SCC. Many questions about the natural history of oral HPV infection remain under investigation. The aim of this review is to highlight the current understanding of HPV-associated oral cancer with an emphasis on its prognosis, detection and management. PMID:26981603

  19. Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

    2015-01-01

    Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management. PMID:26483987

  20. Purification of a protein associated with human bronchogenic squamous-cell carcinoma.

    PubMed

    Kelly, B S; Levy, J G

    1979-03-01

    A heteroantiserum raised in rabbits to extracts of human squamous-cell carcinoma of the lung which exhibited marked tumour specificity was used to monitor the fractionation and isolation of a tumour-associated component of the extract. KC1 extracts of pools of both normal lung and bronchogenic squamous-cell carcinoma were subjected to a series of purification steps involving acid precipitation, salting out, DEAE chromatography and preparative polyacrylamide-gel electrophoresis. At each stage, fractions were tested for their ability to react in the complement-fixation assay with the antiserum. A protein was ultimately isolated which did not appear to be present at detectable levels in an equivalent fraction of normal lung extract, reacted with the heteroantiserum, and appeared to be present in all extracts of squamous-cell carcinoma. PMID:465295

  1. Concurrent Human Papillomavirus-Positive Squamous Cell Carcinoma of the Oropharynx in a Married Couple

    PubMed Central

    García, Joaquín J.; Price, Katharine A.; Gao, Ge; Smith, David I.

    2016-01-01

    Background. Although alcohol and tobacco use are known risk factors for development of squamous cell carcinoma in the head and neck, human papillomavirus (HPV) has been increasingly associated with this group of cancers. We describe the case of a married couple who presented with HPV-positive oropharynx squamous cell carcinoma within two months of each other. Methods. Tumor biopsies were positive for p16 and high-risk HPV in both patients. Sanger sequencing showed a nearly identical HPV16 strain in both patients. Both patients received chemoradiation, and one patient also underwent transoral robotic tongue base resection with bilateral neck dissection. Results. Both patients showed no evidence of recurrent disease on follow-up PET imaging. Conclusions. New head and neck symptoms should be promptly evaluated in the partner of a patient with known HPV-positive oropharynx cancer. This case expands the limited current literature on concurrent presentation of HPV-positive oropharynx squamous cell carcinoma in couples. PMID:27418994

  2. Overexpression of fatty acid synthase predicts a poor prognosis for human gastric cancer

    PubMed Central

    DUAN, JIANGMAN; SUN, LI; HUANG, HONGXIANG; WU, ZHENZHEN; WANG, LIN; LIAO, WANGJUN

    2016-01-01

    Fatty acid synthase (FASN), a lipogenic multi-enzyme complex, is reported to be overexpressed in various types of of tumor tissues and serves an important role in tumor development and progression. However, the expression of FASN and its possible role in gastric cancer (GC) remains to be defined. In the present study, FASN expression in a group sample of 167 GC tissues was detected by immunohistochemistry and its correlation with clinicopathological features was analyzed. By clinical analysis, it was identified that FASN overexpression was positively correlated with the overall survival [P=0.008; hazard ratio (HR), 4.412; 95% confidence interval (CI), 1.463–13.305] and recurrence rate (P=0.014; HR, 1.705; 95% CI, 1.116–2.606) in patients with GC. In addition, expression of the FASN protein in GC tissues was correlated with age (P=0.032), clinical stage (P<0.001), gastric wall invasion (P=0.014), lymph node metastasis (P<0.001) and distant metastasis (P<0.001), however not with gender (P>0.05). In addition, FASN was observed to be overexpressed in GC tissues at an mRNA and protein level, compared with the adjacent non-cancerous tissues (P<0.05). Taken together, it was suggested that FASN was closely associated with GC metastasis and survival, which further provided evidence that FASN may be a promising prognostic biomarker for patients with GC. PMID:26936091

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

    PubMed

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

    1999-01-01

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

  4. Gastric Hamartomatous Polyps—Review and Update

    PubMed Central

    Vyas, Monika; Yang, Xiu; Zhang, Xuchen

    2016-01-01

    Gastric polyps are frequently encountered on endoscopic examinations. While many of these represent true epithelial lesions, some of the polyps may result from underlying stromal or lymphoid proliferations or even heterotopic tissue. Histologic examination is essential for accurate typing of the polyps to predict malignant potential and underlying possible genetic abnormalities. The focus of this review is on gastric hamartomatous polyps, which are relatively rare and diagnostically challenging. Though most of the gastric hamartomatous polyps are benign, certain types are associated with increased malignant potential. These include certain polyps associated with specific genetic familial polyposis syndromes and gastric inverted hamartomatous polyps. Identification of these polyps can result in the prevention or early diagnosis of gastric carcinoma and also help in the identification of family members with polyposis syndromes. The aim of this review is to categorize gastric hamartomatous polyps and aid in the identification of high-risk categories. PMID:27081323

  5. Superior antitumor activity of trastuzumab combined with capecitabine plus oxaliplatin in a human epidermal growth factor receptor 2-positive human gastric cancer xenograft model

    PubMed Central

    HARADA, SUGURU; YANAGISAWA, MIEKO; KANEKO, SAORI; YOROZU, KEIGO; YAMAMOTO, KANAME; MORIYA, YOICHIRO; HARADA, NAOKI

    2015-01-01

    In the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction cancer, it has been reported that the combination of trastuzumab with capecitabine plus cisplatin, or with 5-fluorouracil (5-FU) plus cisplatin, significantly increased overall survival compared with chemotherapy alone (ToGA trial). In addition, adjuvant therapy with capecitabine plus oxaliplatin (XELOX) improved the survival of patients who received curative D2 gastrectomy (CLASSIC trial). However, the efficacy of the combination of trastuzumab with XELOX for patients with HER2-positive gastric cancer remains unknown. The aim of this study, was to investigate the efficacy of the combination of trastuzumab with XELOX in a HER2-positive human gastric cancer xenograft model. Combination treatment with these three agents (trastuzumab 20 mg/kg, capecitabine 359 mg/kg and oxaliplatin 10 mg/kg), was found to exhibit a significantly stronger antitumor activity in NCI-N87 xenografts compared with either trastuzumab or XELOX alone. In this model, treatment with trastuzumab alone or trastuzumab plus oxaliplatin enhanced the expression of thymidine phosphorylase (TP), a key enzyme in the generation of 5-FU from capecitabine in tumor tissues. In in vitro experiments, trastuzumab induced TP mRNA expression in NCI-N87 cells. In addition, NCI-N87 cells co-cultured with the natural killer (NK) cell line CD16(158V)/NK-92 exhibited increased expression of TP mRNA. When NCI-N87 cells were cultured with CD16(158V)/NK-92 cells in the presence of trastuzumab, the mRNA expression of cytokines reported to have the ability to induce TP was upregulated in tumor cells. Furthermore, a medium conditioned by CD16(158V)/NK-92 cells also upregulated the expression of TP mRNA in NCI-N87 cells. These results suggest that trastuzumab promotes TP expression, either by acting directly on NCI-N87 cells, or indirectly via a mechanism that includes trastuzumab-mediated interactions

  6. Serum and Urine Biomarkers for Human Renal Cell Carcinoma

    PubMed Central

    Pastore, A. L.; Palleschi, G.; Silvestri, L.; Moschese, D.; Ricci, S.; Petrozza, V.; Carbone, A.; Di Carlo, A.

    2015-01-01

    Renal cell carcinoma (RCC) diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called “targeted therapies.” The identification of molecular markers in body fluids (e.g., sera and urine), which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients. PMID:25922552

  7. Telomerase activity and telomere length in human hepatocellular carcinoma.

    PubMed

    Huang, G T; Lee, H S; Chen, C H; Chiou, L L; Lin, Y W; Lee, C Z; Chen, D S; Sheu, J C

    1998-11-01

    Telomerase activity is activated and telomere length altered in various types of cancers, including hepatocellular carcinoma (HCC). A total of 39 HCC tissues and the corresponding non-tumour livers were analysed and correlated with clinical parameters. Telomere length was determined by terminal restriction fragment assay, and telomerase activity was assayed by telomeric repeat amplification protocol. Telomerase activity was positive in 24 of the 39 tumour tissues (1.15-285.13 total product generated (TPG) units) and in six of the 39 non-tumour liver tissues (1.05-1.73 TPG units). In the 28 cases analysed for telomere length, telomere length was shortened in 11 cases, lengthened in six cases, and unaltered in 11 cases compared with non-tumour tissues. Neither telomere length nor telomerase activity was correlated to any clinical parameters. PMID:10023320

  8. Phenotypic analysis of nylon-wool-adherent suppressor cells that inhibit the effector process of tumour cell lysis by lymphokine-activated killer cells in patients with advanced gastric carcinoma.

    PubMed

    Koyama, S; Fukao, K

    1994-01-01

    The causes of down-regulation of cytotoxic immune responses in cancer patients have not been fully evaluated. We previously demonstrated that T-cell-growth-factor-activated peripheral blood lymphocytes (PBL) with the surface phenotype CD8+ CD11b-, from patients with widespread metastasis of gastric carcinoma, inhibited the effector process of lymphokine-activated-killer(LAK)-cell-mediated cytolysis. In this study, we examined suppressor cell activity in freshly prepared PBL from 18 patients with advanced gastric carcinoma, and 10 normal healthy individuals. The suppressor cell activity was assayed by recording whether or not PBL inhibited directly the effector process of LAK cell cytotoxicity. Most of the PBL suspensions from cancer patients showed that they contained a population of cells that can directly inhibit the effector phase of tumor cell lysis of the cytotoxic cells. To analyze further the PBL responsible for the suppression, the cells were passed over a nylon-wool column. Nylon-wool-adherent cells significantly augmented the suppression, while the cells passing through abrogated the suppressive effect. Most nylon-wool-adherent cells from 10 normal healthy controls did not inhibit the cytotoxic reaction. To determine further the suppressor-effector population in nylon-wool-adherent cells, negative-selection studies using CD8-, CD4- or CD11b-coated magnetic beads, and positive-selection studies using CD8- or CD4-coated magnetic beads were performed. Finally the results suggest that the suppressor-effector cells comprise at least two different surface phenotypes: CD8+ T and CD8-CD11b+ cells. The possible role of CD4+ T cells and HLA-DR+ LeuM3+ macrophages as suppressor cells was ruled out in nylon-wool-adherent cells. CD8+ T and possibly CD8-CD11b+ cells apparently suppressed the efferent limb of the antitumor immunity. The selective immune suppression mediated by these cells may partly be concerned with escape mechanisms of gastric carcinoma from the host

  9. Labeling of human hepatocellular carcinoma cells by hexamethylene diamine modified fluorescent carbon dots

    NASA Astrophysics Data System (ADS)

    Dong, Wei; Dong, Yan; Wang, Ying; Zhou, Shiqi; Ge, Xin; Sui, Lili; Wang, Jingwen

    2013-12-01

    Fluorescent carbon dots (CDs) were synthesized by a solvothermal method with glucose as carbon source and surface-modified with 1,6-hexamethylene diamine. In this hybrid CDs, the modification played important role for improving the fluorescent performance by introducing nitrogenous compound to passivate CD's surface, making the CDs emit strong fluorescence. The as-prepared CDs were linked with mouse anti-human Alpha fetoprotein (AFP) antibody and goat anti-mouse immunoglobulin (IgG) to directly and indirectly label fixed human hepatocellular carcinoma cells, respectively. The cytotoxicity of these CDs were also tested using the human hepatocellular carcinoma cells. No apparent cytotoxicity was observed, which suggested the potential application of the as-prepared CDs in bioimaging.

  10. Cytotoxic mechanism of flavonoid from Temu Kunci (Kaempferia pandurata) in cell culture of human mammary carcinoma.

    PubMed

    Sukardiman; Darwanto, A; Tanjung, M; Darmadi, M O

    2000-01-01

    The cytotoxic activity of flavonoid from Temu Kunci (Kaempferia pandurata) was tested by brine shrimp lethality test and cell culture of human mammary carcinoma. This compound is pinostrobin, and has antitumor activity. However, the critical biochemical target of these pinostrobin has not been identified. In our present studies, we used DNA topoisomerase I which was isolated from human tumor. This result showed that pinostrobin inhibited DNA topoisomerase I activity. Pinostrobin may be interfere with DNA breakage-reunion reaction by stabilizing a key covalent intermediate between DNA and the enzyme, resulting in the cleavage DNA. An inhibition in the activity of DNA topoisomerase I is suggesting that this could be a possible mechanism of pinostrobin from Temu Kunci for the cytotoxicity observed in cell culture of human mammary carcinoma. PMID:11321439

  11. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro.

    PubMed Central

    Sharma, S A; Tummuru, M K; Miller, G G; Blaser, M J

    1995-01-01

    Gastric infection with Helicobacter pylori activates a mucosal inflammatory response by mononuclear cells and neutrophils that includes expression of cytokines interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, and IL-8. In this study, we analyzed the IL-8 response of human gastric cancer cell lines (Kato III, AGS, and MKN28) to H. pylori infection in vitro. IL-8 mRNA expression was detected by reverse transcription-PCR amplification of RNA extracted from epithelial cells after incubation with different H. pylori wild-type and mutant strains, and IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Exposure to viable H. pylori induced IL-8 mRNA and protein synthesis in all three gastric cell lines but not in nongastric epithelial cell lines. Heat-killed H. pylori and a crude cytotoxin preparation did not induce significant IL-8 secretion. IL-8 mRNA peaked between 2 and 4 h postinfection, and IL-8 protein production was maximal 24 h postinfection. Exposure of gastric carcinoma cells to other gastrointestinal bacteria, such as Pseudomonas aeruginosa, Campylobacter jejuni, and Escherichia coli, but not Campylobacter fetus, induced IL-8 synthesis. Wild-type strains that expressed the vacuolating cytotoxin (Tox+) and a cytotoxin-associated gene (cagA) product (CagA+) induced significantly more IL-8 than did CagA- Tox- strains. However, there was no decrease in IL-8 induction by isogenic mutants of CagA-, Tox-, or Cag- Tox- strains or by a mutant lacking the urease subunits. These results indicate that exposure to H. pylori and other gram-negative organisms that do not colonize the gastric mucosa induces IL-8 production by gastric carcinoma cells in vitro. Although the CagA+ Tox+ phenotype of H. pylori is associated with enhanced IL-8 production by gastric cell lines, other bacterial constituents are clearly essential. PMID:7729872

  12. The association between chemosensitivity and Pgp, GST-π and Topo II expression in gastric cancer

    PubMed Central

    2013-01-01

    Background To investigate the relationship between P-glycoprotein (Pgp), glutathione S-transferase π (GST-π) and topoisomerase II (Topo II) expression and human gastric cancer chemoresistance in vitro. Methods Primary single-cell suspensions were prepared from fresh specimens of primary gastric cancer and exposed to hydroxycamptothecin (HCPT), cisplatin (CDDP), 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin (MMC) for 48 h. Cell metabolic activity and rate of inhibition were evaluated using tetrazolium (MTT) assay. Pgp, GST-π and Topo II expression was determined in gastric carcinoma tissue samples using immunohistochemistry. Results Chemosensitivity of the gastric cancer cells varied; the rates of inhibition of cells exposed to HCPT, CDDP and 5-FU were significantly higher than that of cells exposed to ADM and MMC (p < 0.05). Gastric cancer cells with Pgp expression were resistant to ADM and HCPT (p = 0.008 and p = 0.011, respectively). Cells resistant to 5-FU, CDDP and MMC had significantly higher GST-π expression (p < 0.05). Topo II expression was significantly lower in cells resistant to HCPT, ADM and MMC (p < 0.05). Pgp and GST-π expression may contribute to primary resistance of gastric cancer cells to some chemotherapeutic drugs, while Topo II expression may indicate HCPT, ADM and MMC sensitivity. Conclusions Pgp, GST-π and Topo II detection and the MTT assay could be used as predictors in chemotherapeutic drug administration and for identifying drug resistance in gastric carcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3448329111142964. PMID:24326092

  13. PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation, Migration and Invasion

    PubMed Central

    Huang, Hua; Yang, Qichang; Cai, Jing; Wang, Qiuhong; Zhu, Junya; Shao, Mengting; Xiao, Jinzhang; Cao, Jie; Gu, Xiaodan; Zhang, Shusen; Wang, Yingying

    2015-01-01

    PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer. PMID:26488471

  14. PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation, Migration and Invasion.

    PubMed

    Yang, Lei; Zhu, Jia; Huang, Hua; Yang, Qichang; Cai, Jing; Wang, Qiuhong; Zhu, Junya; Shao, Mengting; Xiao, Jinzhang; Cao, Jie; Gu, Xiaodan; Zhang, Shusen; Wang, Yingying

    2015-01-01

    PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer. PMID:26488471

  15. Synergistic action of tiazofurin and genistein in human ovarian carcinoma cells.

    PubMed

    Li, W; Weber, G

    1998-01-01

    Tiazofurin, an oncolytic drug, reduces PI kinase activity and arrests chiefly in S phase. Genistein, an inhibitor of PIP kinase, tyrosine kinase, and topoisomerase-II, induces arrest in G2 and/or early M phase in most carcinoma cells. Both tiazofurin and genistein reduce second messenger IP3 concentration in ovarian carcinoma cells. Because genistein and tiazofurin attack different enzymic targets and arrest the cell cycle at different phases, we tested the hypothesis that tiazofurin might be synergistic with genistein. Human ovarian carcinoma OVCAR-5 cells were grown in flasks in monolayers. In growth inhibition assay for tiazofurin and genistein the IC50s were 26 and 18 microM, respectively, and in clonogenic assays the LC50s were 17 and 4 microM, respectively. Various combinations of the two drugs were tested. The best protocol took into consideration that tiazofurin decreased GTP concentration in cells by 50% at 12 h after administration. Tiazofurin (20 microM) and genistein (20 microM) as single agents reduced cell counts to 60% and 50%, respectively. The predicted value, as a sum of the effect of two drugs, would have been 30% of controls. However, genistein added 12 h after tiazofurin decreased cell counts to 8%, showing synergistic action of the two drugs for growth inhibition. Similar results were observed in the clonogenic assays, which also revealed synergistic cytotoxicity. The protocol yielding synergism might be of value in the clinical treatment of human ovarian carcinoma. PMID:9700722

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

    PubMed

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

    2012-12-01

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

  17. Effects of recombinant human endostatin on the expression of vascular endothelial growth factor in human gastric cancer cell line MGC-803

    PubMed Central

    WANG, YU-BIN; LIU, JUN-HONG; SONG, ZONG-MIN

    2013-01-01

    The present study aimed to explore the effects of recombinant human endostatin, endostar (ES), on the expression of vascular endothelial growth factor (VEGF) in the human gastric cancer cell line MGC-803. The expression of VEGF protein in MGC-803 cells was examined using immunohistochemistry. Subsequent to treatment with various concentrations of ES, the mRNA and VEGF protein expressions were determined in MGC-803 cells. A high level of VEGF protein expression was detected in MGC-803 cells. Subsequent to ES treatment, the mRNA and VEGF protein expressions were significantly decreased in MGC-803 cells (all P<0.05). In conclusion, ES is likely to inhibit the VEGF expression in MGC-803 cells. PMID:24648897

  18. A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter

    PubMed Central

    2014-01-01

    Background Gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. Vaccinia viral therapy has had promising therapeutic potential for various cancers and has a great safety profile. We investigated the therapeutic efficacy of a novel genetically-engineered vaccinia virus carrying the human sodium iodide symporter (hNIS) gene, GLV-1 h153, on gastric cancers and its potential utility for imaging with 99mTc pertechnetate scintigraphy and 124I positron emission tomography (PET). Methods GLV-1 h153 was tested against five human gastric cancer cell lines using cytotoxicity and standard viral plaque assays. In vivo, subcutaneous flank tumors were generated in nude mice with human gastric cancer cells, MKN-74. Tumors were subsequently injected with either GLV-1 h153 or PBS and followed for tumor growth. 99mTc pertechnetate scintigraphy and 124I microPET imaging were performed. Results GFP expression, a surrogate for viral infectivity, confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1, GLV-1 h153 achieved > 90% cytotoxicity in MNK-74, OCUM-2MD3, and AGS over 9 days, and >70% cytotoxicity in MNK- 45 and TMK-1. In vivo, GLV-1 h153 was effective in treating xenografts (p < 0.001) after 2 weeks of treatment. GLV-1 h153-infected tumors were readily imaged by 99mTc pertechnetate scintigraphy and 124I microPET imaging 2 days after treatment. Conclusions GLV-1 h153 is an effective oncolytic virus expressing the hNIS protein that can efficiently regress gastric tumors and allow deep-tissue imaging. These data encourages its continued investigation in clinical settings. PMID:24383569

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

    PubMed

    Chen, Jian; Yang, Wei-Jun; Sun, Hai-Jian; Yang, Xia; Wu, Yu-Zhang

    2016-08-01

    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

  20. 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

  1. Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer

    PubMed Central

    Xi, H Q; Cai, A Z; Wu, X S; Cui, J X; Shen, W S; Bian, S B; Wang, N; Li, J Y; Lu, C R; Song, Z; Wei, B; Chen, L

    2014-01-01

    Background: Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), which is identified as a novel intestinal stem cell marker, is overexpressed in various tumours. In this study, we explore Lgr5 expression in gastric carcinoma and analyse its role in invasion, metastasis, and prognosis in carcinoma. Methods: A combination of immunohistochemistry, western blotting, and quantitative reverse transcription–polymerase chain reaction were used to detect mRNA and protein expression levels of Lgr5 and matrix metalloproteinase 2 (MMP2). Small interfering RNA against Lgr5 was designed, synthesised, and transfected into AGS cells. The effects of Lgr5 siRNA on cell invasion were detected by transwell invasion chamber assay and wound healing assay. Results: Leucine-rich repeat-containing G-protein-coupled receptor 5 expression was significantly higher in gastric carcinomas than in normal mucosa. Leucine-rich repeat-containing G-protein-coupled receptor 5 expression positively correlated with the depth of invasion, lymph node metastasis, distance of metastasis, and MMP2 expression levels. Multivariate analysis showed that Lgr5 had an independent effect on survival, and that it positively correlated with MMP2. Leucine-rich repeat-containing G-protein-coupled receptor 5 siRNAs inhibited Lgr5 mRNA and protein expression. Transwell assays indicated that these siRNAs resulted in significantly fewer cells migrating through the polycarbonate membrane, and wound healing assay also indicated that siRNAs decreased the migration of cells. Inhibition of Lgr5 resulted in a significant decrease in MMP2 and β-catenin levels compared with those in controls. Conclusions: Leucine-rich repeat-containing G-protein-coupled receptor 5 was correlated with invasion and metastasis. Leucine-rich repeat-containing G-protein-coupled receptor 5 inhibition could serve as a novel therapeutic approach. PMID:24594994

  2. Molecular classification and prediction in gastric cancer

    PubMed Central

    Lin, Xiandong; Zhao, Yongzhong; Song, Won-min; Zhang, Bin

    2015-01-01

    Gastric cancer, a highly heterogeneous disease, is the second leading cause of cancer death and the fourth most common cancer globally, with East Asia accounting for more than half of cases annually. Alongside TNM staging, gastric cancer clinic has two well-recognized classification systems, the Lauren classification that subdivides gastric adenocarcinoma into intestinal and diffuse types and the alternative World Health Organization system that divides gastric cancer into papillary, tubular, mucinous (colloid), and poorly cohesive carcinomas. Both classification systems enable a better understanding of the histogenesis and the biology of gastric cancer yet have a limited clinical utility in guiding patient therapy due to the molecular heterogeneity of gastric cancer. Unprecedented whole-genome-scale data have been catalyzing and advancing the molecular subtyping approach. Here we cataloged and compared those published gene expression profiling signatures in gastric cancer. We summarized recent integrated genomic characterization of gastric cancer based on additional data of somatic mutation, chromosomal instability, EBV virus infection, and DNA methylation. We identified the consensus patterns across these signatures and identified the underlying molecular pathways and biological functions. The identification of molecular subtyping of gastric adenocarcinoma and the development of integrated genomics approaches for clinical applications such as prediction of clinical intervening emerge as an essential phase toward personalized medicine in treating gastric cancer. PMID:26380657

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Lee, Se-Jung; Ryu, Dong Hee; Jang, Lee Chan; Cho, Seok-Cheol; Kim, Wun-Jae; Moon, Sung-Kwon

    2013-04-01

    The thorns of Gleditsia sinensis are a traditional Oriental medicine used for the treatment of swelling, suppuration, carbuncle and skin diseases. In the present study, we identified a novel molecular mechanism by which an ethanol extract of Gleditsia sinensis thorns (EEGS) inhibits the growth of the SNU-5 human gastric cancer cell line. EEGS treatment inhibited cell growth and was associated with G1 phase cell cycle arrest at a concentration of 400 µg/ml (IC50) in SNU-5 cells. Treatment with EEGS also stimulated p21WAF1 expression, which significantly decreased the expression of cyclins and cyclin-dependent kinases (CDKs). Further study suggested that p38 MAP kinase pathways may be involved in the inhibition of cell proliferation through p21WAF1‑dependent G1 phase cell cycle arrest in EEGS-treated cells. In addition, NF-κB and AP-1 transcription factor binding sites were identified as the cis-elements for tumor necrosis factor-α (TNF-α)-induced matrix metalloproteinase-9 (MMP-9) expression in SNU-5 cells, as determined by gel-shift assay. Treatment of cells with EEGS suppressed MMP-9 expression induced by TNF-α via a decrease in the binding activity of both NF-κB and AP-1 motifs. These data demonstrate that EEGS-mediated inhibition of cell growth appears to involve the activation of p38 MAP kinase, subsequently leading to the induction of p21WAF1 and the downregulation of cyclin D1/CDK4 and cyclin E/CDK2 complexes. Moreover, EEGS strongly inhibited TNF-α-induced MMP-9 expression by impeding the DNA binding activity of NF-κB and AP-1. Overall, these results provide a potential mechanism for EEGS in the treatment of gastric cancer. PMID:23381601

  5. Surgically resected human tumors reveal the biological significance of the gastric cancer stem cell markers CD44 and CD26

    PubMed Central

    NISHIKAWA, SHIMPEI; KONNO, MASAMITSU; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; KANO, YOSHIHIRO; FUKUSUMI, TAKAHITO; SATOH, TAROH; TAKIGUCHI, SHUJI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

    2015-01-01

    Cancer tissue is maintained by relatively small populations of cancer stem cells (CSCs), which are involved in chemotherapy resistance, recurrence and metastasis. As tumor tissues are comprised of various cells, studies of human clinical samples are important for the characterization of CSCs. In the present study, an expression profiling study was performed in which an anti-cell surface marker antibody-based array platform, a flow cytometry-based cell separation technique and a tumorigenicity analysis in immunodeficient animals were utilized. These approaches revealed that the markers cluster of differentiation (CD)44 and CD26 facilitated the fractionation of surgically resected human gastric cancer (GC) cells into the following subset populations with distinct tumorigenic potentials: Highly tumorigenic CD26+CD44+ cells (6/6 mice formed tumors), moderately tumorigenic CD26+CD44− cells (5/6 mice formed tumors), and weakly or non-tumorigenic CD26−CD44− cells (2/6 mice formed tumors). Furthermore, exposure to 5-fluorouracil significantly increased the proportion of CD26+ cells in vitro. The present study demonstrated that the combined expression of CD26 and CD44 presents a potential marker of human GC stem cells. PMID:26137071

  6. Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma

    PubMed Central

    Chen, Yu-Jen; Chen, Chien-Chih; Huang, Huey-Lan

    2016-01-01

    Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine “Tianma”. Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alamarBlue® assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In conclusion, our study indicates the potential of armillarikin as an effective agent for hepatoma or leukemia therapies. PMID:27536140

  7. Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma.

    PubMed

    Chen, Yu-Jen; Chen, Chien-Chih; Huang, Huey-Lan

    2016-01-01

    Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine "Tianma". Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alamarBlue(®) assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In conclusion, our study indicates the potential of armillarikin as an effective agent for hepatoma or leukemia therapies. PMID:27536140

  8. Curcumin suppresses migration and invasion of human endometrial carcinoma cells

    PubMed Central

    CHEN, QIAN; GAO, QING; CHEN, KUNLUN; WANG, YIDONG; CHEN, LIJUAN; LI, XU

    2015-01-01

    Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signal-regulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC. PMID:26622667

  9. Three-dimensional Organotypic Culture Models of Human Hepatocellular Carcinoma.

    PubMed

    Takai, Atsushi; Fako, Valerie; Dang, Hien; Forgues, Marshonna; Yu, Zhipeng; Budhu, Anuradha; Wang, Xin Wei

    2016-01-01

    Three-dimensional cell culture methods are viable in vitro approaches that facilitate the examination of biological features cancer cells present in vivo. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells in porous alginate scaffolds can generate organoid-like spheroids that mimic numerous features of glandular epithelium in vivo, such as acinar morphogenesis and apical expression patterns of EpCAM, a hepatic stem/progenitor cell marker highly expressed in a subset of HCC with stemness features. We show that the activation of Wnt/β-catenin signaling, an essential pathway for maintaining HCC stemness, is required for EpCAM(+) HCC spheroid formation as well as the maintenance of the acinous structure. Furthermore, we demonstrate that EpCAM(+) HCC cells cultured as spheroids are more sensitive to TGF/β-induced epithelial-mesenchymal transition with highly tumorigenic and metastatic potential in vivo compared to conventional two-dimensional (2D) culture. In addition, HCC cells in EpCAM(+) spheroids are more resistant to chemotherapeutic agents than 2D-cultured cells. The alginate scaffold-based organotypic culture system is a promising, reliable, and easy system that can be configured into a high throughput fashion for the identification of critical signaling pathways and screening of molecular drug targets specific for HCC. PMID:26880118

  10. Changes in arginase isoenzymes pattern in human hepatocellular carcinoma

    SciTech Connect

    Chrzanowska, Alicja; Krawczyk, Marek; Baranczyk-Kuzma, Anna

    2008-12-12

    Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide affecting preferentially patients with liver cirrhosis. The studies were performed on tissues obtained during surgery from 50 patients with HCC, 40 with liver cirrhosis and 40 control livers. It was found that arginase activity in HCC was nearly 5- and 15-fold lower than in cirrhotic and normal livers, respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic arginase) were identified by Western blotting in all studied tissues, however the amount of AI, as well as the expression of AI-mRNA were lower in HCC, in comparison with normal liver, and those of AII were significantly higher. Since HCC is arginine-dependent, and arginine is essential for cells growth, the decrease of AI may preserve this amino acid within tumor cells. Concurrently, the rise of AII can increase the level of polyamines, compounds crucial for cells proliferation. Thus, both arginase isoenzymes seem to participate in liver cancerogenesis.

  11. Three-dimensional Organotypic Culture Models of Human Hepatocellular Carcinoma

    PubMed Central

    Takai, Atsushi; Fako, Valerie; Dang, Hien; Forgues, Marshonna; Yu, Zhipeng; Budhu, Anuradha; Wang, Xin Wei

    2016-01-01

    Three-dimensional cell culture methods are viable in vitro approaches that facilitate the examination of biological features cancer cells present in vivo. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells in porous alginate scaffolds can generate organoid-like spheroids that mimic numerous features of glandular epithelium in vivo, such as acinar morphogenesis and apical expression patterns of EpCAM, a hepatic stem/progenitor cell marker highly expressed in a subset of HCC with stemness features. We show that the activation of Wnt/β-catenin signaling, an essential pathway for maintaining HCC stemness, is required for EpCAM+ HCC spheroid formation as well as the maintenance of the acinous structure. Furthermore, we demonstrate that EpCAM+ HCC cells cultured as spheroids are more sensitive to TGF/β-induced epithelial-mesenchymal transition with highly tumorigenic and metastatic potential in vivo compared to conventional two-dimensional (2D) culture. In addition, HCC cells in EpCAM+ spheroids are more resistant to chemotherapeutic agents than 2D-cultured cells. The alginate scaffold-based organotypic culture system is a promising, reliable, and easy system that can be configured into a high throughput fashion for the identification of critical signaling pathways and screening of molecular drug targets specific for HCC. PMID:26880118

  12. Wnt-/-β-catenin pathway signaling in human hepatocellular carcinoma

    PubMed Central

    Waisberg, Jaques; Saba, Gabriela Tognini

    2015-01-01

    The molecular basis of the carcinogenesis of hepatocellular carcinoma (HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The aberrant activation of signaling in the HCC is primarily due to the deregulated expression of the components of the Wnt-/-β-catenin. This leads to the activation of β-catenin/T-cell factor-dependent target genes that control cell proliferation, cell cycle, apoptosis, and cell motility. The deregulation of the Wnt pathway is an early event in hepatocarcinogenesis. An aggressive phenotype was associated with HCC, since this pathway is implicated in the proliferation, migration, and invasiveness of cancer cells, regarding the cell’s own survival. The disruption of the signaling cascade Wnt-/-β-catenin has shown anticancer properties in HCC’s clinical evaluations of therapeutic molecules targeted for blocking the Wnt signaling pathway for the treatment of HCC, and it represents a promising perspective. The key to bringing this strategy in to clinical practice is to identify new molecules that would be effective only in tumor cells with aberrant signaling β-catenin. PMID:26609340

  13. Wnt-/-β-catenin pathway signaling in human hepatocellular carcinoma.

    PubMed

    Waisberg, Jaques; Saba, Gabriela Tognini

    2015-11-18

    The molecular basis of the carcinogenesis of hepatocellular carcinoma (HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The aberrant activation of signaling in the HCC is primarily due to the deregulated expression of the components of the Wnt-/-β-catenin. This leads to the activation of β-catenin/T-cell factor-dependent target genes that control cell proliferation, cell cycle, apoptosis, and cell motility. The deregulation of the Wnt pathway is an early event in hepatocarcinogenesis. An aggressive phenotype was associated with HCC, since this pathway is implicated in the proliferation, migration, and invasiveness of cancer cells, regarding the cell's own survival. The disruption of the signaling cascade Wnt-/-β-catenin has shown anticancer properties in HCC's clinical evaluations of therapeutic molecules targeted for blocking the Wnt signaling pathway for the treatment of HCC, and it represents a promising perspective. The key to bringing this strategy in to clinical practice is to identify new molecules that would be effective only in tumor cells with aberrant signaling β-catenin. PMID:26609340

  14. Effects of ToxCast Phase I Chemicals on Steroidogenesis in H295R Human Adrenocortical Carcinoma cells (SOT)

    EPA Science Inventory

    Steroid hormones are essential for proper development and reproduction. Disruption of steroidogenesis by environmental toxicants results in altered hormone levels causing adverse reproductive and developmental effects. H295R human adrenocortical carcinoma cells were used to evalu...

  15. An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells

    PubMed Central

    Yashiro, M; Qiu, H; Hasegawa, T; Zhang, X; Matsuzaki, T; Hirakawa, K

    2011-01-01

    Background: Acquired drug resistance to irinotecan is one of the significant obstacles in the treatment of advanced gastric cancer. This study was performed to clarify the effect of epidermal growth factor receptor (EGFR) inhibitors in combination with SN38, an active metabolite of irinotecan, on the proliferation of irinotecan-refractory gastric cancer. Methods: Two irinotecan-resistant gastric cancer cell lines, OCUM-2M/SN38 and OCUM-8/SN38 were, respectively, established by stepwise exposure to SN38 from the parent gastric cancer cell lines OCUM-2M and OCUM-8. The combination effects of two EGFR inhibitors, gefitinib and lapatinib, with SN38 on proliferation, apoptosis, and cell cycle on gastric cancer cells were examined. Results: Gefitinib or lapatinib showed synergistic anti-tumour effects against OCUM-2M/SN38 and OCUM-8/SN38 cells when used in combination with SN38, but not against OCUM-2M or OCUM-8 cells. SN38 increased the expression of EGFR and HER2 in OCUM-2M/SN38 and OCUM-8/SN38 cells. The combination of an EGFR inhibitor and SN38 significantly increased the levels of apoptosis-related molecules, caspase-6, p53, and DAPK-2, and resulted in the induction of apoptosis of irinotecan-resistant cells. The EGFR inhibitors increased the S-phase and decreased the UGT1A1 and ABCG expression in irinotecan-resistant cells. The SN38 plus Lapatinib group more effectively suppressed in vivo tumour growth by OCUM-2M/SN38 cells than either alone group. Conclusion: The combination treatment with an EGFR inhibitor and irinotecan might produce synergistic anti-tumour effects for irinotecan-refractory gastric cancer cells. The regulation of SN38 metabolism-related genes and cell cycle by EGFR inhibitors might be responsible for the synergism. PMID:21997136

  16. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells

    PubMed Central

    Gong, Jianlin; Avigan, David; Chen, Dongshu; Wu, Zekui; Koido, Shigeo; Kashiwaba, Masahiro; Kufe, Donald

    2000-01-01

    We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs. Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules. The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors. PMID:10688917

  17. Invasiveness and Ploidy of Human Mammary Carcinomas in Short-Term Culture

    NASA Astrophysics Data System (ADS)

    Smith, Helene S.; Liotta, Lance A.; Hancock, Miriam C.; Wolman, Sandra R.; Hackett, Adeline J.

    1985-03-01

    Invasiveness and ploidy were examined in cultures of human epithelial cells derived from nonmalignant breast tissue, primary breast carcinomas, and breast cancer effusion metastases. Successful short-term culture was achieved from approximately 70% of the primary breast cancers. These primary cancers were essentially diploid by flow cytometry and karyotype in contrast to the effusion metastases, which were mostly aneuploid. The diploid tumor cells retained their malignant phenotype in culture as demonstrated by invasion into a denuded human amnion basement membrane. In contrast, epithelial cells cultured from nonmalignant mammary tissue did not invade the amnion. We suggest that the diploid carcinoma cultures may be useful for investigating the essential differences between normal and malignant cells and may complement information derived from studies of tumor cell lines with grossly aberrant karyotypes.

  18. Development and characterization of a monoclonal antibody to human embryonal carcinoma

    SciTech Connect

    Khazaeli, M.B.; Beierwaltes, W.H.; Pitt, G.S.; Kabza, G.A.; Rogers, K.J.; LoBuglio, A.F.

    1987-06-01

    A monoclonal anti-testicular carcinoma antibody was obtained via the somatic cell fusion technique by immunization of BALB/c mice with freshly prepared single cell suspension from a patient with testicular embryonal carcinoma with choriocarcinoma components. The hybridoma supernates were screened against the testicular carcinoma cells used in the immunization as well as normal mononuclear white blood cells isolated from the same patient. An antibody (5F9) was selected which bound to fresh tumor cells from two patients with embryonal testicular carcinoma and failed to bind to fresh tumor cells from 24 patients (2 seminoma, 2 melanoma, 3 neck, 2 esophageal, 1 ovarian, 3 colon, 1 prostate, 2 breast, 1 liposarcoma, 3 endometrial, 1 kidney, 1 adrenal, 1 larynx and 1 bladder tumors) or cell suspensions prepared from normal liver, lung, spleen, ovary, testes, kidney, red blood cells or white blood cells. The antibody was tested for its binding to several well established cancer cell lines, and was found to bind to the BeWo human choriocarcinoma and two human embryonal carcinoma cell lines. The antibody did not react with 22 other cell lines or with hCG. The antibody was labeled with /sup 131/I and injected into nude mice bearing BeWo tumors and evaluated for tumor localization by performing whole body scans with a gamma camera 5 days later. Six mice injected with the antibody showed positive tumor localization without the need for background subtraction while six mice injected with MOPC-21, a murine myeloma immunoglobulin, demonstrated much less tumor localization. Tissue distribution studies performed after scanning showed specific tumor localization (8:1 tumor: muscle) for the monoclonal antibody and no specific localization for MOPC-21.

  19. A prospective study of the relationship between prediagnostic human papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas.

    PubMed

    Sigstad, E; Lie, A K; Luostarinen, T; Dillner, J; Jellum, E; Lehtinen, M; Thoresen, S; Abeler, V

    2002-07-15

    Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2-8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA. PMID:12107839

  20. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    SciTech Connect

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  1. NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations

    PubMed Central

    PARK, EUNJU; PARK, JINAH; HAN, SAE-WON; IM, SEOCK-AH; KIM, TAE-YOU; OH, DO-YOUN; BANG, YUNG-JUE

    2012-01-01

    Aberrations of Phosphoinositide 3-kinase (PI3K)/AKT signaling are frequently observed in many types of cancer, promoting its emergence as a promising target for cancer treatment. PI3K can become activated by various pathways, one of which includes RAS. RAS can not only directly activate the PI3K/AKT pathway via binding to p110 of PI3K, but also regulates mTOR via ERK or RSK independently of the PI3K/AKT pathway. Thus, actively mutated RAS can constitutively activate PI3K signaling. Additionally, in RAS tumorigenic transformation, signal transducer and activator of transcription 3 (STAT3) has been known also to be required. In this study, we examined the efficacy of NVP-BKM120, a pan-class I PI3K inhibitor in human gastric cancer cells and hypothesized that the combined inhibition of PI3K and STAT3 would be synergistic in KRAS mutant gastric cancer cells. NVP-BKM120 demonstrated anti-proliferative activity in 11 human gastric cancer cell lines by decreasing mTOR downstream signaling. But NVP-BKM120 treatment increased p-AKT by subsequent abrogation of feedback inhibition by stabilizing insulin receptor substrate-1. In KRAS mutant gastric cancer cells, either p-ERK or p-STAT3 was also increased upon treatment of NVP-BKM120. The synergistic efficacy study demonstrated that dual PI3K and STAT3 blockade showed a synergism in cells harboring mutated KRAS by inducing apoptosis. The synergistic effect was not seen in KRAS wild-type cells. Together, these findings suggest for the first time that the dual inhibition of PI3K and STAT3 signaling may be an effective therapeutic strategy for KRAS mutant gastric cancer patients. PMID:22159814

  2. Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line.

    PubMed

    Ruffa, M J; Ferraro, G; Wagner, M L; Calcagno, M L; Campos, R H; Cavallaro, L

    2002-03-01

    Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts. PMID:11849838

  3. Comparison of Gastric Microbiota Between Gastric Juice and Mucosa by Next Generation Sequencing Method

    PubMed Central

    Sung, Jihee; Kim, Nayoung; Kim, Jaeyeon; Jo, Hyun Jin; Park, Ji Hyun; Nam, Ryoung Hee; Seok, Yeong-Jae; Kim, Yeon-Ran; Lee, Dong Ho; Jung, Hyun Chae

    2016-01-01

    Background: Not much is known about the role of gastric microbiota except for Helicobacter pylori in human health and disease. In this study, we aimed to detect human gastric microbiota in both gastric mucosa and gastric juice by barcoded 454-pyrosequencing of the 16S rRNA gene and to compare the results from mucosa and juice. Methods: Gastric biopsies and stomach juices were collected from 4 subjects who underwent standard endoscopy at Seoul National University Bundang Hospital. Gastric microbiota of antral mucosa, corpus mucosa samples, and gastric fluids were analyzed by barcoded 454-pyrosequencing of the 16S rRNA gene. The analysis focused on bacteria, such as H. pylori and nitrosating or nitrate-reducing bacteria. Results: Gastric fluid samples showed higher diversity compared to that of gastric mucosa samples. The mean of operational taxonomic units was higher in gastric fluid than in gastric mucosa. The samples of gastric fluid and gastric mucosa showed different composition of phyla. The composition of H. pylori and Proteobacteria was higher in mucosa samples compared to gastric fluid samples (H. pylori, 66.5% vs. 3.3%, P = 0.033; Proteobacteria, 75.4% vs. 26.3%, P = 0.041), while Actinobacteria, Bacteroidetes, and Firmicutes were proportioned relatively less in mucosa samples than gastric fluid. However there was no significant difference. (Actinobacteria, 3.5% vs. 20.2%, P = 0.312; Bacteroidetes, 6.0% vs. 14.8%, P = 0.329; Firmicutes, 12.8% vs. 33.4%, P = 0.246). Conclusions: Even though these samples were small, gastric mucosa could be more effective than gastric fluid in the detection of meaningful gastric microbiota by pyrosequencing. PMID:27051651

  4. Chromosome 5 allele loss in human colorectal carcinomas.

    PubMed

    Solomon, E; Voss, R; Hall, V; Bodmer, W F; Jass, J R; Jeffreys, A J; Lucibello, F C; Patel, I; Rider, S H

    That the sporadic and inherited forms of a particular cancer could both result from mutations in the same gene was first proposed by Knudson. He further proposed that these mutations act recessively at the cellular level, and that both copies of the gene must be lost for the cancer to develop. In sporadic cases both events occur somatically whereas in dominant familial cases susceptibility is inherited through a germline mutation and the cancer develops after a somatic change in the homologous allele. This model has since been substantiated in the case of retinoblastoma, Wilms tumour, acoustic neuroma and several other tumours, in which loss of heterozygosity was shown in tumour material compared to normal tissue from the same patient. The dominantly inherited disorder, familial adenomatous polyposis (FAP, also called familial polyposis coli), which gives rise to multiple adenomatous polyps in the colon that have a relatively high probability of progressing to a malignant adenocarcinoma, provides a basis for studying recessive genes in the far more common colorectal carcinomas using this approach. Following a clue as to the location of the FAP gene given by a case report of an individual with an interstitial deletion of chromosome 5q, who had FAP and multiple developmental abnormalities, we have examined sporadic colorectal adenocarcinomas for loss of alleles on chromosome 5. Using a highly polymorphic 'minisatellite' probe which maps to chromosome 5q we have shown that at least 20% of this highly heterogeneous set of tumours lose one of the alleles present in matched normal tissue. This parallels the assignment of the FAP gene to chromosome 5 (see accompanying paper) and suggests that becoming recessive for this gene may be a critical step in the progression of a relatively high proportion of colorectal cancers. PMID:2886919

  5. Expression and clinical significance of aquaglyceroporins in human hepatocellular carcinoma.

    PubMed

    Chen, Xiao-Feng; Li, Chuan-Fei; Lü, Lin; Mei, Zhe-Chuan

    2016-06-01

    Aquaglyceroporins (AQPs) are a subset of the aquaporin family, and are permeable to water and glycerol. The aim of the present study was to determine the expression and clinical significance of three AQPs, AQP3, 7 and 9 in hepatocellular carcinoma (HCC). Fresh HCC and adjacent non‑tumorous liver tissues were collected from 68 patients diagnosed with HCC. The expression levels of AQP3, 7 and 9 were detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The association between the expression of AQPs and clinicopathological parameters of HCC were investigated. Compared with non‑tumorous liver tissue, HCC tissues exhibited a significant (P<0.05) increase in the expression of AQP3 and a concomitant reduction in the expression levels of AQP7 and AQP9, at both the mRNA and protein levels. Immunohistochemistry revealed that AQP9 was dominantly localized on the plasma membrane of hepatocytes, while AQP3 and AQP7 exhibited a predominantly cytoplasmic and nuclear distribution. High expression of AQP3 was significantly (P<0.05) associated with low expression levels of AQP7 and AQP9. High expression of AQP3 was correlated with tumor grade (P=0.017), tumor stage (P=0.010) and lymphatic metastasis (P=0.031). Low expression of AQP7 was correlated with tumor grade (P=0.043). AQP3 was upregulated, and AQP7 and AQP9 were downregulated in HCC. A high expression of AQP3 and low expression of AQP7 was significantly associated with the aggressive features of HCC. PMID:27121567