Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori causes gastritis, peptic ulcer disease and gastric cancer. The microbe is found in the gastric mucus layer where a pH gradient ranging from acidic in the lumen to neutral at the cell surface is maintained. The aim of the present study was to investigate the effects of pH on H. pylori binding to gastric mucins from healthy individuals. At pH 3, all strains bound to the most charged MUC5AC glycoform and to a putative mucin of higher charge and larger size than subunits of MUC5AC and MUC6, irrespective of host blood-group. In contrast, at pH 7.4 only Le(b)-binding BabA-positive strains bound to Le(b)-positive MUC5AC and to smaller mucin-like molecules, including MUC1. H. pylori binding to the latter component(s) seems to occur via the H-type-1 structure. All strains bound to a proteoglycan containing chondroitin sulphate/dermatan sulphate side chains at acidic pH, whereas binding to secreted MUC5AC and putative membrane-bound strains occurred both at neutral and acidic pH. The binding properties at acidic pH are thus common to all H. pylori strains, whereas mucin binding at neutral pH occurs via the bacterial BabA adhesin and the Le(b) antigen/related structures on the glycoprotein. Our work shows that microbe binding to membrane-bound mucins must be considered in H. pylori colonization, and the potential of these glycoproteins to participate in signalling events implies that microbe binding to such structures may initiate signal transduction over the epithelial layer. Competition between microbe binding to membrane-bound and secreted mucins is therefore an important aspect of host-microbe interaction.
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PMID:Effects of pH on Helicobacter pylori binding to human gastric mucins: identification of binding to non-MUC5AC mucins. 1526 Aug 2

Heat shock proteins (HSPs) exist ubiquitously across all species and function as chaperones stabilizing and delivering peptides. Tumor-derived HSP-peptide complex has been known to induce immunity against the original tumor in preclinical studies. HSP-based vaccines work across tumor types and bypass the need for identifying the responsible peptide(s) for inducing immunity. These vaccines are tumor- and patient-specific in that they capture the tumor cells' fingerprints. HSP-based vaccines have been studied in early phase clinical trials, mostly using HSP glycoprotein 96, for various types of malignancies including melanoma, renal cell carcinoma, gastric cancer, pancreatic cancer, low-grade lymphoma, colorectal cancer and chronic myelogenous leukemia. All showed minimal toxicity and potential efficacy. Phase III studies for melanoma and renal cell carcinoma are ongoing. HSP-based vaccines are a novel vaccine preparation with a promising role in cancer management. Further studies to determine the administering strategy and specific indication are warranted.
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PMID:Heat shock protein-based cancer vaccines. 1527 Jun 45

The over-expression of a new zinc ribbon (ZNRD1) gene has been shown previously to promote a multidrug-resistant phenotype in gastric cancer cells through the up-regulation of permeability-glycoprotein (P-gp). In the present study, siRNA eukaryotic expression vectors of ZNRD1 are constructed and transfected into SGC7901/VCR cells to examine whether or not down-regulation of ZNRD1 increases cell sensitivity towards chemotherapeutic drugs. After transfection, ZNRD1 expression decreased dramatically in ZNRD1 siRNA transfectants compared with that in parental cells and empty vector control cells. Down-regulation of ZNRD1 significantly enhanced the sensitivity of SGC7901/VCR cells to vincristine, adriamycin and etoposide, but not to 5-fluorouracil and cisplatin. Cell capacity to efflux adriamycin decreased markedly in ZNRD1 siRNA transfectants, and correlation between ZNRD1 down-regulation and increased multidrug resistance 1 (MDR1) gene transcriptional activity was observed. These results suggest that the ZNRD1 siRNA constructs down-regulate the expression of ZNRD1 effectively and reverse the resistant phenotype of gastric cancer cells. Furthermore, ZNRD1 might influence transcription of the MDR1 gene and thus play an important role in multidrug resistance in gastric carcinoma.
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PMID:Reversal of multidrug resistance of gastric cancer cells by down-regulation of ZNRD1 with ZNRD1 siRNA. 1564 14

Rebamipide, a gastro-protective drug, was developed in Japan for the treatment of peptic ulcer disease. It was proven superior to the former same category drug cetraxate in a randomized, controlled, double-blind, comparative clinical study in 1989. Rebamipide's mechanisms of actions are different from anti-secretory drugs; it accelerates and improves the quality of ulcer healing and reduces ulcer recurrence rate. Numerous studies have been conducted to explain the mechanisms responsible for these actions, 37 papers were published by 1998. Major properties of rebamipide include: stimulation of prostaglandin and mucus glycoprotein synthesis, inhibition of reactive oxygen species, inflammatory cytokines and chemokines, and inhibition of neutrophils activation. Since 1998, 107 papers were published, clarifying further effects of rebamipide on cyclooxygenase-2, prostaglandin E receptors, growth factors (i.e., HGF, EGF, and VEGF), heat-shock proteins, nitric oxide, adhesion molecules, neutrophils, and Helicobacter pylori- and NSAID-related pathology. Moreover, inhibitory action of rebamipide on gastric cancer growth has also been shown. In this issue we reviewed recent advances in understanding of rebamipide's mechanism of action and its newest clinical applications.
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PMID:15th anniversary of rebamipide: looking ahead to the new mechanisms and new applications. 1618 18

We cloned and characterized human WNT2B (WNT13) in 1996. Following our discovery of human WNT2B, others and we characterized mouse, rat, chicken and zebrafish WNT2B orthologs. Here, comparative integromics analyses on WNT2B and its clinical applications are reviewed. WNT2B-ST7L-CAPZA1 locus at human chromosome 1p13.2 and WNT2-ST7-CAPZA2 locus at human chromosome 7q31.2 are paralogous regions within the human genome. Two splicing variants occur from human WNT2B gene due to alternative promoters. WNT2B splicing variant 1 encodes secreted-type glycoprotein with WNT domain (WNT2B isoform 1), while WNT2B splicing variant 2 encodes transmembrane-type glycoprotein with WNT domain (WNT2B isoform 2). WNT2B splicing variant 2 is the evolutionarily conserved major transcript of human WNT2B gene. Mammalian WNT2B orthologs acquired the transmembrane domain and integrin-targeting RGD motif during vertebrate evolution. Human WNT2B isoform 2 and other vertebrate WNT2B orthologs are canonical WNTs to determine cell fate through the activation of beta-catenin/TCF signaling pathway and SNAIL/EMT signaling pathway. E box and CCAAT box are conserved within mammalian WNT2B promoters. WNT2B functions as the stem cell factor for neural or retinal progenitor cells during embryogenesis, and also for gastric cancer, esophageal cancer and skin basal cell carcinoma during carcinogenesis. Anti-WNT2B monoclonal antibody could be applied as selection marker of stem cells in the field of stem cell biology. Soluble WNT2B protein or small molecule WNT2B mimic compounds could be developed for stem cell expansion in the fields of tissue engineering and regenerative medicine. Anti-WNT2B monoclonal antibodies, WNT2B RNAi compounds, or small molecule WNT2B inhibitors could be developed as novel therapeutic agents for gastric cancer and esophageal cancer in the field of clinical oncology.
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PMID:WNT2B: comparative integromics and clinical applications (Review). 1627 93

Urinary proteins from six patients with esophageal cancer and two with stomach cancer were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Analyses were performed on days-1 to 3, 5, 7, 10, 14, and 21 (or 22) after surgery. The protein patterns were scanned by densitometry and divided into nine fractions. The main proteins in the fractions (Fr.) were identified as follows: immunoglobulin G in Fr. A, Tamm-Horsfall glycoprotein (THP) in Fr. B, transferrin in Fr. C, albumin in Fr. D, alpha(1)-acid glycoprotein in Fr. E, alpha(1)-microglobulin in Fr. F, retinol binding protein in Fr. G, and beta(2)-microglobulin in Fr. I. The protein in Fr. H was not identified. The percentage of each fraction was calculated from the densitometry pattern of each lane. The percentage values were averaged among all the patients, and pre- and postoperative data were compared. The percentage of Frs. E, F, and G increased on days 1-7, and the changes in these three proteins were similar to changes in serum C-reactive protein (CRP). In particular, the percentage of Fr. G peaked within 1 day of operation, which was faster than for CRP. Conversely, other fractions decreased. These results suggest that urinary protein analysis is useful for monitoring the response to surgical stress.
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PMID:Urinary protein analysis in pre- and postoperative cancer patients. 1630 10

The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data.
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PMID:The role of osteopontin in tumor progression and metastasis in breast cancer. 1754 69

The p73 protein is a transcription factor and member of the p53 protein family that expresses as a complex variety of isoforms. DeltaNp73alpha is an N-terminally truncated isoform of p73. We found that DeltaNp73 protein is upregulated in human gastric carcinoma suggesting that DeltaNp73 may play an oncogenic role in these tumors. Although it has been shown that DeltaNp73alpha inhibits apoptosis and counteracts the effect of chemotherapeutic drugs, the underlying mechanism by which this p73 isoform contributes to chemotherapeutic drug response remains to be explored. We found that DeltaNp73alpha upregulates MDR1 mRNA and p-glycoprotein (p-gp), which is involved in chemotherapeutic drug transport. This p-gp upregulation was accompanied by increased p-gp functional activity in gastric cancer cells. Our data suggest that upregulation of MDR1 by DeltaNp73alpha is mediated by interaction with p53 at the MDR1 promoter.
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PMID:DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function. 1795 18

Here, we firstly investigated the roles of DARPP-32 in multidrug resistance of gastric cancer cells. Inhibition of DARPP-32 by small interfering RNA led to decreased sensitivity of cells to chemotherapeutic drugs, accompanied by increased capacity of cells to efflux adriamycin. Inhibition of DARPP-32 expression could significantly up-regulate the expression of permeability glycoprotein (P-gp) and zinc ribbon domain-containing 1 (ZNRD1), but not alter the expression of multidrug resistance-associated protein or glutathione transferase. The DARPP-32 siRNA-mediated MDR could be reversed by inhibitor of P-gp or siRNA of ZNRD1, indicating DARPP-32 might mediate MDR of gastric cancer through regulation of P-gp and ZNRD1.
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PMID:DARPP-32 mediates multidrug resistance of gastric cancer through regulation of P-gp and ZNRD1. 1805 65

Chronic inflammation in the stomach induces cellular transformation and gastric cancer primarily in the distal stomach or antrum. In this issue of the JCI, a study in mice by Ernst et al. provides new insight into the role of IL-11 and its glycoprotein 130 (gp130) receptor in inflammation-associated gastric epithelial cell oncogenic transformation, which they show is mediated by and dependent on increased activation of Stat3 and, to a lesser extent, Stat1 (see the related article beginning on page 1727). Prior studies from this group have shown that Stat3 hyperactivity stimulates the TGF-beta inhibitor Smad7. Collectively, the studies suggest that an important pathway of oncogenic transformation in the stomach is through suppression of growth inhibitory signals, such as members of the TGF-beta family, that originate from the stroma.
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PMID:What lurks beneath: IL-11, via Stat3, promotes inflammation-associated gastric tumorigenesis. 1843 20


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